Current Topics On Fetal 3D 4D Ultrasound 2018

Current Topics on Fetal 3D/4D Ultrasound
Editor
Toshiyuki Hata
Kagawa University School of Medicine
Japan
Co-Editors
Asim Kurjak
University of Zagreb
Croatia
Shiro Kozuma
The University of Tokyo
Japan
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CONTENTS
Foreword i
Preface ii
List of Contributors iii
CHAPTERS
1. Normal Fetal Anatomy and Development 1

Shiro Kozuma
2. 3D / 4D US in Fetal Malformations
Part 1. First Trimestre Anomalies 12

Fernando Bonilla-Musoles, Luiz Eduardo Machado, Franciso Raga, Juan Carlos
Castillo, Newton Osborne, Esperanza Villalaiz, Francisco Bonilla Jr., Fernanda
Machado
Part 2. Second Trimester: Cephalic Pole Malformations 49

Castillo, Newton Osborne, Francisco Bonilla Jr., Fernanda Machado
Part 3. Second Trimester: Skeletal Disorders, Thoracic, Abdominal, Kidney and

Other Malformations 74
Castillo, Newton Osborne, Francisco Bonilla Jr., Fernanda Machado
3. Fetal Central Nervous System 118

Mi Suk Kim
4. Fetal 3D/4D Cardiovascular Imaging 133

Toshiyuki Hata, Junko Noguchi
5. Fetal Weight Estimation and Organ Volume Measurement by Three-Dimensional

Ultrasonography 177
Rodrigo Ruano
6. Placental Volume and Vascularization: The New Concept of ‘Virtual Placental Biopsy’ 192
Luis T. Mercé, María J. Barco
7. Assessment of Fetal Behaviour by 3D and 4D Sonography 212

Asim Kurjak, Iva Lausin, Guillermo Azumendi
i
FOREWORD
Hardly any area in medicine has experienced such dramatic technical advances during the past four decades as
diagnostic ultrasound. With the event and evolution of three-dimensional ultrasound technology during the past
20 years we arrived at the threshold of non invasive diagnosis. The progression from 2D to 3D has brought with
it a variety of new options for storing and processing image data and displaying anatomical structures. This
technology gives ultrasound the multiplanar capabilities that previously were reserved for CT and MRI.
The simultaneous 3D display of organs and their vessels, either in foetuses or tumours, may perhaps in future
form the basis for a better understanding of physiological and pathological features in these systems.
STIC and all his by products provide the best examples of both didactic and antiphobic tools that can help to
overcome the challenge of fetal cardiography.
The newer development of 4D ultrasound available now, due to the fast processing computers, make studies of
the intra uterine fetal behaviour possible. The possibilities of ultrasound in obstetrics and gynaecology have been
endless and I serious believe we have just skimmed the surface of this wonderful technology and hope of its
further development in future.
I wish this book a good success.
Dr. Alfred Kratochwil

Vienna
ii
PREFACE
There have been some review articles on fetal 3D/4D ultrasound. However, most of those review articles focused
on normal and abnormal fetal anatomies. The introduction of new 3D/4D ultrasound techniques such as VOCAL,
STIC, inversion mode, etc. would allow for the assessment of fetal weight estimation, fetal organ and placental
volume measurements, real-time fetal cardiovascular imaging and fetal behavioral assessment. With recent
advance in the 3D power Doppler ultrasound as well as the quantitative 3D histogram analysis, quantitative 3D
power Doppler in the assessment of the vascularization and the blood flow of the fetal organs and placenta has
become feasible. To the best of our knowledge, there has been no review volume on these recent advents of
3D/4D fetal ultrasound. This book complies the efforts of 7 well-established experts in fetal 3D/4D ultrasound in
reviewing the latest advances in the field, with strong emphasis on the usefulness in clinical practice, its
advantage, disadvantages and limitations, and future research on fetal medicine. Therefore, we consider our
review volume to be important enough to be published in the form of a single eBook. This would be interesting,
and has new information for likely audience of readers for our eBook.
Toshiyuki Hata, M.D., Ph.D.

Asim Kurjak, M.D.
Shiro Kozuma, M.D., Ph.D.
iii
List of Contributors
Shiro Kozuma Department of Obstetrics and Gynecology, The University of Tokyo, 7-3-1,
Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan
Fernando Bonilla-Musoles Department of Obstetrics and Gynecology, Valencia School of Medicine,

Valencia, Spain
Luiz Eduardo Machado Universities of Valencia, Salvador de Bahia, Panamá City, Panamá
Franciso Raga Universities of Valencia, Salvador de Bahia, Panamá City, Panamá
Juan Carlos Castillo Universities of Valencia, Salvador de Bahia, Panamá City, Panamá
Newton Osborne3 Universities of Valencia, Salvador de Bahia, Panamá City, Panamá
Esperanza Villalaiz Universities of Valencia, Salvador de Bahia, Panamá City, Panamá
Francisco Bonilla Jr. Universities of Valencia, Salvador de Bahia, Panamá City, Panamá
Fernanda Machado Universities of Valencia, Salvador de Bahia, Panamá City, Panamá
Mi Suk Kim Department of Obstetrics and Gynecology, Flushing Hospital Medical Center,
Flushing NY 11355, USA
Toshiyuki Hata Department of Perinatology and Gynecology, Kagawa University, School of

Medicine, 1750-1 Ikenobe, Miki Kagawa 761-0793, Japan
Junko Noguchi Department of Nursing, Kagawa Prefectural College of Health Sciences, 281-1
Murecho-hara, Takamatsu, Kagawa 761-0123, Japan
Rodrigo Ruano Obstetrics Department, Faculty of Medicine of the University of São Paulo, São
Paulo, Brazil
Luis T. Mercé Department of Obstetrics and Gynaecology, International Ruber Hospital,

Madrid, Spain
María J. Barco Bolonia Gynaecological Medical Center, Zaragoza, Spain
Asim Kurjak Department of Obstetrics and Gynaecology, Sveti Duh Hospital, Sveti Duh 64,
10000 Zagreb, Croatia
Iva Lausin Department of Obstetrics and Gynaecology, Sveti Duh Hospital, Sveti Duh 64,
10000 Zagreb, Croatia
Guillermo Azumendi Prenatal Diagnosis, Ultrasound Unit Centro Gutenberg, Malaga

Current Topics on Fetal 3D/4D Ultrasound, 2009, 1-11 1
CHAPTER 1
Normal Fetal Anatomy and Development
Shiro Kozuma*
Department of Obstetrics and Gynecology, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo, 113-8655,
Japan
Abstract: Normal fetal anatomy and development have been widely investigated with the development of
various ultrasound fetal diagnoses, including estimation of gestational age, detection of fetal anomalies and
evaluation of fetal growth. Our knowledge of fetal development, therefore, has been established through
understanding of sectional images of the fetal body or organs obtained by two-dimensional ultrasound.
Although three-dimensional ultrasound has been widely accepted for clinical use in antenatal care recently, a
powerful tool of three-dimensional ultrasound has not yet been fully utilized. Recent advances of three-
dimensional ultrasound provide us with a distinct aspect of fetal anatomy and development. This chapter
gives a clue to the entry into the new world of the fetus.
1. INTRODUCTION
For more than 30 years, ultrasound has been widely used in the field of perinatal medicine because of its safety,
diagnostic accuracy and convenience. A wide variety of fetal anomalies can be diagnosed by ultrasound, and
their diagnostic criteria are based on two-dimensional ultrasound findings without exception. Trained examiners
have been accustomed to mental reconstruction of three-dimensional structures of fetal anomalies from their
sectional images obtained by two-dimensional ultrasound [1-2]. Conversely, objects of antenatal ultrasound
diagnosis have been limited to the fetal anomalies which can be mentally reconstructed from their sectional
images until recently.
Although a large amount of literature on three-dimensional ultrasound has been produced since more than 10
years ago [3-9], it was only through the recent dramatic development of computer technologies and its
application to ultrasound systems that three-dimensional ultrasound has been widely accepted for clinical use in
antenatal care [10-12]. Three-dimensional ultrasound has the potential to be a tool which helps to overcome
limitations related to two-dimensional ultrasound. However, a wide range of tools in three-dimensional
ultrasound has not yet been perfectly used for several reasons, one of which is that most examiners have not been
fully trained for handling volume datasets, as far as I know. Although several studies have reported on
comparison between two-dimensional and three-dimensional ultrasound for the diagnosis of fetal anomalies,
yielding conflicting results [13-19], it seems to be too early to compare fairly between them, because the roles of
two-dimensional ultrasound for fetal diagnosis have been already established, on the other hand, those of three-
dimensional ultrasound have not at all. Only a small part of benefits of three-dimensional ultrasound has been
revealed until now.
Normal fetal anatomy and development have been widely investigated using two-dimensional ultrasound with
the development of various ultrasound fetal diagnoses, including estimation of gestational age, detection of fetal
anomalies and evaluation of fetal growth [20-25]. It is, therefore, conceivable to me that our knowledge of fetal
development has been established through understanding of sectional images of the fetal body or organs obtained
by two-dimensional ultrasound. Recent development of three-dimensional ultrasound will provide us with a
distinct aspect of fetal anatomy and development in the near future. This chapter gives just a clue to the entry
into another fetal world.
2. THREE-DIMENSIONAL ULTRASOUND OF THE GESTATIONAL SAC AND THE YOLK SAC
The first images that can be obtained at the beginning of pregnancy are those of the gestational sac, which is
visualized at 4.5 to 5 weeks of gestation [26]. The gestational sac has an oval or rounded shape and is covered
with the chorion, which has higher echo intensity than the surrounding endometrial decidua (Fig. 1-A). Three-
dimensional rendering clearly delineates both structures (Fig. 1-B), so that it is uncomplicated to differentiate the
gestational sac from various types of pseudo-gestational sac.
*Address correspondence to Shiro Kozuma: Department of Obstetrics and Gynecology, The University of Tokyo, 7-3-1, Hongo, Bunkyo-
ku, Tokyo, 113-8655, Japan; E-mail: kozuma-tky@umin.ac.jp
Toshiyuki Hata and Asim Kurjak (Eds)
All rights reserved - © 2009 Bentham Science Publishers
2 Current Topics on Fetal 3D/4D Ultrasound Shiro Kozuma
The yolk sac is the first structure to be seen normally within the gestational sac. The yolk sac is seen when the
diameter of the gestational sac is approximately 8mm using transvaginal ultrasound [27], although the secondary
yolk sac actually forms at approximately 4 weeks’ gestation, when the diameter of the gestational sac is
approximately 3 mm [28]. Three-dimensional ultrasound reveals the yolk sac to be a round structure (Fig. 1-C),
even when it looks like a dot in a two-dimensional image (Fig. 1-A).
(A) (B)
(C)
Figure 1: A 5-week pregnancy. A: A two-dimensional image of gestational sac (a), uterine cavity (b), and endometrial
decidua (c). The gestational sac is surrounded with the chorion. B: A three-dimensional ultrasound image of a gestational sac,
chorion and endometrial decidua in the uterus. C: A three-dimensional image of a yolk sac (a) and gestational sac (b). These
images were produced by analyzing a volume dataset provided by GE Healthcare.
(A) (B)
Figure 2: A: An embryo is seen as a laminar structure adjacent to the yolk sac in the gestational sac in two-dimensional
ultrasound. B: A three-dimensional image of the gestational sac (a), embryo (b) and yolk sac (c). These images were
produced by analyzing a volume dataset provided by GE Healthcare.
Figure 3: A 6-week pregnancy. A three-dimensional image of an embryo riding on the yolk sac (a). Only the head (b) of the
embryo is seen. The yolk sac is bigger than the head of the embryo.
Normal Fetal Anatomy and Development Current Topics on Fetal 3D/4D Ultrasound 3
3. THREE-DIMENSIONAL ULTRASOUND OF THE EMBRYO AND THE FETUS

3.1. Embryo
The embryo can be seen one to two days after visualization of the yolk sac, at which time it is 2 to 3 mm long
[26]. In such an early stage, two-dimensional ultrasound shows a laminar structure (Fig. 2-A), but three-
dimensional ultrasound reveals the embryo to be an elongated solid structure (Fig. 2-B). As the gestation
advances, the relationship between the embryo and the yolk sac changes in size and position (Fig 3-6). In 6
weeks’ gestation, the embryo is riding on the yolk sac which is bigger than the head of the embryo (Fig. 3). In 7
weeks’ gestation, the embryo is still in close vicinity to the yolk sac. The head of the embryo is similar to the
yolk sac in size (Fig. 4). In 8 weeks’ gestation, the yolk sac is a little away from the embryo. The head of the
embryo is bigger than the yolk sac (Fig. 5). In 9 weeks’ gestation, the yolk sac is situated in the distance (Fig. 6).
Figure 4: A 7-week pregnancy. A three-dimensional image of an embryo in close vicinity to the yolk sac (a). Only the head
(b) of the embryo is delineated clearly. The head of the embryo is similar to the yolk sac in size. This image was produced by
analyzing a volume dataset provided by GE Healthcare.
Figure 5: A 8-week pregnancy. A three-dimensional image of an embryo detached from the yolk sac (a). The head (b) of the
embryo is bigger than the yolk sac. This image was produced by analyzing a volume dataset provided by GE Healthcare.
3.2. Fetal Extremities

The fetal extremities are ones of the earliest structures that can be evaluated on ultrasound. According to the
textbook of embryology, limb buds appear towards the end of five weeks’ gestation as slight elevations of the
ventrolateral body wall [29]. The upper limb buds develop 2 days before the lower limb buds. The limb buds are
ultrasonically visible at seven weeks' gestation. At the end of seven weeks gestation, the distal ends of the limb
buds flatten into hand- and footplates (Fig. 7). During eight weeks’ gestation, mesenchymal tissue in the hand-
and footplates forms digital rays. The end of the handplate appears to be lobulated in Fig. 8. Separate digits are
formed by the end of nine weeks’ gestation (Fig. 9).
Figure 6: A 9-week pregnancy. A three-dimensional image of an embryo. The yolk sac (a) is situated in the distance like a
moon . This image was produced by analyzing a volume dataset provided by GE Healthcare.
Figure 7: A three-dimensional image of hand- and footplate (a and b) in the embryo. In both limbs, the distal end is slightly
broader than the proximal part. This image was produced by analyzing a volume dataset provided by GE Healthcare.
Figure 8: A 8-week pregnancy. A three-dimensional image of a handplate with digital rays(a). b: the embryo, c: the yolk sac.
This image was produced by analyzing a volume dataset provided by GE Healthcare.
Figure 9: A 9-week pregnancy. A three-dimensional image of separate digits in the hand (a). The arms are bent at the elbow
(b) and the hands are curved over the thorax. This image was produced by analyzing a volume dataset provided by GE
Healthcare.
By eight weeks’ gestation, the limbs extend ventrally and the hand- and footplates face each other (Fig. 7-8).
During nine weeks’ gestation, the upper limbs are bent at the elbow and the hands are curved over the thorax
(Fig. 9). Then, the elbows point caudally and the knees cranially (Fig. 10). During the first half of gestation, the
limbs elongate rapidly in comparison with the head and trunk (Fig. 11-12).
Figure 10: A 11-week pregnancy. A three-dimensional image of the arm and leg in the fetus. The elbow points caudally and
the knee cranially. The arm is shorter than the major axis of the head. This image was produced by analyzing a volume
dataset provided by GE Healthcare.
Figure 11: A 13-week pregnancy. A three-dimensional image of the upper part of the fetus. The arm is slightly longer than
the major axis of the head.
Figure 12: A 16-week pregnancy. A three-dimensional image of the fetus. The arm is definitely longer than the major axis of
the head.
3.3. Fetal Trunk

The shape of the fetal trunk changes in various ways during pregnancy. The long tail –like caudal eminence is a
characteristic feature during a very early stage of gestation [30], although it is hardly seen because of the tininess of
the embryo. A short caudal eminence is visible between the legs in Fig. 13. All evidence of the caudal eminence
disappears by the end of ten weeks’ gestation (Fig. 14). Until eight weeks’ gestation, the embryo has a large bulge
called the heart prominence in the anterior wall of the chest (Fig. 15-16). Around nine weeks’ gestation, the liver
prominence appears (Fig. 17). The umbilical herniation is a normal event in the embryo in this period (Fig. 17),
because the abdominal cavity is too small to accommodate the rapidly growing intestine. The intestines return to the
abdominal cavity during eleven weeks’ gestation. During the first half of gestation, the lower abdomen is small in
comparison with the chest and upper abdomen (Fig. 18). In the second half of gestation, the growth of the lower
abdomen and hip catches up with those of the chest and upper abdomen (Fig. 19-20).
Figure 13: A 8-week pregnancy. A three-dimensional image of the embryo viewed from caudally. A short caudal eminence
(a) is visible between the legs (b). c: trunk, d: umbilical cord. This image was produced by analyzing a volume dataset
provided by GE Healthcare.
Figure 14: A 9-week pregnancy. A three-dimensional image of the embryo viewed from caudally. The caudal eminence is
invisible. a: legs, b: rump, c; trunk. This image was produced by analyzing a volume dataset provided by GE Healthcare.
Figure 15: A 7-week pregnancy. A three-dimensional image of the heart prominence (a) in the anterior wall of the chest. b:
rump, c: head. This image was produced by analyzing a volume dataset provided by GE Healthcare.
Figure 16: A 8-week pregnancy. A three-dimensional image of the heart prominence (a) in the anterior wall of the chest. b:
head, c: umbilical cord. This image was produced by analyzing a volume dataset provided by GE Healthcare.
(A) (B)
Figure 17: A 9-week pregnancy. A three-dimensional image of the liver prominence (a) and the umbilical herniation (b). A:
the frontal view, B: the lateral view. These images were produced by analyzing a volume dataset provided by GE Healthcare.
Figure 18: A 19-week pregnancy. A three-dimensional image of the fetal trunk viewed from backward. The lower abdomen
and hip is small in comparison with the chest and upper abdomen. a: chest, b: hip, c:arm.
Figure 19: A 22-week pregnancy. A three-dimensional image of the fetal trunk viewed from backward. The lower abdomen is
still small in comparison with the chest and upper abdomen. a: chest, b: lower abdomen.
(A) (B)
Figure 20: A 24-week pregnancy. A three-dimensional image of the fetal trunk viewed from backward. A: surface rendering
mode. a: back, b: hip. B: skeleton mode. The lower abdomen and hip become wider than before.
3.4. Fetal Face

The fetal face is a very complex area of fetal anatomy. At five weeks’ gestation, the primitive mouth is
surrounded with the five facial primordial: the single frontonasal prominence, the paired maxillary prominences
and the paired mandibular prominences. The frontonasal prominence grows forward and downward in the
midline [31]. At six weeks’ gestation, the nasal prominences and nasal pits form on the infero-lateral parts of the
frontonasal prominence. Between 7 and 10 weeks’ gestation, the medial nasal prominences merge with each
other and with the maxillary and lateral nasal prominences, resulting in continuity of the upper jaw and lip and
separation of the nasal pits from the stomadeum. These changes are difficult to see ultrasonically, because the
fetal head is pressed against the thorax [32]. A three-dimensional image shows that the eyes are widely separated,
the ears are low set, the nose is flat, and the mandible is underdeveloped around 10 weeks’ gestation, (Fig. 21-
22). The eyelid is open in Fig. 21, but it is closed in Fig. 22. In 13 weeks’ gestation, the nose and mandible is
still underdeveloped (Fig 23). A few weeks later, facial development is completed (Fig. 24). The fetal face is
lean during the first half of the second trimester, and thereafter it becomes wider (Fig. 25). During the third
trimester, the amount of subcutaneous tissue at the face increases with the advancement of gestation [33]. Fig. 26
shows the changes in the appearance of the face in a fetus during 34 and 39 weeks’ gestation. The accumulation
of subcutaneous tissue on the cheek is clearly demonstrated.
4. CONCLUSIONS
We have just taken a glance at the new world of the fetus by using surface rendering ultrasound in this chapter. It
is not always possible to obtain three-dimensional images such as those shown here. If the fetus is in contact
with the placenta or the uterine wall, it is difficult to provide an adequate surface reconstruction. Although three-
dimensional ultrasound of the fetus has some problems that need to be resolved for the acceptance as a reliable
examination method, we certainly started to accumulate knowledge of the fetus by using the technique. Two-
dimensional ultrasound opened the door to the fetus, and hereafter three-dimensional ultrasound will push us into
the new world of the fetus.
(A) (B)
Figure 21: A 9-week pregnancy. A three-dimensional image of the fetal face. A: the frontal view. The eyes (a) are widely
separated and the nose (b) is flat. B: The lateral view. The eye (a) is open , the ear (b) is low set, and the nose (c) is flat.
These images were produced by analyzing a volume dataset provided by GE Healthcare.
(A) (B)
Figure 22: A 11-week pregnancy. A three-dimensional image of the fetal face. A: the fronto-lateral view in surface rendering
mode. a: eye, b: ear, c: nose. B: the fronto-lateral view in skeleton mode. a: frontal, b: maxilla, c: mandible. The ear is low
set, the nose is flat and the mandible is underdeveloped. These images were produced by analyzing a volume dataset provided
by GE Healthcare.
(A) (B)
Figure 23: A 13-week pregnancy. A three-dimensional image of the fetal face. A: the lateral view in surface rendering mode.
a: ear, b: eye, c: nose, d: chin. B: the frontal view in skeleton mode. a: maxilla, b: mandible. The nose is flat and the mandible
is underdeveloped.
(A) (B)
Figure 24: A 16-week pregnancy. A three-dimensional image of the fetal face. A: the frontal view in surface rendering mode.
a: eyes, b: nose, c: chin. B: the frontal view in skeleton mode. a: maxilla, b: mandible. The nose is stil flat, but facial bones
are well-developed.
(A) (B)
Figure 25: A 24-week pregnancy. A three-dimensional image of the fetal face. A : the frontal view in surface rendering mode.
B: the frontal view in skeleton mode. The face is wider than before.
(A) (B) (C) (D)

Figure 26: Serial observations of the face in a fetus using three-dimensional surface mode. The increase in the amount of
subcutaneous tissue on the fetal cheek with the advancement of gestational age is clearly demonstrated. A. 34 weeks, B.36
weeks, C.38 weeks, D.39 weeks of gestation.
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third trimesters in a level III center. Ultraschall Med 2005; 26: 9-16.
[20] Hadlock FP, Shah YP, Kanon DJ, Lindsey JV. Fetal crown-rump length: reevaluation of relation to menstrual age (5-18
weeks) with high-resolution real-time US. Radiology 1992; 182: 501-5.
[21] Hadlock FP, Deter RL, Harrist RB, Park SK. Fetal biparietal diameter: a critical re-evaluation of the relationship to
menstrual age by means of real time ultrasound. J Ultrasound Med 1982; 1:97-104.
[22] Hadlock FP, Deter RL, Harrist RB, Park SK. Fetal abdominal circumference as a predictor of menstrual age. Am J
Roentgenol 1982; 138: 649-53.
[23] Warda A, Deter RL, Rossavik IK, Carpenter RJ, Hadlock FP. Fetal femur length: a critical re-evaluationof the
relationship of menstrual age. Obstet Gynecol 1985; 66: 69-75.
[24] Deter RL, Rossavik IK, Harrist RB, Hadlock FP. Mathematical modeling of fetal growth: Development of individual
growth curve standards. Obstet Gynecol 1986; 68: 156-61.
[25] Hata T, Deter RL. A review of fetal organ measurements obtained with ultrasound : Normal growth. J Clin Ultrasound
1992; 20: 155-74.
[26] Bonilla-Musoles F, Raga A, Villalobos A, Blanes J, Branco J Martinez-Molina V. Demonstration of early pregnancy
with three-dimensional ultrasound. In Merz E, ed. 3-D ultrasound in Obstetrics and Gynecology. Philadelphia,
Lippincott Williams & Wilkins, 1998; 81-93.
[27] Lyons EA, Levi CS. The first trimester. In Rumack C, Wilson S, Charboneau JW, Johnson J. ed. Diagnostic
Ultrasound. St. Louis, Mosby, 2004; 1069- 132.
[28] Moore KL, Persaud TVN. Formation of the bilaminar embryonic disc: second week. In Moore KL, Persaud TVN. ed.
The developing human. Philadelphia, Saunders, 2008: 42-53.
[29] Moore KL, Persaud TVN. The limb. In Moore KL, Persaud TVN. ed. The developing human. Philadelphia, Saunders,
2008: 364-79.
[30] Moore KL, Persaud TVN. Organogenetic period: fourth to eighth weeks. In Moore KL, Persaud TVN. ed. The
developing human. Philadelphia, Saunders, 2008: 72-94.
[31] Moore KL, Persaud TVN. The pharyngeal apparatus. In Moore KL, Persaud TVN. ed. The developing human.
Philadelphia, Saunders, 2008: 159-96.
[32] Patten BM. The face and jaws and the teeth. In Patten BM. ed. Human embryology. New York, MaGraw-hill, 1968:
345-73.
[33] Hata T, Aoki S, Hata K, Miyazaki K, Akahane M, Mochizuki T. Three-dimensional ultrasonographic assessments of
fetal development. Obstet Gynecol 1998; 91: 218-23.
12 Current Topics on Fetal 3D/4D Ultrasound, 2009, 12-48
CHAPTER 2
3D/4D US in Fetal Malformations
Part 1- First Trimestre Anomalies

Fernando Bonilla-Musoles1,*, Luiz Eduardo Machado2, Franciso Raga2, Juan Carlos
Castillo2, Newton Osborne2, Esperanza Villalaiz2, Francisco Bonilla Jr.2 and Fernanda
Machado2
1
Department of Obstetrics and Gynecology, Valencia School of Medicine, Valencia, Spain and 2Universities of
Valencia, Salvador de Bahia, Panamá City, Panamá
Abstract: Transvaginal 2D and 3D allow the detection of about 65-75% first trimester malformations. The
normal embryonic weekly ultrasound timetable is summarized and compared with the appearance of
morphologic and hemodynamic markers of fetal wellbeing and of chromosomopathies located either in the
embryo/fetus, in the adnexae and in the amniotic fluid. Special attention is paid to: the nasal bone, the nuchal
translucency, the fronotmaxillary, mandibulomaxillary angles, mid-face hypoplasia and iniencephaly a
letal defect of the neuropore. All abdominal wall defects which appear the the early 14th weeks are showing,
including the most infrequents as ectopia cordis, bladder and cloacal exstrophy and Cantrell pentalogy.
Urinary tract malformations, 40-50% of all the prenatally detected malformations, can also partially
visualize early in pregnancy. The following hemodynamic embryonic markers are described: subchorionic
flow, cardiac rhythm umbilical cord and fetal vascular anomalies. Finally adnexal malformations such as the
ones located in the amnion, amniotic fluid and umbilical cord are mentioned.
INTRODUCTION
The European Health Organization, an organization similar to the World Health Organization (WHO) for the
European Economic Commonwealth, as well as the European Society for Specialized Training, currently have
among their compulsory rules, training in obstetric and gynecologic ultrasonography for all residents in an
obstetrics and gynecology (Ob/Gyn) training program. For physicians to practice as obstetricians they must have
received theoretical and practical training for three months (a minimum of 450 hours) under direct faculty
supervision (the so-called Level 1) during their specialty training [1-4, 33, 38-42].
As is the case in all of Europe, there are IV levels of ultrasound skill recognized by the Spanish Society of
Gynecology and Obstetrics (SEGO), with a recommendation that Level III proficiency (morphologic and
Doppler) be mastered before offering services for detection and diagnosis of fetal malformations.
By law, it is mandatory to offer all pregnant women the following:
 A first ultrasound survey between weeks 11 and 14, called DP-1 (for prenatal diagnosis 1) [3, 4].
 A second scanning between weeks 18 and 24, known as DP-2 (for morphologic diagnosis).
 A third scanning between weeks 28 and 32 is only a recommendation.
 Our opinion nevertheless, which is common in Europe, is that it is proper to scan all women from
the onset of pregnancy and monthly thereafter until delivery. Obstetricians without an ultrasound
machine in their office, ambulatory care clinic, or multispecialty clinic are very rare these days.
All hospitals in Spain have ultrasound equipment available.
All pregnant women in Spain have a “pregnancy quarterly or passport” where they have recorded all clinical
data, laboratory results, and ultrasound findings (all of which are mandatory) as well as their refusal to have any
of the tests in case they deny consent for a particular test or procedure. The same is the case for amniocentesis,
which must be offered to all pregnant women who are 35 years of age or older.
*Address correspondence to Fernando Bonilla-Musoles: Department of Obstetrics and Gynecology, Valencia School of Medicine,
Valencia, Spain; E-mail: profesorbonillamusoles@hotmail.com
3D/4D US in Fetal Malformations Current Topics on Fetal 3D/4D Ultrasound 13
Because of their importance, all obstetricians should know and be able to evaluate ultrasound findings
detected by:
 Transvaginal sonography [3, 36,38,39]
 Transabdominal sonography [33,40,42]
 Doppler scanning [1]
It is recommended that obstetricians have basic knowledge about use of 3D/4D ultrasonography, the new
modalities in existence, as well as basic knowledge of fetal echocardiography, even if these last two techniques
are reserved for hospital centers.
This chapter is about the contribution of 3D/4D ultrasonography to the diagnosis of fetal malformations, a
technique which between 1990 and 1995, similar to all new techniques in sonography, was at first rejected as
useless by those considered “ Ultrasound Popes” at the time, to be considered of dubious importance between
the years 1996 and 2000. In Europe and Japan, however, several investigators recognized from the outset their
potential use as complementary diagnostic techniques to 2D ultrasonography. The acceptance of 3D/4D
ultrasonography as complementary techniques to 2D has been universal during the first five years of the new
millenium, with a flood of books and articles on the subject saturating our specialty during this time [3].
The new modalities such as inverse mode (IM), echographic tomography (TUI), Virtual Organ Computer-aided
Analysis (VOCAL), Spatial Temporal Image Correlation (STIC), Automatic Volume Calculation (AVC), etc.,
that have arisen in the last few years, coerce us to consider them, as we did with 3D/4D almost two decades ago,
indispensable complements to clarify the nature of many malformations, so that enabling physicians are able to
explain to patients more precisely what kind of future they can expect for their offspring.
DETECTION OF MALFORMATIONS IN THE FIRST TRIMESTER
The overwhelming majority of malformations have their onset in the early stages of gestation, although some
may only become evident later in pregnancy during development of the involved organ or system. Because of
this problem:
 Only 60 - 65% of malformations are detectable with ultrasound in the first trimester of pregnancy.
 It is necessary to diagnose malformations as early as possible because in practically all of Europe

abortion is legally allowed only up to the 22nd week of gestation.
 It is therefore important to perform morphologic ultrasonography between weeks 18 and 24 of

gestation, and preferably, prior to the 22nd week of gestation.
EMBRYONIC ULTRASOUND TIMETABLE
The first ultrasound survey has the following basic goals:
 Determine and document the number of gestational sacs.
 Document the presence or absence of an embryo.
 Document presence or absence of cardiac activity.
 Rule out ectopic pregnancy.
The availability of transvaginal sonography during the first trimester is absolutely fundamental for accurate
knowledge about the course of the rest of the gestation. From this evaluation, knowledge can be gained about the
following [2, 3, 36]:
 Whether the progress of gestation is normal or abnormal.

14 Current Topics on Fetal 3D/4D Ultrasound Bonilla-Musoles et al.
 Presence of anomalies or malformations in the embryo or its adnexal structures.
 Whether there is fetal growth restriction.
 Evidence to suggest loss of fetal wellbeing.
This first trimester evaluation provides in addition fetal age in cases where the last menstrual period (LMP) is
unknown or erroneously reported. By knowing the following criteria, the exact gestational age in weeks can be
determined.
Weekly Embryo Timetable

There is ultrasound timetables for the embryo with the appearance and size of each structure from week to week
and dependent on the ultrasound mode used. (Figs. 1 and 2) This knowledge, which is the subject of another
chapter, is essential for early diagnosis of malformations. We provide a brief summary based on our experience:
Figure 1: Chart of the apparition of structures in the first trimester seen with transabdominal sonography.
Week 5
Abdominal Sonography:
Up to the end of week 5 only decidua and the corpus luteum in activity can be observed. The activity of the
corpus luteum is more evident with Doppler scanning. Neither of these findings guarantees a developing
pregnancy. It is necessary to see a gestational sac, which is visible at the end of the 5th week, to document that
there is a pregnancy.
Vaginal Sonography:
In a pregnancy with accurate dates, the following can be seen:
The active corpus luteum and decidua even before the expected LMP date.
Figure 2: Chart of the apparition of structures in the first trimester with transvaginal sonography.
Appearance of a gestational sac on day 31 ± 1, which may be round or oval and surrounded by a 5 mm ring of
decidua. The ultrasound characteristics of the gestational sac are important, because if they are altered, it signals
a poor prognosis (Fig. 3):
 Appears on day 31 ± 1
 It is always round or oval
 It measures 3 mm initially and grows 1.15 mm/day
The yolk sac appears on day 32 ± 1, it develops from the embryo’s endoderm, it is the largest visible structure
within the sac at this time, and its presence rules out an anembrionic or blighted ovum. It is important to know
the characteristics of the yolk sac, since alterations indicate a poor prognosis (Fig. 3):
 It is the first embryonic structure to appear on day 32 ± 1.
 It is 3 mm on week 5 and 6 to 7 mm on week 10.
 It is always round, has a homogeneous surface, and is echonegative.
Up to the time that the embryo is supplied by an umbilical cord, the yolk sac carries out essential functions for
embryonic development:
 The first vascularity appears on its surface.
 It is responsible for transport and metabolism of the embryo.
 It is involved in abdominal wall closure.

 It is responsible for embryonic immune response.
 It creates the surface tension of the amnios.
Figure 3: Upper part: Two figures showing a case with a white and irregular yolk sac. Bottom part: Two figures showing the
same case in 4D.
The following are normal and abnormal characteristics of the yolk sac (Table 1):
The yolk sac is attached to the abdominal wall of the embryo by the omphalomesenteric duct, which along with
the duct will form part of the umbilical cord. With the development of the amniotic sac on week six the yolk sac
remains out in the extracoelomic space. The omphalomesenteric duct may be too long and have cysts and/or
tumors which are related to chromosomopathies, especially to trisomy 21.
Table 1: Normal and abnormal characteristics of the yolk sac
Characteristic Normal Pathologic

VISIBLE YES NO
SIZE AT 5 WEEKS >3 mm <3 mm
SIZE AT 10 WEEKS <7 mm >7 mm
BORDERS Round Irregular
ECHOGENICITY No Gray, White
VASCULARIZATION Normal Low velocity
Diastolic flow
The embryo appears on day 33 ± 1, as a white, 2 to 3 mm laminar structure, always next to the yolk sac. It
increases in size 1 mm/day.
Cardiac activity is detectable on day 35. It can be seen without Doppler, but it is much easier to see and to
quantify with Doppler. At this stage it has a frequency between 100 and 120 beats per minute (bpm). Cardiac
frequency will increase rapidly to 170 - 180 bpm on week 13 because of sympathetic nervous system maturation
to decrease to 120 - 160 bpm with maturation of the parasympathetic system.
Week 6
Abdominal Sonography
The embryonic button becomes visible at the end of week 6. It appears as a white dot, always in the inferior part
of the gestational sac due to its specific gravity that is somewhat heavier than that of amniotic fluid. Cardiac
activity is not yet visible.
Vaginal Sonography
It is characterized by the apparition of two structures:
 The cephalic and caudal poles of the embryo are visible.
 The amnios appears on the dorsal part, the embryionic part opposite to the surface where
omphalomesenteric duct is. A fine membrane covers the back of the embryo. The growth of this
membrane occurs rapidly, so that within hours it covers the whole embryo forming the amniotic
sac and leaving the omphalomesenteric duct and the yolk sac out, which together with the amnios
will form the umbilical cord. For this reason it is normal to see the embryo within the amniotic sac
with its umbilical cord.
Week 7
At the end of the seventh week cardiac activity is observed. The embryo remains with a rounded shape and lacks
movement.
Vaginal Sonography
The following structures can be seen:
o Lower limb buds appear followed by upper limb buds.
o The medullary canal can be seen on the dorsum.
o The cauda is seen.
o Jerky, fast movements begin to be noticed.
If Doppler is used, the embryo’s vessels can be seen, so that the complete embryonic circulation can be
evaluated, and consists of observing:
o The compact decidua (week 3 - 4).
o The Corpus Luteum (week 3 - 4).
o Cardiac activity (week 5).
o The umbilical cord (week 6).
o The aorta (week 6).
o Cerebral vessels (week 7).
Week 8
The embryo continues in a rounded appearance. The limb buds can be seen as well as jerky, rapid movement.
Vaginal Sonography
The following structures can be observed:
 Limbs fully formed, including hands, are seen. Fingers are not seen.
 The face is defined.
 The physiologic herniation appears.

 The rhomboencephalon appears.
Abdominal closure takes place due to the approximation of four abdominal leaves (superior, inferior, and two
lateral) that meet at the base of the cord. Because growth of the liver and intestines is faster than closure of the
abdominal leaves, a physiologic herniation appears in all embryos and fetuses between weeks 8 and 11. This
herniation presents like a round or flattened button, more or less pronounced, and more or less refringent, that
disappears between weeks 11 and 12 once abdominal closure is complete. Recognition of this physiologic
herniation is essential for definition of abdominal wall malformations (Fig. 4).
As the name suggests, physiologic herniation is a normal event which should not be surprising to the observer. It
is considered pathological, and therefore the start of an omphalocele, when the following is seen:
 It is larger than 7.5 mm.
 It is very irregular and not homogeneous.
 It does not disappear on week 12.
If there is doubt about normalcy of the physiologic herniation, we suggest waiting until the end of the 12th week
before declaring it pathological (Fig.5).
Week 9
The embryo appears to be of an elongated form for the first time. The longer limb buds are seen and the embryo
occupies about one third of the gestational sac.
Figure 4: Development of the abdominal wall
Vaginal Sonography
Starting at this gestational age reference is made to a fetus and it is possible now to evaluate specific structures,
in contrast to what can be seen by the abdominal route, where only form, size, and movement can be evaluated.
By transvaginal sonography the observer can clearly see the following:
 Septum lucidum, lateral ventricles, and choroid plexus.
 Fetal profile.
 Fetal bladder.
 Fetal stomach.
Week 10
The fetus occupies half of the gestational sac. Slower, lazy movements are evident and the embryo turns along
its axis, it leans or bends (see chapter on fetal behavioral assessment). The yolk sac now appears stuck to the
wall of the gestational sac.
Vaginal Sonography
The stomach, the bladder, and both maxillae are now clearly visible.
Figure 5: Transvaginal tomographic ultrasound image of an omphalocele at the 14th week of gestation.
Week 11
The fetus occupies more than half of the space in the gestational sac. An important detail for dating is
observation of the cephalic pole almost completely developed. It will be fully developed in week 12.
Vaginal Sonography
The toes are first seen followed by the fingers in week 11. Umbilical cord coiling is seen and the physiologic
herniation disappears.
Week 12
The fetus occupies two-thirds of the gestational sac space, but the most important detail, is the completely
formed cephalic pole. It is possible to measure biparietal diameter (BPD).
Vaginal Sonography
All fetal structures are developed and observable at week 12.
In Summary:
We now have two avenues for the evaluation of fetal age up to the 12th week of gestation. In every week of the
first trimester sonographers should do the following:
 Follow the embryologic itinerary.
 Measure crown-rump length once the embryo is visible.
Crown-rump length should be measured from the most prominent part of the cranial pole to the rump of the
embryo or fetus. This measurement establishes gestational age within a ± 3 days error.
FETAL BEHAVIOR
We aim to improve on the diagnostic accuracy of fetal malformations by learning about the embryonic and fetal
behavior and kinetics that represent progressive maturation of certain central nervous system (CNS) structures. It
is known that with certain CNS malformations, including the subtle ones, embryonic and fetal movements may
be slower, shorter, or faster and more irregular than normal. We are just pointing out the recognition of these
interesting observations but will not go into further detail at this time since it is the subject of another chapter in
this book [19, 22,30-34,37].
FIRST TRIMESTER SPECIAL OR MALFORMATIVE SITUATIONS

Multiple Gestations
Multiple gestations is a special event that in the first trimester can only be diagnosed and evaluated with
ultrasonography and should be done at this time.
Multiple gestations can occur by two different etiologies:
Bizygotic multiple gestation, which result from polyovulation. In these cases each embryo develops from a
different zygote.
Monozygotic multiple gestation, where embryos develop as a result of division of the same fertilized oocyte,
giving rise to a variety of chorionicity and amnionicity, which are important because of their possible
consequences.
The following can be seen according to the time of division:
If the fertilized oocyte division occurs before day 6, the embryos will be similar to bizygotic twins.
If division occurs between days 7 and 13, only the cell mass will divide and the embryos will share one placenta
and one amnion, but will have to chorions.
If division takes place between days 13 and 14, each embryo will have its own placenta, and there will be two
amnions and two chorions.
If division takes place after day 16, all obstetric texts report that conjoined twins, a virtually lethal condition,
will result.
However, we recognize that conjoined twins develop very early, most likely in days 5 or 6 post-fertilization,
when plasma expansion, or hatching, takes place. If during expansion the embryonic button is trapped during
hatching, conjoined twins result (Figs. 6 and 7).
Figure 6: Pathologic hatching
Figure 7: Left: Thoracopagus diagnosed in week 11, showing only one aorta. Right and down: Sacrococcygeal linked
conjoined twins at 16th week. The fetus on the right side shows also an anencephaly.
Diagnosis of this type of malformation can be made in the first trimester. The diagnostic aim is to determine
early in gestation whether there is a monozygotic or a bizygotic multiple gestation by detecting corionicity and
amnionicity (the presence of one or of several gestational sacs).
Gestational Trophoblastic Disease

A group of neoplastic conditions under this denomination are characterized by the following:
 Abnormal trophoblastic proliferation.
 Villus edema with vesicular transformation of villi.
 Villous vascular atrophy
 Decidual neoangiogenesis formation
 Elevated serum levels of ß-hCG.
 Good response to chemotherapy.
This definition includes several neoplastic lesions classified by WHO as:
 Hydatidiform mole
 Complete or total
 Partial or embryonated
 Invasive mole (chorioadenoma)
 Choriocarcinoma
 Placental site trophoblastic tumor
 Diverse trophoblastic lesions
 Exagerated placental bed
 Placental bed nodule
 Unclassified trophoblastic lesions
Of these, only the first two are of interest, one, because of their frequency and second because of their clinical
gravity. The rest are decidedly rare tumors.
Etiology
The complete mole and the partial mole are two totally different processes, as much for their etiology as for their
evolution and clinical behavior.
 The complete or total mole develops from fertilization of an inactive oocyte by one or two
spermatozoa, and therefore they are always of paternal origin. For anatomopathologic
development to proceed and X chromosome is essential. For this reason an ovum with 46 YY
karyotype never implants.
 Partial or embryonated moles have three origins:
1. Polyspermia, the most common, or fertilization of an oocyte by two or more spermatozoa.

2. Fertilization of a haploid oocyte by sperm that did not undergo chromosomic reduction during the
first meiotic division.
3. Fertilization by normal sperm of an oocyte that did not undergo chromosomic reduction during the
first meiotic division.
Ultrasonography
Total or complete moles show a uterine cavity occupied by echopositive areas. There are no embryonic
elements. These images have been compared with snowflakes or images like television interference.
Partial or embryonate moles show the presence of vesicles, but only in zones and not affecting the entire
placenta. There are lacunar images of partial vesiculation and zonal areas of increased placental thickness. It
should be remembered that even if fetuses appear normal, they are bearers of abnormal karyotypes. (Fig. 8).
Figure 8: Partial mole showing lacunar spaces, observed with 4D and inverse mode.
ULTRASONOGRAPHY OF WEEKS 13 AND 14: MARKERS OF FETAL WELLBEING AND OF

CHROMOSOMOPATHIES
The goal of ultrasonography during the 13th and 14th weeks is early diagnosis of fetal wellbeing or of
malformations by detection of certain ultrasound markers that accompany, but not necessarily demonstrate, the
possible existence of chromosomic alterations or of a, normal fetus.
In Europe ultrasound scanning at this gestational age must be offered to all pregnant women, who have the right
to accept or refuse scanning. In case of refusal, physicians must protect themselves against negligence suits by
having patients sign an informed refusal form. As many as 95% of malpractice claims against obstetricians in
Spain are due to lack of documentation of proper scanning during the prescribed gestational age.
There are several ultrasound markers that have an effect on embryonic or fetal morphology, on embryonic
adnexal structures, or on fetal circulation. All these markers are important, but we will highlight the simplest
ones, which, in our opinion, should be routinely evaluated.
Ultrasound Markers are not only Related to Fetal Wellbeing or to Chromosomal Anomalies, but also to
Postnatal Quality of Life
Ultrasound Markers of the Embryo and Fetus
 Increased nuchal translucency
 Hypoplastic or absent nasal bone
 Mid-face hypoplasia, frontomaxillary, and mandibulomaxillaryangles
 Lemon, strawberry, and banana signs
 Omphalocele
 Encephalocele
 Umbilical cord diameter
 Placental volume
 Conjoined twins
 Embryonic growth retardation
 Other anomalies
Vascular or Hemodynamic Markers

 Cardiac rhythm anomalies
 Vascular anomalies of the umbilical cord
 Fetal vascular anomalies
Markers of the Embryonic Adnexae

 Gestational sac abnormalities
 Abnormalities of the amnios
 Yolk sac abnormalities
 Umbilical cord abnormalities
 Amniotic fluid abnormalities
A summary of the principal abnormalities of ultrasound importance that can be diagnosed in weeks 13 and 14
follows:
ACRANIA, EXENCEPHALY, ANENCEPHALY
These anomalies are due to the same defect in succesive stages of development. The global risk is of 1/1000
pregnancies and the chromosomal risk is minimal (<1%). It is the typical marker of slight genetic risk but of
extremely grave risk to fetal well being. It was thought that this sequence resulted from a vascular defect, since
over 50% of cases were accompanied by single artery umbilical cord. However, we now know that this
malformation sequence results from a primitive osseous defect of cranial bones.
When these bones do not form, the cranial dome does not close, and the so called crania appears. The brain
mass lacks developmental boundaries and protrudes to the exterior through the defect. The exencephalic fetus
appears with brain mass that lacks or that is covered with meninges. The brain is then in contact with amniotic
fluid and develops a sterile encephalitis and cerebral atrophy, progressing then to what is known as the
nencephalic fetus. Because this is a progressive phenomenon that occurs at a relatively fast pace, it is common
to see anencephalic fetuses, but rare to find acranial ones.
Complete closure of the fetal skull occurs during the 14th week, but contrary to what is reported in textbooks, the
defects can be diagnosed much earlier because the cephalic poles of these fetuses have an abnormal shape from
the 8th week on. If there is any doubt, the diagnosis es established by the end of the 14th week (Fig.9).
Figure 9: Above a case of anencephalic fetuse in week 8. Below a case of exencephaly in the 12 week.
ENCEPHALOCELE
This term refers to a bone defect that is preferentially located in the occipital region. However, it can occur in the
frontal, parietal, or temporal regions. The incidence of encephalocele is very low (1 to 4 per 10,000 pregnancies).
But the genetic risk is elevated. Trisomy 18 and 13 are found in 30 to 50% of these cases. (Fig. 10).
Figure 10: A case of first trimestre encephalocele
Figure 11: Second trimester cases of hidrocephaly
HYDROCEPHALY
Hydrocephaly results from excessive accumulation of cerebrospinal liquid in the lateral ventricles. The incidence
appears to be 3 to 6 per 10,000 births. However, the true incidence has not been well established since many
cases end up in miscarriages (Fig. 11).
Diagnosis in the first trimester is practically impossible since the lateral ventricles at this time are relatively
large, the choroid plexuses are big, and barely show signs of hydrocephaly such as the camp tent sign and
dangling choroid plexus. It is therefore common to diagnose hydrocephaly late.
An exception is holoprosencephaly. This is a polymalformative syndrome of which there are three varieties:
alobar, semilobar, and lobar. It is associated with grave defects in cerebral development, such as failure of
septum lucidum development, communication between lateral ventricles, defects in the third ventricle and
cranial base, etc. Although incidence is very low (1 per 10,000 pregnancies), the genetic risk is very high. Over
50% of these are associated with trisomy 13, and less frequently with trisomy 18, trisomy 13q, 18q, or triploidy
(Fig. 12).
Figure 12: 3D/4D and TUI of an alobar prosencephaly case. The arrows point to the abnormal interventricular
communication.
CHOROID PLEXUS CYSTSS
The choroid plexuses are lacunar structures, similar to vascular vessels. They produce cerebrospinal fluid.
Dilatation of these structures generates images that resemble cysts, and for this reason cysts are frequently seen.
They are observed in 1% of fetuses up to the 24th week. The risk of chromosomal anomalies is very low (<1%)
when choroid plexus cysts are seen in isolation. However, if they are associated with another malformation, the
risk of a genetic abnormality (especially for trisomy 18) is 28%, and to a lesser degree a risk for trisomy 21.
Signs of suspiciousness are:
 Bigger than 1 cm.
 Do not disappear after week 24
 Bilateral
 Multiple
 Irregular
 Accompanying other malformations
NASAL BONE ANOMALIES
Down’s early work showed that X-ray images and autopsies of newborn babies with mental retardation, growth
restriction, low set ears, nuchal skin thickening, etc., there was always either nasal bone absence or hypoplasia.
This finding stimulated ultrasonographic studies almost two decades ago, so that presently, because of its
simplicity and easy access nasal bone absence or hypoplasia has become one of the interesting markers at our
disposal.
The face develops from the 5th and 6th branchial arches and as the face develops two nasal bones form (Fig. 14).
However, the nasal bones eventually fuse at their base and therefore appear to be a single bone.
Figure 13: Two cases of suspicious choroid cyts. Irregular and big chorid plexus cyst accompanied by hypothelorim Fetus
with trisomy 18. Low set implantation. micrognathia, exophtalmos and genu varo. These anomalies were seen much clearly
with 3D
Figure 14: 2D and 3D showing to the left the two initial nasal bones, to the right how to exam the nasal bone. Red dot nasal
bone.
Ultrasound examination for detection of nasal bone absence or hypoplasia has the following advantages:
 It is an independent marker from nuchal translucency, but combining both markers increases
diagnostic sensitivity.
 It is independent of maternal age.
 It is independent of fetal age. Nasal bone absence or hypoplasia remains for the length of
gestation.
The problem lies in the way how absence or hypoplasia of the nasal bone should be identified and measured. It is
necessary to have a sagittal view of the fetal profile at the proper face angle to enable the sonographer to
distinguish the nasal bone separately from the covering nasal skin. Findings are considered abnormal if:
 The nasal bone is absent.
 The nasal bone measures less than 4 mm at 20 weeks gestation.
In either of these cases the relative risk (RR) for trisomy 21 is 185 times larger than when findings are normal.
Health care professionals must keep in mind that nasal bone absence or hypoplasia is not as sensitive a marker
for certain ethnic groups (blacks, Asians, Brazilian Indians, for example) and neither is it as sensitive a marker
for other chromosomopathies.
CLEFT LIP AND CLEF PALATE
Isolated cleft lip occurs with an incidence of 1 in 700 to 800 gestations. The risk of chromosomal abnormality in
these cases is less than 1% [4, 15, 16, 30, 33, 35, 37]. However, the presence of bilateral clefts with a central
mound and involvement of the soft or hard palate is associated with the following:
 An elevated risk (>40%) of chromosomal abnormality, especially trisomy 13 and trisomy 18.
 Severe CNS deficit.
 These abnormalities are only part of a much graver polymalformative syndrome.
 Diagnosis prior to 14 weeks gestation is virtually impossible. Diagnosis should be made at the
time of ultrasound morphologic assessment (18 to 24 weeks).
Generally, bilateral clefts are commonly part of polymalformative syndromes. Their presence usually indicates
grave CNS lesions, especially of the 2 to 5 types. See Figs. 15 and 16.
Figure 15: Nyberg Classification

NUCHAL TRANSLUCENCY
Nuchal translucency results from accumulation of lymph in the posterior area of the fetal neck. The causes of
this fluid collection are [4, 8, 17, 33, 43]:
o Incomplete formation of the intervillous space, so that the fetus is in a temporary state of hypoxia.
o The lymphatic duct that empties into the jugular vein either does not form, is stenotic, or is
obstructed.
o The vertebral column at the level of the axis and atlas is not completely closed until weeks 11 to
12, leaving a window of expansion. Figs. 17 and 18.
It is important to understand the following about nuchal translucency:
o It is present with varying thickness in normal fetuses up to the 14th week.
o It is merely a sign of risk and does not necessarily indicate a chromosomal anomaly. It is always
necessary to offer amniocentesis when abnormally thick nuchal translucency is detected.
o Abnormal nuchal translucency also occurs with some fetal pathologies, such as cardiac lesions,
that are unrelated to chromosomal anomalies.
Measurement of nuchal translucency thickness must be carried out in a systematic, meticulous manner Fig. 18.
Figure 16: Ethmocephaly showing cleft lip and palate as well as digital malformations.
Figure 17: Abnormal nucal translucency visualized using 2D/3D
Figure 18: These sketches show how nuchal translucency measurements should be done. The 2D picture shows a fetus with
absence of nasal bone.
The Fetal Medicine Foundation, whose recommendations based on investigations and research we advise to be
followed, proposed the following requirements for nuchal translucency measurements:
1. Use transabdominal sonography.
2. Place the fetus longitudinally in a dorsum posterior position and observe in a sagittal view.
3. Enlarge the image on the screen as much as possible.
4. Measure from the inner surfaces.
5. Measure at gestational ages between 13 weeks and 14 weeks.
6. Identify the amniotic membrane and do not confuse it with nuchal translucency.
7. Consider 3mm thickness to be the upper limit of normalcy.
Several of these guidelines (use of the abdominal route, for example), are suggested because transabdominal
sonography is available to most sonologists, even if they do not have other types of transducers available.
However, we recommend the following:
 Use of the transvaginal route, because the images are of superior quality.
 If available, use 3D with orthogonal planes. Measurements are much better, easier to perform,
faster, simpler, and more accurate with this modality.
 Although the ideal gestational ages for nuchal translucency measurement are weeks 13 and 14, it
can be measured from the 8th week on. Starting at this earlier gestational age is of great interest
since the time of appearance differs with type of associated anomaly. When abnormal nuchal
translucency appears early, for example, it is frequently associated with trisomy 13, trisomy 18, or
Turner syndrome. When it appears at later gestational ages, it is usually associated with trisomy
21.
 When nuchal translucency appears early the severity of the condition tends to be greater. It must
be kept in mind that abnormal measurements obtained at earlier ages do not have the same
significance. Abnormally elevated values at gestational ages between 8 and 10 weeks are
associated with a much higher risk of fetal malformation than the similar values obtained at 14
weeks gestation.
 The following should be evaluated:
 Thickness
 Morphology (A uniform area of translucency has a different diagnostic significance than

translucency with septated areas. The presence of septi correspons more with hygroma colli and is
practically pathognomonic with Turner’s syndrome).
 Observe the upper closure of the vertebral column.
 Relate findings to maternal age.
 Relate findings to gestational age.
 The evaluation of morphology is basic. The forms that develop so that the sonographic image is
one of bullae that are lateral to the neck, or images of several cystic cavities of varying sizes and
shapes, and even extending beyond the neck, or what is known as hygroma colli, are typical of 45
X karyotype or Turner’s syndrome (Fig. 19).
Figure 19: Nuchal translucency showing persistent opening of axis and atlas.
Presently, the taking of these measurements is compulsory. They must be offered to all pregnant women,
independently of maternal age. They are only indicators of risk and not necessarily of a chromosomal anomaly.
Greater thicknesses are associated with a greater risk of anomalies. A nuchal translucency thickness greater than
6 mm is associated with a 65% risk of trisomy. If there is no chromosomal anomaly, an abnormally thick
translucency may be associated with other types of fetal anomaly (Table 2).
Table 2: Nuchal Translucency / Hygroma Colli
Translucency thickness T21 T13/T18 RR

3 mm 3.4% 1.5% 3
4 mm 18.7% 5.7% 18
5 mm 36.4% 15.2% 28
>5 mm 28.2% 31.5% 36
HEAD SHAPE ANOMALIES
Certain cephalic pole alterations and/or internal structures such as the cerebellum are frequently associated with
chromosomal anomalies. It is possible to observe them with ultrasound during the first 16 weeks of gestation,
although they become more evident during the second half of gestation. Of these the most interesting are the
lemon-shaped skull and the banana or strawberry-shaped cerebellum, common anomalies associated with neural
tube defects and with trisomy 21 (Fig. 20) [3,11,25,30,35].
Figure 20: Typical image of a lemon-shaped cephalic pole observed with 2D and 3D.
FRONTOMAXILLARY ANGLE, MANDIBULOMAXILLARY ANGLE AND MID-FACE

HYPOPLASIA
Recently, and surprisingly using only 3D ultrasonography, the Fetal Medicine Foundation group described new
signs for early diagnosis of trisomies (5-13):
 Maxillary Length: This length is measured by a mid-sagittal view of the fetal profile so that the
maxilla as well as the mandible can be seen, including the ramus and the condylar process. The
maxillary length is measured taking care not to include the mandibular processes. Fig. 21.
 The frontomaxillary facial angle (FM): It is defined as the angle that is formed by a line that goes
through the upper surface of the palate, crosses the superior angle of the anterior maxillary surface,
and extends to the external surface of the forehead, which is represented by the frontal bones in a
mid-sagittal cut of the fetal face. The echogenic line beneath the skin and below the metopic suture
that remains open can also be used. Fig. 22.
 The mandibulomaxilar (MM) facial angle: It is defined as the existing angle between the first
arm already mentioned in the FM and a second arm directed downward that is positioned in such a
way that de line connects with the anterior angle of the mandible. Fig. 22.
 Mid-face hypoplasia: It is evaluated in the mid-sagittal plane with the transducer parallel to the
nose. With a transverse cut the fetal face, maxilla, the adjacent rami of the mandible y the nasal
bones are observed. The maxillary depth is defined by the distance between a line drawn on the
posterior part between the maxillary alveoli and a perpendicular line from the mid point of the
interalveolar line and the solid anterior part of the maxilla proper [3,11,30,35].
Figure 21: Measurment of the maxillary length. The fetus on the left side shows absence of nasal bone. The one on the right
side shows typical micrognathia
It seems that these new markers, as is the case with nasal bone:
 Are independent of nuchal translucency, although they improve the diagnostic index if they are
combined.
 Are independent of nasal bone.
 Are independent of biochemical markers.
 are independent of maternal age
Maxillary Length
Maxillary length increases significantly with increasing crown-rump length (CRL). It increases from 4.8 mm
when CRL is 45 mm long, to 8.3 mm when CRL is 84 mm long. With trisomy 21 maxillary length is
significantly shorter, and is even shorter if nasal bone is absent. A significant correlation with other
chromosomopathies has not been found.
Frontomaxillary Angle
In chromosomally normal fetuses, between weeks 11 and 13 the FM angle decreases from 84 to 76.5º as the
CRL increases from 45 mm to 84 mm. No significant association is observed between this angle and nuchal
translucency, pregnancy-associated plasma protein A (PAPP-A), or ß-hCG. When studied between weeks 16 and
24, 65% of fetuses with trisomy 21 were found to have an angle superior to 88.5º, while the angle in normal
fetuses was 84º.
Figure 22: Measurement of the frontomaxillary (FM) and mandibulomaxillary (MM) facial angles in a normal fetus (left)
and pathologic fetus (right). A case of micrognathia (below).
Figure 23: Iniencephaly.

 Trisomy 21. The FM angle is significantly greater between weeks 11 and 14 in fetuses with
trisomy 21 compared to euploid fetuses (89º versus 78º). Seventy percent of fetuses with trisomy
21 had a FM angle greater than 85º, compared to only 5% of normal fetuses, No significant
correlation was found between this angle and nuchal translucency, therefore its importance as an
isolated marker. These measurments have also been applied between weeks 14 and 23. While the
angle continues to decrease in normal fetuses, 80% of trisomy 21 fetuses had an FM angle above
the 95 percentile. There were no differences between T21 fetuses with or without nasal bone. This
angle is therefore considerably larger in T21 fetuses even beyond the 14th gestational week.
 Trisomy 18. In chromosomally normal fetuses, both FM and MM angles decrease significantly
between gestational weeks 11 and 14 as CRL increases. Sixty percent of T18 fetuses have an FM
angle that is significantly greater. On the other hand, 33% of T18 fetuses have an MM that is
significantly smaller. T18 is associated with mid-face hypoplasia, micrognathia or retrognathia,
which can be documented by measuring both these angles (28)
 Trisomy 13. Between gestational weeks 11 and 14, 84% of trisomy 13 fetuses are found to have
holoprosencephaly along with an FM angle above the 95th percentile. However, the FM angle in
T13 fetuses without holoprosencephaly is similar to the angle in normal fetuses. Likewise, there is
no FM angle difference between T13 fetuses with or without cleft lip. Therefore, an FM angle
increase in fetuses with T13 is only observed if associated with holoprosencephaly.
Iniencephaly
Iniencephaly is a very infrequent, lethal defect of neuropore closure at the level of the atlas and axis. It has an
incidence of 1 per 100,000 gestations. It is not associated with chromosome anomalies and is very difficult to
diagnose prior to week 14 of gestation. This malformation (Fig. 23) is associated with:
o An open foramen magnum
o Open first vertebrae
o Open spina bifida
o Cephalic hyperextension
o Short CRL
o Short thorax
o Star-looking face
NEURAL TUBE DEFECTS
The incidence of neural tube defects is low (2 to 4 per 10,000 gestations) and the associated risk of chromosomal
anomalies is also very low. However, neural tube defects, even when mild, with severe postpartum well-being
problems. They are rarely diagnosed during the first 14 gestational weeks. They are usually identified during
morphologic scanning (Fig. 24). We will expand on this in the second chapter.
ABDOMINAL WALL DEFECTS
Abdominal wall closure occurs at about the 12th gestational week by the fusion of four separate folds (two
lateral, one superior, and one inferior). The base of the umbilical cord is also involved in abdominal wall closure.
The defects that can occur, and generally occur early in gestation, are:
o Omphalocele, which is associated with a high risk of chromosomal anomaly.
o Gastroschisis, with a very low risk of association with chromosomal anomaly.
o Ectopia cordis.
o Bladder exstrophy.
o Cloacal exstrophy.
o Limb-Body Wall syndrome.
o Body stalk complex.
o Pentalogy of Cantrell.
The most frequent abdominal wall defects are omphalocele and gastroschisis. We will discuss those that are
detectable in the first trimester.
Figure 24: A case of early mielomeningocele.diagnosis
Figure 25: HD/3D, body glass mode imaging, and 3D Doppler of an omphalocele.
Omphalocele
This defect is characterized by intestinal, liver, and other organ evisceration (the heart in the case of pentalogy of
Cantrell), that are covered by a fine, transparent membrane, that is similar to the amnion. The incidence of
omphalocele is 1 per 300 pregnancies. It can be diagnosed early (by weeks 11 and 12). It should never be
confused with physiologic herniation. (Fig. 25)
Omphalocele is a practically constant marker in fetuses with trisomy 18 (80%), and frequent in triploidies (40%)
and trisomy 13 (30%). Curiously, when evisceration involves only intestinal loops, chromosomal alterations are
more common. This defect and the ones that follow are more commonly detected during morphologic scanning.
We insist, however, that they are early markers associated with a higher risk of severe malformation than nuchal
translucency.
Gastroschisis
Gastroschisis is authentic evisceration of intestinal loops that are found to be freely floating in amniotic fluid.
Evisceration occurs through a small opening, usually located at the left of the umbilical cord, which is
uninvolved in the process. (Fig. 26).
Gastroschisis results from atrophy or necrosis of one of the umbilical arteries. This event can affect intestinal
loops that are nearby. The incidence of gastroschisis is less frequent than the incidence of omphalocele, and is
seldom associated with chromosomal anomalies. For evisceration to occur, the following is necessary:
 The exit hole must increase in diameter (it is rarely larger than 1 or 2 cm).
 Abdominal peristalsis must exist (it appears on week 16).
 Respiratory movements must increase (they start on week 9)
Because of these requirements, later diagnosis is common. Nevertheless, we show examples of early diagnosis.
Figure 26: A case of early diagnosis of gastroschisis
The remaining defects of the abdominal wall are rarely diagnosed in the first trimester. We will show a
few examples that are uncommonly diagnosed early.
Ectopia Cordis
The heart is the most common organ affected by malformations. The prevalence is between 5 and 8 per 1000 live
births. These malformations are responsible for more than half of all neonatal deaths.
The fetal heart completes its development during the 14th week of gestation. It measures 7 mm by week 16.
Determination of normalcy should be done between weeks 18 and 20. Prenatal diagnosis of cardiac
malformations can be difficult. As many as 25% of cardiac malformations remain undiagnosed up to the time of
delivery.
Because many cardiac abnormalities are severe enough to cause hemodynamic alterations or eventual fetal death,
up to 80% of fetuses with these complex abnormalities will display abnormal nuchal translucency during the first
14 weeks of gestation.
Up to 90% of fetuses with chromosomal aneuploidies have associated cardiopathies. A combination of nuchal
translucency and fetal tachycardia identifies 88% of fetuses with trisomy 21 [14].
The following incidences of fetuses with chromosomal anomalies have been reported (Table 3):
Table 3: Incidences of cardiac defectsin fetuses with chromosomal anomalies
Chromosomal Abnormality % with cardiac defect

Trisomy 18 99%
Trisomy 13 90%
Trisomy 21 50%
Turner syndrome (45 XO) 35%
Partial trisomy or chromosomal deletions 40 to 50%
4,5,8,9,13,14,18,22
Because of its motility, the organ with the highest incidence of false negative results (when evaluated with 3D
ultrasonography) is the fetal heart. So far, 3D ultrasonography (except when using STIC mode) has not been as
useful as 2D ultrasonography for the evaluation of cardiac defects.
Very extreme cardiac malformations can occasionally be observed with US early in pregnancy. We show two
cases of ectopia cordis Fig. 27.
Figure 27: Two cases of ectopia cordis diagnosed in the first and second trimester. On the left side the arrows show the heart
floating in the amniotic fluid. Doppler color showed fetal cardiac activity. On the right side a normal heart is shown in the
amniotic fluid.
Urinary Tract Malformations
The metanephros is developed by the 9th week and is producing urine by the 10th week of gestation. By the 12th
week of gestation the fetal kidneys, the suprarenals, and the urinary bladder are visible with transvaginal
sonography.
The incidence of urinary tract malformations is 2 to 3 per 1000 live births. Most of these malformations are
detectable after 20 weeks gestation. Urinary tract malformations are relatively easy to detect. They represent 40
to 50% of malformations detected prenatally. Most urinary tract malformations are associated with indirect signs
such as oligohydramnios, inability to see the urinary bladder, and limitation of movement.
The incidence of chromosomal anomalies in fetuses with isolated urinary tract malformations varies between 2
and 3%. If there are other associated malformations, the incidence of chromosomal anomalies rises to 24%.
When the urethra is obstructed, urine accumulates in the bladder. In these cases a cystic formation is seen that
occupies most of the fetal pelvis. The cystic formation may exceed the size of the normal fetal abdomen. In these
cases there is almost always an associated oligohydramnios. The 3D images are very striking in these cases,
especially when generated with orthogonal planes.
We have observed with 3D US during the first trimester cases of megacystes secondary to urethral obstruction or
to anomalies with urethral valves. These cases are usually associated with hypertrophic bladders, dysplastic
kidneys, hydronephrosis, ureteral dilatations, and absence of abdominal musculature. When there is absence of
abdominal wall musculature, the condition is known as prune-belly syndrome (Fig. 28).
Figure 28: Prune-belly syndrome in early pregnancy
When the urethra is obstructed, urine accumulates in the bladder. In these cases, a cystic formation that occupies
much of the fetal pelvis is seen. The cystic formation may exceed the size of the normal fetal abdomen. In these
cases, there is almost always an associated oligohydramnios. The images with 3D, especially when orthogonal
planes are very striking.
Bladder and Cloacal Esxtrophy

If the defect affects the inferior fold, bladder or bladder and cloacal exstrophy results. The incidence of bladder
exstrophyis one in 30 to 40,000 live births. It is three times greater in male fetuses. Cloacal exstrophy is even
rarer with an incidence of one in 200,000 live births.
When the defect is small, only epispadias may result with little or no consequence. Large defects result in
bladder or cloacal exstrophy, and the urinary tract and the cloaca will remain open and in direct contact with
amniotic fluid Fig. 29.
Figure 29: 2D, Doppler and 3D of a bladder exstrophy. The fetus shows numerous cervical bullae as well as the abdominal
tumor showing the exstrophy and a gastroschisis.
The mesodermal defect, which occurs by day 29 of development, provokes three different anomalies:
 Cloacal septal failure: the urethra, ileum and hindgut remain open.
 Cloacal membrane rupture: exstrophy of pubic branches and omphalocele usually result.
 Medullary canal hernia: anomalous vertebrae in the lumbosacral area appear.
When bladder exstrophy exists, the posterior bladder wall can be depicted due to the wide separation of the rami
of the pubic bones. The navel lies low, the penis is short, and the testes remain undescended. In females the
clitoris is forkedand the anus is imperforate or stenotic.
Typical evisceration consists of evisceration of loops from the ileo-caudal region, imperforate anus, and
duplicate bladder exstrophy, each with its own ureter, omphalocele, vertebral anomalies, and anomalous external
genitalia. Prognosis is worse in cases of superior and inferior fold defects than in cases with other types of
abdominal wall defect. Although 30% of abdominal wall defects diagnosed during the second trimester will be
superior or inferior fold defects, they constitute only 15% of abdominal wall defects seen at the end of the third
trimester, mainly because of the high fetal mortality associated with these defects.
This mesoderm defect, which usually happens by the day 29 of development, provokes three different anomalies:
 Cloaca septum failure: urethra, ileum and hindgut remain opened.
 Membrane of the cloaca rupture: exstrophy of pubic branches and omphalocele usually result.
 Medullar canal hernia: anomalous vertebrae in the lumbar–sacrum region appear.
When bladder exstrophy exists, the posterior bladder wall can be depicted due to the wide separation of the rami
of the pubic bones. The navel lies low, the penis is short, and the testes are undescended. In females, the clitoris
is forked and the anus remains imperforated or stenotic.
Typical cloacal exstrophy, consists in evisceration of loops from the ileo-caudal region, imperforate anus, duplicate
bladder exstrophy each with its own urether, omphalocele, vertebral anomalies and anomalous external genitalia.
The prognosis is worse in cases of superior and inferior fold defects than in cases with other types of abdominal
wall defects. Although 30% of abdominal wall defects during the second trimester will be of the superior or
inferior folds, they constitute only 15% of the wall defects seen at the end of the third trimester, mainly because
of the high fetal mortality associated with these defects.
PENTALOGY OF CANTRELL
This rare malformation results from an abdominal wall closure defect that is secondary to failure of the
embryonic cephalic fold. As a consequence, ectopia cordis is always present. entalogy of Cantrell is one of the
rarest closure defects. Only one case has been published where the diagnosis was made with 3D technology. This
malformation is characterized by:
 Ectopia cordis, which may be associated with herniation of other organs.
 Midline supraumbilical abdominal wall defect.
 Bone defect on the inferior part of the sternum.
 Pericardial diaphragm defect
 Cardiac defects.
To make the diagnosis it is essential that the heart be located outside of the thoracic cavity, whether there is or is
not and association with an omphalocele or herniation of other abdominal organs. The combined use of 2D/3D
ultrasonography seems necessary for detection of cases associated with an omphalocele. In our case, 3D US
completed the diagnosis by allowing visualization of a cleft lip and palate, originally missed with 2D US.
Oligohydramnios, a frequent occurrence with Pentalogy of Cantrel, may make an accurate diagnosis difficult.
Diagnosis of the cardiac defects may also be difficult due to the abnormal position of the heart. In most cases
there is an associated omphalocele, which is of great diagnostic help. When an omphalocele is present, the whole
abdominal wall defect is very large, as is seen in the present case (Fig. 30), due to the combined failure of the
cephalic and lateral folds.
Pentalogy of Cantrell as well as certain other wall defects are frequently associated with chromosomal
anomalies, especially of the 18 pair. Prognosis is usually dismal due to the very serious malformations associated
with these cases. Ultrasound diagnosis is always restricted to the second.
Pentalogy of Cantrell
This rear malformation results from an abdominal wall closure defect due to a failure of the embryonic cephalic
fold, and as a consequence, an ectopia cordis is always present.
Represents one of the rarest closure defects. Only one case has been published using 3D technology.
Is characterized, as cited, by
 ectopia cordis maybe associated with herniation of other organs,
 midline supraumbilical abdominal wall defect,
 bone defect in the inferior part of the sternum, and
 pericardial diaphragm associated with
 cardiac defects.
For the diagnosis it is essential that the heart lie outside of the thoracic cavity whether there is or not an
associated omphalocele or herniation of other abdominal organs. The combined use of 2D/3D seems necessary
for detection of cases associated with omphalocele and as in our case 3D completed the diagnosis by visualizing
the cleft lip and palate initially missed when using 2D.
Olygohydramnios, a frequent occurrence, may make an accurate diagnosis difficult. Diagnosis of the cardiac
defects may also be difficult due to the altered position of the heart.
In most cases an omphalocele is associated, resulting of great diagnostic help. When the omphalocele is
associated the whole abdominal wall defect use to be very large, as is seen in the present case (Fig. 30), because
of joint failure of the cephalic and the lateral folds.
This pentalogy, as well as other cranial wall defects are frequently associated with chromosomal anomalies,
especially of the pair 18.
Prognosis is usually dismal due to the grave associated malformations. The US diagnosis is always limited to the
second trimester.
Body-Stalk Syndrome
Body-stalk syndrome is a lethal anomaly with an incidence of one per 14,000 live born babies. The real
incidence is probably higher due to a high first trimester spontaneous abortion rate in these cases.
This syndrome consists of an abdominal wall defect that involves the four folds that is accompanied by absence
of the umbilical cord. The placenta is then fused with the herniated organs forming a mass continuum.
With 2D and 3D ultrasonography the embryo or fetus appears linked to the placenta or to the uterine wall. The
abdominal organs are outside the fetal abdomen in the space occupied by the placenta and the amnion. Many
cases have been confused with gastroschisis.
Figure 30: Six images of a foetus with Pentalogy of Cantrell diagnosed at 24 weeks gestation. The upper left frames show
the prominent omphalocele arising in the upper thoracic portion. Observe that it almost reaches the neck of the foetus. The
umbilical cord emerges from the central portion of the omphalocele. In the right frame we have a sagital image of the large
omphalocele, because the heart occupies the left side. The cord can be seen in front of the heart. In the lower right frame the
omphalocele can be observed practically to the fetal neck. To the right observe the digital malformations, a poorly defined
cleft lip and the omphalocele at a protrusion site that corresponds to the heart external to the sternum (taken from Bailao L).
Abdominal Herniation
Abdominal herniation is a normal finding which has to be differentiated from abdominal wall defects. Fig. 31
shows a case of abdominal wall herniation. This herniation is really a simple dilatation of the umbilical cord as it
emerges from the navel.
Early Fetal Growth Restriction

The crown-rump length (CRL) is universally used for determination of gestational age during the first trimester.
However, foetuses frequently adopt a position of flexion, which alters the real foetal size on occasions. For this
reason, the term “maximum embryo length” (MEL) has been proposed. To improve the accuracy of
measurements, this foetal assessment relies on 3D evaluations of foetal dimensions using all orthogonal planes.
We hope this technique will help to fill a gap in our understanding of fetal well-being since knowledge about
early growth restriction and its relationship to prognosis and chromosomal defects is scant at present.
Figure 31: Simple herniation at the base of the umbilical cord. The umbilical cord forms a small protrusion at the
implantation site on the abdominal wall.This is a normal finding that can be observed early in pregnancy.
Evaluation of multifetal pregnancies represents an ideal model for the study of embryonic development. Once
upon a time, it was considered that differences in growth between twins only became evident during the second
half of gestation. It is now known that growth restriction and discordant growth may start very early in gestation.
Discordant twins have been observed early in the first trimester. Although there is still disagreement, there are
some evidences that early growth restriction may be related to chromosomal abnormalities. The term “early
growth restriction” has been introduced to describe cases where there is very early growth discordance (up to 8
weeks gestation). This term carries the connotation of a poor prognosis.
ANOMALIES OF VASCULAR FLOW: VASCULAR OR HEMODYNAMIC MARKERS
As already mentioned, it is possible to study existing embryonal and gestational sac vascular flows from the 5th
week of gestation onward. The most interesting vascular flows to evaluate are:
 Subchorionic flow, which in normal gestations reaches the base of the trophoblastic ring. If it
penetrates the ring, prognosis is poor.
 Anomalies of cardiac rhythm.
Cardiac activity becomes evident on the 35th date of amenorrhea. It fluctuates between 120 and 180 beats per
minute up to the 13th week, when it starts to slow down for the remainder of the gestation, settling in normal
cases to frequencies between 120 and 160 beats per minute. Beat to beat fluctuations appear on week 13.
 Tachycardia above 180 bpm beyond the 13th week is a sign that must be noticed and cotrolled.
 Bradycardia of 100 bpm is an ominous sign. If it slows down to 80 bpm practically all embryos
with this complication die.
 Arrhythmias are an indirect sign of a possible cardiac lesion.
 There is a high incidence of cardiac defecs (5 to 8 per 1000 gestations) associated with
chromosomal defects. In cases of trisomy 21 the incidence hovers around 90%.
Vascular Anomalies of the Umbilical Cord

In the early stages of gestation (about week 12 when umbilical vasculature appears) there is absence of diastolic
flow. Presence of reverse flow at this time is synonimous with fetal death.
Fetal Vascular Anomalies

Doppler scanning reveals interesting findings in the ductus venosus and in the inferior vena cava as markers of
fetal well-being or of chromosomal anomalies. Numerous investigations seem to confirm that a diminishing of
the characteristic curves of velocity flow or an increase of the reverse peaks indicate severe fetal anomalies.
ADNEXAL MALFORMATIONS
1. Yolk Sac Pathology
If an exception is made for excessively large yolk sacs that at times are associated with conditions like diabetes
or hypoproteinemia where a few embryos survive (something unusual since 90% of them die), it can be said that
yolk sac anomalies are incompatible with life.
2. Amnion and Amniotic Fluid Pathology

The principal pathologic conditions that can be observed are:
 Amniotic bands.
 Extra-amniotic gestation.
 Early oligohydramnios.
 Early polyhydramnios.
Except for extra-amniotic gestation, of unknown risk due to the extreme rarity of the condition, all other
pathologic conditions of the amnion and amniotic fluid are associated with a high risk of embryonic death.
Amniotic Band Syndrome

The incidence of amniotic band syndrome, a rare and secondary polimalformative disorder, is 1 per 5,000 to
10,000 live births. Amniotic bands are produced either after membranes rupture, or due to a congenital defect of
the amnion. The amniotic bands adhere to fetal structures or organs producing edema, ischemia, necrosis, and
amputations. Although it is difficult to explain all lesions associated with them, they have been described in
cases of cranio-facial malformation, visceral malformation, pentalogy of Cantrell, limb defects or amputations,
and body wall or stalk defects.
It has been shown with experimental animals that the amnion has vasoactive substances that are capable of producing
lesions in mesenchymal and endothelial cells of the embryo and amnion. The lesions can cause band formation,
amputations, and internal injury, independent of pressure or trauma. There are ultrasound evidences of this possibility
by serial observation of bands. Observation over several weeks showed the following sequence:
Band formation  band adherence  constriction  edema  ischemia  fracture  amputation
In 77% of cases of amniotic band syndrome there are anomalies that affect the following:
a) Extremities - Amputations, syndactily, lymphedema.
b) Skull - Anencephaly, encephalocele.
c) CNS - Holoprosencephaly, cerebral dysplasia.
d) Face - Cleft lip, cleft palate, nasal deformities, hypertelorism, microophthalmia.
e) Thorax - Thoracoschisis, cardiac anomalies.
f) Digestive tract - Tracheo-esophageal fistulas, intestinal malrotation, omphalocele, gastroschisis,

bladder exstrophy.
g) Genitals - Ambiguous genitalia, imperforate anus.
The association of amniotic band syndrome with chromosomal anomalis is almost zero. However, chromosomal
anomalies must always be suspected when there are malformations. Amniotic bands can be observed early in pregnancy
with 2D US as clearly as with 3DUS. It is not necessary to use sophisticated technology to detect them. Fig. 32.
Figure 32: Amniotic band syndrome showing multiple malformations.

3. Umbilical cord pathology

Because of its recent contributions as a marker of aneuploidies, umbilical cord pathology merits a special
commentary. The umbilical cord may infrequently (4%) present with cysts and tumors:
 Inclusion cysts of amniotic epithelium.
 Cysts of the omphalomesenteric duct.
 Cysts of the allantoic duct.
 Neoplastic lesions.
 Alterations of Wharton’s jelly.
 Stenosis or obstruction.
 Total or partial loss of coiling.
All the varieties of cysts have been associated with:
 Abdominal wall defects.
 Persistently open urachus.
 Urinary tract obstruction.
 Hydronephrosis.
 Persistence of Meckel’s diverticulum.
 Trisomies 13 and 18, and to a lesser extent, trisomy 21.
Of all these associations, the last is the most interesting (Figs. 33 and 34). Presently high risk or low risk for
malformations is considered according to the following findings (Table 4):
Figure 33: Umbilical cord cysts (arrows), one with peanut form (double arrows).
Figure 34: Umbilical cord cyst observed with TUI, 3D HDI Doppler, AVC and 4D.
Table 4: Low and High risk findings in cases of cord cysts
CYST LOW RISK HIGH RISK

SIZE < 5 mm > 5 mm
DISAPPEARANCE Before week 12 After week 12
BORDERS Regular Irregular
LOCATION Central part of cord Near abdomen or placenta
NUMBER isolated multiple
RISK Minimal (1 t0 2%) 13% Trisomy 13 and 18
Lastly, we show in Fig. 35 a case of umbilical cord stenosis with cord obstruction, an exceptionally rare anomaly
Figure 35: Umbilical cord stenosis with vascular obstruction.
SEE PART 3 FOR REFERENCES.

CHAPTER 2
3D / 4D US in Fetal Malformations
Part 2- Second Trimester: Cephalic Pole Malformations

Castillo2, Newton Osborne2, Esperanza Villalaiz2, Francisco Bonilla Jr.2, Fernanda
Machado2
1
Abstract: Hydrocephaly or ventriculomegaly is caused by an abnormal volume increase of the brain’s

lateral ventricles. Acrania, exencephalia and anencephalia start from a single process as a consequence of
an early closure defect of the anterior neuropore. Encephaloceles are extremely grave bone defects, almost
always of the frontal or occipital bones, often associated with chromosomopathies. Ciclopia and proboscis,
also called “polyfemus”, always letal, are fetuses presenting a frontonasal malformation showing one single
eye with or without a dermo-cartilaginous appendix above the eye anlage, Craniosynostosis is defined as the
premature closure of the calvarian sutures and includes the following anomalies or syndromes: Apert,
Crouzon, Pfeiffer, Saethre-Chotzen, Jackson-Weiss and Antley Bixler. Ear malformations can arise
from embriologic migration or rotation defects and are often associated with other embriopathies, Charge
association, Vacterls syndrome, or chromosomal defects such as trisomies 13-15, 18, 21 and 22. Orofacial
teratomas are extremely rare and occur at the base of the cranium in the roof of the hard palate or on the
mandible. Cleft lipe and cleft palate are generally associated with other major or minor malformations
especially from de CNS and with chromosomopathies. Retrognathia is a condition of facial disharmony
whether Micrognathia is an abnormal smallness of the jaws frequently associated with chromosomopathies
and genetic syndromes. Dandy-Walker is characterized by the presence of a cyst in the posterior fossa that
communicates with the fourth ventricle showing a total or partial defect of the cerebellar vermis. The
aneurysm of the vein of Galen refers to different midbrain arteriovenous fistula malformations associated
with aneurysm dilatation of the veins. 4D Angiodoppler seems to be very useful for the definitive diagnosis.
Congenital goitrus hypothyroidism is very rare but potentially dangerous due to its lifelong consequences.
INTRODUCTION
3D and 4D US have been considered complementary obstetric diagnostic tools for the past decade. They are
used to study surfaces or to try to explain more clearly to parents the nature of a fetal malformation. At present it
should be considered an indispensable tool for clear definition of fetal malformations and to establish postnatal
prognosis.
Some evaluations of facial anomalies such as those mentioned in the previous chapter are being done exclusively
with this technology.
Any center engaged in prenatal diagnosis should have this new technology available.
By law two ultrasound scans must be done during pregnancy: an initial scan and a morphologic assessment scan.
A third scan is recommended in the third trimester of pregnancy. The required morphologic assessment scanning
should ideally be done between the 18th and the 22nd gestational weeks. During this gestational period most
malformations are evident.
Furthermore, in countries where interruption of pregnancy is legal, diagnosis at these gestational ages afford the
option of abortion when certain malformations are detected.
Considering the accessibility and reduction in price of ultrasound equipment, we recommend an ultrasound
examination during each prenatal visit as an integral part of obstetric evaluation.
*Address correspondence to Fernando Bonilla-Musoles: Department of Obstetrics and Gynecology, Valencia School of Medicine,
Valencia, Spain; E-mail: profesorbonillamusoles@hotmail.com

The goals of the required morphologic ultrasonographic scan are:
1. Complete study and measurement of fetal structures since all organs and structures are well
developed and visible. From this gestational age on they are only increasing in size.
2. To diagnose malformations if present.
This scan is clearly meant to be complete and systematic. All organs and structures as well as the placenta must
be seen, assessed for normalcy, and measured. Therefore, morphologic ultrasonography includes detection and
diagnosis of the principal malformations. It is very important to be aware that many malformations are part of
polymalformative syndromes, and it is therefore necessary to arrive as accurately as possible to a complete
diagnosis, since a decision of whether or not to continue with the pregnancy, the route of delivery, and the long-
term future of a baby may well depend on the accuracy of morphologic ultrasound diagnosis. In case there is
doubt about the findings, it is recommended to refer to an experienced prenatal diagnostic center.
It is impossible for a chapter such as this one to present details of all known malformations. For further details we
refer readers to our book “3D Ultrasound in Obstetrics” or to the books written by Kurjak [2, 3, 25, 30, 38, 39].
MAIN MALFORMATIONS
Cephalic Pole Malformations
Hydrocephaly
Hydrocephaly, also called ventriculomegaly, is caused by an abnormal volume increase of the brain’s lateral
ventricles when compared to the growth of other central nervous system (CNS) tissues. In most cases, this
anomaly results from blockage of the cerebrospinal fluid circulatory system. In these cases there is an increase in
pressure which, if not corrected, results in severe CNS damage with devastating consequences [22, 33].
Hydrocephaly seldom starts because of an increase in CSF or by a relative decrease in CNS mass. It is
considered to be a single anomaly when the fetus does not show any other abnormalities besides those related to
increase in intracranial pressure and ventriculomegaly. This is an important concept, since myelomeningocele is
a frequent concomitant anomaly.
Etiology
Hydrocephaly may result from the defects in morphogenesis or may be an acquired fetal malformation. Primary
defects in morphogenesis can result from abnormal formation of CNS structures due to chromosomal
abnormalities, to genetic disorders, or to polimalformative syndromes. Conversely, other etiologies unrelated to
morphogenesis such as intracranial tumors, intraventricular hemorrhage, cysts, vascular malformations, cerebral
mass lesions, and intrauterine infections with inflammatory reactions that cause obstruction of CSF flow, can
have hydrocephaly as a sequela. There are also other CNS malformations such as holoprosencephaly,
encephalocele, and porencephaly that can promote hydrocephaly.
Hydrocephaly has been associated with chromosomal anomalies such as triploidy, trisomy 13, 18, and 21, as
well as with some balanced translocations. Except as is the case with balanced translocations, recurrence of
hydrocephaly in siblings of a fetus who developed hydrocephaly as a consequence of a chromosomal
abnormality is rarely seen.
Pathways of Cerebrospinal Fluid Overproduction

There are four pathways by which an increase in ventricular size can occur:
1) Obstruction of CSF flow, especially in narrow places such as in the aqueduct of
2) Poor absorption of CSF by arachnoid granules.
3) Overproduction of CSF fluid.
4) Abnormal development or destruction of cortical tissue resulting in a relative increase in the size
of the ventricle.
An obstruction in CSF flow is by far the most frequent etiology of hydrocephaly, both in fetuses and in newborn
babies.
A series of fetal malformations are commonly associated with hydrocephaly. The most common is spina bifida,
because of its association with Arnold Chiari malformation, but hydrocephaly can also be associated with
porencephaly, holoprosencephaly, absence of corpus callosus, hydranencephaly, arachnoid cysts, etc.
Ultrasound Diagnosis of Hydrocephaly

Previously, ultrasound diagnosis of hydrocephaly was based on the presence of either a BPD greater than 11 cm
or 2 cm greater than the thoracic diameter. However, these measurements are not enough to establish the
diagnosis. Only measurement of the internal cerebral mass is significant, since it is possible to find an internal
hydrocephaly that does not affect the BPD.
Before the 14th week, diagnosis is extremely difficult since the choroid plexuses and the lateral ventricles are
very wide and occupy most of the cranial pole. Only secondary hydrocephalies or alobar holoprosencephalies
can be seen after the 9th week.
Diagnosis must be established by measurement of the lateral ventricles and their relation with the cerebral
hemispheres. This relation will always be less than 0.45 and decrease as pregnancy progresses. It is equally
important to observe the position of the choroid plexuses, especially during the first half of pregnancy. They
symmetrically occupy the posterior portion of the central part of each ventricle. When the ventricles swell, both
plexuses become centered like a tent and they can be shaken by the transducer movements.
Nowadays there are many lateral ventricles normograms. They comprise the body, the atrium, or the frontal,
occipital and temporal lobes and allow early diagnosis of the anomaly.
In cases of advanced hydrocephaly, even in early pregnancies, any measurement or even the mere sight of the
internal cerebral mass is enough to establish the diagnosis. 3D ultrasound can help complete the diagnosis, either
if orthogonal planes or a multiplanar system is used, as they allow internal and external views of the
malformation.
Acrania, Exencephalia, Anencefalia and Iniencefalia

These severe malformations are thought to evolve around three phases that start from a single process and as a
consequence of an early closure defect of the anterior neuropore, which normally occurs in the 4th week.
Anencephalic fetuses have the absence of the cranial vault and partial or total absence of cerebral hemispheres.
Fetuses with exencephaly and acrania on the other hand, show partial or total absence of the calvarium, but have
complete or partially preserved cerebral masses.
It is important to highlight that in both animal and human pregnancies it is possible to observe how the
sonographic images evolve as the pregnancy progresses. It starts in early pregnancy as an acranium fetus (absent
skull bones). It progresses with gestational age to exencephaly (presence of brain tissue, with or without
meninges, exposed in the amniotic fluid). The last stage of the sequence is the anencephalic fetus, which, as
mentioned earlier, is the most common variety of the sequence observed in newborn babies.
The final mechanism causing these defects is still unknown. Approximately 50% of cases are accompanied by a
single artery umbilical cord. May be, an early onset vascular defect would be responsible for the precocious
closure of the rostral neuropore.
Two possible etiologies have been suggested:
1. Anencephaly results from a secondary rupture of the neural tube. The common existence of dense
amniotic fluid observed sonographically supports this etiology.
2. A partial or total absence of the protector calvarium. This bone defect etiology seems more logical,
since it better explains the mechanical or chemical effect of amniotic fluid on brain tissue that
results in lesions that progress to total or partial disintegration of the fetal brain.
Consequently, the amniotic fluid shows floating particles of low echogenicity which gives amniotic fluid the “milky”
consistency that can be clearly observed during sonographic examinations, and even better with fetoscopy.
There is evidence that the beginning of the cranial ossification takes place in the 10th week and is completed in
the 14th week. Ultrasound shows that in week 11 there is a hyper-echogenicity in the cranial vault superior to all
adjacent tissues.
Many of these fetuses also show abnormal cephalic pole contour and other cephalic and medullar canal
abnormalities before week 11. Nevertheless, we agree that definitive diagnosis should not be made before the
12th week.
Sonographic Diagnosis
In cases of acrania the cranial vault is not observable. The shape of the head can be normal, but most commonly
it is irregular or flattened. At times, only a diminished bone echogenicity is seen. In cases of exencephaly, a part
of the cerebral tissue protrudes from the fetal head outside the fetal pole and is in contact with amniotic fluid.
The diagnosis of these two anomalies is suggested when one or several of the following characteristics are
observed (See part 1):
1. Absence or diminished echogenicity of the calvarium.

2. Disorganized brain tissue in contact with, or floating in the amniotic fluid which may or may not
be covered by meninges. The meninges may initially be preserved. However, the membranes
eventually break up or disintegrate. If the meninges remain intact, hydranencephaly must be part
of the differential diagnosis.
3. Incomplete or total absence of the cranial vault, which is the dominant characteristic in cases of
anencephaly. The defect may vary in size, but is usually extensive. Brain tissue in contact with
amniotic fluid has suffered progressive degeneration and atrophy, and is reduced by now to a small
mass or “sponge” that represents the remains of the rostral brain. Anencephaly, the commonly
used term, is therefore incorrect, since brain tissue is not totally absent. Brain tissue is flattened
and exophthalmos, or so called “frog eyes” appear because of approximation failure of the
ophthalmic protuberances during embryonic facial development.
There are many other anomalies associated with anencephaly. They include low-set ears, micrognathia, absence
of the nasal bridge, partial or total rachischisis, or opening of the medullary canal, and polyhydramnios.
Because of leakage of cerebrospinal fluid into the amniotic fluid combined with absent or ineffective fetal
swallowing, acrania, exencephaly, and anencephaly are almost always accompanied by polyhydramnios.
Agitating the maternal abdomen with the hands or with the transducer provokes irritation of the exposed fetal
nervous tissue causing sudden, Moro-type reflex movements. This maneuver is helpful when trying to diagnose
anencephaly using 2D ultrasonography. Several high-risk patients studied with transvaginal 2D and 3D
ultrasonography in the 13th and 14th weeks of gestation and subsequently evaluated with abdominal 2D
examination between the 18th and 20th weeks demonstrated a diagnostic sensibility of 100% for the 2D and 3D
ultrasonographic evaluations done at 13th and 14th weeks.
3D/4D ultrasonography allows better image resolution and a much simpler identification of the type of lesion
involved (Fig. 1).
Hidranencephaly is a very infrequent lesion that is always lethal. There is complete absence of the cerebral
hemispheres, but preservation of the midbrain and cerebellum. The following etiologies have been suggested:
- a wide vascular occlusion in the flow distribution of the internal carotid arteries,
- a severe hydrocephaly,
- an infection which could accompany hydrocephaly,
- the result of serious embryonic defects of genetic or teratologic origin.

Figure 1: Two cases of anencephalic foetuses.

Iniencephaly: See part one
CEPHALIC TUMORS
Encephalocele
Encephaloceles are extremely grave bone defects, almost always of the frontal bones, but they can occur in other
parts of the cranial pole (i.e., occipital, parietal, etc.). They are frequently present in fetuses with trisomy 18.
The differential diagnosis from frontal encephalocele includes: epignathus, vascular and lymphatic
hemangiomas, teratomas, retinoblastoma, dacryocystocele, hygroma colli, goiter, and nasal glioma.
Some paranasal facial masses (i.e., encephalocele, teratoma, hemangioma) are usually associated with CNS
malformations or anomalies of other organ systems which render unfavorable prognoses. 3D/4D is ideal for
localization, morphology and sonolucency of the tumor.
A frontal encephalocele appears as a midline mass, solid and/or cystic, projecting as a frontal skull defect. The
size and form can be variable, but frontal encepahaloceles are normally round.
Hemangioma
Hemangiomas are heterogeneous protruding masses that typically form an obtuse angle with the calvarium. Color
Doppler may show blood flow within the tumor. The Kasabach-Merritt Syndrome is a variety of hemangioma that
has been described on the forehead and neck and that is associated with thrombocytopenia. These tumors may be
large and can cause cardiopathy. All of them are richly vascularized. Involvement of the cranial pole is rare. They
tend to localize in other organs. They are part of the Klippel-Trenaunay-Weber Syndrome.
Nasal teratomas are usually irregularly shaped and are heterogeneous. With color Doppler it can be shown that
they are poorly vascularized tumors.
Retinoblastoma may appear as a heterogeneous mass arising directly from the eye.
Dacryocystocele is a hypoechoic cyst arising from the lacrimal duct and abuts the orbits medially.
Nasal glioma, also known as nasal cerebral heterotopia, is a rare, benign, congenital tumor of neurogenic origin.
It is a firm, heterogeneous, non-pulsatile mass, arising intra and/or extranasally. It may have an intracranial
extension.
Prenatal 2D and 3D have been used to evaluate fetal facial masses. 3D is especially useful because the complex
curvature of the face and the relationship of surface tumors to the surrounding anatomy (Figs. 2 and 3).
Figure shows a case of parietal encephalocele associated with cleft lip and palate which illustrates how
frequently these tumors are associated with other malformations.
Ciclopia and Proboscis

The cyclops or “polyphemus” is a fetus presenting a frontonasal malformation characterized by one single eye with
or without proboscis and a dermo-cartilaginous appendix or appendices located above the eye anlage (Fig. 4).
Figure 2: This figure shows a case of frontal encephalocle diagnosed at week 14. 2D shows clearly the frontal tumor as a
solid-cystic mass. In 3D the fetus is touching the tumor with its left hand.
Craniofacial malformations include a very wide and heterogeneous range of anomalies, of which many are the
consequences of a defect in the cleavage of the median line of the anterior brain.
Most of fetuses with any of the varieties of hypotelorism present holoprosencephaly. Both are associated with
mendelian anomalies as well as with chromosomal pathologies. They may also accompany microcephaly, and
the syndromes of Meckel-Gruber, Coffin-Lowry, Golabi-Rosen, the “cat scream” (monosomy 5), Pena-Shokeir,
Roberts, Robinow, Noonan, Fraser and other facial malformations.
The most severe facial malformations, such as cyclopia, are always associated with alobar holoprosencephaly.
The classification of holoprosencephalies described in 1977 by de Myer is still used today:
According to the severity of the damage in the cleavage, holoprosencephalies are divided into:
Alobar: presence of only one ventricle, the two lateral ventricles are merged into one with no dividing
line, known as the holosphere. There is thus no inter-hemispheric division, hence preventing
ultrasonographic vision of the septum pellucidum and of the inter-hemispheric sulcus. The thalamus
and the corpus striatum are likewise undivided, with an absence of the corpus callosum, olfactory
bulbs and olfactory tracts.
Semilobar: there are rudimentary cerebral lobes with a more or less developed posterior inter-
hemispheric sulcus. The anterior portion is absent. The corpus callosum is rudimentary and the
olfactory bulbs and tracts are either hypoplastic or absent.
Lobar: in these cases there is more continuity of the median line instead of the inter-hemispheric
sulcus. The olfactory tracts and bulbs may be absent, hypoplastic, or normal. The cleavage in the
median line of the thalamus and of the corpus striatum is incomplete.
Classification of the Anomalies of the Faces

Facial anomalies are classified into four types (Table 1):
Ultrasonographic Diagnosis
Cyclopias with proboscis were described even in the first trimester using 3D ultrasound. The diagnosis was
established thanks to the visualization of the CNS lesions which accompany the three varieties of
holoprosencephaly. Not all cyclops are carriers of the cartilaginous appendix (proboscis). 3D/4D undoubtedly
proves the value of this technology by showing proboscis with great clarity (Fig. 4).
The etiology of holoprosencephaly includes both genetic and environmental factors. There are several types of
holoprosencephaly. They range from the type associated with cyclopia, ethmocephaly or agenesia/dysgenesia of the
corpus callosum, mental retardation and hypotelorism to the type showing a simple maxillary central incision.
Table 1: Classification of the facial anomalies
a) Cyclopia with one single eye or severalfold degrees of the

eye anlage with or without proboscis, and no nose:
b) Ethmocephaly with hypotelorism and proboscis localized

between the eyes along with absent nose.
c) Cebocephaly with hypotelorism and rudimentary nose with

a single nostril.
d) Cleft lip with median cleft palate, that is, with premaxillary
agenesia and hypotelorism.
Figure 3: Lateral encephalocele observed in 2D and 3D. Observe in 2D the big opening between the two parietal bones. 3D
shows that the fetus is also affected from bilateral CL-P (arrows). The third picture shows in 3D the cephalic opening with
the protrusion of the brain
Holoprosencephaly is genetically heterogeneous and involves at least 12 loci in 11 chromosomes with

chromosomal anomalies present in 24 to 45% of those born alive. The minimal critical regions have been
defined as: HPE1 in 21q22,3; HPE2 in 2p21; HPE3 in 7q36; HPE4 in 18p11,3; HPE5 in 13q32 ; but known
associated genes include Sonic Hegdebog (SHH) in 7q36 Z1C2 in 13q32; S1X3 in 2p21 and TG1F in 18p11.3
Proboscis may also appear with median cleft lips.
All trisomies are frequently associated with holoproscenphaly and oligohydramnion. It is evident that 3D rapidly
reinforces the diagnosis of cylopia with or without proboscis; helps determine the variety of cyclopia and
produces much more real and convincing images than 2D.
Craniosynostosis: Apert Syndrome

Craniosynostosis is defined as the premature closure of the calvarial sutures. It is a group of heterogeneous
conditions with often-distinct clinical, genetic and molecular characteristics. This anomaly affects approximately
one infant per 2000 live births. Almost 100 different types of craniosynostoses have been described and half of
them have a genetic basis with mainly an autosomal-dominant mode of transmission [11,18,25,30,35].
Figure 4: Ciclopia and proboscis
Craniosynostoses are usually classified into syndromic, when associated with other abnormalities (Table 2) and
non-syndromic, when they are isolated.
The classification of skull deformities in craniosynostoses is based on the suture(s) involved (Table 3).
Premature closure of the sagittal, coronal and metopic sutures is associated with scaphocephaly or
dolichocephaly, brachycephaly and trigonocephaly, respectively. Plagiocephaly develops when only one coronal
or lambdoid suture is closed.
Scaphocephaly is the most frequent form of simple craniosynostosis. Cloverleaf and oxycephaly are complex
forms that involve various combinations of closure of coronal, lambdoid, squamous and sagittal sutures.
Syndromic craniosynostoses such as Crouzon’s, Apert’s and Pfeiffer’s syndromes are mainly complex
autosomal-dominant forms associated with other abnormalities. Isolated craniosynostoses occur as a result of
various developmental abnormalities including vascular disruption, early amnion rupture sequence and other
forms of early compression of the developing skull, teratogenic effects of sodium valproate or hydantoin effects,
9p deletions, osteochondrodysplasias such as chondrodysplasia punctata, hypophosphatasia, thanatophoric
dysplasia, and Meckel-Gruber, Williams, Ruvalcaba and Baller-Gerold syndromes. Finally, some have been
described as autosomal-recessive forms.
Table 2: Main Syndromic forms of Craniosynostosis
Main Syndromic Forms Of Craniosynostosis

Syndrome Sutures Involved Skull Deformities Other Abnormalities
Apert Coronal, sagittal, Brachycephaly, oxycephaly, Syndactily, symmetrical hands
lambdoid midface hypoplasia, and feet, ”mitten-like” hand,
hypertelorism marked nasal broad thumb, broad great toc
bridge, prominent often mental retardation
Crouzon Coronal, sagittal Brachycephaly, oxycephaly, no limb abnormality, no mental
midface Hypoplasia, retardation
exophthalmia, hypertelorism
Short upper lip, mandibular
prognathism
Pfeiffer Coronal, sagittal Brachycephaly, cloverleaf Polysybdactyly, abducted
skull thumb,no mental retardation
Saethre- Chotzen One or two coronal Plagiocephaly,brachycephaly Polysyndactyly (hands and fett)
sutures flat facies,high forehead,ear Coarse hands, hypoplastic distal
Abnormalities phalanx, no mental Retardation
Jackson- Weiss Coronal, sagittal Oxycephaly, brachycephaly, Enlarged great toes, syndactyly
midface hypoplasia second and third toes, normal
Intelligence
Antley- Bixler Coronal Brachycephaly, midface Radiohumeral synostosis
hypoplasia, frontal bossing multiple joint contractures
Mental retardation
Table 3: Major sutures involved in craniosynostosis and skull deformities based on the suture(s) involved
Prenatal diagnosis relies mainly on the identification of associated anomalies and on molecular DNA analysis,
which is only feasible in some syndromic forms in well-documented families.
Apert Syndrome
Apert Syndrome (AS) is characterized by craniosynostosis (namely coronal sutures), simetric syndactyly of
hands and feet, and midface hypoplasia. The incidence has been calculated to be 1:60,000 to 160,000 live births.
In the general population it is estimated to occur in 1 per 2 million individuals.
Most of the cases (98%) show de-novo mutations with an otherwise normal karyotype. The hallmark is a
mutation located in the Fibroblast Growth Factor Receptor II (FGFR 2), with a serin-to-tryptophan substitution
in the aminoacid 252 (S252W) being the most frequent event, resulting from a C934G transversion. The second
mutation stands for a C937G transverssion, resulting in a proline-to-arginine substitution in aminoacid 253
(P253R). Quite often, the parents in these cases are of advanced age. Since it is an autosomal dominant condition
it carries a 50% of risk of transmission if one parent is affected.
Ultrasound Findings
Head
There is synostosis of coronal sutures. In the face often asymmetric, there is maxilary hypoplasia, low nasal
bridge, frontal bossing, and mandibular protrusion (Fig. 5). There are low implantation ears, hypertelorism,
exophtalmos, and strabismus. There is a supraorbital horizontal groove. In the skull the antero-posterior diameter
diminishes showing a flat occiput with prominent parietal bones. The head appears brachicephalic. It has a
characteristic of wide, mid-line calvarial defect. There are prominent lateral ventricles. In the limbs there is
syndactily in hands (mitten-like hands) and feet (cutaneal and sometimes osseal) (Fig. 5), especially affecting the
second, third, and fourth fingers, with the appearance of spoon-like limbs.
Figure 5: Apert syndrome showing craniosynostosis of the coronal sutures, maxillary hypolasia, forehead protrusion, low-set
ears, hypertelorism and exophtalmos. The fronto-occipital diameter is reduced, the occiput is flat, and the parietal bones are
prominent. Apert syndrome is also characterized by hands and feet asimmetry with syndactily.
Other less common findings are thickened nuchal fold, cleft lip and/or palate, short humerus, radius-humerus
synostosys, pyloric stenosis, lung aplasia, pulmonary artery stenosis, interventricular septum defects, anomalous
tracheal cartilage, diaphragmatic hernia, and hydrocephaly.
The differential diagnosis includes other cranio-facial syndromes (Pfeiffer, Crouzon, Saethre-Chotzen) that may
also be associated with syndactily (Carpenter, Noack, Sakaty-Nyhan, Goodman).
Craniosynostosis: Antley-Bixler Syndrome

The Antley-Bixler syndrome is an extremely rare polymalformative chondrodysplasia characterized by
multisynostotic osteodysgenesis (principally radio-humeral), fracture of long bones, severe mid facial
hypoplasia, arachnodactyly, femoral arching, ulnar arching, vertebral anomalies, and articular contractures
secondary to synostosis (especially radio-humeral synostosis). Due to the rarity of the syndrome the incidence
remains unknown (Fig. 6).
Figure 6: Views of the baby shortly after birth.
Although some cases seem to result from sporadic mutations, other reports suggest an association with
pathologic steroidogenesis (i.e., luteomas, congenital adrenal hyperplasia, and hyperandrogenism) during
pregnancy.
Over 90% of babies with the Antley-Bixler syndrome die in the neonatal period.
Hyper and Hypotelorism

The interorbitary distance, measured between the outside of both orbits, represents the 0.45 of the BPD. A too
long distance can be produced by the administration of some drugs (epilepsy, etc.). Its reduction often is linked
to chromosomopathies.
Ear Malformations
Embryonic development of the ears is a complex event that depends on two fundamental processes: fusion and
migration of the ear buds. The ear buds make their first appearance in the 8 to 11 mm embryo. They originate
from six mesenchymal proliferations located in the dorsal ends of the first and second pharyngeal arches. These
ridges fuse and develop progressively until they acquire the normal shape and arrive at the proper location.
During development, ear migration from an initial inferior position to a temporal location at the level of the eyes
occurs when the jaw forms. There also is an axis rotation of the ear from an antero-transverse to a lateral, vertical
orientation.
Brachial groove dysmorphogenesis, whether due to embryopathy or to a chromosomal defect, may interfere with
ear growth and/or migration and result in low set ears and /or ears oriented along an abnormal axis. Nevertheless,
there is scanty information regarding the earliest time during fetal development when ear growth and/or
migration abnormalities can be detected.
The complexity involved in the embryonic process of ear formation means that abnormalities of fetal ears are not
infrequent. Generally, minor ear malformations are not clinically significant. The most severe abnormalities are
commonly associated with complex malformations.
Ear anomalies are associated with two major types of problems:
Syndromes Associated with Abnormal Fetal Ears

Chromosomal Abnormalities
 Turner, Trisomies [13-15,18,21, 22]
 First and second pharyngeal arch syndromes:
o Treacher Collins [18]

o Di George
o Pierre Robin [20]
 Holoprosencephaly
 Anencephaly
 Crouzon’s dysostosis
Figure 7: Normal implanted and positioned ears. Turner and T18 syndromes. Low set and abnormally positioned ears.
Trisomy 13. Absence of ears
CHARGE Association: Coloboma, heart defect, choanal atresia, retarded growth, genitourinary defects, ear
abnormalities.
VACTERL Syndrome: Vertebral defects, anal atresia, cardiac anomalies, tracheo-esophageal fistula, renal
defects, limb defects and genital anomalies.
 Congenital defects.
 Acquired embryopathies:
1. Secondary to infections (rubella, syphilis, etc.).
2. Ischemic lesions.
3. Toxic exposure (thalidomide, tretinoin, etc.).

Fetuses with trisomy 21 may have sonographic markers that are much more subtle and difficult to detect than
those with trisomies 18, 13 or Turner syndrome. Nevertheless, aside from hypotonia, short ears are the most
consistent clinical characteristic in making the clinical diagnosis of Down syndrome.
These findings suggest that the measurement alone of the ear length could be expected to detect one-third or
more of all fetuses with aneuploidies, as well as to increase the rate of detection for trisomy 18 and trisomy 13.
The abnormalities of fetal ears detected so far with 3D are:
Mohr Type 1 Orofaciodigital Syndrome

Abnormal lobulations of the antihelix, the antitragus, agenesis of the concha (grade 1 microtia), and an anterior
orientation.
Micrognathia
Grade 1 micrognathia, lateral orientation, low implantation, and low axis inclination.
Trisomy 18
There is agenesis of antitragus and antihelix (grade 1 microtia). The smaller lobe was in a cranial direction. Low
axis inclination and low set ears. Small ears with a lateral implantation (Fig. 7) [28].
Trisomy 13
Axis inclination and low set ears.
Trisomy 21
Axis inclination and low set ears. Agenesis of antitragus and antihelix (grade 1 microtia). Small ears.
Holoprosencephaly
Axis inclination and low set ears (grade 1 microtia).
Anencephaly
Axis inclination and small, low set ears. (Fig. 7).
Hydrops fetalis
Edematous ears with loss of the annular shape.
Three-dimensional ultrasonography provided evidence that ear anomalies are not always symmetrical (Fig. 7). In
some cases of trisomy 18 and 21 there were subtle implantation and ear size differences. Furthermore, 3D US
allowed observation of middle ear lesions.
Nasal Bone: See part one.
Orofacial Teratomas: Epignathus

Fetal teratomas are rare. They occur with an incidence of 1 in every 20,000 to 40,000 live births. The most
common are the sacrococcygeal teratomas (40%) followed by those of an intracranial location. Cervical
teratomas account for only 5 to 6% of all fetal teratomas.
Epignathus is one of the variations of cervical teratomas, probably one of the rarest, with an incidence ranging
between 1 in every 35,000 to 200,000 live births.
Epignathus occurs exclusively at the base of the cranium, most often at the roof of the hard palate or on the
mandible. They have the appearance of a large polyp in the mouth, that forces the mouth to be permanently open
and from which the cauliflower-shaped mass emerges.
Teratomas are tumors originating from germ cells. They have tissues from the three embryonic layers (ectoderm,
mesoderm, and endoderm). They may be either mature or immature, sometimes with neoplastic transformation,
although this has never been described in epignathus. This embryological condition leads to very high levels of
alpha fetoprotein and CEA in maternal serum and in amniotic fluid.
Ultrasound
Their embryonic origin from several tissues results in solid and cystic tumors set within a heterogeneous mass. Fifty
percent of them have calcified areas, whereas cartilaginous and bone tissues occur with less frequency (Fig. 8).
Figure 8: 2D, 3D and macroscopic picture of the newborn.
The tumoral mass can be seen emerging from the mouth, with all other facial structures appearing normal, as
these are very seldomly affected. The obstruction of the esophagus prevents ultrasound observation of the gastric
chamber.
Differential diagnosis includes cervical teratoma, cystic hygroma, lymphangiona, hemangioma, cervical
meningocele, thyroglossal duct cyst, esophageal diverticulum, dermoid cyst, brachial duct cyst, goiter and epulis.
Cleft Lip and Cleft Palate

With a frequency ranging between 25 to 66%, these defects are associated with other major and minor
malformations or form part of polymalformative syndromes. Therefore, there is a need for a multidisciplinary
approach in the management of these malformations.
Cleft lip (CL) with or without cleft palate (P) is the most typical and frequent example of facial malformation,
despite having an apparently low incidence (1 per every 700 to 1000 live newborns).
The Spanish proverb “the face is the mirror of the soul” has a medical equivalent: “the face predicts the brain”,
reporting that, except for isolated cleft lip, 90% of all the varieties of CL/P are associated with additional
malformations of the central nervous system (CNS), the heart, the kidneys, the skeleton, or the intestines.
Associated defects are more frequent in fetuses with central (100%) and bilateral clefts (72%) than with
unilateral clefts (48%). Fetuses with unilateral CL-P also have a better survival rate (52%) than those with
bilateral (35%) or central CL-P (0%).
Definitions
A cleft lip (CL) is a fusion defect of the primary palate, involving the prolabium, premaxilla and the anterior
hard palate, anterior to the incisor foramen. The cleft palate is a fusion defect of the secondary palate.
Methods and US Planes of the Examination

The optimum period for examination is between 18 and 24 weeks of gestation. The examination must include
three types of ultrasound sections:
Sagittal Vision of Fetal Profile: of little interest for detection of unilateral CL or CL-P, as these will not be
revealed by this section, but it is a useful view for observation of micrognathia and of the frontal mass which is
always present and whose vision is essential for the diagnosis of bilateral CL [5-13,30,35] (Fig. 9).
Figure 9: Sagittal view of the face
Frontal Vision of the Face

This is the best view for the observation and localization of the CL. It appears in the prelabial area as an
echonegative area that projects towards the base of the nose, on one or both sides. Occasionally the premaxillary
or the hard palate areas can appear to be affected (Fig. 10).
Figure 10: Frontal view showing a central CL-P
Transaxial or Coronal Visualization of the Maxillar Alveolum

This view at the level of the maxilla enables observation of the location and size of the palatal clefts. Likewise, it
is ideal for observing the frontal mass, specific to bilateral CL-P, which must always be sought out.
Occasionally, an isolated palatal cleft can be observed, if the position of the tongue and other tissues should so
allow, but view of an isolated palatal cleft is quite an exception.
The combination of the sagittal section of the nasal profile measuring the angle formed by a theoretical line at
the level of the most prominent lip and the jaw on the one hand, and another theoretical line horizontal to the
cranium at the height of the upper portion of the nasal bone, has been recommended for the diagnosis and
differential diagnosis of retrognathia and micrognathia (see part one), both of which can be associated with these
anomalies (Fig. 11).
Internal Facial View

Recently, it has also been recommended to study the frontal view of the face using the internal bones
visualization (Fig 12). In these cases the three orthogonal planes are located in the internal surface of the eyes
and nose.
Figure 11: Transaxial view of the maxillar alveolum
3D US
Since the introduction of 3D, the diagnosis of fetal malformations has been one of the best applications of this
new technology. Visualization is much more life-like than that obtained with 2D and offers a much better view
of the fetal face, as well as of any lesion in the fronto-nasal surface or on the lips.
The uses of orthogonal planes, transparency modes, inner surface mode, or 4D, greatly improve the diagnostic
capabilities of 3D. Simultaneous visualization on the screen of the three bidimensional orthogonal planes is
required for complete exploration of facial CL and for 3D-rendering.
Aside from a greater diagnostic sensitivity, other advantages of 3D have been reported, such as the possibility of
offering parents a more life-like and understandable picture of the fetal anomaly along with a more
comprehensive understanding of eventual fetal outcome, although this is difficult to estimate and assess.
As an example of the importance of 3D, even though it bears no relation to cleft lip, a 2D/3D comparative case
was recently published on a harlequin fetus. The visualization of the 3D images of the face, aside from being
exceptional, shows the incredible assistance provided by 3D in the diagnosis.
Ultrasound Classification
The best ultrasound classification available, as yet unsurpassed, and followed by most others, owes its existence
to Nyberg (see part one). It was also the first to indicate that both type and bilaterality correlate with fetal
evolution, with associated malformations and with karyotype anomalies. The use of this classification has
resulted in diagnostic index rates ranging between 88 and 100% (Fig, 13).
Figure 12: Internal view of the facial bones
The frontal protrusion is observed with 2D and with 3D. This finding is of special interest to establish the
diagnosis of bilateral cleft lip with or without cleft palate (Van der Woude syndrome) (Fig. 13).
Figure 13: TYPE 1; Cleft lip without cleft palate. TYPE 2; Unilateral cleft lip with cleft palate. TYPE 3: Bilateral cleft lip
(Van der Woude syndrome). TYPE 4: Central cleft lip.
This variety of cleft lip/palate must be considered as separate from the previous types, and nowadays it is
associated with frontonasal malformations, a term which includes an etiological and pathological range of
anomalies involving the eyes, the nose, the forehead and occasionally the brain.
The most common images are of a very marked hypertelorism, cranium bifidum occultum (which represents a
deficit in the midline frontal bone and widow’s peak hairline), abnormal nose (bifida, hypoplastic or cleft, with a
wide and flattened base) occasionally associated with cleft lip. In very severe cases there is frontal encephalocele
and occasionally micro-ophthalmia, agenesis of the corpus callosum, lipoma of the corpus callosum, and
tetralogy of Fallot.
The development of these frontonasal anomalies can be understood at a gross level as an embryological field
defect. The face develops early, with the formation of bilateral nasal placodes into nasal tubes, until the embryo
reaches a crown-rump length of 17 mm. The internasal groove is present between the nasal tubes and, at this
stage of development; the normal embryo has a flat nose and hypertelorism. Later in development, the nasal
septum grows and the distance between the eyes decreases. If the nasal capsule fails to develop normally, the
primitive brain fills the space which is normally occupied by the nasal capsule, producing an anterior cranium
bifidum occultum. This results in a morphological arrest of the upper facial development at that stage, with the
eyes and nostrils maintaining their fetal position, thus resulting in hypertelorism and nasolabial clefting. The
etiology of this malformation is unknown, but it is considered to be a sporadic anomaly.
Associated Malformations, Chromosomal Pathologies, and Outcome

Approximately 25% of the newborns with CL-P present associated malformations, polymalformative
syndromes, or aneuploidies. The incidence of associated trisomies and multiple malformations which are
potentially fatal is higher in fetuses (80%) than in newborn babies. For instance, in fetuses affected with T13 and
T18 the incidence of CL-P is established at 60% and 40%, respectively. They either die in uterus, during the first
postnatal hours, or are aborted, many pending diagnosis of CL-P.
Consequently, the fetuses affected with CL-P which have been identified using ultrasonography, form part of a
different group of malformed subjects. It is not surprising that, whereas some do not observe any associated
anomalies, others report frequencies of up to 49%. The malformations observed and their distribution by organ is
extremely varied. The most common associated malformations were cardiac and large vessel malformations,
whereas other associations were quite diverse (isolated cases of syndromes of Pierre Robin, Opitz, Roberts,
Apert, multiple dysmorphia and renal hypoplasia).
VAN DER WOUDE SYNDROME
This syndrome is characterized by lower lip pits or excavations and a CL or CL/P, a combination existing in
70% of affected fetuses (Fig. 13). It has an extremely low incidence of 1 in 100,000 to 200,000 newborns and
represents only 1 to 2% of all CL and /or CL/P cases. Other associated anomalies such as congenital heart
defects, facial defects (maxillary hypodontia, biphid uvula, newborns with teeth, etc.) and limb anomalies have
been described (See type III CL/P in Fig. 13).
Eighty percent (80%) of the affected fetuses show inferior and medial lip pits located over the nose portion of the
lip, 30% CL or CL/P, and 20% isolated CL. The syndrome is autosomic dominant, and the gene is located in the
chromosomic region Iq32. Approximately a 30-50% are “de novo” mutations, and 25% show minimal
phenotypic anomalies. New investigations have shown that the phenotypic manifestations can be dependent on
genetic modifications found in the chromosomic region 17p11 and Ip34. These last would be non- syndromic.
Retrognathia and Micrognathia

Retrognathia is a condition of facial disharmony in which one or both jaws are posterior to normal in their
craniofacial relationship. Micrognathia is abnormal smallness of the jaws, especially smallness of the mandible
[3, 11, 30, 35].
They are associated with more than two hundred genetic syndromes. The following are the main bodies of
dysmorphic manifestations associated with mandibular anomalies: Pierre Robin sequence [20], Treacher Collins
syndrome [18], Pena-Shokeir and Seckel syndromes, Hanhart’s syndrome, and several chromosomal
abnormalities (trisomies 13 and 18, triploidies, translocations and genetic deletions).
Micrognathia affected fetuses are at increased risk of abnormal karyotypes. The jaw develops from the
mesenchyme which covers the Meckel cartilage, on the first brachial orpharyngeal arch. Although it
subsequently disappears, its mesenchymal surface develops the mandible. Its development is therefore not
associated either with the alveolar or the osseous maxilla. Mandibular anomalies may appear without any
nasofacial alterations.
DEVELOPMENT ANOMALIES (SEE ALSO PART ONE)
Many developmental anomalies form part of the so-called syndrome of the first brachial or pharyngeal arch,
consisting of a series of malformations which occur as a result of the disappearance or abnormal development of
certain components of this first arch. The origin of the defects probably lies with a deficiency in the cells of the
neural crest as a result of insufficient migration, cellular necrosis, or reduction in proliferation.
The factors underlying these defects may be of a genetic or environmental nature. We do know that a deficiency
in vitamin A can produce serious defects in the face and the thymus due to interference with the development of
the neural crest. Furthermore, given that these cells help to form the septa in aortic and pulmonary arteries, this
first arch syndrome is often accompanied by cardiac anomalies, such as transposition of the large vessels and an
interruption in the arch of the aorta.
The above mentioned Treacher Collins syndrome (mandibulo-facial dysostosis), Pierre Robin syndrome
(mandibular hypoplasia, palatal fissure, defects in eye and ear) and the Di George syndrome (absence of thymus
and parathyroid glands, malformations in the mouth: short sub-nasal groove or fish mouth, nasal clefts and
cardiac anomalies) belong to the group of first arch syndromes, which have also been associated with
chromosomal abnormalities and Mendelian defects.
It is therefore important whenever possible to have an intrauterine diagnosis, differentiating between simple
anomalies of position or retraction – retrognathia – and anomalies in size – micrognathia. The first is simply a
condition of facial disharmony (mandibular retraction). The second is a developmental defect of variable degree
(Fig. 14).
Diagnosis
Some measurements are shown in part one. They include the entire length of the mandible from the temporo-
mandibular joint to the symphysis mentis. This would increase in a linear fashion between week 18 (measuring 2
cm) and week 28 (measuring 3,7 cm).
3D ultrasonography has helped with the description of images of the mandible and dental buds as well as with
the study of the profile of the fetal face. The importance of this new technology in the diagnosis of this type of
malformation following analysis in three orthogonal planes is further manifested by the discovery that the
sagittal section obtained with 2D does not coincide with the “real” section in 30% of the cases.
Undoubtedly, the study by orthogonal frames, enabling a simultaneous frontal, sagittal and para-axial viewing of
the mandible is indeed the technique of choice, since it is considerably better than that of 2D. The measurements
made by 3D have been the most accurate and the only ones which have allowed a differential diagnosis to be
made between retrognathia and micrognathia. The most accurate diagnosis requires three measurements:
 the lower facial angle
 the width of the mandible
 the width of the maxilla
The lower facial angle is measured by sagittal section, where an orthogonal line crosses the vertical line of the
forehead, which passes at the level of the synostosis of nasal bones, and a second line joins the chin with the
anterior contour of the most protruding lip (Fig. 14).
The widths of the maxillary bone and the mandible are measured in an axial plane, caudal to the base of the
cranium at the height of the dental arches, in the alveoli. A line orthogonal to the sagittal axis is traced,
approximately 10 mm behind the anterior bone contour, at the height of the canine teeth. The measurement of
both maxillary and mandibular widths has allowed calculation of the ratio between them (mandibular
width/maxillary width).
Figure 14: Upper: Lower facial angle. Retrognathia. Middle: Comparison 2D and 3D in a case of micrognathia in a fetus
with trisomy 18. Note that the diagnosis can be established with both US techniques, but the anomaly is much more evident
using 3D. Bottom: This case shows an agnathia in a fetus with trisomy 18. Whether 2D or 3D technology is used, the
diagnosis of an absent mandible is obvious. However, the 3D picture is more realistic.
The lower facial angle undergoes no variation between weeks 18 and 28 of pregnancy. On average, it measures
65º. Values under 50º define retrognathia (Fig. 14).
Fetuses affected by the Pierre Robin syndrome (range 36 – 46º), Treacher-Collins syndrome (range 28 – 40º),
and acrofacial postaxial dysostosis (angle of 35º), fell below the 65º angle. But it was only lower in 20% of cases
of trisomy 21 and 5% of cases of trisomy with a harelip/cleft palate, for which a lesser degree of mandibular
retrognathia has been reported to be of frequent appearance.
The widths of the mandible and maxilla increase with gestational weeks and measure on average between 2 and
2.5 cm between weeks 18 and 28, whereas the MD/MX ratio remains constant (1.017 + 0.116). The coefficient
0.785 defines existence of micrognathia (Fig. 14).
It is important to rule out chromosomal anomalies, specially Trisomy 18, in cases of micrognathia, since
chromosomal anomalies and polymalformative syndromes are frequently associated with micrognathia but not
with retrognathia.
Cleft in the Maxilla

Maxillary clefting is a very rare malformation that originates during development of Meckel’s mesenchyme
development. It is associated with other genetic anomalies and tumors like hamartomas, etc.
Treacher Collins Syndrome

Mandibulo-facial dysostosis, is a dominant autosomal genetic disorder resulting from the malformation or
disruption in the development of the first and second branchial arches. It is associated with polyhydramnios,
absence of the stomach, antimongoloid palpebrae downward fissures (clearly seen with 3D and difficult to
identify with 2D), micrognathia due to development of only one mandible, abnormal nose with narrow nostrils,
low-set dysplastic ears, cleft lip, and cleft palate. It reveals an extraordinarily hypoplastic mandible. These
fetuses possess a very arched palate and malar hypoplasia, characterized by malformations of the eyes, ears and
mandibles [18].
Pierre Robin Syndrome

This is another variety of developmental defects in the first pharyngeal arch which manifests with micrognathia,
glossoptosis, high arched U-shaped posterior palate, and cardiac defects. It is frequently associated with
deformities of the palate similar to a post-alveolar cleft or a very high arch of the palate. An autosomal recessive
trait and an autosomal dominant trait with variable penetration have been suggested as a cause of this syndrome
[20].
Nager Syndrome
Acrofacial dysostosis, is an extremely rare malformation complex characterized by external ear anomalies,
hypoplasia of the maxilla, micrognathia, down-slanting palpebral fissures, scant lower eyelashes, radial limb
hypoplasia (mesomelia), absence of the thumb and/or other digits, and a normal karyotype. The etiology is
unknown, although both autosomal dominant and autosomal recessive inheritance have been hypothesized.
TAR Syndrome
Thrombocytopenia-absent radius (TAR) syndrome is a very infrequent syndrome which never has micrognatia
but is accompanied by absent radius, complete mesomelia, in the presence of a small or even normal thumb
starting at the elbow. Thrombocytopenia is usually present at birth. It is inherited by an autosomal recessive
pattern.
Mohr Syndrome
This orofacial syndrome is characterized by micrognathia, ear anomalies, radial hypoplasia, polidactily, biphid
hallux and normal karyotype.
Robert Syndrome
This orofacial syndrome never has micrognatina but shows clefting, ear anomalies hypoplasia or absent radius,
normal digits and the karyotype shows premature centromere separation. It is transmitted as an autosomal
recessive condition. Tetraphocomelia is associated with cleft lip/palate, hypotelorism and microcephaly.
Hydrocephalus, spina bifida and encephalocele have also been described. Most affected infants die during the
neonatal period.
Dandy Walker Complex and other Cerebral Cysts

This complex is characterized by the presence of a cyst at the posterior fossa that communicates with the fourth
ventricle through a total or partial defect of the cerebellar vermis, showing ventriculomegaly of variable degree.
Another entity, the Dandy-Walker variant, consists of hypoplasia of the cerebellar vermis with or without
communication with the cisterna magna (Figs. 15 and 16).
Currently it is believed to be due to a defect in the superior part of the fourth ventricle and it is associated with
numerous genetic syndromes, among which trisomy 13, trisomy18, triploidies, and deletions in the long arm of
chromosome 13, and less frequently with deletions in other chromosomes.
In 60-75 % of cases it is accompanied by other structural malformations. Among the more frequent
malformations are cardiac anomalies, choroid plexus cysts, agenesis of the corpus callosum, urogenital tract
anomalies, and polidactily. It is present in one out of every 30,000 newborn babies and represents 4% to 12 % of
congenital hydrocephaly cases.
Sonographic Diagnosis
The classic image is the presence of an echo-negative area located in the posterior fossa, with a diameter greater
than 10 mm, with total or partial absence of the cerebellar vermis which is usually observed as an echogenic
structure located at the mid line of the posterior fossa. The defect allows the communication of the cystic area
with the fourth ventricle. In a 20% of these cases ventriculomegaly, of variable magnitude, is diagnosed in utero
(Figs. 15 and 16).
The Dandy Walker cyst must be differentiated from other cysts of the same location. The arachnoid cyst of the
posterior fossa, which is located at the midline and may be accompanied by ventriculomegaly by compression,
presents an intact vermis that separates the cyst from the fourth ventricle. The brain and cerebellum are normal in
these cases. The mega-cisterna magna or accumulation of CSF at the posterior fossa, causes dilatations greater
than 10mm and does not affect the cerebellar vermis. The choroid plexus cysts characterized by echo-free zones
located in the posterior horns of the lateral ventricles. The majorities are small, of physiologic nature, without
any clinical transcendence and may be undetected. They are interesting because they are present in 77% to 80%
of cases of Edward´s syndrome, (see part one), therefore they have to be considered a sonographic marker of
aneuploidies.
Figure 15: Dandy-Walker complex showing the posterior cyst (arrows) with absence of vermis, communication with the
IVth ventricle, lateral ventricles dilatation, micrognatia, and rocker bottom feet. Trisomy 18.
Vaginal ultrasound is not recommended for the establishment of these diagnoses because the cerebellar vermis
completes its fusion after the 16th week of gestation.
Aneurysm of the Vein of Galen (see below)

The use of a semicoronal plane at the time of the sonographic examination may lead to a false positive diagnosis
of aneurysm of the vein of Galen because it can provide a false sense of enlargement of the cisterna magna.
Furthermore, a vermian defect may be diagnosed when what is being observed is the space between the
cerebellar tonsils and the brain tissue. The ideal ultrasound plane for diagnosis must include the cavum septi
pellucidii at the front and the cerebellum posteriorly.
Figure 16: Dandy-Walker syndrome showing talipes hand, finger anomalies and rocker bottom feet.
Aneurysm of the Vein of Galen

The denomination of aneurysm of the vein of Galen refers to different midbrain arteriovenous fistula
malformations associated with aneurysmal dilatation of the vein of Galen. It consists of an echo–free intracranial
lesion, surrounded by a refringent wall, showing turbulent mixed vascular flows within the cystic structure in
2D/3D color Doppler sonography.
Doppler seems to be the most useful non-invasive method for the differential diagnosis of midline brain cystic
structures (i.e. arachnoid cysts, porencephalic cysts, etc.), for the precise localization and identification of the
vascular anomaly and the feeding arteries in cases of cerebral arteriovenous malformations, and for the
evaluation of the cardiovascular hemodynamic consequences (Fig. 17).
Another cyst or dilatation in the CNS is due to agenesis of the corpus callosum. This is an extremely severe fetal
malformation that in 80% of cases is associated with mental retardation (Fig. 18). It is fully described in another
chapter.
Choroid Plexus Cysts (see part one)

Although lymphangiomas can occur in any part of the body where lymphatic ducts are located, 95% of them are
found either in the neck, the head, or the axilla. When they occur in the lateral and posterior neck region, they are
frequently associated with chromosomal abnormalities and with hydrops. Isolated lymphangiomata in other parts
of the body are not associated with other malformations or with chromosomal syndromes.
Lymphangiomata can vary from simple small collections of fluid (i.e., hygroma colli), to large cavernous cysts.
Their characteristic sonographic appearance is that of thin-walled, multiseptate, multicystic, hypoechogenic
masses that can be diagnosed in the first trimester. Although some can disappear during gestation, the presence
of septae or fetal anasarca is associated lack of resolution and with a poor outcome (Fig. 19). Edema, hydrops,
and polyhydramnion are commonly seen in cases of lymphangioma.
The ultrasound image of cervical teratomas is similar to lymphangiomas because they contain solid and cystic
areas within a heterogeneous mass. Unlike lymphangiomas, 50% of teratomas have calcifications that represent
either bone or cartilaginous structures. In addition, teratomas have active vascular mapping with Doppler
scanning, a phenomenon never seen with lymphangiomas.
Figure 17: 2D, Color Doppler and 3D color energy of an aneurysm of the vein of Galen. The green arrows show the Circle
of Willis. The white arrows point to the vein of Galen and the yellow arrows to the aneurysm.
Figure 18: Typical case of corpus callosum agenesis.
It can be equally difficult to distinguish between lymphangiomata and epignathus (Fig. 19).
Figure 19: Neck lesion. Multicystic, thick septations. The lesion is predominantly on the left side. Three-dimensional view.
Thick outer margin and thick septations in the portion that extends into the left cheek. The mass can be seen distorting the left
eye and left corner of the mouth. Frontal view of the neonate.
Congenital Goitrous Hypothyroidism

The incidence of congenital hypothyroidism ranges between 1 in 3,000 to 5,000 live births. Although fetal goiter
is very rare, it is potentially dangerous due to its lifelong consequences (mental retardation, neuromotor
disorders, abnormal intellectual development, spatial and visual deficits, reduced perception and language
abilities, etc).
The most frequent causes of congenital hypothyroidism are thyroidal dysgenesis (80%), hypothalamus-pituitary
disorders (5%). The remaining 15% are consequence of thyroidal dyshormonogenesis caused by recessive
biochemical hereditary defects in some of the stages of the synthesis of iodothyronin. The two most common
defects are a result of mutations in the thyroperoxidase and thyroglobulin genes which either lead to an
inefficient organization of iodine or to an abnormal synthesis or secretion of thyroglobulin.
Fetal goiter causes neck hyperextension, airway obstruction, and abnormalities of structure and function of the
trachea and esophagus. These problems lead to polyhydramnios due to impaired swallowing. In addition, they
cause dystocia due to abnormal fetal presentation during labor.
Ultrasound Diagnosis
The following signs can be observed (Fig. 20):
Figure 20: Sagittal view of the fetal hyperextended head with the fetal profile and neck tumor (arrow) visible.
 Polyhydramnios secondary to oesophageal obstruction. - A solid tumor is present, generally

bilobulated and refringent, which may reach highly variable sizes and which may compress the
neck.- The fetus reveals a marked hyperextension in the neck.- Restriction of fetal growth is not
infrequent.
SEE PART 3 FOR REFERENCES.

CHAPTER 2
3D / 4D US in Fetal Malformations
Part 3- Second Trimester: Skeletal Disorders, Thoracic, Abdominal, Kidney and

Other Malformations
Castillo2, Newton Osborne2, Esperanza Villalaiz2, Francisco Bonilla Jr.2 and Fernanda
Machado2
1
Abstract: The acardius fetuses or TRAP, consequence of vascular anastomoses in the placenta, may disrupt
organogenesis in the recipient.They are classified as acardius amorphous, acormus, acephalus and anceps.
Diagnosis is now possible during the first trimester by using trasnvaginal 3D Doppler Angiography. Conjoined
twins are variants of monozygotic twins that occur by incomplete dissociation of cells from the internal cellular
mass, especially during the hatching process. Thanatophoric dysplasia is the most common lethal
osteochondrodysplasia. The different skeletal dysplasias, the mentioned, dysostosis, idiopathic osteolisis,
disorders resulting from chromosomal defects and resulting from primary metabolic disorders, are showed by
using their US typical images. Achondroplasias, an autosomal dominant disorder related to a defect in the short
arm of chromosome 4, can be homozygous (lethal) or heterozygous (most live newborn). Osteogenesis
imperfecta includes disorders of the connective tissue and bone fragility, particularly of the skeletal system. Lung
malformations, bronchogenic cyst and cystic adenomatoid malformation have characteristic differential 3D US
images. Cardiac tumors are rear findings and have been identified with fetal echocardiography, improving the
perinatal outcome. Neural tube defects, myelomeningocele and spina bífida, are among the most difficult
malformations to diagnose, requiring considerable experience and the use of 3D. Sacrococcygeal teratomas
represent more than half of all fetal solid tumors. Fetal limb malformations are classified depending on whether
the anomalies are predominantly of bone length or of digital deformities. Congenital multiple arthrogriposis or
joint gryposis describe a syndrome consisting of multiple contractures and joint dislocations of a very poor
perinatal outcome. Gastrointestinal malformations are numerous with different locations and prognosis. We are
showing all of them by using 3D/4D, paying special attention to the most common ones: gastroschisis and
omphalocele. Renal and other urinary tract malformations represent 20% of all congenital anomalies. It is now
possible to detect a wide spectrum using 3D. These may be either isolated or part of polimalformative syndromes.
There are very few reports of intersexes and other Genital malformations. Amniotic band syndrome is
characterized by multiple malformations secondary to amniotic bands that compress fetal parts causing
amputations and other lesions
THORACIC MALFORMATIONS AND TUMORS

1. Fetus Acardius
Fetus acardius is an extremely rare complication of monozygotic multifetal gestation that is thought to result from
what is known as the twin reversed arterial perfusion sequence (TRAP) [3].
These very malformed fetuses may have rudimentary heart tissue (pseudo-cardia) or may completely lack a heart
(holoacardia) (Figs. 1 and 2). This anomaly is always present with other severe fetal malformations. It occurs in
0.3% of monozygotic twin gestations, which amounts to a frequency of about 1 per 35,000 deliveries.
Fetus acardius is a consequence of vascular anastomoses in the placenta that result in feto-fetal transfusion. Until
recently; it was thought that the twin with a heart perfused the acardiac twin through at least 2 anastomoses, 1 artery
*Address correspondence to Fernando Bonilla-Musoles: Department of Obstetrics and Gynecology, Valencia School of Medicine, Valencia,
Spain; E-mail: profesorbonillamusoles@hotmail.com

3D / 4D US in Fetal Malformations Current Topics on Fetal 3D/4D Ultrasound 75
to artery and 1 vein to vein, and that the circulation of the acardiac twin was therefore reversed. There is evidence,
however, that vascular anomalies in these cases may be more complex.
Figure 1: Pseudocardia and holoacardia.
Above: 2D sagittal view of the acardiac fetus. There is a short, single-artery umbilical cord between the placenta and
the fetus. Observe that the flow in the fetus is toward the lower extremities. Observe the absence of a head, well-
developed thorax, and upper extremities. The lower extremities are abnormal (arrow head).
Figure 2: 2D/ 3D pictures of an acardiac fetus, acardius anceps, showing an omphalocele and the lower extremities.
Twin-to-twin transfusion may disrupt organogenesis in the recipient in such a way that development of certain
"nonessential" organs such as heart, brain, and arms may not occur. The donor twin may have cardiac hypertrophy,
cardiac failure, intrauterine growth restriction, or intrauterine death.
Diagnosis is now possible during the first trimester of pregnancy by detecting inversion of vascular flow in the
recipient acardiac fetus on transvaginal Doppler ultrasonography (see part one) [2, 3, 38, 39].
Classification:
l. Acardius amorphus. This type of acardiac fetus is the least differentiated form. On histological
analysis, only bones, cartilage, muscles, fat, blood vessels, and stroma can be identified. It is the most
striking variant. If rudimentary nerve tissue is present, then this form is called acardius
myelanencephalus. It is likely that some of the teratomas in neonates are remnants of acardius
amorphus types of malformation.
2. Acardius acormus. This type of acardiac fetus lacks a thorax. The umbilical cord inserts in the head.
Because rudiments of thoracic structures are almost always found on histological examination, it is
debatable whether this variation is real or justified.
3. Acardius acephalus. This type of acardiac fetus lacks a head, a thorax, and upper extremities. There
may be additional malformations in some of the remaining organs. It is the most common type
described. Three of the cases in this report are of this type.
4. Acardius anceps. This is the purest form of acardiac fetus. These fetuses have a head, a thorax, and
abdominal organs but lack even a rudimentary heart. It is likely that many of the other types start off as
acardius anceps and evolve into one of the other forms because of poor oxygen supply.
2. Conjoined Twins
Conjoined twins are variants of monozygotic twin gestation that occur by incomplete dissociation of cells from the
internal cellular mass between days 9 and 13 of embryonic development.
The incidence varies between 1 in 50,000 and 1 in 100,000 deliveries, with the highest observed in cases of multiple
gestation resulting from the use of assisted reproduction technology. This incidence also seems to be higher in
women during their late reproductive years than in younger women, presumably because of a thinner zona pellucid.
The time of monozygotic twin development has traditionally been based on hypothetical mechanisms. According to
the most recent evidence, embryological division would occur shortly after fertilization, but before preimplantation
while the embryo is still within the zona pellucida.
It has also been suggested that twinning occurs shortly after blastocyst implantation. Recent observations have
concentrated on involvement of the zona pellucida in monocygotic twinning. According to this theory, monozygotic as
well as bizygotic twins are produced during "hatching", when embryos are trapped in the opening of the zona pellucida.
Alternatively, conjoined twining can occur when there is incomplete cleavage in the embryonic disc between days 13
and 15 following fertilization (Table 1 and 2).
When conjoined twins or other fetal anomalies are identified, 3D sonography is likely to provide images that are
easier for the physician and parents to understand than are those from 2D, therefore allowing them to make informed
decisions on the basis of more comprehensible information (Figs. 3-5).
This refers to isolated malformations of single bones or of combination of bones. A few examples of this anomaly
are craniosynostosis, craniofacial dysostosis or Crouzon disease, mandibulofacial dysostosis, achiria, apodia,
polydactyly, syndactyly, Poland syndrome, and brachydactyly.
3. Thanatophoric dysplasia
The skeletal anomalies comprise a number of entities of low incidence (2/10.000 newborn). Half of them are lethal
because of a narrow thorax with hypoplastic lungs.
Thanatophoric dysplasia, the most common lethal osteochondrodysplasia, occurs with an estimated frequency of 0.5
to 0.69 cases in 10.000 newborn [3, 4, 33, 40, 42].
Figure 3: 3D of thoracopagus. The linkage is better observed with this technology.
Dicephalus
Figure 4: Dicephalus conjoined twins. This anomaly shows two separated heads, one or beginning of two rachis, one thorax and
pelvis the four extremities.
Figure 5: Dipygus parasiticus
Table 1: Summarizes the classes of conjoined twinning that can occur. The most common unions occur at the trunk
(thoracopagus, xiphopagus, and omphalopagus) Relationship between the aparition of embrionic division, cause of twining, and
placentation
Days After Ovulation Type Of Placentation Twining Cause

Classical Model
1-3 Bichorial biamniotic preimplantation split
3-8 Monochorial biamniotic mixed causes
8-12 Monochorial monoamniotic embryonal disc split
13-15 Conjoined incomplete disc split
Hatching Model
6 Bichorial biamniotic Throphoblastic split in gap Hatching
>6 Monochorial biamniotic Mixed causes
>6 Monochorial monoamniotic Split cellular masses and conjoined internal but
not throphoblast
Table 2: Classification of conjoined twins.
Class Place of union

Thoracopagous Thoracic region (Figs. 3-5)
Xiphopagous Xiphoid process of sternum
Omphalopagous umbilical region
Rachiopagous Fusion of upper spinal column, back to back
Pygopagous Sacrum; back to back most common
Pygodidymous Cephalothoracic region; duplicate pelves and lower extremities.
Pygomelous Sacral or coccygeal region; additional limb or limbs at or near buttock.
Ischiopagous Pelvis, ischial region, end to end
Craniopagous Head
Iniopagous (craniopagous occipitalis) Head, at parasitic occipital region
Epicomous (craniopagous parasiticus) Smaller, parasitic twin joined to larger auto site at occiput
Monocephalous Single head with two bodies
Diprosopous Single head and body with two faces
Dicephalous Symmetric body with two heads
Dipygous parasiticus Head and thorax completely merged: pelvis and lower extremities duplicated
Sincephalous Face
Clasification
Skeletal dysplasias are usually divided into five different types:
Osteochondrodysplasias
These involve alterations in the growth and development of bone and cartilage. The most frequent forms are
osteogenesis imperfecta, achondroplasia, thanatophoric dysplasia, and achondrogenesis.
Dysostosis
Idiopathic osteolysis
This is a disorder associated with multifocal bone resorption.
Skeletal disorders resulting from chromosomal defects

These disorders may result from either de novo chromosomal mutations or aneuploidy. In some cases, these
disorders can result from dominant or recessive Mendelian in heritance.
Skeletal abnormalities resulting from primary metabolic disorders

Skeletal abnormalities resulting from primary metabolic disorders are conditions such as hypophosphatasia (i.e.
osteogenesis imperfect, see below), in which severely demineralized bone secondary to congenital alkaline
phosphatase deficiency leads to skeletal abnormalities that are incompatible with postnatal life.
Thanatophoric dwarphism: the typical cloverleaf-shape skull image is usually seen in 14% of cases. This finding
allows classification into:
 Type I the most frequent ones, is characterized by:
 Curved and short long bones.

 Femur with shape of a telephone receiver.
 Fibulae shorter than tibiae.
 Platyspondylia resulting in mild kyphosis.
 Cloverleaf-shape skull is absent.
The narrow, short ribs along with flat vertebrae bodies result in a short and narrow chest. The presence of a mid-face
hypoplasia, depressed nasal bridge, and a full forehead gives them the appearance of having a “boxer’s face”.
- Type II, have in addition a:
- “clover leaf”shape skull
- trilobed skull
- with straighter femora and
- taller vertebral bodies than those seen in fetuses with Type I.
US Diagnosis: Ultrasound presumptive diagnosis is based on:
 Megacephaly with cloverleaf–shape skull (Figs. 6 and 7) and progressive hydrocephaly
 Hypoplastic thorax that is disproportionately small in relation to the abdomen (bell-shape thorax in the
form of a “champagne bottle cork”).
 Ribs and bones of the extremities those are short and curved. Femurs which often show the shape of a
“telephon receiver”.
 Excess of skin that confers a “boxer’s face” aspect.
 Flattened vertebrae with diminution of the intervertebral space, giving the vertebral body the form of
an “H” and increasing the short and narrow appearance of the thorax.
 Presence of polyhydramnion in most cases.
Although an autosomic recessive transmission has been suggested for Thanatophoric dysplasia, the etiology of this
disorder, which has an estimated recurrence rate of 2%, is likely to be multifactorial.
The 3D global vision of the fetus facilitated direct observation of the macrocephalic head, of the short, angulated,
thick arms, legs, hands, and feet. Also the visualization of the short and narrow thorax with prominent abdomen.
Achondrogenesis has a severe shortening of the femoral length (femur length is 30% of the length of femurs for the
gestational age for normal fetuses). In osteogenesis imperfecta type II and thanatophoric dysplasia the shortening is
moderate (FL is 40-60% of FL for gestational age) and in cases of hypochondrodysplasia and achondroplasias, there
is a modest shortening (FL is 80% of FL for gestational age).
The different osteochondrodysplasias have the following characteristics:
Achondroplasias
Autosomal dominant disorders related to a defect in the short arm of chromosome 4 that can be homozygous (always
lethal) or heterozygous (most live newborn).
Figure 6: Thanatophoric dwarphim. Tipical faces with big heads.Thanatophoric dwarphim. Short thorax and protruding abdomen.
Short extremities
Figure 7: Thanatophoric dwarphim. Protruding abdomen, short thorax and cloverleaf head.
The diagnosis is made on the basis of family history (although most are “de novo” mutations) and by the following
US markers:
 Short extremities, mainly rhizomelias.
 Long and narrow thorax and lumbar lordosis.
 Enlarged head with frontal swelling (attention should be paid to the relationship biparietal
diameter/thorax diameter).
 Sometimes, megalencephaly is observed by disproportion between the base of the skull and the vault.
For that reason, the cases can also present with hydrocephaly.
Joint hyperextension, especially of the knee.
Osteogenesis imperfecta type II (see below)

Osteogenesis imperfecta
Osteogenesis imperfecta (OI) is a clinically and genetically heterogeneous entity of osteochodrodisplasia that
includes disorders of the connective tissue and bone fragility, particularly of the skeletal system. Consequently, it is
characterized by bone demineralizations that are invariably transmitted as mendelian traits (Fig. 8) [3, 21, 33, 41].
The underlying defect is a mutation affecting encoding of type I collagen and resulting in the production of collagen
of abnormal quantity (Osteogenesis imperfecta type I) or quality (Osteogenesis imperfecta types II-IV) [24].
Four types have been recognized:
Type I: is transmitted in an autosomal dominant fashion. Affected individuals are normal at birth, but they have blue
sclerae and bone fragility that in time may lead to fractures.
Type II: is transmitted as an autosomal recessive condition. Neonates have short limbs, multiple fractures of the long
bones and ribs, and demineralization of the skull. This condition is uniformly lethal (Fig. 8).
Figure 8: Osteogenesis imperfecta letal type II. 2D images of osteogenesis imperfecta deformities, short long bones and fractures
are showed. Osteogenesis imperfecta. Broken and deformed long bones. Hypogenic and deformed skull. Deformities, short
irregular bones and fractures in long bones can be clearly observed in these 3D pictures using minimum and maximum
transparency system.
Type III: may be transmitted as either an autosomal dominant or autosomal recessive trait. The sclerae are blue, and
fractures are found usually at birth. This condition is not lethal but carries significant disability.
Type IV: is the mildest form of the disease. Patients have blue sclerae, but fractures and deformities are uncommon.
This form is transmitted as an autosomal dominant trait.
Osteogenesis imperfecta type II is characterized by intrauterine or early neonatal death. Its birth incidence is very
low, about 1 per 60.000 newborns, with most cases occurring from new autosomal dominant mutations.
This entity has been diagnosed through the following findings:
- Shortening of all the long bones. Specially the limbs.
- Hypoechogenicity of bones.
- Presence of fractures (long bones, ribs, etc).
- Bones and thorax severely deformed.
- Demineralization of the skull.
- Polyhydramnion is frequently found.
Also abnormal compressibility of the fetal head (the outline of the head can be significantly molded even by slight
pressure), low echogenicity of the calvarium and unusual clarity of visualization of cerebral structures, although not
pathognomonic, have also been described.
4. Bronchogenic cysts and cystic adenomatoid malformation of the lung

Bronchogenic cysts (BC), as pulmonary sequestration (PS), cystic adenomatoid malformation (CAM), and
conngenital lobar emphysema (CLE), are a rare group of congenital cystic lung that arise from an error in the
embryologic development of the lung The incidence is unknown [3,4].
Bronchogenic cysts are the result of anomalous development of the ventral foregut and lung budding during the first
trimester. They are usually single but may be multiple. They have been found all along the tracheoesophageal course,
in perihilar or intraparenchymal sites, with a predilection for the area around the carina. When developed early in
pregnancy they are more frequent located in the mediastinum (30%). When the development start latter, then
localization is more frequent in the lung.
This entity id often associated with other malformations such as esophagi duplication, tracheo-esophagic fistulae,
neuroenteric cysts, lung secuestration and vertebral defects.
Antenatal sonographic diagnosis of a pulmonary bronchogenic cyst requires the identification of a single, well-
marginated, unilocular, echogenic mass within the lung parenchyma. It consists almost entirely of a dilated air space
that becomes a large cyst filled with mucinous secretions. The cyst does not communicate with the normal airways,
as it should.
Cystic Adenomatoid malformation

Is a congenital malformation characterized by an overgrowth of terminal respiratory structures resulting in the
formation of intercommunicating cysts of various sizes. This condition can affect part of a lung or the whole organ.
The precise aetiology is unknown. It is thought to be produced by an arrest of normal pulmonary development. It is
estimate that this condition occurs 1 in 25,000 newborns. CCAM represents 25% of all congenital lung
malformations.
Sonographic diagnosis is based on: (Fig. 9).
I. Single or multiple large cysts > 2 cm. diameter.
II. Multiple small cysts < 1 cm diameter.

III. Echogenic bulky lesion of lung tissue, formed by small cysts (0.5mm).
Cystic Adenomatoid Malformation of the Lung is associated 10 to 50% to other malformations such as Potter
syndrome, sirenomelia, and septal ventricular defects (Fig. 9).
Figure 9: 2D and 3D of the bronchogenic cyst (above) and Cystic adenomatoid malformation of the lung accompanied by edema,
hydrops and to small heart (below).
5. Cardiac Tumors
Fetal cardiac tumors are rare findings, also at birth. In recent years increasing cases have been identified with fetal
echocardiography, improving the perinatal outcome and providing adequate management of labour and delivery,
with appropriate postnatal monitoring and treatment.
There are several types of cardiac tumors; the most common are Rabdomyoma, following in frequency the teratoma,
fibroma, lipoma, hemangioma, and osteoma. Malignant transformation is exceptional (Fig. 10) [3, 14].
Over 50% of foetuses with cardiac Rabdomyoma will have tuberous esclerosis, an autosomal dominant condition
characterized by the development of hamartomas in the brain, kidneys and skin, which is associated with seizures and
mental retardation.
Currently it’s possible to make antenatal diagnose at 20 weeks, but the majority become apparent during the late mid and
third trimester. These tumors can be seen as an isolated growth or as multiple solid masses arising from the fetal
myocardium.
Rabdomyoma usually are seen as multiple echodense masses in the interventricular septum or in the free wall of the
ventricle of the myocardium, the size is variable.
Teratomas are extracardiac and well encapsulated masses showing a complex echogenicity with cystic and solid
parts, with obvious amounts of pericardial effusion.
Cardiac fibromas are single, echogenic, sharply demarcated masses, without acoustic shadowing, occurring in the
free wall of the left ventricle or in the interventricular septum, they have been associated with Gorlin’s Syndrome.
Hemangiomas can arise from anywhere in the vicinity of the heart. The most common origin is the base adjacent to
the right atrium. Echocardiography shows mixed echogenicity. Pericardial effusion are usually present, the mass are
sessile and non – encapsulated, the absence of blood flow signals is commonly observed, it’s presence depends on
vascular type, amount of arteriovenous shunting and proliferation of endothelial cells.
Figure 10: Heart Fibroma (yellow arrow) associated with pleural effusion (red arrow). 3D. Yellow arrows showing the tumour.
Red arrows: the pleural effusion
Smaller tumors might be asymptomatic in early pregnancy, tending to be evident in the late second or even third
trimester. Sequential sonographyc examination is very important in patients with unexplained arrhythmia since these
could be the first sign of disruption of the conduction system of the heart by a growing tumor.
6. Situs Inversus
This is an extremelly infrequent malformation which shows the heart and all the great vessels located at the right
thoracic site. We are showing one of the first cases of the Literatura observed with 3D (Fig. 11).
Figure 11: Situs inversus totalis

NEURAL TUBE DEFECTS
Myelomeningocele and Spina bifida

Spinal defects with marrow externalization are among the most difficult malformations to diagnose, requiring
considerable experience.Many of these defects and anomalies are diagnosed well into the second and third trimester
with 2D, frequently as a result of abnormally elevated maternal serum alpha-fetoprotein (MSAFP) levels [3, 38, 39].
Etiology and classification: NTDs are malformations, starting early in pregnancy, that result from either a failure to
close or from a defective closure of the neural tube during the fourth week of embryonic development.
The most severe form of failure, craniorachischisis, is a lack of closure along the entire length of the medullary
canal. It occurs when the brain and neural tube have not completed the neutralization process, remaining open. The
mildest form is spina bifida occulta .
Spina bifida occulta, although no less dramatic than the others, is resulting when the two halves of the vertebral arch
fail to fuse. This is referred to exclusively as a bone defect and not as a marrow protrusion.
Neural tube fusion starts in the area of the fourth somite and extends cephalad and caudad. Failure of primary closure
results in upper tube defects frequently associated with severe cephalic pole defects, while low thoracic, lumbar, and
sacral defects result from failure of secondary closure.
The most frequent location is in the lumbosacral region, 60% of cases, followed by thoracolumbar, 36% of cases,
and sacral, 4% of cases.
Current classification: NTD have been divided into the following (Scheme 1):
 Hidden spina bifida
 Open spina bifida:
 Partial and complete rachischisis
 Cystic spina bifida:
 meningocele
 myelomeningocele
 myelocele
When there is open spina bifida, membranes alone, or with neural tissue, may protrude through the vertebral defect
giving rise to a meningocele, myelomeningocele, or a myelocele.
Along with the vertebral arches, the adjacent soft dorsal tissue is also affected. As a result, the presence or absence of
meninges, regardless of their content, determines whether the defect is “open” or “hidden”.
In hidden spina bifida the defect is covered by the skin or a membrane most frequently affecting the level lumbar 5
or sacrum 1.
Ultrasound diagnosis of NTDs should include the following parameters
1. Identification of the defect, localization, extension, and degree of opening.

2. A search for associated CNS lesions. More than 50% are associated with hydrocephaly, banana, and
lemon, and strawberry signs.
3. A search for associated lesions besides CNS lesions.
4. An estimate of the neurological and functional consequences of the defect by observation of limb
movements, presence of polyhydramnion, skull or brain abnormalities, and involvement of other
organs.
Scheme 1
Meningocele results when the posterior neural arch fails to fuse and the herniated sack does not contain neural
tissue. This defect is commonly associated with other malformations.
In myelomeningocele, the most frequent open NTD, the herniated sack does contain neural tissue (Figs. 12-13).
Figure 12: The image clearly shows the width of the neural tube defect, affecting 5 dorsal vertebrae
Figure 13: This myelomeningocele was accompanied by an internal hydrocephaly. Sagital view left. Sacral Myelomeningocele-
Comparison between 2D and 3D. Frontal view right
The most frequent associated CNS malformation, accompanying 50-75% of the cases, is ventriculomegaly, and
hydrocephaly in its most severe form.
Arnold-Chiari syndrome is nearly always accompanied by ventriculomegaly. This defect consists of a posterior
brain injury characterized by the displacement of a small portion of tissue from the cerebelar vermix. The
displacement, in turn, causes the marrow and IVth ventricle to descend.
Sacrococcygeal Teratomas
Sacrococcygeal teratoma (SCT) represents more than half of all fetal tumors. Their incidence is still only 1 in 40,000
births [3, 23, 33].
It has been reported that the course of SCT diagnosed on routine sonography is associated with a higher-than-
expected incidence of prenatal and perinatal complications.
3D allows volume calculation of the fetal spine and provides data about volume changes in the developing fetal spine
between 16 and 25 weeks' gestation (Fig. 14).
Most extragonadal teratomas derive from more than one of the primitive germinal layers and usually contain
histological elements of all three. Although these tumours are of variable size, most of the diagnosed prenatally are
large, mainly because they are fast growing and usually diagnosed late.
Approximately 80-85% of external fetal teratomas are benign. Similarly, 5 -20% of partial or complete fetal
intrapelvic tumors are malignant.
Sacrococcygeal teratomas arise from the anterior surface of the sacrum or coccyx. The focus of origin is usually their
only point of attachment.
The localization of teratomas is related to their cells of origin. Sacrococcygeal teratomas originate from pluripotent
cells of Hensen's nodule, the anchorage point of sexual cells. They are thus related to germinal line cells (Boveri's
Keimbahn).
The tumors are histologically classified as mature teratomas, immature teratomas, and embryonal carcinomas with or
without teratomas. It is not possible to definitely distinguish between them with sonography.
It has been suggested that these tumors are abortive forms of twinning. The occasional presence of organ-like
elements and the impression that the twin index in the families of patients with teratomas is higher than average
support this idea.
Sacrococcygeal teratomas are usually external tumors with variable intrapelvic extension. However, they can be
completely intrapelvic without any external manifestations.
The structures most frequently affected are the terminal bones of the medullary channel. These tumors are most
frequently associated with the worst prognosis. Although many of these teratomas affect large portions of the sacrum
and coccyx, there are occasional cases in which these bones are minimally affected, with excellent postnatal surgical
prognosis.
It is possible to determine the localization and size of the SCT along with the degree of involvement of intra-pelvic
structures with sonography.
Most SCTs are solid or solid-cystic tumors. Only 15 % are purely cystic.
The likelihood of malignancy is increased up to 70% if the uterine size is larger than expected for gestational age due
either to a large fetal tumor or to the presence of polyhydramnion.
The ultrasound image is of a heterogeneous mass attached to the fetal buttocks that can be solid, cystic, or mixed.
The mass may be dense and of variable size having echo-dense areas with acoustic shadows that suggest calcification
(Fig. 14).
If the tumor is external the differential diagnosis includes myelomeningocele along with other caudal entities. If the
location is internal the differential diagnosis includes meconial cysts, ovarian cysts, hydrocolpos, bowel dilatation or
duplication, mesenteric cyst, bladder duplications or cystic neuroblastoma. If the tumor is solid, the differential
diagnosis includes cordomas, neurogenic tumors, lipomas, hemangiomas, and malignant melanomas.
Other ultrasound signs include the presence of hydrops and changes induced by mass compression such as bladder
displacement, urethral obstruction, and hydronephrosis.
The advantages of 3D make it easier to outline SCTs and distinguish them from other clinical entities. The possibility
of rotation and removal from view of ínterfering structures with 3D allows detailed observation of the dorsal part of
the vertebral column in those cases in which it is difficult or impossible to see clearly these areas with 2D.
Figure 14: 3D view of two sacrococcigeal tumors (arrows). Above left in the third trimester. The other three pictures in week 16
FETAL LIMB MALFORMATIONS
Limb abnormalities may result from skeletal dysplasias, a heterogeneous group of anomalies that interfere with the
growth and normal development of bones caused by exposure to certain teratogens or by certain primary metabolic
disorders.
The prevalence of skeletal dysplasias is estimated to be approximately 2.4 cases per 10,000 live births.
It is frequently not possible to distinguish between the different types of bone dysplasias with 2D, especially those
classified as osteochondrodysplasias.
The four most common types of osteochondrodysplasias are: thanatophoric dysplasia, achondrogenesis,
achondroplasias, and type II osteogenesis imperfecta (see below).
US Diagnosis of Limb Malformations

All long bones should be reviewed closely and measured to determine whether there is: -absence, -shortening or
lengthening, -deformities such as curvatures, angulations, fractures, or atypical forms.-echogenicity. Examination of
the acoustic bone impedance and shadows reflects the degree of demineralization [3, 27].
Although there are nomograms from the 10th week, the long bones and the size and shape of the bones of the toes and
fingers can only be properly evaluated from the 12th week on.
The examination is complete if the sonographer is able to evaluate images of open and closed hands with flexed and
extended fingers, observe the palm, and be able to see the feet, soles, toes and finger position. It is also of utmost
interest to use 4D in order to visualize hands, feet, toes and finger movements.
Sonographers must keep in mind that frequently, an image of the extended fingers is difficult to obtain before the
20th week because the fetus tends to keep a closed fist during the first 16 weeks. However, with patient exploration,
these structures can be observed earlier.
A sagittal view of the leg and foot should be obtained along with visualization of the plantar surface while observing
the feet. This view is necessary to rule out anomalies of angulation (i.e multiple congenital contractures) or
prominent calcaneus and astragalus .This is important for the diagnosis of anomalies such as “rocker-bottom” or
club-feet. All segments of the limbs should be observed and measured.
Limb Abnormalities
Abnormalities of the extremities are classified depending on whether the anomalies are predominantly of bone length
or of digital malformations (scheme 2):
Scheme 2
Bone length Abnormalities

Amelia: Absence of one or all extremities (Fig. 15).
Fig. 15 show a case of amelia of the four extremities (tetraamelia, also bad called tetrafocomelia). Tetraamelia has
been cited due to the use of a vitamin complex called thalidomid. Although cases have been described linked to
chromosomal aberrations like trisomy 18, and other malformations (omphalocele; diaphragma agenesia; TAR
syndrome; extrahepatic biliar agenesia) most of the cases showed normal karyotypes.
Figure 15: Tetraamelia
Hemimelia: Absence of extremity below the elbows or knees.
Micromelia: Shortening of all segments of the limb (Fig. 16).
Rhizomelia: Shortening or absence of proximal segments of the limb (i.e., of the humerus or femur; (Fig. 16).
Figure 16: Rhizo-mesomelia with oligodactilia. Two cases of thanatophoric dwarfism. Observe the shortening of the three
segments in the upper limbs. The fetus at the left display a relative macrocephaly, a narrow thorax, and a prominent abdomen. The
lower frame shows in addition a rocker-bottom foot (arrow). In the second case, to the right micromelia with thick arms are
evident.
Mesomelia: Shortening or absence of the mid segments of the extremities, i.e., radius, cubitus, fibula or ulna (Figs.
17 and 18).Bilateral mesomelia is usually associated with chromosomal disorders and other polymalformative
syndromes.
Figure 17: Mesomelia. TAR syndrome.Fetus with trisomy 13. Both upper extremities are short. Complete bilateral absence of the
intermediate segments. Genu varus. Abnormal fingers. Microdactylia with syndactilia along with missing fingers
Figure 18: Camptomelia, twisted and curved low (left) or upper (right) extremities. Absence of one hand. Presence of abnormal
fingers. TAR syndrome.
Acromelia: Shortening or absence of the distal segments of the extremities, i.e., hands, feet (Fig. 18). Combined
cases of these abnormalities can also appear. Fig. 18 shows a fetus with absent distal and middle segments (acro-
mesomelia) and the existing proximal segments also abnormal (phocomelia).
The distal and middle segments are missing and the existing proximal upper segments are abnormal: acro-mesomelia
with phocomelia.
Phocomelia: Preservation of the distal segments of arms and legs with absence or alteration of either the mid or
proximal segment.
Syrenomelia: total or partial fusion of the lower extremities (see below)
Camptomelia: twisted or curved extremity/ies (Fig. 18).

Absence of Hands and Feet

Achiria: absence of one or both hands
Apodia: absence of one or both feet
Achiropodia: absence of hands and feet
Adactilia: absence of fingers in / or hands and feet (Fig. 19).
Figure 19: Partial adactilia with sindactilia
Abnormalities of the fingers and/or toes

Polydactilia: Presence of more than five fingers or toes. Also fingers or toes on a duplicated leg. Polydactilia can be:
- preaxial: supernumerary digit is located medial to the thumb or big toe.
- postaxial: supernumerary digit is located after the third digit, the ulnar side of the index finger, or on
the side of the foot (Fig. 20).
Oligodactilia: The number of digits is less than five. There are, or can be, other digital anomalies such as amorphous
or irregular fingers or toes, or irregular angle formation of one digit with the others, that are also classified as
oligodactilia (Fig. 21).
Figure 20: Polydactilia. Hand with six fingers

Figure 21: Oligodactily (above), fetus with a neural tube defect located in the cervico-dorsal region and affected of micro and
syndactily. One hand has only four fingers (yellow arrow) and the second the fingers are linked (white arrow). Sindactily.
Syndactylia: Fusion of digits, caused by either bone or soft tissue fusion (Fig. 20).
Clinodactylia: Shift in the axis of one of the digits, causing overriding of one over the other digit. The most
common is the small finger over the ring finger, seen in cases of trisomy 21 (Fig. 22).
Figure 22: Clinodactylia. Brachydactylia.
Brachydactylia: Abnormally short digits (Fig. 22).
Ectrodactylia: Claw hand. Fusion of digits into two groups. With other malformations such as cleft lip and palate
and ectodermal dysplasia, it can form part of a syndrome or it can occur as an isolated malformation. Both are
dominant autosomal.
Position Deformities
Talipes equinovarus (club foot): The foot is in a planter flexion and internal rotation (Fig. 23). This abnormality is
detected by viewing the relationship between the axis of the leg or of the tibial bone and the axis of the foot or the
plantar surface.
It appears as an isolated occurrence in 1 out of 1200 newborn, usually as a result of asymmetric intrauterine preasure
caused by oligohydramnion, amniotic bands, Mullerian malformations, or intrauterine tumors. It can also result from
chromosomal anomalies such as trisomy 13 and 18, or as part of other genetic or central nervous system disorders.
Talipes hand: persistent angulation with respect to the longitudinal axis of the forearm (Fig. 23).
Rocker bottom feet: This malformation is seen with trisomy 18, 13, 18q syndrome, and type II Pena-Shokier
syndrome.
It is characterized by a prominent heel caused by abnormalities in the astragalus and calcaneus bones. There is filling
of the normal concavity of the plantar arch so that instead of the normal arch there is a convexity (Fig. 24).
Equino foot: Hyperextended foot
Multiple congenital contractures (arthrogryposis multiple congenital) (see below)
Common Syndromes Associated with Poly/Syndactilia

In Table 3 we have highlighted those malformations associated with polydactily and syndactily [18, 20, 28].
Figure 23: Above: left side club feet. Right: Talipes equinovarus in fetus with TAR syndrome. Below left: Talipes hands and feet
in a case of trisomy 13. Arthrogriposis multiple congenital. Below right: Talipes hand with absent fingers
Figure 24: Trisomy 18 exencephalic fetus with multiple malformations (red arrows). Observe the leg abnormalities with
rhizomelia, rocker-bottom foot (yellow arrow), and the abnormal heel.
Table 3: Common Syndromes with Poly/Syndactyly
COMMON SYNDROMES WITH POLY / /SYNDACTYLY

POLYDACTYLY SYNDACTILY
MECKEL-GRUBER (acrocephalosyndactily) APERT
ELLIS VAN CLEVELD ORAL-FACIAL-DIGIT
GREIG cephalopolysindactyly (pseudothalidomide) ROBERTS
GREBE CARPENTER
SRP
Acrocephalopolysyndactily
JEUNE (asphyxiating thoracic dystrophy)
JOUBERTS
Trisomy 13
Sirenomelia
Sirenomelia or mermaid syndrome is an extremely infrequent malformation, occurring in 1 of 60,000 live born. Is
the most severe form of caudal regresion Syndrome. However, recent studies categorize it as a different nosologic
entity. Even though its etiology is unknown, it has been associated to maternal diabetes, cocaine consumption during
the first month of gestation, or exposure to high doses of etretinate or cyclophosphamide
The diagnosis should be suspected from echographic finding of oligohydramnios and bilateral renal agenesis during
the second trimester.
Morphologic alterations of lower limbs are of variable extension and are classified in three types, according to the
number of feet during the diagnosis:
Symelia apus: it is the most frequent type, the fetus has no feet nor a rudimentary one, it has one femur, one or two
tibial bones and no perone.
Symelia unipus: there is only one foot, which can have up to 10 toes; the lower limb has a pair of femur, tibial and
peroneal bones.
Symelia dipus: both feet are present giving the fetus a mermaid like appearance.
Lower limb malformations are associated with other skeletal or visceral anomalies, the most frequent are: Sacral
agenesis; Anorectal atresia; Renal agenesis or renal cystic dysplasia; Internal and external dysplasia of the genitalia;
Single umbilical artery, cardiovascular malformations, abdominal wall defects, severe scoliosis, and cerebral anomalies.
An early lesion in the caudal mesoderm has been suggested as the cause of this complex (Fig. 25).
Caudal Regression Syndrome (See Also Part One)

This syndrome, of which sirenomelia is the most severe. It is formed by a group of anomalies that associates
vertebral agenesis, genito-urinary and digestive malformations. Malformations can vary from anal atresia to sacral
lumbar or thoracic vertebrae defects.
Even though some cases of this syndrome have been found to be of inherited nature, most appear de novo and risk of
recurrence is less than 3%.
Congenital Multiple Arthrogriposis

The flashy term “arthrogryposis” (AMC) or joint gryposis has hitherto served, to describe a “syndrome” mainly
consisting of multiple contractures and joint dislocations of a very poor perinatal prognosis. The incidence is
between 1 in 5,000-10,000 live births [3, 24, 33].
Figure 25: 2D of the unique visible low extremity. 3D of the sirenomelia. Compare this finding with the macroscopic and
radiographic ones.
We now know that this is not a syndrome, but is rather a heterogeneous group of skeletal disorders that result in the
birth of babies with multiple joint contractures limiting fetal general or extremities movements, those is also called
fetal akinesia deformation sequence .
These contractures are the result of limitation of motion of joints that may either be primary, or secondary to
anomalies of the peripheral or central nervous system, or to anomalies of the muscular, connective tissue, or skeletal
system. Oligohydramnios, especially in early pregnancy, can also be the cause of these contractures.
There is no evidence that joint contractures result from chromosomal anomalies or that they constitute a
polymalformative syndrome. Although these malformations are almost always detected close to, or beyond the fetal
age of postnatal viability, ultrasound identification of joint contractures and limitations of limb motion should trigger
detailed examination of fetal morphology.
There are several pathological conditions that can give rise to arthrogryposis:
a) A peripheral or central nervous system problem (55%)
b) A muscular system problem (8%)
c) A problem of the connective tissue and of the skin (11%)
d) Skeletal malformations (6%)
e) A result of oligohydramnios or of amniotic bands (7%)
Cases are usually sporadic. However, there is a recessive myogenic type (dystrophic, aplastic, or myopathic) that
involves the overwhelming majority of cases, and a rarer dominant neurogenic type.
The most accepted classification divides these cases in:
A) GENERALIZED ARTHROGRIPOSIS (affects all 4 extremities)
1) Frequent
- -Classical congenital multiple arthrogryposis
- -Larsen’s syndrome
- -Congenital contractured arachnodactily
- -Nail-Patella syndrome
- -Schwartz’s syndrome
2) Rare and/or lethal
- -Potter’s syndrome
- -Pena-Shokeir syndrome
- -Kink-Denborough syndrome
B) ARTHROGRYPOSIS THAT AFFECTS DISTAL PARTS (hands, feet, face)
1) Syndrome of distal arthrogryposis
2) Trismus-pseudocamptodactily syndrome
3) Freeman-Sheldon syndrome
4) Möebius syndrome
C) SYNDROME OF MEMBRANES (Pterygia)
1) Multiple pterygium syndrome
2) Popliteal pterygium syndrome
3) Syndrome of localized and single membranes.
D) SYNOSTOSIS SYNDROME
1) Humero-radial
2) Peripheric
Diagnosis requires detection of reduced or absent limb movement or of strange and bizarre attitude of the extremities
which persist in successive observations on the same day or on different days.
When arthrogryposis involves the upper extremities, the shoulder joint is usually in internal rotation with the
forearms in permanent pronation. There may be congenital dislocation of the radii and wrist joints or the wrists may
be severely flexed.
When the lower extremities are affected, the legs are flexed at the hip joint and there may be a dislocation at this
point. The knees may be hyperextended and close to each other while the feet are in an equinovarus position.
The classical image of the fetus is in a Buddha position with wrist joints severely flexed, and typical pes
equinovarus.
When arthrogryposis is part of polymalformative syndromes, it is associated with skeletal, cardiac, and renal
malformations. However, the most common association (10% to 55%) is with malformations of the central nervous
system.
Contracture deformities are generally symmetrical. In many cases all four extremities are compromised, although in
a small number of cases only the lower extremities are involved. The severity of the condition increases distally,
reaching a maximum in hands and feet (Figs. 26 and 27).
Figure 26: Trisomy 18 fetus. Polyhydramnios and a hand deformity. Also an irregularity in the other hand. The marked hand
deformity is more severe than what is usually observed for arthrogryposis. Contractures can be observed in the upper extremities,
especially the right limb, which is in front of the fetus’s head. Below: Unilateral cleft lip in a fetus with severe contractures in all
joints of the upper extremities, including the phalanxes. The postnatal picture is identical to the 3D images observed in the fetus
Figure 27: Multiple joint contractures. Hands and feet are in a varus deformity, with polyhydramnios, and TRAP sequence. The
fetus has gastroschisis with evisceration of the liver and intestinal loops. Observe how there is an aberrant attitude and direction of
the extremities, including fingers, along with the obvious joint contractures.
GASTRO-INTESTINAL MALFORMATIONS
The following anomalías can be examined with 3D/4D US [1-4, 26, 33, 36, 38-42]:
 Esophageal atresia
 Situs inversus
 Ascitis and anasarca
 Diaphragmatic defects
 Abdominal wall defects
 Omphalocele (see also part one)
 Gastroschisis (see also part one)
 Cantrell pentalogy (see part one)
 Exstrophies (see part one)
 Bladder
 Cloaca
 Ectopia cordis
 Limb-body wall complex (see part one)
 Body stalk complex
 Intestinal atresia
o Duodenal
o Ileal
o Yeyun
o Cloaca
o Miscellaneous
o Umbilical cord herniation (see part one)
o Lever calcifications
o Meconium peritonitis
In many cases, the diagnosis is “suspected” visualizing indirect signs as:
1. Polihydramnios
2. IUGR
3. Ascitis or Anasarca
4. Unique umbilical Artery
5. Associated Malformations
6. Elevated serum or amniotic Alfafetoprotein
Esophageal Atresia
Congenital abnormality characterized by the lack of full development of the esophagus that commonly occurs with
tracheoesophageal fistula. Its frequency is 1/5000 new born. The etiology is still unknown and is suspected
visualizing indirect signs as: polyhydramnios.
The chromosomic risk is around 8 – 27% (trisomy 21 and 18).
Other associated malformations are (50 – 70%): Cardiovascular, especially IAC and IVC (15-39%), genitor-urinary
(13%), duodenal [28], muscle-skeleton (11%), facial anomalies (6%).
The most used classification is:
Type I: Isolated without tracheoesophageal fistula (7. 7 – 10%)
Type II: Associated to proximal fistula (1-2%)
Type III: Associated to distal fistula (86-90%)
Type IV: Associated to proximal and distal fistula (1-5%)
Type V: Fistula without atresia – “H” shaped fistula (< 1%)
VACTERL Síndrome
Very infrequent and associated to: tracheoesophageal fistula, anal imperforation, cardiopathy, hemivertebrae, kidney
malformation and limb dysplasia (aplasia of the ulna).
Ultrasound of Fetal Edema and Anasarca: The Glass Baby

Fetal ascites occurs in about 1 in 1500 to 4000 births, a relatively frequent event that happens with several serious
obstetric problems and that tests the diagnostic capabilities of health care professionals. There are many conditions
that can result in fetal anasarca. The etiology may be any of a variety of obstetric problems that range from
immunological disorders, including Rh isoimmunization, to fetal infection, metabolic disorders, and fetal
malformations.
On ultrasound, fetal hydrops is characterized by abdominal distension with very thin abdominal wall, variable
amounts of intraperitoneal fluid, reduced echoes of masses compressed against the vertebral column that correspond
to abdominal organs and intestinal loops along with some free-floating abdominal organs. Because of the
intraperitoneal fluid it is possible to see individual organs much more clearly than usual.
When edema involves the entire fetal body it is called anasarca, fetal hydrops, or Ballantine syndrome. The
presence of fetal hydrops suggests the presence of a grave and probably fatal fetal pathology (Tables 4 and 5).
Polyhydramnios is usually marked and occurs frequently (50% to 75% of cases).
Table 4: Causes of fetal ascites. They may be due to
Maternal disease
Placental anomalies
Fetal disease or anomalies
Umbilical cord anomalies
Table 5: Non-immune hydrops fetalis Etiology
Maternal disease Diabetes, toxemia

Cord anomalies Thrombosis, tumors, knots, aneurysms
Multiple gestation Twin, holocardius, twin-twin transfusion
Cardiac anomalies Malformations, tumors, rhythm anomalies, myocarditis, fibroelastosis
Vascular anomalies Various
Pulmonary anomalies Adenomatous cystic disease, tumors, hypoplasia
Renal disorders Various
Digestive disorders Volvulus, meconial peritonitis
Tumors Chorioangioma, hygromas, teratomas
Hematological disorders Thalassemias, sickle-cell disease
Metabolic disorders Gaucher disease, Landing disease, etc.
Chromosomal anomalies Trisomies, monosomies
Fetal infections Parvovirus B19, TORCH
Other disorders Achondroplasia, polymalformative syndromes
Idiopathic Unknown cause
Fetal hydrops may present as an isolated event or it may be accompanied by other findings such as hydrothorax,
pericarditis, hygroma, hepatosplenomegaly, or an increase in placental thickness and refringency.
A. Isolated fetal ascites or anasarca
This form of fetal ascites is usually associated with an anomaly of the abdominal lymphatic system. Ultrasound-
guided aspiration of ascites fluid will characteristically reveal lymphocytosis. If fetal hydrops is associated with
abnormal cardiac rhythm, one must suspect supraventricular tachycardia or cardiopathy.
B. Fetal ascites associated with other ultrasound anomalies
If fetal hydrops is associated with other abnormalities such as hydrothorax, pericarditis, hygroma,
hepatosplenomegaly, or an increase in placental thickness or refringency, it is safe to assume there is non-immune
hydrops fetalis. In these cases there may be multiple etiologies [3, 26] (Table 5).
The presence of fetal hydrops requires a systematic ultrasound evaluation of the fetus and placenta along with
Doppler studies and fetal echocardiography. There must also be maternal screening to rule out metabolic
abnormalities or infection. It is important to obtain fetal blood and ascitic fluid to rule out fetal anemia, chromosomal
anomalies, hypoproteinemia, bacterial or viral infections, and thalassemia. In spite of a complete work-up, the
etiology of fetal hydrops remains idiopathic in up to 30% of cases. A summary of the most important causes for non-
immune fetal hydrops are listed in Table 5 (Fig. 28).
Diaphragmatic Defects:
The most frequent can be observed:
o The hiatal herniation (Fig. 29).
o The diaphragmatic hernia. These are a group of diaphragmatic in which part of the abdominal content
is located in the thoracic cavity. There are:
o Bochdaleck (2%) or retroesternal
o Morgagni or posterior defect (98%)
All of them are often associated with other nine malformations such as:
Cromosomic (trisomy 18 and 21); legs (genu varo, etc.); heart; facies; cardiovascular, genitourinary and
gastrointestinal ones.
They appear as cysts (isolated or multiple) located in the thoracic cavity and displacing the heart and lung.
Figure 28: 2D and 3D images of a fetus with anasarca. Observe the marked fetal edema that deforms the forehead and parietal
areas (glass baby). The face of the fetus is edematous. Observe the pleural effusion and the abdominal fluid. The remaining
images show ascites fluid isolating the liver, ligamentum teres, spleen, and bowel next to the vertebral column.
Figure 29: Diaphragmatic herniation

 Abdominal wall defects
 Omphalocele (see also part one)
 Gastroschisis (see also part one)
 Cantrell pentalogy (see part one)
 Exstrophies (see part one)
 Bladder
 Cloaca
 Ectopia cordis (see part one)
 Limb-body wall complex (see part one)
 Body stalk complex(see part one)
Abdominal Wall Defects (See also Part One)

Abdominal wall defects are very uncommon malformations that occur when the abdominal folds fail to close. Skin,
subcutaneous tissue and muscle constitutes the anterior wall of the fetal abdomen and its normal development
depends on the correct fusion of four ecto-mesoderm folds (the superior, inferior and both lateral layers).
Altogether they have an incidence below one in every 3.000 live births.
In the 5th week the dorsal side of the yolk sac folds into the embryonic disc forming the primitive gut which is
divided in three parts: foregut, midgut and hindgut. The superior and inferior mesenteric arteries and the coeliac
artery supply these structures.
From the foregut, the pharynx, breathing tract, oesophagus, stomach, proximal half of the duodenum, liver and
pancreas are derived. The midgut gives rise to the distal part of the small intestine and the proximal part of the large
intestine. The hindgut gives rise to the distal colon, rectum, bladder and vagina.
The stomach develops at 6 weeks; it gets into the abdomen in the 7th week, and can be distinguished by week 9.
Peristaltism starts when the muscles are developed in the 11th week and it can be detected by ultrasound at 16 weeks.
Also at 16 weeks meconium production starts, and accumulates during pregnancy, being detected in the third
trimester when it distends the gut loops producing their typical smooth cystic appearance with a thick wall.
From the embryological point of view, an omphalocele develops if the lateral ecto-mesoderm folds fail to fuse along
the midline during the 4th week.
If the failure affects the caudal fold a hypogastric omphalocele with bladder extrophy results.
Beckwith-Wiedemann’s syndrome is a rare condition that is characterized by omphalocele, macrosomia, and

organomegaly, with special manifestation in a thick and large tonge.
The pentalogy of Cantrell evolves from a failure in the cephalic fold to close.
Omphalocele or Exomphalos
It consists in a fetal ventral wall defect characterized by herniation of some of the gut into the base of the umbilical
insertion (Fig. 30).
The whole herniation is coated by a fine limiting membrane, nearly transparent and very similar to the amnion or
peritoneum, through which the herniated abdominal structures can be seen in the newborn (Fig. 30).
The umbilical cord is always inserted, and folly conserved, in the herniated sac apex, where the vessels arrive, which
can be clearly studied with color Doppler.
Figure 30: 2D and 3D of and other omphalocele diagnosed in week 24. 3D allows the clear visualization of the wall defect size.
In this case the abdominal gap is small, but the tumour is big.
The most common herniated organs are the gut loops, the stomach, and depending on the sac size the liver, and in
exceptional cases the heart (i.e., pentalogy of Cantrell).
The prevalence is of 30% in the second trimester and only 15% at birth which shows the high mortality rate during
pregnancy.
The diagnosis can be established in the first trimester of pregnancy (see part one), but it is much easier, and we
recommend to wait, after week 12 to avoid the confusion with a physiological herniation.
Chromosome disorders and other malformations: The omphalocele is usually associated with chromosomal
abnormalities (35-60%). Most of them are trisomy 18 (70-80%) and, in lesser number, trisomy 13, triplody, and
Klinefelter’s syndrome. Chromosomal anomalies are very usual when the herniation contains only gut loops (65%),
and are very rare when the liver is the herniated organ. Nevertheless, this second eventuality is usually associated
with other structural malformations.
Among the most frequent other associated organ malformations in omphalocele with aneuploidies (50%) are: facial,
renal, neural or limb defects.
When there is no a chromosomal disorder, omphalocele is also frequently found associated with other structural
anomalies such as cardiac (50%), kidney, gastrointestinal, facial, neural, limb anomalies or growth restriction.
Gastroschisis (See also Part One)

Gastroschisis results from a partial failure of midline abdominal closure (Fig. 31). The incidence is about 0.3 to 2 per
10.000 newborn. It is considered a sporadic malformation, though familiar gastroschisis has been described where a
dominant autosomal inheritance of variable expression is suggested.
The gut loops float freely in the amniotic fluid through a small gap by the navel, almost on its right side.
Nevertheless, the umbilical cord and its abdominal insertion are always completely normal.
Through the gap the gut loops and, less frequent, the liver and stomach, stick out. The absence of the surrounding
membrane and the small gap are the main differences with omphalocele.
The exact ethiology is unknown. It is accepted that the defect results from a lack of blood supply caused by very
early right umbilical artery failure or obstruction. Also a failure in the vascularization of the omphalomensenteric
duct has been argued. These would cause an interruption in the blood supply to the structures irrigated by these
arteries. Finally another hypothesis has been proposed: the involution of the right umbilical vein.
Diagnosis: Depends on the identification of a cauliflower-shaped anterior abdominal wall mass that contains uniform
small cystic areas (Fig. 31) or, at times, a solid-cystic mass.
Figure 31: 2D images of a gastroschisis. Gut loops are free-floating in the amniotic fluid. The loops have a thick wall.
Gastroschisis in week 14. The umbilical cord goes left to the tumour. Macroscopic findings
In more advanced gestations, movement of the extra-abdominal mass can be observed in the amniotic fluid with fetal
movement, with the proper loop movements or by ballottement of the amniotic fluid with the transducers.
Chromosomal disorders and other malformations

Available evidence suggest that gastroschisis is not associated with chromosomal anomalies. However, in 25% of
cases there are associated gastrointestinal problems such as adhesions, stenosis, obstruction, atresia, and loop
malrotation. In addition intrauterine growth restriction and polyhydramnion are common associated findings.
Other Fold Defects: (See Part One)

Duodenal Atresia
It is the most common atresia of the small intestine. Incidente: 1 case / 4000-10000 new born. The etiologhy is
unknown. Some reports suggest a genetic component (piloric-duodenal atresia) with autosomic reccesive inheritance.
Clasification:
1. Complete obstruction of the intestinal lumen, but with persistence of the duodenum (30-40%).
2. Partial lumen obstruction (50%), normally bellow the Vater ampulla.
3. Complete obstruction (rare) with a fibrous tract between both extremities.
4. External obstruction associated to anular pancreas, bands or intestinal malrotation (20%).

Almost 85% are associated to malformations (vertebral anomalies, gastroinstestinal, heart, etc), chromosomopaties,
specially trisomy 21, chromosome 9 deletion, Vacterl syndrome and caudal regression.
The typical double bubble sign appears when the atresia is located some below in the duodenum.
Jejunum Ileal Obstruction, Ileocecal Valve Atresia

Atresy (95%) are much more frequent than stenosis. These obstructions are distributed regularly from Treitz
ligament until the ileocecal valve. They are more frequent than duodenal obstructions. Incidence: 1/5000 new born.
Associated malformations: Gastrointestinal pathology (45%), the most common: intestinal malrotation and
duplication, volvulus, gastroschisis.
The typical image shows multiple cysts of several sizes due to intestinal dilatations; diffencial diagnosis should be
made with kindey pathology (Fig. 32).
Figure 32: Jejunum-ileal atresia
Meconium Peritonitis
This name is given to a chemical aseptic peritonitis that results from fetal digestive tract perforation. Usually follows
an ischemic obstructive process.
Classification
There are 3 types of meconium peritonitis:
1. Fibroadhesive peritonitis, which is characterized by an intense adhesive peritoneal reaction without

intestinal peristalsis,
2. Cystic peritonitis, which shows a localized cystic cavity, formed by adherent, contiguous intestinal
loops, and
3. Generalized peritonitis, which shows no calcifications or adhesions.
Meconium peritonitis occurs in 1 out of every 35,000 live births. Most are diagnosed in the post-natal period during
evaluation of neonatal vomiting, acidosis, abdominal distension, and radiological images of diffuse abdominal
calcifications.
An etiologic factor can only be found in 50% of cases. Meconium peritonitis is usually associated with cystic
fibrosis. In up to 65% of cases it may be associated with other intestinal processes such as stenosis, idiopathic
obstruction, atresia, or ischemia. Finally, meconium peritonitis can be associated with infections due to
cytomegalovirus, with trisomy 21, and less frequently, with other chromosomal anomalies.
Sonographic findings suggesting meconium peritonitis are:
- An echogenic single mass or multiple intra-abdominal masses that are fairly delimited, are of greater
refringence when compared to normal intestinal loop segments, and are generally not homogeneous,
showing sonic shadows, especially when associated with polyhydramnios and ascites (Fig. 33).
- Diffuse, small, abnormal calcifications, which at times can be very large, and forming a strongly
refringent ring with inferior acoustic shadow and an anechoic central region (Fig. 33).
Figure 33: Meconium peritonitis. Two different but typical 2D images: the calcified ring and the irregular and concentrated
calcifications. 3D of a meconium peritonis observed in week 24. A clear hyper-refringent and non homogenous mass located in
the abdominal cavity next to the medullary canal is depicted (arrows). Macroscopic finding showing the loop perforation
Not infrequently one may find small peripheral abdominal echoes that correspond to other areas of calcification.
These result from the presence of meconium in the abdominal cavity, where it tends to cause fibrosis, and eventually
calcify.
The meconium that escapes into the peritoneal cavity causes a fibro-adhesive process that obliterates the peritoneal
space, and produces the calcifications at the site of perforation or in the areas over which meconium spreads. This
perforation generally occurs at the site where we find intestinal stenosis or loop obstruction (65%).
On ultrasonographic examination one may find the following:
- The walls of the intestinal loops are usually hyperechogenic with double contours, high density
contents, and active peristalsis.
- There is greater abdominal circumference.
- Polyhydramnios is not always present. However, when observed, it is associated with intestinal
obstruction.
- Ascites and anasarca
- The other abdominal organs (liver, spleen, kidneys), as well as the uninvolved segments of intestine,
and the genitourinary tract, are usually normal.
- The diagnosis of meconium peritonitis should be considered if the foetal bowel is observed to be
dilated or whenever an area of foetal intraabdominal hyperechogenicity is detected. The likelihood of
perforation is increased if a small rim of ascites is also demonstrated.
RENAL AND OTHER URINARY TRACT MALFORMATIONS

Renal and other urinary tract malformations represent about 20% of all congenital malformations. It is now possible
to detect a wide spectrum which may be either isolated or part of polymalformative syndromes [28].
1. Renal Agenesis
Renal agenesis results from a developmental failure of the ureteral ramifications of the mesonephros. The failure
may be partial, complete, unilateral, or bilateral. Many cases are sporadic. However, some cases are related to
recessive or dominant autosomic inheritance, to X-linked inheritance, or to multifactorial genetic inheritance (Fig.
34).
Figure 34: Renal Agenesis. This figure shows to the left the 2D image with marked oligohydramnion, absence of urine bladder
and kidney. To the right the same 3D image, showing the column and pelvic bones. No kidney are visible (yellow arrows).
The most striking ultrasound findings with bilateral renal agenesis are absence of kidneys, severe oligohydramnios,
lack of bladder visualization, and fetal growth restriction. Bilateral renal agenesis is frequently associated with other
genital anomalies (50%) or with anomalies in other organ systems (44%), malformations of the lower half of the
body, of the gastrointestinal tract, of the cardiovascular system, or of the central nervous system. See Table 6.
Table 6: Anomalies associated with bilateral renal agenesis
Organ System Percentage

Genital malformations 50 %
Lower body abnormalities 40 %
Gastrointestinal malformations 19 %
Cardiovascular malformations 14 %
Central nervous system malformations 10 %
2. Renal Hypoplasia
In renal hypoplasia there are a decreased number of nephrons without presence of undifferentiated tissue (also
known as dysplasia). Renal hypoplasia is generally unilateral
3. Renal Dysplasia
Renal dysplasia consists of a developmental anomaly that results in the formation of abnormal collecting tubules and
nephrons. Poorly differentiated tubules and abundant stroma that forms cartilaginous islets are characteristic. Cysts
may be present
4. Renal Cystic Disease

In cases of renal cystic disease there are dilatations of the collecting tubules that can be either microscopic or
macroscopic. They may be accompanied by parenchymal dysplastic elements.
There have been several attempts to classify renal cystic disease. The most frequently used classification adds
genetic considerations. See Table 7.
Table 7: Classification of renal cystic disease
Type Non Hereditary

1. With Dysplasia
1a Multicystic dysplasia (Potter type II) (Fig. 34)
1b Peripheral, cortical, obstructive, cystic dysplasia (Potter IV) (Fig. 35)
1c Segmental multicystic dysplasia
2. Without Dysplasia
2a Parapyelic cyst
2b Serous cyst
2c Hemorrhagic cyst
2d Multilocular cyst (cystic multilocular nephroma)
Type Hereditary
1. Polycystic renal disease
1a Autosomal recessive (Potter infantile Type I)
1b Autosomal dominant (Potter adult Type III)
2. Medullary cystic disease
3. Congenital nephrosis
Infantile microcystic disease
Familial nephrotic syndrome
4. Cysts associated with polymalformative syndromes
Multicystic Dysplasia
It appears as a consequence of urinary tract obstruction before the tenth week of embryonic development, resulting in
ureteral and renal pelvis atresia. Atresia interferes with ureteral development and leads to a reduction in division of
collecting tubules and inhibition in induction and maturation of nephrons. For this reason few nephrons develop, and
the collecting tubules increase in size and form cysts. The renal parenchyma is thus replaced by multiple cysts of
variable sizes. The cysts may vary in diameter from a few millimeters up to eight centimetres
Multicystic kidneys may appear larger than normal, but they may be of normal size or smaller than normal. They are
several thin-walled cysts of variable size and random distribution that do not communicate with each other. There is
no normal parenchyma and highly refringent zones of fibrous tissue can be seen in between.
Peripheral Cortical Renal Dysplasia

This anomaly results from severe, but incomplete obstruction of the inferior urinary tract.
When there is urinary tract obstruction, the kidneys may appear abnormally refringent. For this reason small cysts on
the cortex are rarely seen with ultrasound. The increased sonic reflection is due to multiple microscopic cysts along
with an increase in parenchymal fibrotic tissue. As a rule, the renal contour is unaffected.
Segmental Multicystic Dysplasia

This condition usually affects the superior pole of the kidney. The ultrasound image is similar to what is seen with cortical
dysplasia. However, the small cysts and the increased sonic reflection are limited only to the superior kidney poles.
POLYCYSTIC RENAL DISEASE
This term includes two genetic anomalies:
1. Infantile polycystic renal disease, which appears during the first two decades of life and has an
autosomal recessive pattern of inheritance.
2. Adult polycystic renal disease, which occurs on rare occasions in children, and has an autosomal
dominant pattern of inheritance.
Renal cystic disease is classified into (see Table 8);
Table 8: Renal Cystic Disease Potter’s Classification
Type I Infantile polycystic disease

Type II Dysplastic multicystic kidney
II - a Increase in volume without pelvic dilatation. Cysts of different sizes.
II - b Small, hyperechogenic kidney. Cysts around hilum.
II - c Large, single cysts.
Type III Adult polycystic disease
Type IV Obstructive cystic dysplasia
1. Autosomic recessive polycystic kidney disease

(Potter type I infantile congenital hepatic fibrosis-renal cystic disease complex)
In these cases the kidneys retain their normal shape but there is bilateral, symmetrical kidney enlargement. There are
numerous cysts that range between 1 and 3 mm in size. The typical ultrasound image is of highly refringent enlarged
kidneys that maintain their smooth surface
2. Autosomic dominant polycystic kidney disease

(Potter type III adult renal cystic disease)
Autosomic dominant polycystic kidney disease is located on chromosome 16. The condition consists of thin-walled
cysts in adult patients that vary in size from a few millimeters to several centimeters. The calyceal system may be
distended but the renal pelvis and the ureters are normal. Ultrasound diagnosis: Increased renal echogenicity along
with numerous small cysts are visible
CYSTS ASSOCIATED WITH MULTIPLE MALFORMATION SYNDROMES
Cystic dysplasia can be found in several rare hereditary syndromes. Among these, the following are of note:
Meckel-Grüber Syndrome
The Meckel-Grüber syndrome is a lethal, autosomic recessive condition that has a 25% risk of recurrence. It has an
incidence of 1 in 12,000 births. Ultrasound diagnosis requires identification of at least two characteristics of the
classical triad:
a) Polycystic kidneys
b) Occipital encephalocele, and
c) Postaxial polydactyly
Jeune Syndrome
Multicystic dysplasia can also be seen in association with Jeune syndrome, also known as asphyxiating thoracic
dystrophy.
Zellweger Syndrome
Zellweger syndrome, also known as cerebro-hepato-renal dysplasia, can also present with kidneys that are identical
to those seen in cases of obstructive multicystic renal dysplasia.
Trisomy 18
Multicystic renal dysplasia has been found in association with some cases of trisomy 18 [28].
URINARY TRACT MALFORMATIONS
The malformations that can be detected prenatally are those that produce dilatation of the urinary tract. These
dilatations result either from distal obstruction or from non-obstructive causes such as vesico-ureteral reflux, or less
frequently, neurological lesions or megaureter. Urinary tract obstruction may be partial, complete, unilateral, or
bilateral. Obstructions occur generally at the uretero-pelvic junction. However, they can also occur at the uretero-
vesical junction or in the urethra.
Hydronephrosis
Hydronephrosis may appear sporadically but can also be familial, acquired, congenital, isolated, or secondary to
other anomalies of the urogenital tract. Hydronephrosis presents as a dilatation of the renal pelvis without dysplasia.
It is evaluated by measuring the antero-posterior diameter of the dilated renal pelvis in the axial plane.
Hydronephrosis is diagnosed when the diameter of the renal pelvis exceeds the gestational age by 5 mm in
pregnancies that are less than 20 weeks gestation, by 8 mm in pregnancies between 20 and 30 weeks, and by 10 mm
after 30 weeks gestation (Fig. 36).
Posterior Urethral Valves

The most common cause of bladder obstruction in children is posterior urethral valves. In some cases obstruction can
be almost complete, provoking oligohydramnios and renal dysplasia. About 50% of newborn babies with significant
urethral obstruction have had antenatal ultrasound diagnosis.
The ultrasound image shows distention of the urinary bladder and of the proximal urethra with thinning of the
bladder wall. The ureters may be also dilated, and associated with varying degrees of hydronephrosis bilaterally (see
also part one).
Posterior urethral valves are the most common cause of Prune Belly syndrome (hypotonic abdominal wall, hypotonic
bladder, cryptorchidism, and dilated ureteres).
GENITAL MALFORMATIONS
There are very few reports on cases of intersexes and other genital anomalies. We are showing cases of ambiguous
genitalia caused by intersexuality, inherited hypogonadismus and a giant sacrococcygeal teratoma [3, 29] (Fig. 37).
Figure 35: Potter II multicystic kidney variety. Macroscopic cysts and dysplasia. The kidney are smaller (yellow arrow)
hiperrefringent (white arrow), and shows with histopatology multiple microscopic cysts. Potter IV variety. These cases show
oligohydramnion, renal failure and both kidneys full of cysts of different sizes. Same of them are very big.
Figure 36: Fetal hydronephrosis the central cyst is of irregular shape and do not affect the kidney parenchyma. Multicystic
disease affecting only one kidney (red arrow, left image). Its origin is a stenosis and hypoplasia of the ureter (yellow arrow). The
stenosis produce dilatation of the ureteral portion near the kidney pelvis (red arrow).
Figure 37: Ambiguous genitalia. Intersex. The ambiguous genitalia observed with 3D (yellow arrows)
THE AMNIOTIC BAND SYNDROME
The amniotic band syndrome is characterized by multiple malformations secondary to amniotic bands that compress
fetal parts and as a result cause amputations and lesions on the fetal parts they attach to (Fig. 38).
Figure 38: Amniotic band syndrome with 2D. The yellow arrows show the bands. The red arrows show the cephalic pole
malformation. The broken amnion is branched and showed in 3D.
The earlier in gestation these bands occur, the more severe the consequences. It has been suggested that band lesions
during the first trimester are associated with visceral and craniofacial malformations, pentalogy of Cantrell, limb and
body wall deformities, or body stalk defects. Amniotic band lesions during the second half of pregnancy are
associated with constrictions, amputations, and even fetal death.
The aetiology of this condition remains unknown.
The proposed theories do not explain internal visceral lesions that occur with the syndrome. With experimental
animals it has been shown that even with intact amniotic membranes there are vasoactive substances that can
produce lesions in mesenchymal and endotelial cells of superficial embryonic blood vessels and in amniotic tissue.
These substances are capable of producing rupture of epiblastic cells, secondary amputation of members, and induce
deformity of fetal extremities. The formation of bands, according to this theory would result secondary to a primitive
vascular lesion.
US findings: The variety of presentations is such that the possibility of missing the diagnosis in many cases of
otherwise unexplained multiple malformations must be seriously considered.
As already mentioned, severity varies between fetuses. The presentation can consist of lesions that go from simple
oedema to ischemia and amputation of an extremity, digits, or craniofacial, visceral, or organ abnormalities.
Craniofacial malformations include lesions from all sorts of clefts (lip, palate, lateral, mouth, etc.), to brain
malformations.
The most common visceral abnormality is gastroschisis, although there are reports of omphaloceles, bladder
extrophy, ambiguous genitalia, imperforate anus, vertebral hypoplasia, and rib agenesis. In 77% of cases there are
multiple anomalies: Remaind:
A. Bands are multiply, they may be branched, and they must make contact with the fetus
B. Bands can be seen as constriction rings around digits.
C. There is usually oligohydramnios and reduced fetal movement.
D. Multiple, polimorphic malformations, think amniotic band syndrome.
FETAL SOFT TISSUE TUMOURS
Malignant tumors in newborn babies are very rare. The estimated incidence lies between 1, 7 and 3, 6 per 100,000
live births [3, 21, 33, 41].
Sarcomas are very rare tumors and rhabdomyosarcomas are among the rarest varieties of these tumors.
Rhabdomyosarcomas are soft tissue tumors which commonly affect the extremities (Fig. 39). These tumours usually
develop in the third trimester.
Any fetal soft tissue tumour, whether small or large, should be considered to be a fetal sarcoma, particularly if it affects the
distal extremities. Nevertheless, it must be kept in mind that 25% of tumours in children occur in soft tissues.
Differential diagnosis includes other rare soft tissue tumors such as lymphangiomas and epignatus.
It is advisable to determine with 2D and 3D whether long bones of the affected limb are involved, and to find out
whether there mobility or limitation of motion in the affected limb. These determinations are very important for
establishing the differential diagnosis of bone tumours, which are also very rare.
Excluding tumours of a vascular origin, which are easily identifiable by Doppler, these soft tissue tumours show very
similar echographical images.
Figure 39: Sagittal 2D view of the forearm mass. The bones are clearly seen and not affected. The hypoechoic mass is shown to
be of soft tissue origin. 3D scan of the tumour showing the soft tissue mass as well as the bones which are not affected.
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translucency. J Perinat Med 1999; 27: 97-102.

CHAPTER 3
Fetal Central Nervous System
Mi Suk Kim*
Department of Obstetrics and Gynecology, Flushing Hospital Medical Center, Flushing, NY 11355, USA
Abstract: Greatly improved diagnosis and investigation of fetal central nervous system abnormalities is the result
of impressive technologic advances in ultrasonographic imaging. This applies as well to the study of spinal and
facial abnormalities that are associated with central nervous system anomalies. More attention has been paid to
midbrain structural defects, such as agenesis of the corpus callosum and abnormalities of the cerebellum, with the
introduction of three- and four- dimensional ultrasound. Notwithstanding all these recent rapid technologic
advances, many professionals --- except for a few pioneers --- have difficulty keeping up-to-date. The purpose of
this review of basic principles and various applications of three-dimensional ultrasound to the fetal central nervous
system evaluation is to inform professionals working in obstetric ultrasound of those advances. We will focus
primarily on normal findings of three-dimensional sonography of the fetal central nervous system. We will also
discuss a range of topics from methods of real-time scanning and software manipulation to the application of these
techniques to each section of the fetal nervous system.
1. INTRODUCTION
There are no randomized clinical trials to support the contention that three- and four-dimensional ultrasonographic
imaging is superior to conventional ultrasound for the diagnosis and evaluation of anomalies of the fetal central
nervous system. It is rather difficult to do any objective studies comparing two-dimensional sonography with three-
dimensional sonography because the former is performed as a preliminary step to for the latter in clinical practice.
Nonetheless, published observational studies on three-dimensional ultrasound have shown not only improved
diagnosis of fetal central nervous system anomalies, [1, 2] but better insights into embryologic development [3, 4].
Three-dimensional ultrasound is no longer considered experimental. It has become an accepted part of our practice.
In particular, the introduction of three-dimensional ultrasound for study of the fetal central nervous system has made
this field easier to understand than ever. Our discussion starts with methods of real-time scanning and software
manipulation and their applications to the first-trimester pregnancies and ends with detailed focus on the assessment
of the fetal brain and spine. We will deal mainly with current basic methodologies and normal anatomical ultrasound
findings.
2. METHOD
Three-dimensional ultrasound images are produced by a three-step process, which consists of (1) volume acquisition,
(2) storage and (3) display and manipulation.
2.1. Acquisition
Acquisition is the most important step in the whole process. It is essential to acquire a good quality two-dimensional
image before volume acquisition. A poor volume scan will lead in turn to poor quality three-dimensional images. If
reconstructed images are necessary, their resolution will be diminished because the resolution of the reconstructed
planes are degraded compared with those of the acquisition planes.
Standardizations and guidelines for ultrasound examination of the fetal central nervous system have been developed,
including those of three-dimensional ultrasound of the fetal head in the views of volume acquisition and volume
display [5-8]. An axial view of the fetal head at the plane of the level of the lateral ventricles, which serves as the
*Address correspondence to Mi Suk Kim: Department of Obstetrics and Gynecology, Flushing Hospital Medical Center, Flushing, NY 11355,
USA; Tel: 718-670-5440; E-Mail: Misuksmile@Gmail.Com
Toshiyuki Hata and Asim Kurjak (Eds.)
Fetal Central Nervous System Current Topics on Fetal 3D/4D Ultrasound 119
reference plane, can usually be obtained by transabdominal imaging. The acquisition box should contain the fetal
head. The box boundaries should be placed just outside the fetal skull (Fig. 1).
Figure 1: After a brain volume has been acquired by transabdominal axial plane imaging, the multiplanar display is shown. Axial
view of the fetal brain in plane A is the reference plane. Three orthogonal planes are perpendicular to each other: (1) The coronal
section in plane B; (2) the sagittal section with fetus facing the right side of the screen in plane C; and (3) the axial section in
plane A. This volume was obtained from a scan done on a normal 21-week fetus in breech presentation. This display is
recommended for use as the standard for obtaining multiplanar views.7
Coronal and sagittal views can be obtained by aligning the transducer with the sutures and fontanels of the fetal head.
They can usually be obtained by transvaginal ultrasound on fetuses in cephalic presentation and by transabdominal
ultrasound on fetuses in breech presentation (Fig. 2). These examinations are able to provide useful and powerful
images for the diagnosis of complex malformations. They are collectively referred to as a “dedicated
neurosonogram” [6].
Figure 2: After a brain volume has been acquired by imaging at the transabdominal sagittal plane, the multiplanar display is
shown. The sagittal view of the fetal brain in plane A is the reference plane. This volume was obtained from a scan of a normal
19-week fetus in breech presentation. The sagittal view can also often be acquired by transvaginal examination.
Three-dimensional ultrasound of the fetal spine has been extensively investigated [9-11]. The best images can be
obtained by either sagittal or coronal views as the reference plane when the transducer is aligned parallel with the
120 Current Topics on Fetal 3D/4D Ultrasound Mi Suk Kim
fetal back. The acquisition box can contain the whole length of bony parts of spine of a midtrimester fetus, with the
ribs as the reference level (Fig. 3). An angle of rotation of 30-40 degrees is sufficient [8].
Figure 3: Multiplanar view of spine volume is displayed. The sagittal section in plane A is initially scanned as the reference plane
for the spine volume. The volume is acquired after the transducer is aligned parallel to the fetal spine of a normal 20-week fetus in
cephalic presentation.
First-trimester three-dimensional ultrasound images can be acquired without difficulty. The volume acquisition by
transvaginal transducer is accomplished in only a few seconds during the first trimester because the fetus is small and
quiescent. In contrast to the more complex dedicated neurosonogram done later in pregnancy, there are no
restrictions to image acquisition at this early gestational age.
2.2. Storage
After acquisition, the volume data can be archived in the ultrasound machine; it can be exported as Cartesian data
files. The volume data can also be transferred to a compact disc (CD) as a data file or it can be stored on a computer
hard drive.
2.3. Display and Manipulation

It is always possible to use the stored or archived data file with compatible software whenever it might be needed.
During the scanning, a menu for visualization modes appears on the ultrasound screen. The same menu appears on
the computer screen when stored data are used with the software. After selection of visualization mode, render mode
and algorithm menu become available for use. In this chapter, we will only discuss the practical mode and the
algorithm in the examination of the fetal central nervous system.
2.3.1. Visualization Mode - Multiplanar Display (Sectional Planes)

Multiplanar display is the basic form of the visualization mode. It is called “Orthogonal Planes” because the planes
are at right angles to each other. Each plane can be moved at the operator’s command to scroll though the volume as
needed. Multiplanar display of the three-dimensional volume of the fetal central nervous system shows the axial
view (reference plane) in the left upper plane (plane A), the coronal view in the right upper plane (plane B) and the
sagittal view in the left lower plane (plane C), respectively (Fig. 1).
2.3.2. Visualization Mode - Tomography Ultrasound Image (Tomography Display) (TUI)

With tomography ultrasound imaging in the visualization mode, we can see multiple parallel slices at different
spacing intervals through a volume at the same time on the ultrasound screen. In addition, this function makes it
possible to reconstruct many different planes within a rapidly obtained volume, comparable to those obtained by
computed tomography and magnetic resonance imaging (Fig. 4).
Figure 4: Tomographic ultrasound image (TUI) or tomographic display shows serial sagittal sections from left to right of the fetus
facing right on the screen. The highlighted box is the central picture. More left slices are seen in this display which was made with
a slice interval of 2 mm. The marker dot is inside the corpus callosum. The left side views show the ventricular structure. The
sections were obtained from a normal 19-week fetus.
2.3.3. Visualization Mode - Volume Contrast Image (VCI)

Volume contrast image (VCI) mode is another software application that increases tissue contrast and, therefore,
decreases distracting artifacts of speckles and noise between tissues. It consists of thick slice volume images
projected on a two-dimensional screen. VCI can be used as a post-processing technique for static volumes that have
already been acquired (static VCI) or as a modality for rendering in a four-dimensional mode (dynamic VCI in the
coronal plane, VCI-C). Static VCI can demonstrate multiplanar analysis of the fetal brain. In reality, it can be used
any time to clarify the image border (Fig. 5 A, B). Dynamic VCI (VCI-C) is also available and has the advantage of
minimizing movement artifact. [8]Both static and dynamic VCI are used advantageously for visualization of the
cerebellar vermis [11,12].
2.3.4. Render Mode - Surface Rendering

Surface rendering is the best known display mode of three-dimensional ultrasound. By means of this mode, surface
features can be seen as in a photograph (Fig. 6). It is useful when the fetus has a facial anomaly, such as those
associated with brain abnormalities like cyclopia with holoprosencephaly.
Figure 5: A is the sagittal section of an 11-week fetus showing a cystic hygroma (C) on the neck. B shows the posterior
delineation of the cystic hygroma much more clearly after the volume contrast image (VCI) is applied. The border is clarified by
eliminating noise and by enhancing the edge.
Figure 6: Surface rendered image shows a 10-week embryo inside the gestational sac in a normal pregnancy. Physiologic midgut
hernination (H) is rendered obvious by this imaging technique. Volume is acquired easily by transvaginal examination.
RENDER MODE - INVERSION RENDERING
In the inversion rendering mode, the cystic portions within the volume are displayed as an echogenic image, while
the gray scale portions of the image are rendered as transparent. The processed image shows a cast of all the cystic
portions within a volume while suppressing the view of the solid portions. The inversion mode is useful for
evaluating the fetal brain by displaying the entire ventricular system without the surrounding brain (Fig. 7).
Figure 7: Multiplanar display with inversion rendering mode shows normal three-dimensional ventricular system anatomy in an
8-week embryo. This inversion rendered image demonstrates only the fluid-filled cavity. Most of the secondary brain vesicles
consist of a fluid-filled cavity at this gestational age. The rendered image can readily illustrate the landmarks of the secondary
brain vesicles, which are T (telencephalon), D (diencephalon), Ms (mesencephalon), Mt (metencephalon), 4V(fourth ventricle), M
(myelencephalon). Adult derivates of these five brain vesicle cavities are as follows: Lateral ventricle-telencephalon, third
ventricle-diencephalon, aqueduct-mesencephalon, upper part of fourth ventricle-metencephalon, and lower part of fourth
ventricle-myelencephalon.4
RENDER MODE - COLOR RENDERING
Three-dimensional power Doppler ultrasound allows for the three-dimensional reconstruction of vessels after their
visualization using power Doppler ultrasound (Fig. 8). The application of color Doppler ultrasound for evaluation of
vascular structure and blood flow within the fetus and placenta has been investigated. The application is useful when
one suspects a congenital vascular malformation of the central nervous system or a congenital malformation
accompanied by a vascular abnormality. When agenesis of corpus callosum is suspected, the pericallosal artery color
mode can confirm the diagnosis.
Figure 8: Color mode shows the cerebral arterial branches: ACA, anterior cerebral artery; MCA, middle cerebral artery; PCA,
posterior cerebral artery. After color Doppler contained volume is acquired, color mode-light is selected, as shown here in a
normal 20-week fetus.
RENDER ALGORITHM - TRANSPARENT MODES
Transparent mode functions include minimum, maximum and x-ray modes. By means of these modes, the images of
the bony parts, such as cranium, spine, fontanel and suture, can be visualized. Primary fetal ossification centers in the
cranial vault are easily identified with maximum mode in an early second-trimester fetus (Fig. 9). This finding can
confirm the presence of fetal ossification centers [13].
Figure 9: The maximum transparency mode shows ossification centers both in the parietal bone (Parietal B) and the temporal
bone in a 14-week fetus, seen here. Primary ossification centers in the cranial vault appear after gestation age 13 weeks in the
transvaginal ultrasound examination. In contrast, they first appear after 14 weeks by radiologic study.13
VOLUME MEASUREMENTS WITH VOCALII (VIRTUAL ORGAN COMPUTER-AIDED ANALYSIS)

SOFTWARE
Volume measurements have been investigated to determine the gestational age and other diagnostic elements relative
to fetal development. They are done by using automatically determined fetal part volume after a three-dimensional
image is obtained. In the process of volume calculation after measurement, certain computer software --- either
multiplanar technique or rotational technique (VOCAL or VOCAL II) --- can be used to calculate the exact target
volume. Measured volume can be used to determine the physiologic characteristics based on known values.
Volume measurements of various components of the fetal central nervous system, including fetal brain and
cerebellum, as well as the nuchal translucency area, have been reported in published studies [14-16]. Although
volume measurements are investigational at present, three-dimensional volume might replace the current two-
dimensional technique in the near future. From the perspective of technical detail, volume measurement could be
acquired by different segmentation methods and different modes of sample contour generation. A study assessing the
best methods has been reported [17]. More technological details in this regard are beyond the scope of our
discussion. The measurement of the embryonic brain vesicle by manual operation is displayed in the multiplanar
planes as sample volume (Fig. 10).
3. FIRST TRIMESTER CENTRAL NERVOUS SYSTEM
The development of the central nervous system during the first trimester of fetal life is an incompletely understood
field because of the practical limitations of histological study. Early liquefaction of embryonic and fetal brain tissue
interdicts the proper fixation process so as to negate good pathologic study. Ultrasound development in obstetrics,
especially transvaginal ultrasound, has focused considerable attention on this field. The term “sonoembryology” has
been applied to the sonographic delineation and description of embryonic development after the introduction of the
high-frequency transvaginal transducer [18]. In particular, because the brain is such a prominent organ during early
intrauterine development, it has been focused on by investigators over time [19-21].
Figure 10: The brain volume of an 8-week embryo was calculated as 0.114 cm3 by manual operation using virtual organ
computer aided analysis (VOCAL) II software.
Development of three-dimensional ultrasound and its applied clinical applications has given rise to a new
terminologic designation, “three-dimensional sonoembryology” [22]. Many reports of three-dimensional ultrasound
studies of first trimester central nervous system have now elucidated the details of the three-dimensional
reconstructed anatomy of brain vesicles [23,24].
Two recent studies showed even more vivid features of first trimester fetal brain development, especially brain
ventricular development, by using the inversion rendering mode which highlighted the ventricular system after
removal of the brain tissue image.3 4. These reports confirmed previous studies on the early developing brain. They
also provided enhanced diagnostic images of fetuses with ventriculomegaly and holoprosencephaly (Fig. 11).
Figure 11: Inversion rendering image of holoprosencephaly in a 12-week fetus shows the fused prosencephalon from above in B.
The axial section of fetal head shows fusion of both prosencephalon and thalamus. The fetal head is facing to the right in A.
4. THREE-DIMENSIONAL VOLUME ASSESSMENT OF FETAL BRAIN BEYOND FIRST TRIMESTER
Before three-dimensional ultrasound became available, the basic ultrasound scan for fetal anatomy assessed only
axial planes, which included transventricular, transcerebellar and transthalamic planes. This basic scan noted
anatomic structures, such as head shape, lateral ventricles, cavum septi pellucidi, thalami, cerebellum and cisterna
magna [6]. Today, if the basic examination identifies suspicious findings, dedicated neurosonography is indicated.
The basic approach of the neurosonographic examination of the fetal brain is to view the vertical plane by aligning
the transducer with the sagittal suture and the fontanels of the fetal head [5]. Among vertical planes, the midsagittal
(median) plane is essential for diagnosing abnormalities of the corpus callosum and the cerebellar vermis [1].
However, the learning curve is long for learning how to obtain accurate imaging of these appropriate planes. It needs
time and training. Skill and familiarity with vaginal examination is also necessary.
Three-dimensional ultrasound enables visualization of the median plane by the reconstruction and navigation of
multiple sections through multiple planes, even with the conventional transabdominal approach [25]. Multiplanar
display of three-dimensional volume makes it easier and faster to assess the midline structures, such as the corpus
callosum, cavum septi pellucidi and cerebellar vermis (Fig. 12). By means of the tomography display, the ventricular
system can also be easily visualized. Frontal coronal plane made the evaluation of anterior fontanel possible. In this
section, we will discuss the anatomical evaluation of the corpus callosum, ventricular system, cerebellar vermis and
fontanel and cranial sutures.
Figure 12: Two-screen display format from the TUI (tomography ultrasound image) mode visualizes the initial plane in the left
screen and the reconstructed median plane in the right screen. The comma-shaped sonolucent structure is the combined corpus
callosum (CC) and cavum septi pellucidi (CSP). The cerebellar vermis and third ventricle (V) are also well visualized. The brain
volume is acquired from the axial plane of the starting scan from a normal 21-week fetus. The marker dots in both screens are
located in the middle of the corpus callosum.
5. CORPUS CALLOSUM AND CAVUM SEPTI PELLUCIDI
Although the median plane can be reconstructed by three-dimensional ultrasound, it is not always possible to obtain
the necessary planes to assess the corpus callosum in any position. Appearance of corpus callosum differs depending
upon the acquisition plane [8, 26, 27]. In the midsagittal planes, the corpus callosum is seen as a thin sonolucent strip
with well-defined echogenic contours (Fig. 13 A). In contrast, the reconstructed median plane shows a comma-
shaped echogenic structure overlying the cavum septi pellucidi instead of the echolucent corpus callosum (Fig. 13
B). In reconstructed median planes, the corpus callosum and the cavum septi pellucidi are frequently not clearly
separated. In this case, the sonolucent area is considered to be the corpus callosum and cavum septi pellucidi
together. This is because there cannot be a cavum septi pellucidi without a corresponding covering corpus callosum.
However, there can be a corpus callosum alone without a cavum septi pellucid [27].
The corpus callosum can be seen in its full developmental shape from 18-20 weeks of gestation. The cavum septi
pellucidi should be seen in all fetuses between weeks 18 and 37. During this period, if the cavum septi pellucidi
cannot be seen, it should raise the suspicion that it is absent. Absence of the cavum septi pellucidi is a feature
associated with agenesis of corpus callosum, holoprosencephaly, septo-optic dysplasia, schizencephaly,
porencephaly/hydranencephaly, basilar encephaloceles and severe hydrocephaly [27].
Figure 13: The corpus callosum (CC) and cavum septi pellucidi (CSP) are seen separated in A of this midsagittal section obtained by
axial contrast from the brain volume of a 19-week fetus. Contrastingly, the separation between these two structures may not be seen in
the reconstructed midsagittal section, as shown in B. The dot marker identifies the middle of cavum septi pellucidi. In most cases, this
sonolucent comma-shaped area is considered to represent both the cavum septi pellucidi and the corpus callosum together.
6. CEREBELLAR VERMIS AND POSTERIOR FOSSA
In the median plane, the cerebellar vermis, fourth ventricle and cisterna magna can be visualized (Fig. 14). The
cerebellar vermis and hemisphere cover the fourth ventricle at around 18 weeks of gestation. The vermis grows from
rostral to caudal during its development. Before 18 weeks’ gestation, agenesis of the cerebellar vermis cannot be
diagnosed [28]. After 18 weeks, however, several advantages of three-dimensional ultrasound of the fetal vermis
evaluation exist in this regard [29]. Regardless of the fetal lie or presentation, three-dimensional planes obtained
from axial acquisitions are simpler and easier to view. Most importantly, using volume contrast image (VCI) and
tomography ultrasound image (TUI) allows depiction of small parts, such as the primary fissure, with improved
resolution and contrast. This improved imaging should prove helpful in the early diagnosis of vermian lesions, such
as Dandy-Walker malformation.
7. THE VENTRICULAR SYSTEM
The ventricular system consists of the lateral ventricles, the third and fourth ventricles, and their connecting
foramina. There are four foramina: (1) The foramen Monro connects the lateral ventricles to the third ventricle; (2)
the cerebral aqueduct (Sylvius) connects the third ventricle with the fourth ventricle; (3) the median aperture
(Magendi) connects the fourth ventricle with subarachnoid space and cerbellomedullary cistern (CM); and (4) the
lateral apertures (Luschka) connect the fourth ventricle with the subarachnoid space as well as the cistern of the great
cerebral vein.
Figure 14: Multiplanar display of a three-dimensional ultrasound of the fetal brain is acquired by sagittal plane from a normal 21-
week fetus. In plane A, the presence of the cerebellar vermis is shown by echogenic tissue in between the slightly less echogenic
cerebellar hemispheres. The cerebellar vermis and the cisterna magna are well visualized in the midsagittal section in plane C.
The fetus is facing to the right. The corpus callosum and the cavum septi pellucidi are also visualized in the same plane.
The measurement of the atrial width of the lateral ventricle has been the core element of basic study of the fetal
central nervous system [6]. Ventriculomegaly is defined as a width is more than 1 cm. Ventriculomegaly is one of
the most challenging findings in obstetric ultrasound. It has been studied by many investigators. Mild
ventriculomegaly has no clinical significance if the karyotype is normal and there are no other associated anomalies
[30]. Three-dimensional ultrasound does not seem to add meaningful advantages to two-dimensional ultrasound in
the diagnosis of ventriculomegaly itself. A more important contribution is the possibility of thorough evaluation of
whole central nervous system when the ventriculomegaly is flagged in two-dimensional ultrasound. In addition, the
tomography ultrasound image can reveal the whole ventricular system in one screen at the same time through the
navigation technique, using a dot marker (Fig. 4). Furthermore, after the lateral ventricle is identified, it can be
displayed in detail (Fig. 15).
Figure 15: Lateral ventricle is well visualized from the parasagittal section of the median plane. The dot marker in the right
screen is located in the same plane as the thick dissection line in left screen. This volume is from a normal 19-week fetus.
8. FETAL FONTANELS AND CRANIAL SUTURES
Cranial sutures are fibrous connective tissues that connect the six bones of the skull, which are frontal bone, occipital
bone, two parietal bones and two temporal bones. Fontanels are spaces between bones where the sutures met.
Fontanels and sutures gradually become closed, solid bony areas postnatally after certain time period. Anterior
fontanel is rhomboid space located in the uppermost of cranium where two coronal sutures bilaterally, metopic suture
anteriorly and sagittal suture posterioly met. Their premature and delayed ossifications are related to many genetic
and non-genetic conditions [31].
More detailed evaluation of the fontanels and the cranial sutures became possible after three-dimensional ultrasound
became available. At first, attention was paid exclusively to the normal and the abnormal findings in cranial sutures
[32, 33]. More recently, studies of the anterior fontanels were published [34, 35]. All suture lines and fontanels are
readily accessible through appropriate acquisition and manipulation of the stored volume. In particular, metopic
suture can be assessed in depth with three-dimensional ultrasound with frontal coronal view. It is difficult to obtain
frontal coronal view in two-dimensional mode. The rendering image can be acquired by dynamic volume contrast
image (VCI-C) as well as by maximum mode with three-dimensional static acquisition (Fig. 16).
Figure 16: Maximum mode rendered image clearly shows the anterior fontanel of a 19-week fetus. The brain volume is acquired
by imaging in the sagittal plane. The rendered image was rotated to visualize whole anterior fontanel and associated sutures.
Distances between each suture can be measured and abnormal development can be predicted when the measurements are out of
standard range.
9. THREE-DIMENSIONAL POWER DOPPLER ANGIOGRAPHY
In prenatal diagnosis, power Doppler has many advantages over conventional color Doppler ultrasound [36].Power
Doppler angiography has been shown to be three- to five-fold more sensitive than conventional color Doppler in
visualizing small vessels and vessels with slower flow. In addition, vessel visualization is not affected by the angle of
insonation. There is better edge definition as well. All these features make this mode ideal for use in three-
dimensional reconstruction of vasculature. Early studies have focused on the placenta and, to a lesser degree, on fetal
vasculature [37].
The advantage of power Doppler angiography with three-dimensional ultrasound is its ability to provide accurate
spatial representation of abnormal vasculature viewed in their original site in the body. In recent case reports, three-
dimensional power Doppler ultrasound showed exactly the same features found postnatally on intracranial
angiography [38, 39].
THE FETAL SPINE
Although the full detailed examination of the fetal spine is not considered a part of the basic examination, a
longitudinal section of the fetal spine should be obtained. Longitudinal section shows the whole length of the spine in
one single view in two-dimensional ultrasound. This longitudinal sagittal view shows the abnormality by recognizing
the disruption of alignments. Adding three-dimensional ultrasound, either with reconstructed or primary acquired
coronal views of the fetal spine, facilitates evaluation of the bony parts by navigating and dissection plane with
tomography ultrasound imaging (Fig. 17).
The volume can be displayed conveniently by choosing various modes, such as tomography ultrasound image,
multiplanar mode or maximum mode, which simultaneously demonstrates the ossification centers of each vertebra. It
is easy to display corresponding ribs in the view as reference. The vertebral segments are counted starting with the
one connected to the last identifiable rib; this usually corresponds to the twelfth thoracic spine (Fig. 18) [5].
Figure 17: Tomography ultrasound image of the coronal section of the fetal spine. Serial section planes show the details of the
bony spine from the vertebral body to the transverse process. The dot marker is located in twelfth thoracic spine, which
corresponds to the last identifiable rib.
Figure 18: The skeleton-maximum mode was selected to show the ossification centers of the spine and the ribs. The ribs are
countable. The last rib is the reference for the twelfth vertebra (T12). The volume was acquired from the sagittal plane parallel to
the longitudinal axis of the fetus.
Three-dimensional examination of the fetal spine with congenital anomalies has been addressed in several studies
[40-42]. Spina bifida is one of the most extensively studied anomalies [40]. Surface rendering of the volume can be
used to demonstrate cutaneous lesions of open spina bifida and the possible presence of a meningocele, but it offers
no diagnostic advantage over standard two-dimensional ultrasound examination. However, it is more precise and
accurate for three-dimensional ultrasound to locate the extent and position of a defect. When using standard two-
dimensional ultrasound scanning, one identifies the defective area of the spine by obtaining a midsagittal view and
then counting the vertebral segments starting from the lowest, usually corresponding to the fourth sacral vertebra
[43]. In contrast, the lowest rib can be used reference, which corresponds to the twelfth thoracic vertebra when using
three-dimensional ultrasound.
COMMENTS
Central nervous system malformations are some of the most common of all congenital abnormalities. However, their
diagnosis is challenging in many aspects.
For example, development of the central nervous system continues from the beginning of conception to well beyond
the neonatal period. Certain fetal anomalies are therefore undetectable in early intrauterine life because they only
become manifest at a later gestational age and in the neonatal period [44].
Advanced technology in ultrasound has made it easier to visualize the fetal central nervous system. Intrauterine
photographic imaging of the lesion, precise localization of the lesion and estimation of the neurologic sequelae have
become possible in cases with open neutral tube defect such as spina bifida and meningomyelocele. The contribution
of three-dimensional ultrasound in the diagnosis of midline brain anomalies, such as agenesis of corpus callosum, is
predominant among all its other benefits. Furthermore, some authors have shown that the three-dimensional
ultrasound data set alone can be used in the evaluation of the anatomy of the central nervous system and the
diagnosis of its anomalies [45].
We conclude that three-dimensional ultrasound has more than a complementary role in the evaluation of the anatomy
of fetal central nervous system and the diagnosis of its anomalies. It is easy to learn and understand. Examinations
using this technology take shorter time than two-dimensional ultrasound. Three-dimensional ultrasonography will
undoubtedly prove to be an essential investigative and diagnostic tool in the near future.
ACKNOWLEDGMENTS
With any words, the gratefulness cannot be expressed enough for the thoughtful advices and affectionate
encouragement of Emanuel A Friedman, MD and Allan J Jacobs, MD. The kind support of Hajoon Chun, MD and
Laura Wyckoff, RDMS for providing the ultrasound images is also appreciated.
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Obstet Gynecol 2001: 18: 81-3
[44] Kollias SS, Goldstein RB, Cogen PH, Filly RA. Prenatally detected myelomeningoceles: sonographic accuracy in
estimation of the spinal level. Radiology 1992; 185: 109-12.
[45] Malinger G, Leman-Sagie T, Watemberg N, Rotmensch S, Lev D, Glezeman N. A normal second-trimester ultrasound
does not exclude intracranial structural pathology. Ultrasound Obest Gynecol 2002; 20: 51-6
[46] Gonçalves L, Nien JK, Espinoza J, et al. What does 2-dimensioanl imaging add to 3- and 4-dimensional obstetric
ultrasnography? J Ultrasound Med 2006; 25: 691-9
CHAPTER 4
Fetal 3D/4D Cardiovascular Imaging
Toshiyuki Hata1,* and Junko Noguchi2
1
Department of Perinatology and Gynecology, Kagawa University, School of Medicine, 1750-1 Ikenobe, Miki
Kagawa 761-0793, Japan and 2Department of Nursing, Kagawa Prefectural College of Health Sciences, 281-1
Murecho-hara, Takamatsu, Kagawa 761-0123, Japan
Abstract: We present herein the latest three-dimensional (3D)/four-dimensional (4D) sonographic studies on fetal
heart and blood vessels using STIC (spatiotemporal image correlation) or real-time 3D fetal echocardiography.
These new 3D/4D ultrasound techniques include VOCAL (Virtual Organ Computer-aided AnaLysis), TUI
(Tomographic Ultrasound Imaging), SonoVCAD (Sonography Based Volume Computer Aided Diagnosis),
color/power Doppler ultrasound and HD (High-Definition)-flow, B-flow and inversion mode. Fetal 3D/4D
echocardiography provides a novel means for evaluation of fetal heart and blood vessels in 3D in real time, and of
fetal intracardiac hemodynamics in the second and third trimesters. These novel techniques may assist in the
evaluation of fetal cardiac anatomy and hemodynamics, and offer the potential advantages relative to conventional
two-dimensional fetal echocardiography and Doppler flow mapping. 3D/4D ultrasound may be an important
modality in future fetal cardiac research and in evaluation of congenital heart disease in the fetus.
1. INTRODUCTION
Recently, a new faster fetal three-dimensional (3D) echocardiography, which proves capable of providing continuous
3D sonographic images in real time without a need for an external workstation or other additional, costly equipment,
has become available [1-6]. One of the major advantages of this real-time 3D method is the fact that gating of the
heart rate is not required. Using this system, we can perform real-time 3D observations of the fetal heart, and obtain
instantaneous rendered 3D images of the beating fetal heart. Rendered displays of volume data allow surgeon’s eye
views of important and unique fetal cardiac anatomic structures not easily visualized or understood on conventional
two-dimensional (2D) imaging.
Spatiotemporal image correlation (STIC) is an another recent advance that allows dynamic multiplanar slicing and
surface rendering of heart anatomy, and a new approach for clinical assessment of the fetal heart [7, 8]. This feature offers
an easy to use technique to acquire data from the fetal heart and its visualization in a four-dimensional (4D) cine
sequence. Fetal heart volumes are acquired with a single automated sweep of the transducer, and spatial and temporal
information are combined to display real-time images that can be extracted from volume datasets [7]. This cine sequence
presents the fetal heart beating in real time in multiplanar and rendered displays. The examiner can navigate within the
heart, re-slice, and produce all of the standard and unique planes necessary for comprehensive diagnosis [9].
The introduction of new 3D/4D ultrasound techniques such as real-time 3D echocardiography, VOCAL (Virtual
Organ Computer-aided AnaLysis) and STIC with TUI (Tomographic Ultrasound Imaging), SonoVCAD
(Sonography Based Volume Computer Aided Diagnosis), color/power Doppler ultrasound and High-Definition
(HD)-Flow, B-Flow and inversion mode allowed for the assessment of real-time cardiovascular imaging in normal
fetal heart and congenital heart disease (CHD) in utero [10-15]. This chapter presents the state-of-the-art on latest
fetal 3D/4D cardiovascular imaging with the use of real-time 3D and 4D fetal echocardiography.
2. REAL-TIME 3D FETAL ECHOCARDIOGRAPHY
Real-time 3D fetal echocardiography is the latest development in 3D ultrasound, and is providing clinicians a new,
and arguably much improved, view of the complexities and inter-relationships of fetal cardiac anatomy non-
invasively [16]. Real-time 3D fetal echocardiography has been the need to capture a large volume of data (inclusive
*Address correspondence to Toshiyuki Hata: Department of Perinatology and Gynecology, Kagawa University, School of Medicine, 1750-1
Ikenobe, Miki Kagawa 761-0793, Japan; Tel:+81-(0)87-891-2174; Fax: +81-(0)87-891-2175; E-mail: toshi28@med.kagawa-u.ac.jp
134 Current Topics on Fetal 3D/4D Ultrasound Hata and Noguchi
of most or all of the heart) and be able to process the volume while it is moving [16]. This imaging system has been
made possible by the development of a transducer that can interpret the entire volume of the heart as opposed to one
2D slice. The transducer has ~3000 elements as opposed to previous conventional transducers that had 128 [17].
These transducers, which are capable of imaging the heart in 3D in real time, have incorporated into the head of the
transducer 3000 crystals that emit and receive sound. In order to do that, each crystal has to be connected to a
particular channel. The innovative engineering feat is that all of the boards have been miniaturized and housed within
the transducer [18]. This 3D sonographic machine proved capable of providing continuous 3D sonographic images
every 0.05 and 0.035 seconds (the frame rate being in the region of 20-28 frames per second). The frame rate of the
system, the number of pictures per second (the frame rate being in the region of 20-28 frames per second), is fairly
adequate in order to resolve the definition of the heart as it moves. There have been some reports on real-time 3D
sonographic observation of fetal heart in the normal fetus and those with CHD [1-6]. One of the major advantages of
this real-time 3D method is the fact that gating of the heart rate is not required. Using this system, we can perform
real-time 3D observations of the fetal heart, and obtain instantaneous rendered 3D images of the beating fetal heart
(live 3D images of the fetal heart). Rendered displays of volume data allow surgeon’s eye views of important and
unique fetal cardiac anatomic structures not easily visualized or understood on conventional 2D imaging (Figs. 1-3
and Video clip 1-3). Moreover, a track ball on the echocardiographic machine allows the operator to turn and rotate
the 3D image in any direction deemed necessary [19].
Figure 1 & Video clip 1: Real-time 3D fetal echocardiographic observation of opening and closure of mitral and tricuspid valves
at 31 weeks of gestation. LA, left atrium; LV, left ventricle; MV, mitral valve; RA, righr atrium; RV, right ventricle; TV, tricuspid
valve. (Reprinted with permission from J Obstet Gynecol Res 2006;32:42-46[4]).
Fetal 3D/4D Cardiovascular Imaging Current Topics on Fetal 3D/4D Ultrasound 135
Figure 2 & Video clip 2: Real-time 3D fetal echocardiographic observation of short-axis view at 31 weeks of gestation. Three
semilunar valves of the aortic valve (AoV) were clearly identified in diastole. PA, pulmonary artery; PV, pulmonary valve; RA,
right atrium; RV, right ventricle; TV, tricuspid valve.
Figure 3 & Video clip 3: Real-time 3D fetal echocardiographic volume-rendered display of multiple cardiac tumors (*) at 37
weeks of gestation. LA, left atrium; LV, left ventricle; RA, right atrium; RV, right ventricle.
There have been only two reports on real-time 3D color Doppler echocardiographic imaging of the fetal heart in the
normal fetus and CHD during pregnancy [1, 6]. This technology allows for the depiction of the shape, direction and
propagation of color flow jets in three-dimensions for analysis of ventricular septal defects, valvar and subvalvar
stenosis, regurgitant jets, etc [19]. In (Fig. 4 and Video clip 4), real-time 3D color Doppler echocardiography
showed clear relationship between hypoplastic aorta and large pulmonary artery in hypoplastic lefe heart syndrome.
The present and future application of real-time 3D (with/without color Doppler) fetal echocardiography to the
prenatal diagnosis of fetuses with CHD might be promising. However, this is not to imply that real-time 3D
(with/without color Doppler) fetal echocardiography will replace conventional 2D fetal echocardiography [19]. This
novel technique may assist in the prenatal diagnosis of fetal cardiac anomalies, and offer the potential advantages
relative to conventional 2D fetal echocardiography and color Doppler flow mapping.
Figure 4 & Video clip 4: Real-time 3D color Doppler echocardiographic volume-rendered display of hypoplastic left heart
syndrome. Hypoplastic aorta (Ao) and large pulmonary artery (PA) are clearly demonstrated.
3. 4D FETAL ECHOCARDIOGRAPHY
3.1. STIC
Another advent of 3D/4D fetal echocardiography is the development of STIC technique. STIC is a recent advance
that allows dynamic multiplanar slicing and surface rendering of heart anatomy, and a new approach for clinical
assessment of the fetal heart [7, 8]. This feature offers an easy to use technique to acquire data from the fetal heart
and its visualization in a 4D cine sequence. Fetal heart volumes are acquired with a single automated sweep of the
transducer, and spatial and temporal information are combined to display dynamic images that can be extracted from
volume datasets [7]. This cine sequence presents the fetal heart beating in real time in multiplanar and rendered
displays. The examiner can navigate within the heart, re-slice the acquired data at any time, and produce all of the
standard and unique planes necessary for comprehensive diagnosis [9]. Other important advantages are that we can
create any cutting images from the data set stored for the use of assessing fetal heart anatomical structures for later
evaluation. By acquiring the entire fetal heart instantaneously as a single volume, 4D ultrasound with STIC may
facilitate fetal cardiac anatomy evaluation. Conventional prenatal screening for CHD involves a time-consuming and
highly operator-dependent acquisition of the four-chamber view and outflow tracts. By acquiring the entire fetal
heart instantaneously as a single volume, 4D echocardiography with STIC may facilitate fetal cardiac screening [9,
20]. The advantages of using such a volume for an Internet link evaluation were also emphasized, showing the
potential for gaining a second opinion by experts as a remote site [8, 12, 21-23].
The STIC technology usually results in 40 volumes, each one representing a “snapshot” of the heart during a complete
cardiac cycle. For general analysis of dynamic morphology of the fetal heart, Deng proposed using a minimum volume
rate of about 25 Hz (equivalent to a maximum of 40 ms for each imaging volume sampling period) as the cut-off point
between direct and indirect volume scanning [10]. A 50 Hz (20 ms) scan is only capable of capturing the phase
maximally in one imaging volume per cycle, with no accuracy for the measurement, a 500 Hz volume rate may be
necessary. This is far beyond the capability of any of real-time 3D or 4D systems, which are still struggling to achieve a
50 Hz volume rate. However, the latest very high frame-rate acquisition has fairly made it possible for the spatial and
temporal correlation to be completed immediately after a scan, resulting online 4D display [11].
3.2. Rendered Display

STIC shows the fetal heart beating in real time in any rendered displays. We can navigate within the heart, re-slice
the acquired data, and produce all of the standard and unique planes we want (Figs. 5-12 and Video clips 5-12).
Viñals et al. [24] assessed the feasibility and clinical potential of 4D volume rendering of the atrioventricular valve
junction, and displayed the atrioventricular valve junction morphology in normal fetuses and in those with a
complete atrioventricular septal defect. Volume rendering of the left ventricle showed the position of the
anterolateral and posteromedial papillary muscles in 90% of normal fetuses. At the level of right ventricle, the septal,
anterior and posterior papillary muscles were visualized in 82% of normal fetuses. In cases of complete
atrioventricular septal defect, the morphology of the anterosuperior bridging leaflets and the abnormal position of the
papillary muscles could be depicted in all cases.
Figure 5 & Video clip 5: Rendered display of the normal fetal heart using 4D echocardiography with STIC at 33 weeks of
gestation. CS, coronary sinus; FFO, flap of foramen ovale; LA, left atrium; LV, left ventricle; MV, mitral valve; OPV, orifice of
pulmonary vein; RA, right atrium; RV, right ventricle, TV, tricuspid valve. a, diastolic phase; b, systolic phase.
Figure 6 & Video clip 6: Rendered display of the Ebstein’s malformation using 4D echocardiography with STIC at 34 weeks of
gestation. The septal cusp (*) of the tricuspid valve is foreshortened and displaced inferiorly toward the right ventricular apex.
The anterior cusp (AC) is elongated, redundant, and likewise displaced inferiorly. The distance between the usual position of the
tricuspid annulus and the actual imaged position of the septal and the anterior cusps of the tricuspid valve defines the atrialized
right ventricle. LA, left atrium; LV, left ventricle; MV, mitral valve; PC, posterior cusp; RA, right atrium; RV, right ventricle;
TV, tricuspid valve. a, diastolic phase; b, mid-systolic phase; c, systolic phase.
Figure 7 & Video clip 7: The en-face view of both atrioventricular valves and great vessels in a normal fetal heart at 36 weeks of
gestation. Each leaflet (*) of both atrioventricular valves is clearly identified. Ao, aorta; LA, left atrium; LV, left ventricle; MV,
mitral valve; PA, pulmonary artery; RA, right atrium; RV, right ventricle; TV, tricuspid valve.
Figure 8 & Video clip 8: The en-face view of both atrioventricular valves and great vessels in a normal fetal heart at 26 weeks`
gestation. This en-face view is shown from apex side. Each leaflet (*) of both atrioventricular valves is beautifully depicted. Ao,
aorta; MV, mitral valve; PA, pulmonary artery; TV, tricuspid valve.
Figure 9 & Video clip 9: The en-face view of both atrioventricular valves in Ebstein’s malformation. Elongation of the anterior
cusp (AC), shortening of the septal cusp (SC), the arterialized portion (*) of the right ventricle, and the inferior and apical
displacement of the tricuspid valve (TV) apparatus from its annulus are clearly noted. Ao, aorta; LA, left atrium; LV, left
ventricle; MV, mitral valve; PC, posterior cusp; RA, right atrium; RV, right ventricle.
Figure 10 & Video clip 10: The en-face view of both atrioventricular valves and great vessels in a hypoplastic left heart
syndrome at 37 weeks of gestation. Hypoplastic aorta (Ao) and large pulmonary artery (PA) are clearly demonstrated. Small left
ventricle (LV) is also evident. RV, right ventricle. a, diastolic phase. Large ventricular septal defect (*) is noted. b, systolic phase.
Each leaflet (*) of right atrioventricular valves is clearly identified.
Figure 11a & Video clip 11a: Rendered display of the interventricular septum imaged from within the right ventricle (RV) shows
a rough characteristic traveculations and ventricular septal defect (VSD).
Figure 11b & Video clip 11b: Rendered display of the interventricular septum imaged from within the left ventricle (LV) shows
the relative smoothness of the ventricular wall as compared to the right-sided wall (a) and ventricular septal defect (VSD). RV,
right ventricle.
Figure 12 & Video clip 12: Rendered display of the interventricular septum imaged from within the left ventricle (LV) shows
large ventricular septal defect (VSD). Single atrium is also noted.
Yagel et al. [25] applied STIC rendering to visualize the virtual planes of the interventricular and interatrial septa as
well as the atrioventricular annuli plane just distal to the semilunar valves (coronal atrioventricular plane) in normal
and pathological fetal hearts. In 96.3% of normal scans the interventricular and interatrial septa were visualized
successfully, while in 93.4% of normal fetuses the coronal atrioventricular plane was successfully visualized. In 13
out of 35 anomalous cases the interventricular septum plane improved ventricular septal defect evaluation, and in 4
the interatrial septum plane contributed to foramen ovale evaluation.
Recently, Shih et al. [26] reported that the en-face view of both atrioventricular valves and great vessels in fetuses
with transposition of the great arteries (TGA) displays the main pulmonary artery situated side-by-side with the aorta
(‘big-eyed frog’ sign). The big-eyed frog sign may prove helpful in the prenatal diagnosis of TGA.
3.3.TUI
TUI, a new display modality that automatically slices 3D/4D datasets, provides simultaneous visualization of up to
eight parallel planes in a single screen [27]. Motion information in volume datasets acquired using 4D ultrasound is
not lost, and multiple sections of a beating heart can be analyzed at the same time (Figs. 13 and 14 and Video clips
13 and 14). Moreover, volume datasets could be acquired with color Doppler (Fig. 15 and Video clip 15). Standard
transverse planes commonly used to examine the fetal heart can be automatically displayed with TUI in the majority
of fetuses undergoing 4D ultrasound with STIC [27]. The examiner could adjust the number and position of the
slices, and the most suitable mean interslice distance was 2.7 mm at 19-23 weeks of gestation and 4.0 mm at 30-33
weeks, respectively [28]. Paladini et al. [28] also stated that TUI-STIC allows a complete sequential analysis of CHD
in all fetuses studied.
Figure 13 & Video clip 13: Tomographic ultrasound imaging of a normal fetal heart.
Figure 14 & Video clip 14: Tomographic ultrasound imaging in a fetus with tetralogy of Fallot at 29 weeks` gestation. Ao, aorta;
LV, left ventricle; RV, right ventricle; VSD, ventricular septal defect.
Figure 15 & Video clip 15: Color Doppler tomographic ultrasound imaging in a fetus (same as Fig. 14) with tetralogy of Fallot at
29 weeks` gestation. Mitral and tricuspid regurgitant flows and shunt flow through ventricular septal defect are recognized. Ao,
aorta; LV, left ventricle; RV, right ventricle.
3.4. SonoVCAD
SonoVCAD is the software that automatically retrieves diagnostic cardiac planes from a 4D volume of the fetal chest
obtained with STIC in the second trimester of pregnancy [29]. Standarization of 4D volumes was performed in Plane
A (the reference plane: four-chamber view) alone (Fig. 16 and Video clip 16), and TUI was added to the display of
each diagnostic plane [30]. The four-chamber view plane (Start plane: four-chamber view) (Fig. 17 and Video clip
17), the left ventricular outflow plane (Cardiac plane 1: outflow tract of left ventricle, aorta) (Fig. 18 and Video clip
18), the right ventricular outflow plane (Cardiac plane 2: pulmonary artery) (Fig. 19 and Video clip 19), the
abdominal circumference plane (Cardiac plane 3: abdominal circumference, stomach) (Fig. 20 and Video clip 20),
the right atrial inflow plane (Cardiac plane 4: superior vena cava, inferior vena cava) (Fig. 21 and Video clip 21) and
the ductal arch plane (Cardiac plane 5: pulmonary artery, ductus arteriosus) (Fig. 22 and Video clip 22). SonoVCAD
will improve the diagnostic acumen of ultrasound imaging in normal fetal heart and CHD, and thus prove
advantageous to clinical practice [29-31]. SonoVCAD also has the potential for improving the efficacy of ultrasound
imaging by reducing the time needed to complete an ultrasound examination, thereby resulting in increased
throughput of ultrasound laboratories [30].
Figure 16 & Video clip 16: Multiplanar display of a 3D volume obtained at the level of the four-chamber view (plane a) in a fetus in a
cephalic presentation at 20 weeks of gestation. We have to adjust green figures for four-chamber view of the heart and U-shaped ribs to
actual size of these anatomical structures of the fetus. On the plane B, we have to depict the sagittal view of the spine.
Figure 17 & Video clip 17: Start plane shows the normal four-chamber view. LA, left atrium; LV, left ventricle; RA, right
atrium; RV, right ventricle.
Figure 18 & Video clip 18: Cardiac plane 1 depicts the left ventricular outflow tract. Ao, aorta; LA, left atrium; LV, left
ventricle; RV, right ventricle.
Figure 19 & Video clip 19: Cardiac plane 2 displays the right ventricular outflow tract. Ao, aorta; PA, pulmonary artery; SVC,
superior vena cava.
Figure 20 & Video clip 20: Cardiac plane 3 shows abdominal circumference. St, stomach.
Figure 21 & Video clip 21: Cardiac plane 4 depicts the right atrial inflow tract. IVC, inferior vena cava; SVC, superior vena
cava.
Figure 22 & Video clip 22: Cardiac plane 5 displays the ductal arch (DA). PA, pulmonary artery.
3.5. Color/Power Doppler and HD-Flow

3D power Doppler ultrasound is a recent development of ultrasound technology which allows the 3D reconstruction of
vessels after their visualization using power Doppler ultrasound [32-35]. Several studies have shown potential clinical
applications in obstetrics [36-38]. 3D power Doppler ultrasound has also been shown to be useful in fetal vasucular
anatomy and malformations (Fig. 23 and Video clip 23) [39-42]. However, conventional 3D power Doppler ultrasound is
still static, not dynamic or real-time. Recently, 4D color/power Doppler ultrasound with STIC, which proves capable of
providing continuous 3D sonographic images in real time, has become available [43-46]. STIC in combination with color
Doppler ultrasound is a promising new tool for multiplanar and 3D/4D rendering of the fetal heart [44]. 3D color/power
Doppler ultrasound with STIC has the potential to simplify visualization of the outflow tracts (Figs. 24 and 25 and Video
clips 24 and 25), and improve the evaluation of the location and extent of ventricular septal defects. Other applications
include 3D/4D evaluation of regurgitation jets and venous streams at the level of the foramen ovale [43-46]. Paladini et
al. [47] reported that the reconstructed en-face view by 4D echocardiography with color Doppler can demonstrate the
different types of spatial relationship of the arterial trunks in fetuses with transposition of the great arteries with a high
degree of accuracy (Figs. 26 and 27 and Video clips 26 and 27).
Figure 23 & Video clip 23: 3D power Doppler sonographic reconstruction of the abdominal vessels in a normal fetus. Ao, aorta;
CIA, common iliac artery; UV, umbilical vein.
Figure 24 & Video clip 24: Color Doppler sonographic glass-body rendered imaging of the normal fetal heart using 4D
echocardiography with STIC. It is clearly shown that the pulmonary artery (PA) crosses in front of the aorta (Ao). (Courtesy by
GE Yokogawa Medical Systems, Tokyo, Japan)
Figure 25 & Video clip 25: Power Doppler sonographic imaging of the normal fetal heart using 4D echocardiography with STIC
at 33 weeks of gestation. It is clearly shown that the pulmonary artery (PA) crosses in front of the aorta (Ao).
Figure 26 & Video clip 26: En-face view of the four cardiac valves using 4D color Doppler echocardiography with STIC in a 22-
week normal fetus. Ao, aorta; LV, left ventricle; MV, mitral valve; PA, pulmonary artery; RV, right ventricle; TV, tricuspid
valve. a, diastolic phase; b, systolic phase.
Figure 27 & Video clip 27: En-face view of the four cardiac valves using 4D color Doppler glass-body rendered imaging with
STIC in a case of transposition of the great arteries. The side-by-side spatial arrangement of the great vessels is clearly shown.
Ao, aorta; LV, left ventricle; MV, mitral valve; PA, pulmonary artery; RV, right ventricle; TV, tricuspid valve. (Courtesy by GE
Yokogawa Medical Systems, Tokyo, Japan)
HD-Flow is a bi-directional power Doppler technique that delivers high-definition axial resolution and increased
sensitivity for imaging small vessels [14]. In addition, it reduces special overlap of tissue signals by application of
small sample volumes, and provides optimal clutter elimination with adaptive wall filtering. 3D/4D HD-Flow is
unique for 3D reconstruction of fetal heart and vascular tries in the whole body (Fig. 28). There has been only one
report on the usefulness of STIC with HD-flow for the diagnosis of CHD (fetal coarctation of the aorta) [48].
Figure 28: 3D HD-flow image of the normal fetal heart at 27 weeks of gestation. LV, left ventricle; RV, right ventricle.
3.6. B-Flow
Conventional grayscale ultrasound (B-mode) cannot be used to evaluate blood flow because the particulate
components of blood are very weak reflectors [49]. B-flow sonographic technique was recently developed to provide
direct visualization of blood flow with gray-scale sonography [50]. B-flow imaging is a non-Doppler technology that
directly displays flowing intravascular echoes on real-time grayscale images [51]. B-flow sonography utilizes
digitally encoded ultrasound technology, and extends B-mode imaging capabilities to blood flow [50]. Compared
with color Doppler sonography, B-flow imaging’s attributes include a wider bandwidth, higher frame rate, and
higher dynamic range for higher spatial, temporal, and contrast resolution imaging. To the best of our knowledge,
there have been two reports on B-flow imaging of the umbilical cord in obstetrical fields [52, 53]. The 4D ultrasound
with STIC and B-flow is the latest development in 4D ultrasound, and is providing clinicians a new dynamic 3D
sonoangiographic view of the physiologic and abnormal hemodynamics of fetal cardiac blood flows and blood
vessels non-invasively (Figs. 29-33 and Video clips 29-33). There have been five reports on 4D cardiac blood flow
observation of the fetal heart and blood vessels using 4D ultrasound with STIC and B-flow [54-58]. Gonçalves et al.
[54] showed that 3D images created by 4D echocardiography with STIC and B-flow as ‘ digital casts’ and this
modality allowed visualization of the relationships, size, and course of the outflow tracts, thus helping the examiner
to better understand the special relationships between the vessels. Pooh et al. [55] used STIC and B-flow for
visualization of fetal cardiac blood vessels, and found that not only extracardiac vessels but also small vessels with
low velocity blood flow could be immediately identified on 2D B-flow and examined in detail on saved image data
on STIC and B-flow. Volpe et al. [56] also suggested that 4D echocardiography with STIC and B-flow can provide
thorough visualization of very small vessels and of the arterial blood supply to the lungs of fetuses with pulmonary
atresia and ventricular septal defect. Moreover, 4D ultrasound examination with STIC and B-flow imaging is
apparently able to facilitate identification of the anatomical features of total anomalous pulmonary venous
connection [57]. The 4D echocardiography with STIC and B-flow may provide a novel and unique information for
the assessment of fetal cardiac blood flows and hemodynamics, and appears promising as an adjunct to Doppler
evaluation of blood flow in the fetal heart [58].
Figure 29 & Video clip 29: 4D echocardiography with B-flow and STIC observation of the normal fetal heart. LA, left atrium;
LV, left ventricle, RA, right atrium; RV, right ventricle. a, diastolic phase; b, systolic phase.
Figure 30 & Video clip 30: 4D echocardiography with B-flow and STIC observation of digital casts of the normal fetal outflow
tracts at 22 weeks of gestation. Ao, aorta; LV, left ventricle; PA, pulmonary artery; RV, right ventricle.
Figure 31 & Video clip 31: 4D echocardiography with B-flow and STIC observation of extracardiac fetal vessels at 17 weeks of
gestation. Ao, aorta; BCA, brachiocephalic artey; DA, ductus arteriosus; DAo, descending aorta; IVC, inferior vena cava; LCCA,
lefe common carotid artery; LSA, left subclavian artery; LV, left ventricle; PA, pulmonary artery; RV, right ventricle. (Courtesy
by GE Yokogawa Medical Systems, Tokyo, Japan)
Figure 32 & Video clip 32: 4D ultrasound with B-flow and STIC observation of the normal umbilical cord at 31 weeks of
gestation. UA, umbilical artery; UV, umbilical vein.
Figure 33 & Video clip 33: 4D ultrasound with B-flow and STIC observation of the single umbilical artery (UA). UV, umbilical
vein.
3.7. Inversion Mode

The inversion mode is a novel post processing tool that inverts the gray scale of the volume voxels [59, 60].
Therefore, anechoic structures such as the heart chambers, vessel lumen, stomach, gallbladder, renal pelvis, and
bladder appear echogenic in the rendered images, whereas structures that are normally echogenic before gray scale
inversion (e.g., bones) appear anechoic [54]. Recent reports have shown the role of this technique in visualizing
cardiac chambers, great vessels, and systemic venous connections in normal fetal heart and congenital heart
anomalies (Figs. 34-40 and Video clips 34-40) [12, 54, 59, 61-63]. The main advantage of this technique is that the
image is similar to that acquired by power Doppler but without the difficulties encountered in adjusting the image
[12]. The volume can be acquired in grey scale as a 3D static or as a STIC volume at a high frame rate and
resolution. The application of inversion mode with STIC generates information about the anatomy and pathologic
characteristics of the fetal heart (digital casts) that cannot be obtained with 2D fetal echocardiography [54].
Figure 34 & Video clip 34: 4D inversion mode with STIC observation of normal fetal heart at 20 weeks of gestation. Ao, aorta;
LA, left atrium; LV, left ventricle, PA, pulmonary artery; RA, right atrium; RV, right ventricle. a, diastolic phase; b, systolic
phase.
Figure 35 & Video clip 35: 4D inversion mode with STIC observation of normal fetal heart at 31 weeks and 2 days of gestation.
Ao, aorta; LV, left ventricle, PA, pulmonary artery; RA, right atrium; RV, right ventricle.
Figure 36 & Video clip 36: 4D inversion mode with STIC observation of normal fetal heart and great vessels at 20 weeks of
gestation. BCA, brachiocephalic artey; DAo, descending aorta; LCCA, lefe common carotid artery; LSA, left subclavian artery;
LV, left ventricle; PA, pulmonary artery; RV, right ventricle.
Figure 37 & Video clip 37: 3D inversion mode observation of normal fetal heart and great vessels at 22 weeks of gestation. Ao,
aorta; BCA, brachiocephalic artey; DA, ductus arteriosus; DAo, descending aorta; LCCA, lefe common carotid artery; LV, left
ventricle; PA, pulmonary artery; RPA, right pulmonary artery; RV, right ventricle.
Figure 38 & Video clip 38: 4D inversion mode with STIC observation of great vessels in a case of hypoplastic left heart
syndrome at 32 weeks and 3 days of gestation. Ao, aorta; DAo, descending aorta; LV, left ventricle; PA, pulmonary artery; RA,
right atrium; RV, right ventricle.
Figure 39 & Video clip 39: 3D inversion mode observation of great vessels in a case of hypoplastic left heart syndrome at 37
weeks of gestation. Ao, aorta; LV, left ventricle; PA, pulmonary artery; RV, right ventricle.
Figure 40 & Video clip 40: 4D inversion mode with STIC observation of great vessels in a case of double-outlet right ventricle at
32 weeks of gestation. Great arteries left from the right ventricle (RV) in parallel were clarly shown. Ao, aorta; PA, pulmonary
artery.
3.8. Volumetry
There have been five reports on fetal ventricular volume measurements using 4D echocardiography with STIC in
normal fetuses and fetuses with CHD [63-68]. However, there is a lack of uniformity in methodology of
measurements. The first method was the parallel (or multiplanar) technique [64, 68], the second the rotational
technique with VOCAL (Virtual Organ Computer-Aided Analysis, GE Healthcare, Milwaukee, WI, USA) [65, 67],
and the third the inversion mode with VOCAL [66], respectively (Fig. 41). There was a difference for predicted
values of the fetal cardiac stroke volume during normal pregnancy among three studies (Fig. 42) [65, 67, 68]. Further
studies involving a larger sample size are needed to assess the reliability and reproducibility of fetal 4D
echocardiographic ventricle volumetry.
Figure 41: Fetal ventricular volumetry using 4D echocardiography with STIC is shown in a normal fetal heart at 20 weeks`
gestation. Left and right ventricular stroke volumes in diastole and systole were calculated using the rotational technique with
VOCAL and the inversion mode with VOCAL, respectively. LV, left ventricle; RV, right ventricle.
Figure 42: Left (LVSV) and right ventricular stroke volume (RVSV) values at different gestational ages in each different study.
4. CONCLUSION
This chapter focused on 3D/4D sonographic studies on the fetal heart and blood vessels. Many new technologies
shown in this chapter are the latest developments in 3D/4D ultrasound, and is providing clinicians a new, and
arguably much improved, view of the complexities and interrelationships of fetal cardiovascular anatomy
noninvasively. The influence on fetal cardiology by these advances in echo technologies might include (1) unique
information on normal and abnormal intracardiac anatomy, (2) real-time 3D observation of in utero procedure for
CHD, (3) quantitation of the fetal ventricle’s pumping ability (accurate measurements of ventricular volume and
ejection fraction), (4) possibility to image color/power flow Doppler in 3D/4D for improved spatial orientation of
regurgitant jets and shunt flows, (5) evaluation of the fetal heart in the first trimester, (6) fetal screening for CHD,
and (7) excellent imaging of complex CHD. The present and future application of these new modalities to the
prenatal diagnosis of fetuses with congenital heart disease might be promising. However, this is not to imply that
these new modalities will replace conventional 2D fetal echocardiography. These novel techniques may assist in the
prenatal diagnosis of fetal cardiovascular anomalies, and offer the potential advantages relative to conventional 2D
fetal echocardiography and color Doppler flow mapping.
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CHAPTER 5
Fetal Weight Estimation and Organ Volume Measurement by Three-Dimensional
Ultrasonography
Rodrigo Ruano*
Obstetrics Department, Faculty of Medicine of the University of São Paulo, São Paulo, Brazil
Abstract: With great advancement in medical imaging methods, it is possible to measure the volume of fetal
organs and structures. Two principal techniques have been described, the ‘parallel technique’ and the ‘rotational
method’, but the latest one is more used over the world in clinical practice because of being easier and faster as
well as allowing corrections on the multiplanar imaging. Recent studies have been using 3DUS in order to
incorporate the soft-tissue thickness into the mathematical formulas to estimate fetal weight. A few equations have
been reported which are present in this present chapter. 3DUS can also be applied for estimating fetal organ
volumes. Fetal lung volumes can be useful for the prediction of pulmonary hypoplasia in thoracic malformations,
while fetal heart volume for fetal heart function. To assess the status of fetal growth and nutrition, fetal liver has
been proposed. Fetal renal volumes may be an interesting tool for the monitoring of renal conditions, including
nephromegaly, hypoplasia and hydronephrosis. Fetal adrenal gland volumes could be of interest to evaluate
adrenal tumors and to predict labor, since adrenal hormonal changes are implicated in triggering labor. Fetal brain
volumes are also suggested to provide an insight into the nature of abnormal fetal growth. In conclusion, 3DUS
can be indicated to improve the prediction of fetal organ dysfunction and weight disturbances.
1. INTRODUCTION
The latest decade is marked by the greatest technological advancement in medical imaging methods. The three-
dimensional ultrasonography (3DUS) represents one of these advances, since it contributes to improve the imaging
quality by giving a new option to evaluate a specific organ or part of it in three orthogonal plans at the same time or
even on a three-dimensional image (rendered mode). Besides, this method allows measuring the volumes of the
organs with new faster technologies, such as the rotational technique, which may be more precise than only using
diameters in two dimensional views. This possibility may be useful especially in Fetal Medicine and in modern
Obstetrics, since it can be applied for the evaluation of fetal organ volumes and growth.
Many studies have been published regarding the potential useful of the volumetric assessment by 3DUS in Fetal
Medicine during this decade. The main interest may be in evaluating fetal growth and fetal organs, which may
improve the diagnosis of macrossomia or growth restriction and the prognosis of few fetal malformations such as the
prediction of pulmonary hypoplasia.
This chapter will present the different methods of assessing volumes by 3DUS and its potential clinical applications
in actual Fetal Medicine.
2. DIFFERENT METHODS TO CALCULATE THE VOLUME USING THE THREE-DIMENSIONAL

ULTRASONOGRAPHY
Basically there are two simple and direct methods to assess the fetal organ volume using the three-dimensional
ultrasound approach [1]. The first one, which is the oldest method, consists in adding together the areas of serial
parallel slices of the studied organ. The “technique of the parallel slices” is based on “cutting” the organ in many
slices and measuring the areas from one side to another with specific pre-established thickness (Fig. 1). The main
disadvantage of this method is that it may be difficult for small organs with irregular shapes [1]. Other limitations are
described such as the impossibility of repairing one incorrect area contouring.
*Address Correspondence to Rodrigo Ruano: Obstetrics Department, Faculty of Medicine of the University of São Paulo, São Paulo, Brazil;
Email: rodrigoruano@hotmail.com; rodrigoruano@usp.br
178 Current Topics on Fetal 3D/4D Ultrasound Rodrigo Ruano
Figure 1: 3DUS parallel slices technique.
More recently, a specific organ volume can be assessed by the rotational technique, which has become possible
through the introduction of the “Virtual Organ Computer-aided AnaLysis” (VOCALTM) imaging program, an
extension of the 3D View TM (GE, Kretztechnik, Zipf, Austria). This method allows measuring the organ volume by
fixing one axis and then serial contouring the organ surface after rotating the volumetric image (Fig. 2). The
volumetric image can be rotating using different angles. This is faster than the first method and has the great
advantage over the other in allowing corrections and verifications on the three-dimensional image. Despite of many
studies have been demonstrating similar values, variations and reproducibility (agreement) with these two methods,
nowadays the “rotational technique” is more employed and preferable due to its facilities.
3. MEDICAL APPLICATIONS OF THE THREE-DIMENSIONAL VOLUMETRIC EVALUATION

3.1. Fetal Weight Estimation
One of the main objectives of the prenatal care is the correct detection of fetal growth abnormalities. The large
number of methods published in this respect is a clearly evidence of the importance of fetal weight estimation during
prenatal care. Both fetal macrossomia and growth restriction increase perinatal morbidity and mortality. Fetuses with
growth restriction are at increased risk of hypoxia and perinatal deaths. On the other hand, macrossomic fetuses are
associated with increased risk of cesarean-section, postpartum hemorrhage and maternal-fetal injuries. Macrossomic
fetuses are generally associated with shoulder dystocia leading to clavicular fracture and brachial plexus injury.
Two-dimensional ultrasonography (2DUS) is applied routinely with this purpose. It estimates fetal weight indirectly
by measuring defined segments of the body and then using specific mathematical equations, appropriate tables and
integrated computer programs. The most frequently used fetal parameters are the biparietal diameter (BPD), head
Fetal Weight Estimation and Organ Volume Measurement Current Topics on Fetal 3D/4D Ultrasound 179
circumference (HC), abdominal circumference (AC) and femur length (FL) (Fig. 3). There are so many formulas for
estimating fetal weight which is clear evidence that none of those is accepted universally. All these formulas for fetal
weight estimation have a mean error of 7-10%, even in ideal ultrasound conditions.
Figure 2: 3DUS rotational technique rendered imaging of right and left fetal lung volumes.
The reason for the high error of these formulas may be the fact that none of these established equations takes the
soft-tissue thickness into account. It is known that fetal fat deposition represents approximately 90% of caloric
accretion at term and that neonatal fat mass constitutes 12-15% of birth weight. There have been many studies using
different methods to take the soft-tissue content into account on 2DUS, especially by including the limb diameters,
with varying results.
Figure 3: Fetal parameters for fetal weight estimation. A. Biparietal diameter and head circumference. B. Abdominal
circumference. C. Femur length.
Recently, with the advent of new volumetric methods using 3DUS technology, measurements of circumference and
volume have become possible and reproducible through the three orthogonal sections of the specific fetal organ.
Regarding the potential use for the estimation of fetal weight, the main interest becomes the possibility of measuring
fetal limb diameters and volumes on these sections, which has the advantages of being more efficient and faster than
the 2DUS technologies [2-10].
Table 1: Fetal weight estimation formulae using 3DUS measurements
Author Regression Equation

Lee et al. 2001 [2] FW= 20.95 x Tvol + 113.571 x AC - 2375.068
LogFW= 11.1372 x BPD2 - 67.2281 x BPD + 1.2175 x AC2 - 17.3004 x AC - 0.0490 x Tvol2 + 25.3052 x
Lee et al. 2006 [3]
Tvol + 285.429
FW= 656.41 + 1.8321 x ABDvol + 31.1981 x HC + 5.7787 x FEMvol + 73.5214 x FL + 8.3009 x AC -

Schild et al. 2008 [5]
449.8863 x BPD + 32.5340 x BPD2
FW= 2088.4904 + 81.0519 x HC - 0.1214 x HC2 - 69.0966 x AD + 0.4741 x AD2 + 6.4044 x Tvol + 0.0534 x
Lindell & Marsal 2009 [4]
ABDvol
FW: fetal weight; BPD: biparietal diameter; HC: head circumference; AC: abdominal circumference; FL: femur length; Tvol: thigh volume;
ABDvol: abdominal volume.
In order to improve the accuracy of estimating fetal weight, fetal limb volumes have been measured (Figs. 4 and 5)
and introduced in the mathematical formulas (Table 1). Reference values of humerus volumes throughout gestational
age are shown in (Table 2).
Figure 4: Fetal tight volume. A. sagital section. B. transverse section. C. coronal section. D. rendered imaging.
Table 2: Percentiles of fetal humerus volume (cm3) estimated by 3DUS using the rotational technique (VOCALTM) in accordance
to gestational age in weeks
Fetal humerus volume (cm3)
Centiles
GA 10% 50% 90%
20 0.71 0.77 0.82

22 0.86 0.97 1.07
24 1.05 1.20 1.35
26 1.28 1.48 1.67
28 1.54 1.78 2.02
30 1.84 2.12 2.41

32 2.17 2.50 2.83
34 2.54 2.91 3.29
36 2.94 3.36 3.79
38 3.38 3.85 4.32
40 3.85 4.36 4.88
Modified from Chang et al., Ultrasound in Medicine and Biology, 2005 [8].
Figure 5: Fetal arm volume. A. sagital section. B. transverse section. C. coronal section. D. rendered imaging.
3.2. Fetal Organ Volumes

Three-dimensional ultrasound (3DUS) was first introduced during the 1980s and has gained increasing acceptance in
obstetrics as technological improvement. Its use has revolutionized the prenatal detection of fetal structural
anomalies, growth aberrations and multiple gestations. In recent years, 3DUS has undergone rapid advances and
continues to progress quickly. More recently, one of its most promising applications in Obstetrics is the estimation of
fetal organ volumes. With the advent of 3DUS, studies of precise quantitative measurements of the fetal organ
volumes has been published, including heart volume, liver volume, lung volume, brain volume, renal volume and
adrenal volume. Unquestionably, 3DUS of fetal organs is gaining increasing importance in prenatal diagnosis and
will likely become an integral part of it in the near future.
The essential prerequisites for measurement of a fetal organ volume are: first, acquisition of the volume with ‘the
organ of interest’ facing the transducer, second, this acquisition must be in the absence of fetal movements, and third,
accurate definition of the whole organ with good identification of its borders. Gestational age may interfere with the
quality of the volumetric acquisition and, therefore, posterior analysis, depending on the ‘organ of interest’. For
example, lung volumes are more reproducible before 32 weeks differently of the kidney volumes. Other important
point is that acquisition and volumetric analysis depend on the amniotic fluid and other organs shadows.
3.2.1. Fetal Lung Volumes

Precise lung volume measurements may be useful for the prediction with more accurate in conditions associated with
pulmonary hypoplasia such as congenital diaphragmatic hernia and oligohydramnios. Conventional two-dimensional
ultrasound (2DUS), which is used routinely in Obstetrics, has proved to be insufficiently reliable to diagnose and
predict prognosis of determinate congenital malformation, for example, in fetuses at high risk for pulmonary
hypoplasia. Recent studies have indicated the value of 3DUS for this purpose [11-25]. This technology has the same
advantages as 2DUS of cost-effectiveness, feasible and speed of use, and patient acceptability, but, in addition,
enables visualization of perpendicular planes simultaneously (multiplanar imaging) and measurement of the volume
of different organ systems (volume rendering).
Nowadays, studies demonstrate that both methods of measuring fetal lung volumes can be used, the parallel slices or
the rotational technique. However, the rotational technique is preferable for small and irregular lungs, especially to
evaluate lung volumes in congenital diaphragmatic hernia (Fig. 6).
Figure 6: Fetal lung volume. A. transverse section. B. sagital section. C. coronal section. D. rendered imaging.
Assessing fetal lung volumes has been shown to be one of the best ways to predict neonatal prognosis in cases with
congenital diaphragmatic hernia [26-29]. The importance of predicting neonatal outcome in those fetuses is based on
the possibility to select cases for antenatal interventions. Actually, fetuses with congenital diaphragmatic hernia
presenting worse prognosis with high risk to develop severe pulmonary hypoplasia after birth may benefit from
transitory tracheal occlusion during fetal life [30-36]. The advantages of evaluating fetal lung volumes by 3DUS over
assessing measurements on 2DUS are that the entire lung is considered in one image alone and that the lung
ipsilateral to the diaphragmatic defect may be included in the analysis.
Predicting the severity of pulmonary hypoplasia may also be useful in fetuses with large hyperechogenic pulmonary
lesions (adenomatoid malformation or pulmonary sequestration). For those fetuses, depending on the severity of the
pulmonary hypoplasia, a few cases will benefit for early postnatal intervention which is EXIT (Ex-utero Intrapartum
Treatment) and ECMO (extracorporeal membrane oxygenation) [37-39].
More recent studies have also suggested that fetuses with very early and prolonged premature rupture of the
membranes may also benefit from fetal tracheal occlusion [40-41]. Fetal lung volumetric analysis may also be useful
for the selection process in those cases.
There are so many reports on normal values and ranges of fetal lung volumes throughout gestational age. We have
demonstrated that the right, left and total lung volumes vary from 5.37cm3, 4.66cm3 and 9.95cm3 at 20 weeks to
46.6cm3, 37.34cm3 and 84.35cm3 at 37 weeks, based on mathematical formulas: right lung volume =exp(4.07/[1 +
exp(21.90 – gestational age/5.44)]); left lung volume = exp(3.82/(1 + exp[22.03 – gestational age/5.17)]); and total
lung volume =exp(4.72/[1 + exp(20.30 – gestational age/6.05)]) (Table 3) [24].
Table 3: Percentiles of fetal lung volume (cm3) estimated by 3DUS using the rotational technique (VOCALTM) in accordance to
gestational age in weeks
Right fetal lung volume (cm3) Left fetal lung volume (cm3) Totalfetal lung volume (cm3)
Centiles Centiles Centiles
GA 10% 50% 90% 10% 50% 90% 10% 50% 90%
20 4.31 5.37 6.75 3.60 4.66 6.05 8.03 9.95 12.45
22 6.23 7.77 9.68 5.21 6.69 8.58 11.59 14.66 18.28
24 8.94 11.25 14.15 7.61 9.68 12.30 16.83 21.22 26.88
26 12.81 15.96 20.09 10.28 13.60 17.12 23.66 29.70 37.52
28 17.12 21.54 27.11 14.15 18.36 23.34 31.97 39.74 50.17
30 21.98 27.66 34.47 18.73 23.34 29.96 40.73 50.63 63.99
32 27.39 33.78 42.95 21.98 28.22 35.87 49.47 61.50 76.90
34 32.14 39.25 49.90 24.78 32.46 41.68 57.84 71.62 92.03
36 35.87 43.82 54.60 27.66 35.87 46.53 64.55 80.47 101.85
Modified from Ruano et al., Journal of Ultrasound in Medicine, 2006 [24].
3.2.2. Fetal Heart Volumes

Heart volume is a valuable parameter used in the evaluation of fetal heart condition, being mandatory for early
detection of impending collapse of fetal circulation. Its accurate assessment becomes indispensable for prenatal
diagnosis and management of fetal cardiac situations, such as in fetal high-output failure, hydrops fetalis and many
clinical pathological conditions. The classical method using 2DUS for assessing heart volume which assumes that
heart shape is spherical or elliptical is imprecise. However, before the advent of an appropriate non-invasive research
tool such as 3DUS, this was difficult to be evaluated in human fetuses.
Traditionally, fetal heart volume has been assessed by the equation: heart volume = 0.5233 x H1 x H2 x H2, where
H1 is the largest longitudinal diameter of the fetal heart at the four-chamber view and H2 is the largest transverse
diameter at the same plane.
Fetal heart volumes can be evaluated by the rotational technique on 3DUS (Fig. 7) [17-42]. There have been a very
few reports on normal values of fetal heart volume throughout gestational age. Fetal heart volume may vary from
0.63 (0.40-0.86) cm3 at 12 weeks to 26.60 (16.40-36.80) cm3 at 32 weeks (Table 4) [42].
Figure 7: Fetal heart volume. A. transverse section. B. sagital section. C. coronal section. D. rendered imaging.
3.2.3. Fetal Liver Volumes

Determination of fetal liver volume is very useful in assessing the status of fetal growth and nutrition. Fetuses with
intrauterine growth restriction or macrosomia are related to the change of liver volume. However, to measure human fetal
liver in utero precisely and noninvasively is not an easy task. In the past, many studies have performed several attempts to
indirectly assess liver size, using different parameters such as abdominal circumference and diameters (anteroposterior,
transverse and cephalocaudal) using 2DUS, and then multiplied by a constant which had been obtained from adult liver
studies, to estimate fetal liver weight. Currently, fetal liver volume is measured using its longest diameter, which may be
less reproducible. With the advent of three-dimensional ultrasound (3DUS) and the improvement of its technology, fetal
liver volume assessment becomes possible, easier and more reproducible (Fig. 8) [43-45]. Besides, it has become an easy
and noninvasive approach to obtain precise measurement of fetal liver volumes, and good correlation has been
established between liver volume and other fetal growth parameters.
Table 4: Percentiles of fetal heart volume (cm3) estimated by 3DUS using the rotational technique (VOCALTM) in accordance to
Fetal heart volume (cm3)

Centiles
GA 2.50% 50% 97.50%
12 0.40 0.63 0.86
14 0.17 0.53 0.88
16 0.46 1.14 1.81
18 1.24 2.42 3.61
20 2.44 4.33 6.23
22 4.04 6.83 9.62
24 5.99 9.87 13.80
26 8.24 13.40 18.60
28 10.80 17.40 24.00
30 13.50 21.80 30.10
32 16.40 26.60 36.80
Modified from Peralta et al., Ultrasound in Obstetrics and Gynecology, 2006 [42].
There have been very few studies reporting on normal ranges of fetal liver volumes assessed by 3DUS. Fetal liver
volumes range from 11.73cm3 at 20 weeks to 131.51cm3 at 40 weeks (Table 5) [44].
3.2.4. Fetal Renal Volumes

Renal diseases, both morphologic or functional, are not uncommon in fetal life and some of them might be treatable
or carry a better outcome if detected earlier. Evaluating fetal renal size may be a valuable tool in the detection and
monitoring of renal conditions, including nephromegaly, hypoplasia and other anomalies. Besides, assessing fetal
renal size may be useful to evaluate renal function. Konje et al. [46] demonstrated that fetal renin concentration is
related to fetal size. The classical way of measuring fetal renal size using 2DUS is not precise. With the application
of 3DUS, it becomes feasible and more accurate by estimating fetal renal volumes (Fig. 9).
There have been very few reports on the distribution of fetal renal volumes throughout gestational age. Hsieh et al.
[47] describe good correlation between fetal renal volumes and gestational age, suggesting the following
mathematical formulas: right fetal renal volume = 0.4032 x gestational age – 6.2097; left fetal renal volume = 0.3954
x gestational age – 6.3068. Yu et al. [48] report the following mathematical formulas: right fetal renal volume =
0.74053 x gestational week – 13.318; left fetal renal volume = 0.76093 x gestational age – 13.421 (Table 6).
3.2.5. Fetal Adrenal Gland Volumes

The fetal adrenal glands are important organs to fetal growth. In utero, the normal fetal adrenal glands can be
scanned using 2DUS as hypoechogenic structures located immediately above the fetal kidneys bilaterally. Some
pathologic conditions of fetal adrenal glands, such as adrenoblastomas or neuroblastomas, can be diagnosed on
ultrasound exams. These fetal adrenal tumors may have abnormal sizes. Therefore, measuring this gland volume may
be useful for the early diagnosis of this condition.
Table 5: Percentiles of fetal liver volume (cm3) estimated by 3DUS using the rotational technique (VOCALTM) in accordance to
Fetal liver volume (cm3)

Centiles
GA 10% 50% 90%
20 5.05 11.84 18.63
22 11.82 19.17 26.51
24 17.00 24.90 32.80
26 21.73 30.18 38.63
28 27.18 36.13 45.13
30 34.32 43.38 53.44
32 44.46 54.57 64.69
34 58.67 69.34 80.00
36 78.08 83.30 100.53
38 103.83 115.61 127.38
40 137.05 149.38 161.71
Figure 8: Fetal liver volume. A. transverse section. B. sagital section. C. coronal section. D. rendered imaging.
Table 6: Percentiles of fetal renal volumes (cm3) estimated by 3DUS using the rotational technique (VOCALTM) in accordance to
Right fetal renal volume (cm3) Left fetal renal volume (cm3)

Centiles Centiles
GA 10% 50% 90% 10% 50% 90%
20 0.58 1.49 2.41 0.90 1.80 2.70
22 1.73 2.97 4.21 1.96 3.32 4.68
24 2.89 4.46 6.02 3.03 4.84 6.65
26 4.05 5.94 7.83 4.10 6.36 8.63
28 5.20 7.42 9.63 5.16 7.88 10.61
30 6.36 8.90 11.43 6.23 9.41 12.58
32 7.52 10.38 13.24 7.30 10.93 14.60
34 8.68 11.86 15.04 8.36 12.45 16.54
36 9.83 13.34 16.85 9.43 13.97 18.51
38 10.99 14.82 18.65 10.50 15.50 20.49
40 12.15 16.30 20.46 11.57 17.16 22.47
Modified from Yu et al., Ultrasound in Medicine and Biology, 2000 [48].
Figure 9: Fetal renal volume. A. sagital section. B. transverse section. C. coronal section. D. rendered imaging.
Other interest in assessing fetal adrenal gland volumes can be related to a potential use in predicting labor, especially
preterm labor. Several mechanisms have been implicated in triggering preterm labor, like genetic predisposition,
decidual hemorrhage, fetal stress and inflammation / infections. In most animal species, the fetal hypothalamic-
pituitary-adrenal axis plays a special role in the initiation of parturition.
The irregular shape of fetal adrenal glands makes difficult to evaluate its volume using 2DUS. With the advent of
3DUS, using the rotational technique, it becomes feasible and noninvasive method to evaluate its volumes (Fig. 10)
[49, 50]. Reference values may vary according to the following equation: adrenal gland volume = -0.2683 x
gestational age + 0.0082 x (gestational age)2 + 3.1927 (Table 7) [50].
Figure 10: Fetal adrenal gland volume. A. sagital section. B. transverse section. C. coronal section. D. rendered imaging.
3.2.6. Fetal Brain Volumes

Both fetal biparietal diameter and fetal head circumference are standard parameters in establishing normal and
abnormal fetal biometry. Fetal brain volume measurement in conjunction with fetal liver volume determination could
provide insight into the nature of abnormal fetal growth. Up to date, there have been few studies reporting on the use
of 3DUS to assess fetal brain volume (Fig. 11) [51]. Fetal brain volumes vary from 53cm3 at 20 weeks to 316cm3 at
34 weeks according to the following equation: fetal brain volume = 0.75 x gestational age -7.71 (Table 8) [51].
4. CONCLUSIONS
The advance in quality and options of fetal imaging will lead to a better prenatal investigation of organ functions and
growths with consequent improvement in predicting fetal organ dysfunction and weight disturbances. 3DUS
volumetric methods are on evaluation regarding these aspects, but the studies published up to date have shown to be
the future tool for those purposes.
Table 7: Percentiles of fetal adrenal gland volumes (cm3) estimated by 3DUS using the rotational technique (VOCALTM) in
accordance to gestational age in weeks
Fetal adrenal gland volume (cm3)
Centiles
GA 10% 50% 90%
22 0.86 1.24 1.63
24 1.01 1.45 1.90
26 1.22 1.73 2.25
28 1.50 2.08 2.65
30 1.85 2.49 3.13
32 2.26 2.96 3.67
34 2.74 3.51 4.27
36 3.28 4.11 4.94
38 3.89 4.78 5.68
40 4.56 5.52 6.48
Figure 11: Fetal brain volume. A. transverse section. B. sagital section. C. coronal section. D. rendered imaging.
Table 8: Percentiles of fetal brain volumes (cm3) estimated by 3DUS using the rotational technique (VOCALTM) in accordance to
Fetal brain volume (cm3)

Centiles
GA 5% 50% 95%
20 38.00 53.00 71.00
22 58.00 77.00 100.00
24 82.00 116.00 133.00
26 109.00 139.00 173.00
28 140.00 177.00 218.00
30 174.00 219.00 269.00
32 211.00 265.00 326.00
34 252.00 316.00 389.00
Modified from Roelfsema et al., American Journal of Obstetrics and Gynecology 2004 [51].
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Ultrasound Med Biol 2003; 29(9): 1267-72.
CHAPTER 6
Placental Volume and Circulation: The New Concept of ‘Virtual Placental
Biopsy’
Luis T. Mercé1,* and María J. Barco2
1 2
Department of Obstetrics and Gynaecology, International Ruber Hospital, Madrid, Spain and Bolonia
Gynaecological Medical Center, Zaragoza, Spain
Abstract: Three-dimensional power Doppler angiography allows villous vessels to be evaluated ‘directly’, and in
this way should be able to establish both normal development characteristics and anomalies. The study of
placental circulation is of interest because the fetal growth restriction has been associated with deficient
development of the placental vascular tree. Placental vascular patterns acquired using 3D color angiography at
various stages of pregnancy reflects the development of the villous tree and intervillous space in vivo faithfully.
‘Virtual placental biopsy’ consists of taking a sample of the thickness of the placenta using 3D power Doppler
angiography to study the volume and circulation of the placenta. Placental volume increases gradually and
significantly with gestational age. 3D power Doppler indices are also significantly related to gestational age,
though it is the flow index which shows the best correlation (r = 0.58). 3D power Doppler indices are decreased in
IUGR when umbilical Doppler is altered, and we should be evaluated if these indices are predictive markers of
this fetal growth abnormality.
1. INTRODUCTION
Fetal growth is directly related to the development of the placental vascular tree. Poorly-vascularized villi will lead
to fetal growth restriction. Up to now, Doppler imaging of the umbilical artery has been able to give only indirect
information on vascular alterations of the villi. This has the disadvantage that a perfusion deficit of more than 50% of
the villous vascular tree is needed in order to give rise to increased resistance of the umbilical artery. This is where
3D power Doppler angiography comes into its own. This technique allows villous vessels to be evaluated ‘directly’,
and in theory should be able to establish both normal development characteristics and anomalies. If these
expectations are justified, the approach to prediction and diagnosis of intrauterine fetal growth problems in our
exploratory routine will change.
This chapter describes the physiopathological bases of the application of 3D power Doppler ultrasound and
angiography to the study of placental circulation. The ‘virtual placental biopsy’ technique, a practical solution for
exploring the placental vascular tree, is explained, and normal morphological and quantitative development via 3D
power Doppler indices are described for placental circulation throughout normal pregnancy. The idea of how this
new exploration might fit into the monitoring and oversight of fetal growth is also introduced.
2. PHYSIOPATHOLOGICAL BASES
The study of placental circulation is of interest for clinical application for two main reasons. Firstly, fetal growth
abnormality has been associated with deficient, abnormal development of the placental vascular tree [1, 2]. Secondly,
it has been shown that the decrease in intraplacental blood flow can be anticipated on the basis of increased umbilical
resistance in the cascade of vascular alterations which occur in restricted fetal growth [3].
In pregnancies with restricted fetal growth, there is anomalous development of peripheral villi, which show a sparse
capillary network with few branches and few loops [4-7]. The vessels of the tertiary villi are characterized by thick
walls and a narrower lumen, while terminal villi show reduced development. In general, the villous vascular tree
shows a deficit of branching of the villi capillaries, which will appear elongated, like threads [2]. These
characteristics are normally associated with early-onset restricted fetal growth with greatly increased umbilical artery
Address correspondence to Luis T. Mercé: Department of Obstetrics and Gynaecology, International Ruber Hospital, Madrid, Spain; E-mail:
ltmerce@sego.es
Placental Volume and Circulation Current Topics on Fetal 3D/4D Ultrasound 193
resistance (absence of the diastolic component or reversed diastolic flow). The impairment to the villous vascular
tree will result in reduced oxygen removal at the intervillous space (placental hyperoxia), which leads to post-
placental fetal hypoxia [8]. When the opposite happens, and restricted fetal growth begins late, as in pre-eclampsia,
and the diastolic component is preserved in the umbilical Doppler, there is increased branching of the villous
vascular tree. In other words, there will be an adaptation response to reduced uteroplacental flow (pre-placental
hypoxia) [8]. In either case, as has recently been shown, it is restricted fetal growth rather than pre-eclampsia which
causes alterations in the villous vessels [9].
As stated above, the physiopathological basis underlying increased vascular resistance in the umbilical artery in
restricted intrauterine growth is the alteration of the villous vascular tree. However, the resistance of the umbilical
artery will only increase when 70% of placental vessels are affected [10-13]. This explains why umbilical Doppler
has very low sensitivity for diagnosing restricted intrauterine growth, or in other words reflects abnormal vascular
changes in the villous tree late [3]. With color Doppler and power Doppler, it has been shown that the number of
arteries and villous branches which can be detected in restricted fetal growth is significantly lower than in normal
pregnancy, and that in contrast umbilical vascular resistance and resistance of the villous arteries is not significantly
increased [14]. As a result, alteration of placental circulation precedes increased resistance of the umbilical artery.
Three-dimensional power Doppler angiography allows the villous vascular tree to be viewed at various stages of the
development of the human placenta. Konje et al. [15] have compared the vascular maps obtained by 3D angiography
with classical histological patterns and electronic microscopy patterns of normal placentas. This has yielded a
description of the following phases in the development of the villous vascular tree (Fig. 1):
- Week 13: The villous tree consists of thick (200-400 μm), immature intermediate villi with few
branches. Vessels are present only in stems close to the chorionic plate, and cross approximately one
third of the intervillous space. The intervillous space at this stage is wide (150-250 μm).
- Week 20: The placenta consists of wide villi, with thick villous vessels (diameter greater than 200 μm).
The intervillous space gradually shrinks as it is filled by villous branches.
- Week 24: At this stage the first mature, narrow villi and the terminal villi develop. The villous tree
from the chorionic plate to the basal plate can be viewed for the first time, though with few branches
and a thickness of less than 1 mm in angiography. The width of the intervillous space decreases to 60-
150 μm.
- Week 32: The thickness of the placental vessels increases throughout the placenta. They acquire their
characteristic tree shape, with a thickness of up to 2-4 mm. The intervillous space continues to shrink.
- Week 38: The villous tree is fully developed. The peripheral branches form a very dense cluster of villi
around thicker stems. The central trunk may be up to 3-5 mm wide, while the branches reach 1-2 mm
in angiography. The intervillous space cannot be viewed, as it is too narrow and intervillous circulation
is very slow.
(Table 1) shows the thickness of the intervillous space and the villous trunks and branches. Angiography was able to
identify all vessels with a lumen greater than 200 μm. Only thinner villous stems and terminal branches could not be
identified with this technique. This means that the placental vascular patterns acquired using 3D color angiography at
various stages of pregnancy reflect the development of the villous tree and intervillous space in vivo faithfully [15].
3. VIRTUAL PLACENTAL BIOPSY TECHNIQUE AND VALIDATION
As described above, 3D power Doppler ultrasound and angiography can give a very faithful representation of the
villous tree throughout pregnancy. However, from the point of view of application it currently has a significant
technical disadvantage. Current ultrasound waves only allow the whole diameter and volume of the placenta to be
explored during the first trimester of pregnancy (Fig. 2). From the second trimester onwards, the 2D sweeping angle
and 3D volume acquisition angle are not sufficient to explore the whole placenta. In order to overcome this
194 Current Topics on Fetal 3D/4D Ultrasound Mercé and Barco
disadvantage, the ‘virtual placental biopsy’ technique was created, using 3D power Doppler ultrasound and
angiography. Virtual placental biopsy consists of taking a sample of the thickness of the placenta using 3D power
Doppler ultrasound and angiography, in order to study the volume and circulation of the placenta. The VOCAL
program automatically calculates the volume of the placental sample and three 3D power Doppler indices:
vascularization index (VI), flow index (FI) and vascularization flow index (VFI) for intervillous and uteroplacental
circulation. The vascularization index (VI) measures the number of color voxels (smallest units of volume) in the
volume, representing the vessels in the tissue, and is expressed as a percentage (%). Flow index (FI) is the mean
color value in the color voxels, indicating the average intensity of blood flow, and is expressed as a whole number
ranging from 0 to 100. The vascularization flow index (VFI) is the mean color value in all the voxels within the
volume; it therefore represents both vascularization and blood flow. It is also expressed as a whole number ranging
from 0 to 100. It might be added that there is no reason a single sample should represent what is happening all over
the placenta and the placental vascular tree. However, this technique also allows various samples to be taken from
various parts of the placenta, particularly when 2D power Doppler exploration shows clear differences in the
distribution of the power Doppler map [16]. The biopsy can also be performed when the 2D power Doppler shows
more affected circulation. In any case, only practical experience will be able to determine what diagnostic strategy is
most suitable for each clinical situation.
Figure 1: cont….
Figure 1: Angiographic recreation (left-hand column) and electronic microscopy (right-hand column) of placental villi at 13 (A &
B), 20 (C & D), 24 (E & F), 32 (G & H) and 38 (I & J) weeks’ gestation. See text for explanation. Based on data of Konje et al
[15], modified and adapted by Luis E. Mercé.
Table 1: Mean width in μm of the intervillous space and fetoplacental villous arteries during normal pregnancy
Weeks’ gestation Intervillous space 1st-order branches 2nd- to 4th-order branches

≤ 12 >250 >100 ~ 100
13 150-250 100-250 100-150
20 100-200 200-400 100-250
24 60-150 300-600 300-400
32 30-60 300-800 300-600
38 16-32 500-1500 400-1000
Data adapted from Konje et al [15].
Power Doppler is chosen for angiographic examination of the placenta, due to its particular ultrasound
characteristics. Unlike conventional color Doppler, which uses average frequency to represent the color map, power
Doppler represents the vascular tree on the basis of the amplitude of the Doppler signal [17, 18]. This gives it great
sensitivity, and it represents a color map independent of the angle of insonation, with no aliasing. However, it does
have its disadvantages. For example, the signal decreases with the depth of the vessel, and artifacts are caused by
movements. This means that volumes must be captured with no movement of the probe, and with the patient as still
as possible. To avoid artifacts, some authors also recommend that scanning be performed using low-resolution rapid
acquisition [19, 20].
The ‘virtual placental biopsy’ technique with the power Doppler angiography is performed as follows:
A)
Figure 2: cont….
B)
Figure 2: Multiplanar angiographic representation of intraplacental (intervillous) circulation at 7 (A) and 9 (B) weeks’ gestation.
Current ultrasound scans can only explore the whole placental volume during the first trimester of pregnancy.
1) The Doppler window is activated with particular adjustments, which will be used for all explorations:
pulse repetition frequency 600 Hz, wall filter 50 Hz. These characteristics ensure acquisition of an
adequate, reproducible color map of the villous tree, although up to 6% of volumes have been recorded
with artifacts (Fig. 3A).
2) The whole volume of the placenta is scanned with the power Doppler window, aiming to view all
vessels from the basal plate to the chorionic plate, including both. Unless the distribution of the color
map shows great heterogeneity, the central area of the placenta will be chosen as the biopsy site. This
is generally the thickest part of the placenta, where the highest vascular density is captured (Fig. 3B).
A
Figure 3: cont….
D
Figure 3: cont….
F
Figure 3: ‘Vascular biopsy’ of the placenta using 3D power Doppler angiography. A) The power Doppler window is activated on
the placenta thickness using a pulse repetition frequency of 600 Hz and a wall filter of 50 Hz; B) The whole placental volume is
scanned, and a 3D volume of the best-vascularized area in the centre of the placenta is obtained; C) Using the VOCAL program
off-line, the limits of the virtual axis are positioned between the basal and chorionic plates; D) A sphere is obtained automatically,
and it is checked that all the vessels in the placental volume are included, without the basal or chorionic plates; E) Angiographic
representation of the placental vessels captured in the biopsy; F) Finally, 3D power Doppler indices are calculated.
Although we recommend the sphere due to its simplicity, it is also possible to use the whole volume captured to
obtain the 3D power Doppler indices, as recommended by other authors [21] (Fig. 4).
B
Figure 4: A) Study of placental circulation by capturing the greatest volume of the centre within the ultrasound scan for each
pregnancy and gestational age; B) Multiplanar and surface angiographic representation using glass-body rendering of placental
vessels for the same case.
We validated the placental ‘vascular biopsy’ method by carrying out two consecutive studies using 3D power
Doppler angiography. A first study examined a normal placenta at 38 weeks’ gestation. Ten 3D volumes of the
vascular tree in the central part of the placenta were taken successively. Next, five consecutive measurements of the
3D Doppler indices were performed using the VOCAL program, for each volume. All these indices showed
intraclass correlation coefficients above 0.90 (22). In a subsequent study, 30 ‘virtual placental biopsies’ were taken in
the same number of normal pregnancies between 14 and 40 weeks, and two measurements were carried out in each
volume using the VOCAL program. The 3D power Doppler indices showed good intraobserver reproducibility, with
intraclass correlation coefficients close to 0.90, and average differences between two consecutive scans less than one
for all parameters. Placental volume, the grey index and the vascularization flow index are the parameters with the
best reproducibility and intraobserver agreement (Table 2) [23].
Table 2: Intraclass correlation coefficients, confidence interval and intraobserver differences (mean and SD) for 3D power
Doppler placental vascular examination parameters (n=60)
Parameter ICC 95% ICC confidence interval Mean difference SD

PV (ml) 0.98 0.96-0.99 0.04 1.47
GI (units) 0.94 0.88-0.97 0.44 1.56
VI (%) 0.88 0.76-0.94 -0.83 4.52
FI (units) 0.88 0.76-0.94 -0.52 2.82
VFI (units) 0.89 0.79-0.95 -0.31 1.71
PV: placental volume; GI: grey index; VI: vascularization index; FI: flow index; VFI: vascularization flow index; ICC: intraclass correlation
coefficient; SD: standard deviation.
Guiot et al. [16] have recently evaluated intra- and interplacental variability of 3D power Doppler indices using the
variation coefficient of five measurements (one central spherical sample, two peripheral samples and two
intermediate samples between the central and peripheral samples) in 30 pregnancies with intrauterine growth
restriction (IUGR) and 15 normal pregnancies between 23 and 37 weeks’ gestation. The index with the best
variability, both in normal pregnancies and in pregnancies with IUGR, was the flow index, while the vascularization
and vascularization flow indices had high intra- and interplacental variation coefficients. The variability was greater
in pregnancies with low or absent late diastolic velocities in the flow velocity wave of the umbilical artery. There
was no evidence that this depended on gestational age or posterior placenta location.
4. PLACENTAL CIRCULATION AND 3D POWER DOPPLER INDICES DURING NORMAL

PREGNANCY
Three-dimensional power Doppler angiography is currently the most suitable technique for exploring the placental
vascular tree. On the one hand it allows complete, detailed study of the various branches of the villous vessels [24,
25], and on the other hand it is also able to quantify placental circulation using the 3D power Doppler indices of the
VOCAL program [21].
This technique can be used to view first-, second- and third-order villous vessels [24, 25], achieving a higher viewing
percentage than 2D Doppler [25]. Two-dimensional power Doppler examination establishes that in normal
pregnancies villous arteries up to the fourth order can be evaluated, observing that the detection percentage for third-
and fourth-order villous arteries or terminal arteries typically grows between 28 and 38 weeks’ gestation [14]. As
described above, 3D power Doppler angiography can identify all vessels with a lumen greater than 200 μm. In our
experience, this technique makes it relatively simple to identify all vessels in the villous tree and in the chorionic and
basal plates during the third trimester of normal pregnancies (Figs. 5 and 6).
(Fig. 7) shows 3D angiographic maps between 16 and 40 weeks of normal pregnancy. As can be seen, before 20
weeks power Doppler signals come mainly from the vessels in the chorionic and basal plates, and only a few first-
order trunks are observed. From 26 weeks onwards, second- and third-order branches are observed. As they develop,
these occupy the whole intervillous space during the third trimester. The density of the villous vascular tree is very
high at full-term gestation, forming an overlapping network which barely leaves room for intervillous circulation.
Three-dimensional power Doppler indices enable placental circulation to be quantified. Thus the vascularization
index defines the number of vessels, the flow index expresses blood flow, and finally, the vascularization flow index
will indicate placental perfusion. Evaluation of 86 pregnancies has been used to confirm that the placental volume
studied using the ‘virtual placental biopsy’ technique increases gradually and significantly with gestational age.
Three-dimensional power Doppler indices are significantly related to gestational age, though it is the flow index
which shows the best correlation (r = 0.58). While the flow index shows a linear increase throughout pregnancy, the
vascularization index shows a clear dispersal of values, flattening out from the week 30 onwards and decreasing
from week 37 onwards. The vascularization flow index reflects the behavior of both these indices, vascularization
and flow, on which it is based (Table 3, Fig. 8) [26]. Similar results were obtained by Yu et al. [21], although these
authors do not explain how choices are made or what placental volume is taken as representing placental circulation.
Recently, Rizzo et al. [27] have evaluated placental circulation between weeks 11 and 14, confirming that all 3D
power Doppler indices increase significantly during this early stage of gestation.
Figure 5: Placental volume rotated and represented using glass-body rendering, which highlights the vessels in the chorionic and
basal plates of a placenta in the third trimester of pregnancy. VU: umbilical vessels; VC: chorionic vessels of placenta surface; EI:
intervillous space; AR: arcuate arteries; RA: radial arteries, which become uteroplacental arteries before emptying into the
intervillous space.
Table 3: Regression equations of placental volume and vascularization, flow and vascularization flow indices of placental
vascular biopsy by gestational age (weeks).
Parameter Constant b c SD r p
PV -13.375 0.893 - 117.20 0.46 < 0.01
VI -19. 668 2.144 -0.033 77.29 0.29 < 0.05
FI 17.930 0.565 - 53.98 0.58 < 0.01
VFI -6.530 0.678 -0.010 32.76 0.32 < 0.01
PV: placental volume; VI: vascularization index; FI: flow index; VFI: vascularization flow index; SD: standard deviation.
A B
Figure 6: cont….
C D
E F
Figure 6: Gradual development of the placental vascular tree, rendered to highlight possible divisions of villous vessels during
the course of a normal pregnancy. A) 14 weeks; B) 18 weeks; C) 22 weeks; D) 26 weeks; E) 34 weeks; F) 38 weeks. PB: basal
plate; PC: chorionic plate; VV1: first-order villous vessels; VV2: second-order villous vessels; VV3: third-order villous vessels;
TV: terminal vessels.
A
D
G
J
Figure 7: Multiplanar angiographic representation of placental circulation during normal pregnancy. A & B) 16 weeks; C & D)
20 weeks; E & F) 28 weeks; G & H) 34 weeks; I & J) 38 weeks.
100
Placental volume (PV, ml)

80 
60


40  
   

   
20     
   
    
  
  
    
  
  
     
 
0 
       
14 16 18 20 22 24 26 28 30 32 34 36 38 40 42
A Gestational age (weeks)
40
Vascularization index (VI, %)
35  
 
30 
   
25 
 

20 
  

15  



  

      
10  


 
  
     
 


5        
   


   
0 
 
14 16 18 20 22 24 26 28 30 32 34 36 38 40 42
B Gestational age (weeks)
60
50 
 
  
 
   
Flow index (FI)
  
40    
    


   
  
 



30       

   
   
     

 
20 
10
0
14 16 18 20 22 24 26 28 30 32 34 36 38 40 42
C Gestational age (weeks)
14
Vascularization Flow index (VFI)

12   
 
 
10  
 
     
8  
     
6  

   
 
4   
   
  
 

2     

 


  

   
0 
  
14 16 18 20 22 24 26 28 30 32 34 36 38 40 42
D Gestational age (weeks)
Figure 8: Volume and 3D power Doppler indices during normal pregnancy. A) Volume of placental biopsy; B) Vascularization
index; C) Flow Index; D) Vascularization Flow Index. Data taken from Mercé et al. 2005 [25].
Three-dimensional Doppler indices are significantly correlated with fetal biometric parameters, except
vascularization index and fetal weight. However, the strongest correlation is between flow index and biometric
variables. There is also a significant correlation between 3D Doppler indices and the umbilical artery resistance
index, although correlation is also stronger for the placental flow index (Table 4). Yu et al. [21] also find a positive
correlation between placental 3D Doppler indices and fetal biometric parameters.
Table 4: Correlation of placental volume and vascularization, flow and vascularization flow indices of placental vascular biopsy
with biometric parameters of fetal growth and umbilical Doppler (n=52).
Parameter BPD HC AC FL Weight URI

PV 0.46** 0.51** 0.46** 0.48** 0.44** -0.34**
VI 0.28* 0.27* 0.25* 0.27* 0.20 -0.24*
FI 0.64** 0.62** 0.64** 0.64** 0.60** -0.48**
VFI 0.33** 0.31** 0.31** 0.32** 0.27* -0.27*
BPD: biparietal diameter; HC: head circumference; AC: abdominal circumference; FL: femur length; US: umbilical systolic velocity; URI:
umbilical resistance index; PV: placental volume; VI: vascularization index; FI: flow index; VFI: vascularization flow index; * p < 0.05; ** p <
0.01.
5. CLINICAL APPLICATION IN INTRAUTERINE GROWTH RESTRICTION
As stated above, umbilical Doppler alterations reflect abnormal vascular changes in the villous tree at a late stage, which
inevitably gives it a low diagnostic sensitivity [3]. It must therefore be assumed that blood flow in the intraplacental
vascular tree may be affected in some cases in which umbilical Doppler readings are normal [14]. In fact, the
intraplacental vascular resistance obtained by multi-window spectral Doppler is more sensitive, and precedes umbilical
Doppler alterations in detecting fetal growth restriction [13]. It has also been shown that in pregnancies with fetal growth
restriction the number of first-, second- and third-order villous arteries is significantly reduced, and no fourth-order
vessels can be detected, despite showing normal umbilical resistance [14]. Lastly, 3D Doppler angiography can help us
distinguish between the causes of fetal growth restriction. While shortening and thickening of villous stems is observed in
placental restriction, in pre-placental growth restriction (anemia, pre-eclampsia) villi show advanced development even
though they are small and immature [15]. In some cases of fetal growth restriction, a clear decrease in the number of
branches of the villous vascular tree can be seen (Fig. 9). However, it is possible that 3D power Doppler indices of the
placental ‘vascular biopsy’ will contribute the most objective criteria to corroborate all these hypotheses. For this
purpose, a prospective study is needed which evaluates the predictive and diagnostic ability of this technique in a
population at risk of fetal growth restriction. This makes it essential that we know the normal curves of the
vascularization, flow and vascularization flow indices in normal pregnancy.
A
D
F
Figure 9: Multiplanar angiographic representation of placental circulation in restricted fetal growth. A & B) 28 weeks; C & D)
34 weeks; E & F) 38 weeks. Compare with angiographic maps of normal pregnancy (Fig. 7) for similar gestational ages.
Very interesting results were obtained recently by Guiot et al. [16], who used a ‘virtual placental biopsy’ technique
to show that the vascularization and vascularization flow indices were significantly lower than in control pregnancies
(15 cases) when the late diastolic velocities of the umbilical artery were lower (9 cases) or absent (15 cases). The
flow index showed a significant decrease only in pregnancies in which umbilical diastolic flow was absent.
One question which should be asked is when placental circulation should be evaluated to rule out any possible
alteration. If the aim is to determine whether the cause is placental or pre-placental, it would be sufficient to evaluate
placental circulation when fetal biometrics change, or even later. However, if the aim is to find a marker of fetal
growth restriction, it should be evaluated during the second trimester, before fetal measurements are affected
(Fig. 10). During this period, it may be inconvenient that under normal conditions the villous tree is not yet well
developed, but it is also possible that 3D power Doppler indices will be sufficiently sensitive to act as predictive
markers of this fetal abnormality.
Placental biopsy
Fetal biometry
PC Umbilical Doppler
20-24 w 28-32 w 34-38 w
UC F
G PP
Uterine Doppler 50%
R
AUARI
ACPR AEDVUA
AMCARI ADVRI
AUVV
15d 10d 5d 3d 2d 1d DELIVERY
REDVUA
ACTG
PUV
AAFI
B
Figure 10: A) Development of alteration in placental circulation and various diagnosis techniques in fetal growth restriction. PC:
circulation of placental villi; UC: uteroplacental circulation; FGR: fetal growth restriction; PP: placental perfusion. B) Sequence
of alteration of Doppler parameters in fetal growth restriction with hemodynamic decompensation. AUARI: increased umbilical
artery resistance index; ACPR: abnormal cerebroplacental rate; AMCARI: abnormal (reduced) middle cerebral artery resistance
index; AAFI: abnormal amniotic fluid index; ADVUA: absent diastolic velocities of umbilical artery; ADVRI: abnormal ductus
venosus resistance index; ACTG: abnormal fetal cardiotocography; AUVV: abnormal umbilical vein velocity; RDVUA: reversed
diastolic flow of umbilical artery; PUVF: pulsating umbilical vein flow.
Lastly, it should also be added, as has been shown with Doppler examination of the umbilical artery and the uterine
artery, that this examination should have a high negative predictive value. In other words, when normal placental
circulation is confirmed by ‘virtual placental biopsy’ of the villous vascular tree, the possibility of fetal growth
restriction that may affect the viability of the fetus ought to be very close to zero. To put it another way, a normal
placental vascular biopsy ought to be able to predict normal fetal growth with only a small margin of error.
6. REFERENCES
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[3] Yagel S, Anteby EY, Shen O, Cohen SM, Friedman Z, Achiron R. Placental blood flow measured by simultaneous
multigate spectral Doppler imaging in pregnancies complicate by placental vascular abnormalities. Ultrasound Obstet
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[4] Macara L, Kingdom JCP, Kaufmann P et al. Structural analysis of placental terminal villi from growth-restricted
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diastolic flow velocity in the umbilical artery is associated with maldevelopment of the placental terminal villous tree. Am
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[7] Kingdom J, Huppertz B, Seaward G, Kaufmann P. Dvelopment of the placental villous tree and its consequences for fetal
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[13] Fok RY, Pavlova Z, Benirschke K, Paul RH, Platt LD. The correlation of arterial lesions with umbilical artery Doppler
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Doppler flow imaging in growth-restricted fetuses. Am J Obstet Gynecol 2002; 186: 297-302.
[15] Konje JC, Huppertz B, Bell SC, Taylor DJ, Kaufmann P. 3-dimensional colour power angiography for staging human
placental development. Lancet 2003; 362: 1199-201.
[16] Guiot C, Gaglioti P, Oberto M, Piccoli E, Rosato R, Todros T. Is three-dimensional power Doppler ultraound useful in the
asseessment of placental perfusion in normal an growth-restricted pregnancies. Ultrasound Obtet Gynecol 2008: 31:171-6.
[17] Rubin JM, Bude RO, Carson PL, Bree RL, Adler RS. Power Doppler US: a potentially useful alternative to mean
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Gynecology. New York: Springer-Verlag Inc., 1997; 68-87.
[19] Jarvela IY, Sladkevicius P, Tekay AH, Campbell S, Nargund G. Intraobserver and interobserver variability of ovarian
volume, gray-sacle and color flow indices obtained using transvaginal three-dimensional power Doppler ultrasonography.
[20] Jarvela IY, Sladkevicius P, Kelly S, Ojha K, Nargund G, Campbell S. Three-dimensional sonographic and power Doppler
characterization of ovaries in late follicular phase. Ultrasound Obstet Gynecol 2002; 20: 281-5.
[21] Yu CH, Chang CH, Ko HC, Chien WC, Chang FM. Assessment of placental fractional moving blood volume using
quantitative three-dimensional power Doppler ultrasound. Ultrasound Med Biol 2003; 29: 19-23.
[22] Mercé LT, Bau, S. “Biopsia vascular placentaria” mediante mapa de amplitud tridimensional: Validación de la técnica. Rev
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[23] Mercé LT, Barco MJ, Bau S. Reproducibility of the study of placental vascularization by three-dimensional power
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[24] 24 Pretorius DH, Nelson TR; Baergen RN, Pai E, Cantrell C. Imaging of placental vasculature using three-dimensional
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2007; 30: 259-62.
CHAPTER 7
Assessment of Fetal Behaviour by 3D and 4D Sonography
Asim Kurjak1,*, Iva Lausin1 and Guillermo Azumendi2
1
Department of Obstetrics and Gynaecology, Sveti Duh hospital, Sveti Duh 64, 10000 Zagreb, Croatia and 2Prenatal
Diagnosis, Ultrasound Unit Centro Gutenberg, Malaga
Abstract: During the past few decades, morphological studies of fetal brain as well as ultrasound imaging of fetal
intrauterine activities in the real time provided invaluable information about the most important events in the
development of human central nervous system. Analysis of the dynamics of fetal behaviour has led to a conclusion that
fetal behavioural patterns directly reflect developmental and maturational processes of fetal nervous system. It has been
suggested that the ultrasound assessment of fetal behaviour could be used for the evaluation of fetal central nervous
system and, possibly, for the detection of functional or structural brain disorders. The new and advanced imaging
techniques such as four dimensional sonography might open a new perspective for the study of fetal behavioural
patterns and facilitate the development of diagnostic strategies for early detection or prevention of brain dysfunctions.
The aim of this chapter is to review the clinical application of three and four dimensional sonography in the assessment
of fetal behaviour.
1. INTRODUCTION
Introduction of ultrasound technique into obstetrics practice opened a waste spectrum of possibilities; from
evaluation of fetal growth and biometry, different malformation, tool of help in invasive diagnostic procedures, to a
new field of interest that will be discussed in this chapter- fetal behavior. The ultrasound study of embryo and fetal
movements began in 1968 with the work of Hinselmann [1], and was developed through research of many other
authors [2-7]. Ultrasound techniques have revealed a diversity of information on fetal morphology and fetal
intrauterine activities. Analysis of fetal behavior in comparison with morphological studies had led to a conclusion
that fetal bahavior patterns directly reflect developmental and maturation processes of the fetal central nervous
system. 3D sonography can be used in ultrasonography for small parts, among other medical areas [8-12]. Obtaining
sonographic volumes rather than single tomographic slices makes it possible to demonstrate data in any plane and
any direction [12, 13]. 3D and 4D US provide additional information for the diagnosis of facial anomalies,
evaluation of neural tube defects and sceletal malformations [8]. Reports using 4D ultrasound technique in
assessment of fetal behavioural patterns are encouraging [14-21]. First reports have proved that 4D sonography can
assist in better understanding of both somatic and motor development of the fetus [19]. It has overcome some
limitations of two dimensional ultrasonography such as need for observer interpretation. Using 4D US, quantitative
assessment of fetal motility can be performed almost equally precisely as by conventional 2D US even at the very
early period of gestation. The quantitative assessment might be even more informative because 4D US allows the
simultaneous visualization of the whole fetal body [20,22]. Four dimensional sonography offers the possibility of
studying fetal behavior and general movements in a more global way than with 2D US. In assessment of fetal
bahavior, fetal face is a big and important field of investigation. Simultaneous imaging of complex facial movements
and the evaluation of facial expression was impossible using real time 2D US. On the other hand, 3D US provide
images with recognizable expression, but it remains impossible to determinate the duration of facial activity. 4D US
integrates the advantages of the spatial imaging of the fetal face with the addition of time [18]. Using it, it is now
feasible to study a full range of facial expressions including smiling, crying, scowling and eyelid movement [20, 23-
25].With 4D sonography it is possible to produce measurable parameters for the assessment of normal
neurobehavioral development. 4D US has an ability to study fetal activity in the surface-rendered mode, and it is
particularly superior for fast fetal movements [23].
2. CNS DEVELOPMENT, ULTRASOUND AND FETAL BEHAVIOUR
Analysis of dynamics and fetal behaviour has led to a conclusion that fetal behavioural patterns directly reflect
*Address correspondence to Asim Kurjak: Department of Obstetrics and Gynaecology, Sveti Duh hospital, Sveti Duh 64, 10000 Zagreb,
Croatia; Telephone: +385 1 3712317; Fax: +385 1 3745534; Email: asim.kurjak@public.carnet.hr

Assessment of Fetal Behaviour by 3D and 4D Sonography Current Topics on Fetal 3D/4D Ultrasound 213
developmental and maturational processes of the fetal central nervous system. These findings implicated that
understanding the relation between fetal behaviour and developmental processes in different periods of gestation
would make possible the distinction between normal and abnormal brain development, as well as the early diagnosis
of various structural or functional abnormalities [20, 25]. Even after delivery, behavioural patterns frequently provide
the most useful indicators of brain function. It has been shown that fetal activity occurs far earlier than a mother can
register it, as early as the late embryonic period (Power point slide 1, see Appendix). The quantitative and qualitative
spectra of behavioural patterns expand rapidly as the pregnancy progresses, and the random movements of the fetal
body, which are the earliest signs of fetal activity, change into the well-organized behavioural patterns, observed later
in gestation. 4D sonography makes it straight forward to comprehend some morphological dynamics, such as
yawning, sucking, smiling, crying and blinking (Fig. 1). This offers a practical means for assessment of
neurophysiological development, as well as for detection of anatomical pathology. Recently, reference ranges with
gestational age for fetal neurobehavioral development parameters in normal pregnancies were established. Standard of
movement pattern and facial expression pattern curves were constructed through all trimesters of pregnancy [20, 25].
Figure 1: 3D ultrasound of fetal jawning movements, hand to face movements and tongue expulsion.
Behavior may not correspond to CNS function. However, the data has been published that fetuses with abnormalities
of CNS reveal unusual behavioral patterns compared to those without these circumstances, and that normal fetal
behavior reflects normal CNS functioning [26].
3. FETAL BEHAVIOR AND FETAL MOVEMENTS
Fetal behavior can be defined as fetal activities observed or recorded using ultrasonic equipment. As it is not yet
possible to assess functional development of the CNS directly, scientists have started to analyze fetal behavior as a
measure of neurological maturation [22].
Since fetal body movements give important information about the condition of the fetus, their quantitative as well as
qualitative aspects were analyzed. De Vries and colleagues described the developmental pathway of fetal movements
in a longitudinal study of 12 multiparous women. They reported not only how to describe a particular movement, but
also how these movements were performed in terms of speed and amplitude [3].
Fetal movements were evaluated by different authors through all trimesters of the pregnancy. De Vries and
colleagues have focused on the first trimester of the pregnancy, while Roodenburg and colleagues have investigated
second half of the pregnancy [27, 28]. Sparling and Wilhelm described spontaneous movements from 12 to 35 weeks
of gestation and have recorded the characteristics of the movements [29]. Based on investigation of de Vries and
colleagues of typical spontaneous human movements they have recorded variations in “general movements” (Fig. 2).
They believe that those can suggest abnormalities of the CNS. General movements were described as “gross
movements” involving the whole body. They can last from a few seconds to a minute. The movement is fluent and
elegant and creates an impression of complexity and variability [30]. Recently, the descriptor of “general
movements” has been applied to the movement of preterm newborns [31]. Through investigating general movements
they can be assessed both in quantity and quality. Prechtl has reported that general movements in sick preterm infants
are reduced in elegance and fluency, as well as the variability and fluctuation of intensity and speed of motor
performances, rather than change in incidence of distinct motor patterns [30]. It is possible today to underestimate
the importance of such observations, but it is becoming more and more evident that the qualitative changes in motor
214 Current Topics on Fetal 3D/4D Ultrasound Kurjak et al.
patterns of both the fetus and the preterm infant precede quantitative changes when the integrity of the nervous
system is damaged [32].
Figure 2: 4D ultrasound sequence of the fetus at 12 weeks of gestation, showing general movements. The complex movements of
the limb, trunk and head are clearly visible and cause a shift in fetal position. In the first sequence, the right limb is bent at the
elbow joint. In the next sequence, the fetus has dropped the hand and has begun to deflect the elbow joint. In the last sequence,
further elevation of the hand is seen.
4. CLASSIFICATION OF MOVEMENT PATTERNS
According to Prechtl, movement patterns could be classified fallowing activities: [27]
1. Startles are quick, generalized, starting always in the limbs and often spreading to the trunk and neck.
The duration on startles is 1 sec or less. Usually they occur singly but sometimes they may be
repetitive. (Power point slide 12, see Appendix)
2. General movements are gross movements, but they are slow and involve the whole body. They may
last from a few seconds to a minute. A peculiarity of these movements is the indeterminate sequence of
arm, leg, neck and trunk movements. They wax and wane in intensity, force and speed. Despite this
variability, they must be considered as a distinct pattern and easy to recognize if they occur.
3. Hiccups are phasic contractions of the diaphragm, often repetitive at regular intervals. A bout of
hiccups may last as long as several minutes. In contrast to the startle, the hiccup always starts in the
trunk but may be followed by involvement of the limbs.
4. Fetal breathing movements are usually paradoxical. Every contraction of the diaphragm (which after
birth leads to an inspiration) causes an inward movement of the thorax and a simultaneous outward
movement of the abdomen. The sequence of “breaths” can be either regular or irregular. No amniotic
fluid enters the lungs during breathing movements. Isolated breaths may resemble a sigh.
5. Isolated arm and leg movement may occur without other parts of the body moving. The speed and
amplitude of the movement may vary. (Power point slides 3-5, see Appendix)
6. Twitches are quick extensions or flexions of a limb or the neck. They are never generalized not are
they repetitive.
7. Clonic movements are repetitive, tremulous movements of one or more limbs at a rate of
approximately three per second. They are rarely more than three to four in normal fetuses.
8. Isolated hand movements occur when the fingers flex or extend together repetitively or in isolation.
Some hand postures may resemble hand gestures seen in later life. The hand may also rotate outward
or inward (supination or pronation).
9. Hand -face movements is made when the hand accidently touches the face either by an arm movement
in the direction of the face or by head movement in the direction of the hand. Hand-mouth contact
occurs, but it is often difficult to judge precisely where the hand makes contact. (Power point slides
13-15, see Appendix)
10. Retroflexion of the head is the backward bending of the head, varying in speed from slow to fast. The
head may remain in a retroflexed position from 1 sec to 1 min, often accompanied by an overextension
of the spine. (Power point slide 10, see Appendix)
11. Lateral rotation of the head occurs when the head is rotated from the midline to a lateral position or
vice versa. This movement occurs in isolation. The speed is usually slow and the amplitude may vary.
(Power point slide 11, see Appendix)
12. Rhythmical side-to-side movements of the head are slow and may cover a range of 180o. As in
postnatal rooting, the regularity is not accurate.
13. Anteflextion of the head is the forward bending of the head, which is usually slow but always consists
of a lift-off from the surface on which the fetus is resting. (Power point slide 8, see Appendix)
14. Opening the mouth occurs in isolation and the amplitude and speed may vary. Sometimes tongue
protrusion is observed.
15. Yawn is a slow opening of the mouth, followed by maintenance of the position for several seconds and
then by quick closure. (Power point slides 26,27, see Appendix)
16. Rhythmical mouthing is a small and rhythmical quiver of the jaws without opening of the mouth,
occurring in bursts of 5 to 10 movements with a rate of approximately four or five per second. (Power
point slide 29, see Appendix)
17. Sucking is a burst or rhythmical jaw movements with a rate of about one per second and of varying
length, sometimes fallowed by swallowing, which indicates that the fetus is drinking amniotic fluid.
18. Stretch is a complex motor pattern consisting of overextension of the spine, retroflexion of the head,
abduction, external rotation and elevation of the arms. The movement lasts several seconds and occurs
singly. (Power point slide 9, see Appendix)
19. Rotation of the fetus may occur along the longitudinal axis or the transverse axis of the fetal body. This
movement is always forceful.
20. Alternating leg movements occurring in the feet are contacting the uterine wall, and may result in a
somersault over the head. Rotation around the sagittal axis is initiated by either rotation of the head or
of the hip.
21. Eye movements can be distinguished as a slow, rapid and repetitive (nystagmoid). The displacement of
the eyeball can be seen as a flicker of the echo behind the orbit or, more clearly, as shifts in the
position of the echoes of the lenses. (Power point slide 22,23, see Appendix)
5. FIRST TRIMESTER
Prenatal motility is considered to reflect developing CNS, but also involved functional and maturational properties of
fetal hemodynamics and muscular system. The early embryonic period is characterized by the immobility of the
embryo. The earliest synapses can be detected in the spinal cord shortly before the onset of embryonic motility, at the
6th to 7th postconceptional weeks. Therefore, the neural activity leading to the first detectable movements in
considered originating from the spinal motoneurons [33, 34].
5.1. Early Fetal Brain Development

The appearance of fetal movements occurs parallel with the fetal brain development, thus it is important to know
basic steps in brain development to understand the appearance of fetal movements [18, 22, 34]. During the
embryonic and early fetal period, the hystogenic events (proliferation, migration and early cytoarchitectonic
organisation ) lead to the formation of cortical anlage below the pial surface and the formation of different nuclei in
the brain stem, diencephalon and basal forebrain. Events related to the development of neuronal connections begin
during this early fetal period. The earliest afferent axons (of unknown origin) approach the cortical zone through the
marginal and subplate zone. The development of synapses in human cortex begins after the formation of the cortical
palte at the end of the 8th week of gestation [34-36]. Number of synapses increases significantly during the
formation of the new deep synaptic zone, so called subplate-zone between 13 and 15 weeks of gestation. Kostovic at
al emphasise that the major event in early fetal period is the ingrowing of afferent fibers through the spacial fetal
subplate zone. Earlier developmental periods are dominated by proliferative, migratory processes while later, in the
prenatal period, neuronal differentiation and synaptogenesis dominate.
5.2. Movements
First spontaneous fetal movements can be observed with conventional 2D US around 8th gestational week, while late
developed 4D US allows the visualization of fetal motility one week earlier [20,22,25,37,38]. The very first
movements seen in any fetus are slow extensions of the neck at 7-7, 5 weeks of gestation (Fig. 3).
Figure 3: 4D image sequence of the fetus at 7 weeks gestation showing extension of the neck.
Figure 4: 4D imaging sequence of the fetus 7-8 weeks of gestation showing a rapid phase contraction of the limbs with complex
movements involving neck and trunk.
They are present for a few days and then followed by the appearance of startles and general movements. While the
first type consists of a rapid phase contraction of the limb muscles, often with secondary involving of neck and trunk
muscles, the later are complex movements involving neck, trunk and limbs (Figs. 4, 5 and 6). They vary in speed
and are forceful but fluctuating in intensity [22, 37]. Just discernible movements were found between 7 and 8 weeks
of gestation by de Vries and co-workers [3, 27, 37] (Power point slide 1, see Appendix). They reported not only
how to describe a particular movement, but also how these movements were performed in terms of speed and
amplitude [3,37]. These movements are visible for less than 2 weeks.
Figure 5: Fetus at 7-8 weeks gestation. Fetal hands are located in front of the chest and no movements of the wrist and fingers are
visualized.
Figure 6: Fetus at 8-9 weeks gestation. Isolated hand movements in front of the chest are visualized. Wrist and fingers are in the same
level.
Figure 7: Scatterplot and multiple regression analysis of the first trimester frequency of general movement pattern versus the
gestational age.
General movements are the first complex fetal movement patterns observed by 2D US [20, 22, 25, 27]. They can be
recognized from the 8th to 9th weeks of pregnancy and continue to be present until 16-20 weeks after birth [39].
According to Prechtl, these are gross movements, involving the whole body [40]. They wax and wane in intensity,
force and speed, and they have a gradual beginning and end (Fig. 7) [3, 27, 41].
Startles are the next movement, and it can be found between 8 and 9 weeks of pregnancy, and last for about 1 second
(Fig. 8) [28]. (Power point slide 12, see Appendix).
Figure 8: Scatterplot and multiple regression analysis of the first trimester frequency of startle pattern versus the gestational
weeks.
Goldstein and colleagues found embryonic body movements between 8 and 9 weeks of gestation by two-dimensional
transvaginal sonography [42]. This results are in agreement with those of others [3,27,43]. De Vries and co-workers
found isolated arm and leg movement at the 8th week of gestation [3,27]. With 4D US, limb movements at the 8 to 9
weeks were found (Figs 5 and 6) [18]. Organisation of the appearance of the movement pattern occurs in increasing
frequency [14] (Power point slide 3, see Appendix). It seems that fetal arms explore the surrounding environment
and cross the midline, while the palmar surface is oriented to the uterine wall. Fetal legs are extended to the uterine
wall [20,37,28,41,44].The elevation of the hand, extension of the elbow joint, with a slight change in direction and
rotation can be seen simultaneously [45]. After the 9th gestational week the repertoire expands rapidly. Hiccups
appear, often in series, for up to seven minutes, and isolated arm and legs movements can be observed. This is
important in two aspects. First, that the young fetus is able to perform isolated movements of one limb, and second,
unexpected finding of the simultaneous onset of arm and leg movements. After 10 weeks, head movements of
various types can be seen. (Power point slides 3-6, see Appendix). They consist of lateral rotation of the head and
overextension of the neck (Power point slide 11, see Appendix). They are carried out in moderate speed and appear
in isolation. At about the same age, hand-face contact is seen for the first time. Fetal hand movements and facial
expressions were studied by Kurjak and co-workers in the first and second trimester of the pregnancy [21]. They
have studied seven types of hand movements: hand to head, hand to mouth, hand near mouth, hand to face, hand near
face, hand to eye and hand to ear (Fig. 9) (Power point slide 13-15, see Appendix).
Figure 9: Fetal hand to head movement,hand near face movement and hand to eye movement.
Graph 1: The incidence of isolated hand movements obtained Graph 2: The indidence of hand to head movements
in 15 fetuses from 13 to 16 weeks gestation by 4DUS according to gestatinal age showed by 4DUS.
The advantage of 4D US was the possibility of precise assessment of the direction of the hand movement and target
of the fingers. The incidence of isolated arm movements increased gradually from 8 through 19 weeks of gestation
(Graph 1, 2) [21, 25]. Such a discordance of the results with those reported by de Vries and co-workers was
explained by limitations of 4D US. Since 4D US provides only a near real-time reconstruction of intrauterine
movements, fast and slow hand movements were not registered.
Between 10, 5 and 12 weeks fetus starts to make breathing movements. At 11 weeks opening of the jaw, bending
forward of the head and complex stretch movements can be observed. (Power point slides 8-11, see Appendix). A
little later than irregular jaw movements, yawns occur (Fig. 10). They have the same pattern as in children or adults
and are easy recognizable. Changing in finger position can be seen around 11th week and easily recognizable
clenching and unclenching can be observed at 12 to 13 weeks of gestation (Power point slide 7, , see Appendix).
Finally, at the 13 to 14 weeks, isolated finger movements can be seen, as well as an increase in the activity and
strength of the hand and finger movements (Fig. 11) [21,25]. At 13 weeks, rhythmical sucking movements occur in
bursts. The rate of these sucking movements at 14 weeks is already about the same as in term infants during
brestfeeding. Fetal drinking regulates the amount of amniotic fluid [21].
In the first trimester one could notice a tendency towards an increased frequency of fetal movements with increasing
gestational age. Only startle movement pattern seems to occur stagnantly during the first trimester [46] (Power point
slide 12, see Appendix).
Figure 10: On image sequence, the same movement pattern is showed by 4DUS. Yawning can be observed as a movement
pattern identical to that seen in infants, children and adults.
In the study that have compared 2D and 4D sonography Zagreb group shown that several movement patterns, such as
sideway bending, hiccup, breathing movements, mouth opening and facial movements could be observed only by 2D
sonographic technique in the first trimester. They have concluded that both 2D and 4D sonography are important for
the assessment of fetal behavior and motor development [22] (Fig. 12).
6. THE SECOND TRIMESTER
Only a few studies are available on fetal movement patterns in the second trimester [28]. De Vries and colleagues
have studied fetal movements from 20 and from 24 postmenstrual weeks onward [47, 48]. During the second
trimester of pregnancy, the incidence of body movements increased considerably. The periods of quiescence became
longer and eye movements were clearly visible [48-50] (Power point slides 22, 23, see Appendix). The incidence of
hiccups, startles and stretches decreased, whereas other movement patterns (jaw movement, hand
face movement, head movement) showed no clear developmental changes [48]. At 28 postmenstrual weeks,
Roodenburg and associates presented the following ranges and median values based on 1h observations, jaw
movements 60-460, median 95; head rotations 4-29, median 37; head retroflexions 4-29, median 12. From a
developmental point of view, one could say that in the second trimester the development continues, but there are no
new movements appearing for the first time [28].
Figure 11: Leg and hand movements shown using 2D sonography. Isolated finger movement can be depicted from the 13th week
of pregnancy.
Figure 12: Fetal motor development in the first trimester of the pregnancy.
Results of Zagreb group longitudinal study has shown that by 14-19 weeks fetuses are highly active with the longest
period between movements is only 5-6 minutes. In the 15th week, 15 different types of movement can be observed.
Besides the general body movements and isolated limb movements, retroflexion, anteflexion and rotation of the head
can be seen [20, 25, 45] (Power point slide 28, see Appendix). Simultaneously with the decrease in the number of
general movements, an increase in facial movements, including opening and closing of the mouth and swallowing
can be observed (Power point slide 25, see Appendix). That pattern is considered to be a reflection of the normal
neurological development of the fetus [51,52]. The application of 4D technology made it possible to investigate the
existence of full range of facial expressions including grimacing, tongue expulsion and eye-lid movements, similar to
emotional expressions in adults [14, 21, 25, 37, 44, 53, 54]. In longitudinal study, a grimacing pattern begins to
appear around the 20th week of gestation. Until now, it is not clearly known in which period of gestation the facial
expressions begin to appear. The nuclei of facial nerve, a structure that controls those movement patterns, are
developed by the end of the first trimester, indicating that some facial grimaces could appear rather early in
gestation. Significant trend in fetal eye movement organisation can also be observed during the second trimester of
the pregnancy, and continues to the third trimester. The earliest eye movements appear at the 16 to 18 weeks of
gestation, as sporadic movements with limited frequency. In the longitudinal study it was found that isolated eye
blinking patterns appear more frequently and begin to consolidate at the 24 to 26 weeks of gestation [20, 25, 54].
Fetal eye movements were discovered by Bots and Bernholz, who reported the onset of slow, rolling eye movements
at 16-18 weeks followed by rapid eye movements at 20-22 weeks which include also nystagmoid movements. In
conclusion of longitudinal study it was found that fetuses begin to display a tendency towards increased frequency of
observed facial expression up to the end of the second trimester. All of the types of facial expression patterns display
peak frequency at the end of the second trimester, except isolated eye blinking which began to increase during the
beginning of the 24th week of gestation since before that period fetuses cannot open their eyelids (Power point slide
22, see Appendix). All of the type of head movements and hand to body contact indicated a tendency to decrease
frequency from the beginning of the second trimester to the end of the third trimester [20, 25].
The incidence of hand movements and facial expression was investigated by Zagreb group through all trimesters. In
the early second trimester 4D US provides simultaneous visualization of all four extremities and enables confident
recognition of isolated arm movements and their direction. They have determined the incidence of each subtype of
isolated hand to head movements between 13 and 16 weeks of pregnancy. The incidence of hand to head movements
decreased, followed by the plateau at 14 weeks of gestation.
The highest range of hand to mouth was found at 15 weeks of gestation, at 13 weeks plateau was observed and with
mild fluctuations the plateau continued until 16 weeks. Hand near mouth movement decreased gradually from 13
weeks onward with a single fluctuation in the 14th week. The incidence of hand near face movement was stabile
between 13 and 16 weeks with a slight increase at 14 to 15 weeks (Power point slide 13, 14, see Appendix). The
incidence of hand to ear movement showed a rapid trend of decrease between 13 and 16 weeks while the incidence
of the hand to eye movement pattern showed the same developmental trend as the hand to head and hand to face
movement patterns [21,54]. In the study of Kuno and co-workers of bahavior patterns in the second trimester
movements of head, mouth, arm, trunk and leg were observed[17] (Fig. 13). The most active fetal behavior pattern
was arm movement in each fetus, and the least active was mouth movement. All fetal movement were synchronized
with other fetal movements in second half of the pregnancy [3, 17].
7. THE THIRD TRIMESTER
In the third trimester fetal heart rate pattern and eye and body movements can be detected. The association of these
movements increases steadily, and in the last weeks of the pregnancy, fetal behavior can almost completely be
described in terms of behavioral states, which are stable over the time and recur repeatedly, not only in the same
infant, but also in similar forms in all infants [55-57]. The concept of behavioral states has been used as a descriptive
categorization of behavior, and also as an explanatory concept in which states are considered to reflect particular
modes of nervous activity that modify the responsiveness of the infant [56].
By term, the average number of general movements per hour was found to be 31 ranges 16-45 with the longest
period between movements ranging from 50 to 75 minutes [58]. Although this decrease was first explained as a
coincidence of the decrease in amniotic fluid volume, it is now considered to be a result of cerabral maturation
processes. As the medulla oblongata matures myelinates and stabilizes, these spontaneous movements are less easily
triggered and begin to be controlled by more stabile intrinsic activities generated within the brain stem [59].
Simultaneously with the decrease in the number of general movements, an increase in the number of facial
movements, including opening/closing of the jaw, swallowing and chewing can be observed (Power point slide 17-
20, see Appendix). These movements can be seen in periods of absence of general movements, and this pattern is
considered to be a reflection of the normal neurological development of the fetus [60].
Figure 13: Isolated leg movement observed in a fetus at 28 weeks of gestation. These sequences show rapid and slow
movements, and involve extension, flexion and external and internal rotation of the lower extremity.
In the study about fetal hand and facial body movements done by Zagreb group of investigators ten gravidas in the
third trimester between 30 and 33 weeks of pregnancy were observed [21]. The incidence of eyelid movements
ranged between 4 and 20 with the median value of 17, mouthing movements ranged between 2 and 19, with the
median value of 12, and mouth and eyelid movements ranged between 0 and 13,median value of 5. The incidence of
the pure mouth movement such as mouth opening ranged between 4 and 13, median value of 5, tongue expulsion
ranged between 0 and 2 with the median of 2, yawning ranged between 0 and 2, median of 1, and pouting ranged
between 0 and 9 with a median of 3. The incidence of fetal expressions such as smiling ranged between 2 and 7,
median of 2, and scowling between 2 and 4, median of 2. In that study it was shown that eyelid and mouthing
movements dominated in the third trimester of the pregnancy (Fig. 14) [21, 61].
Figure 14: Facial expressions showing movements of the hand to face, the hand to the eye and eye-opening of the fetus at 33
weeks of gestation.
Mokoruma and co-workers have done a study of simplified ultrasound screening for fetal brain function based on
behavioral patterns in the third trimester of the pregnancy. They devised a brief ultrasound examination to
distinguish fetuses with compromised central nervous system function from general population. The study design
compared behavioral findings obtained by retrospectively reviewing of ultrasound examinations of 5 fetuses that had
abnormal behavior with prospectively obtained findings of 29 normal fetuses. Median for investigation was 50
minutes. With that study they showed that using the method of screening test may make it possible to include
assessment of fetal brain function as the part of the routine antenatal care [62].
In the other study done by Yan and co-workers fetal facial expression was observed in the early third trimester [63].
They evaluated characteristic facial expressions in fetuses aged from 28 to 34 weeks using 4D sonography. Results
showed that mouthing was the most frequent facial expression with range between 2 and 19, median 6,5, whereas the
least frequent were scowling with range between 0 and 9, and median of 1, and sucking, range between 0 and 2,
median of 1. Mouthing was evident in all fetuses and significantly more frequent than any other movement (Power
point slide 24, see Appendix). They concluded that 4D sonography provides a means of evaluating fetal facial
expression in early third trimester and it may be a key to predicting fetal brain function and well-being and an
important modality in future fetal neurophysiologic research [63].
7.1. Fetal Face Movements in the Third Trimester of the Pregnancy

4DUS has additional advantages in studying fetal activity in the surface rendered mode and is particularly superior
for fast fetal movements [8, 54, 64] (Fig. 15 and 16). With 2DUS, fetal movements such as yawning, swallowing
and eyelid movements cannot be displayed simultaneously while with 4DUS, the simultaneous facial movements can
be clearly depicted [23] (Fig. 17 and 18)
Figure 15: Various displays of fetal face movements in the second half of the pregnancy.
The qualitative and quantitative aspects of behavioural patterns expand rapidly as the pregnancy progresses, and the
random movements of the fetal body, which are the earliest signs of fetal activity, change into the well-organized
behavioural patterns, observed later in gestation. Analysis of the dynamics of fetal behaviour has led to the
conclusion that fetal behavioural patterns directly reflect developmental and maturational processes of the fetal
central nervous system. With 4D sonography it is now possible to produce measurable parameters for the assessment
of normal neurobehavioral development.
There are several types of jaw movement patterns such as isolated jaw movement, sucking and swallowing, which
can be observed by 2DUS [65]. The possibility of observing facial expressions in detail may be of both scientific and
diagnostic value, opening up an entire new field of investigation with many unanswered questions [17, 65]. Two
examples of questions that remain to be answered are: (1) when do facial expressions start; and (2) which facial
expression predominates in fetal life and at what gestational age it can be first observed?
Figure 16: 3D surface rendering mode makes it easy to obtain smooth visualization of fetal face and body details.
Figure 17: 3D image shows small anatomical face details; fetal face in the second half of the pregnancy.
2DUS and 4DUS are complementary methods used for the evaluation of fetal movements. However, the quality of
each fetal movement can be visualized and evaluated more precisely by 4DUS [66]. Fetal behavioural patterns in the
third trimester between 30th to 33rd weeks of gestation and the continuity between fetal and neonatal behaviour have
been recently evaluated [14,67].
Figure 18: Illustration of different facial expressions that can be studied: isolated eye blinking, yawning, grimacing, tongue
expulsion, mouthing and swallowing.

Figure 19: Demonstration of open eyelids in the second half of the pregnancy.
In the second and third trimesters, all facial movements can be visualized by 4DUS. Furthermore, 4DUS opened, for
the first time, the possibility of visualizing the full range of facial expressions, including subtle grimaces, similar to
emotional expressions in adults [20, 25]. The most frequent facial movement patterns in the second trimester were
isolated eye blinking, grimacing, suckling and swallowing, whereas mouthing, yawning, tongue expulsion and
smiling could be seen less frequently [20,25,54] (Power point slide 17-26, see Appendix). We noted a tendency
towards decreased frequency of observed facial expressions with increasing gestational age. At the beginning of the
second trimester, the fetuses began to display a tendency towards increased frequency of observed fetal facial
expression to the end of second trimester. All types of facial expression patterns display the peak frequency at the
end of second trimester, except in isolated eye blinking which began to increase at the beginning of 24 weeks of
gestation because the fetuses cannot open the eyelids before this period (Fig. 19). During the third trimester, the
fetuses began to display decreasing incidence or paucity of fetal facial expression [20, 25, 54].
The systematic investigations of fetal facial expressions confirmed that all components of the fetal yawning pattern,
prolonged jaw opening followed by a quick closure and accompanied by head flexion and elevation of arms, can
easily be recognized by 4DUS in this period [68] (Power point slide 26, 27, see Appendix). Furthermore, when the
fetal yawning in the third trimester was compared with the yawning in the neonates during the first week of life, no
differences were found in the frequencies of this reflex. The frequency of yawning gradually increased between 15th
and 24th week when a short plateau was observed from 24th to 26th week and was followed by a slight decrease
towards the term [20, 25, 54]. A clear gestational age-related trend in the frequency of yawning could be interpreted
as the maturation of the brain stem and possibly the acquisition of control of more cranial structures over yawning
pattern. These findings have provided new information about the course of neurodevelopment of this interesting, but
poorly understood reflex. Whether this is altered in cases of neurodevelopmental disturbances and whether such
alterations can give us insight into the function of fetal nervous system in high risk pregnancies, remains to be
determined [54].
Fetal yawning is still quite a mysterious phenomenon, and its possible relation to the pathological conditions,
particularly those affecting fetal central nervous system has not been investigated so far, despite the clearly altered
incidence of yawning in a wide spectrum of CNS disorders, observed in adults. The early reports of yawning
movements in the 20 weeks old fetus indicated that 4DUS might facilitate the investigation of this infrequent
movement pattern [68].
This impressive finding however, raises a number of questions, many of which are yet to be answered. First, precise
criteria to distinguish between these facial expressions in the fetus should be established (Fig. 20). The exact onset of
facial expressions has not been determined and it is still unclear whether their appearance is gestational age related.
The maturation of midbrain also begins in the second trimester. It consists of the dopamine-producing substantia
nigra, the inferior-auditory and superior-visual colliculus, and cranial nerves III-IV, which together with the medial
longitudinal fasciculus and the VI cranial nerve, control eye movements [69]. This explains the delayed onset of eye
movements, which cannot be registered before 16th postconceptional week. The maturation of the medulla oblongata
is also revealed by the appearance of the breathing movements as well as the swallowing, hiccups, yawning and jaw
opening, visible between 9th and 11th week [69]. Facial movements, which are also controlled by V and VII cranial
nerve, appear around 10-11 weeks, while delayed onset of more specific functions, such as the selective response to
sounds and vibration, can be explained by the prolonged pontine maturation. The nuclei of the facial nerve, a
structure that controls these motor patterns, are developed by the end of first trimester, indicating that some facial
grimaces could appear rather early in gestation [70,71]. The possibility of studying such subtle movements certainly
opens a completely new area of investigation. One potential value of such observations could be the detection of
facial nerve paresis in utero. It remains to be determined to what extent are the facial motoric patterns related to the
function and integrity of the CNS. Nevertheless, the fact that even in the embryonic period, the same inductive forces
that cause growth and reshaping of the neural tube influence the development of facial structures, and that many
genetic disorders affecting the CNS are also characterized by dysmorphology and dysfunction of facial structures,
emphasize the importance of these investigations. Obviously, the story of fetal intrauterine activity is far from being
complete; the development of new recording techniques should enrich the perspective of intrauterine life. Table 1
shows the classification of fetal face movemen assessted by 3D and 4D ultrasonography.
Table 1: Classification of fetal face movements based on 3D/4D ultrasound
Yawning Movement very similar to postnatal yawning. Prolonged wide opening of the jaws followed by quick closure,
with retroflexion of the head and elevation of arms. This movement pattern is non-repetitive. (Power point
slide 26,27, see Appendix)
Swallowing Indicates that the fetus id drinking amniotic fluid. Swallowing consist of displacements of tongue and/or larynx.
It develops before sucking. (Power point slide 25, see Appendix)
Sucking Very frequent pattern of fetal behavior including regular jaw opening and closing and lasting one second.
Sucking of the thumb or other fingers can be visualized.
Smiling It consists of elevation of the mouth angles. (Power point slide 18,19, see Appendix)
Tongue expulsion Facial expression characterized by expulsion of the tongue. (Power point slide 19,20, see Appendix)
Grimacing The wrinkling of the brows or face in frowning. (Power point slide 21, see Appendix)
Mouthing A facial expression characterized by mouth manipulation to investigate an object. Mouthing it the most
common in fetus and it may develop into a persistent, stereotyped bahavior pattern. (Power point slide 29, see
Appendix).
Eye blinking A reflex that closes and opens eyes rapidly. Brief closing of eyelids by involuntary normal periodic closing, as a
protective measure, or by voluntary action. (Power point slide 22,23, see Appendix)
Figure 20: Frequency of observed facial expressions versus gestational age.

8. BEHAVIORAL PATTERN CONTINUITY FROM PRENATAL TO POSTNATAL LIFE
Characteristics of motor activity level in early childhood following delivery probably originate through out fetal life,
and the fact of fetal to neonatal continuity of leg movement has been proved [72, 73]. Fetal motor activities seem to
indicate typical features as regards regulatory behaviors in the first month, and they are the starting point for
individual differences in reactivity and regulation in infancy [73, 74]. Fetal condition reflects the stage of growth of
the CNS and it is a stabile individual attribute indicating the postnatal state organization [75, 76]. Assessment of the
integrity of the fetal and neonatal nervous system is a major task in modern perinatal medicine. The new diagnostic
tool, 4D ultrasound, makes it possible to have direct assessment of functional condition of the nervous system. It
makes it a straight -forward matter to comprehend some morphological dynamics, such as yawning, sucking, crying
and blinking. Consequently, it offers a practical means of assessment of neurological development, as well as for
detection of anatomical pathology [14]. First reports have proved that 4D sonography can assist in the better
understanding of both the somatic and motor development of the fetus [35]. Even after birth, assessment of behavior
undertaken in this way is often more informative about brain function, despite direct access to more neurological,
physiological and other methods of investigation being available. The main challenge is to discover the proportion of
fetal movements that are similar in both preterm and term infants, and the proportion that differs [77].
The goal of the study about the continuity from prenatal to neonatal period was to investigate whether the same
behavioral patterns were present pre- and postnataly, and whether there were any differences in the frequency in fetal
and in early neonatal life [14]. Ten out of the 37 pregnant women in the third trimester were enrolled in the
investigation. Ten terms, appropriate for investigation newborns were enrolled in the study. Fetuses were
investigated using the 4D technology, and after the birth, neonates were recorded using video cameras. The
frequency of facial expressions and hand movements in the fetal and neonatal period was compared in the study (Fig.
21). There were no movements observed in fetal life that were not present in neonatal life, while Moro reflex was
present only in neonates.
The most frequent fetal and neonatal movements were scowling, eye and mouth opening, hand to face, hand to eye,
and hand to head movements. Isolated blinking, mouth to eyelid movement, yawning, tongue expulsion and scowling
were more frequent in neonates than in fetuses, although the difference was not statistically significant. Hand to
mouth movements were more frequent in neonatal than in fetal life while all other hand movements were less
frequent in neonates than in fetuses, although the difference did not reach statistical significance [14].
The study concluded that 4D sonography is a powerful tool in the assessment of the fetal behavior and it showed that
there is continuity from prenatal to postnatal life (Fig. 22).
Figure 21: Frequency of facial movements in the fetal and neonatal period.
Development of so called “goal directed bahavior” in fetuses and neonates proceeds due to structural changes and
electrophysiological maturation of the central nervous system [78-80]. Progressive differentiation of the CNS
correlates with the development of general movements in the early fetal period, while transient organization of CNS
is expressed as a behavioral pattern resembling goal directed behavior in the late fetal period and transient behavioral
pattern in the early neonatal period [79-81]. Assessment of fetal and neonatal behavior was developed mainly as a
diagnostic tool for the early detection of brain dysfunction [82].
9. MOVEMENT BEHAVIORAL PATTERNS IN HIGH RISK PREGNANCIES
There is a growing pool of evidence that many severe neurological disorders as well as the minimum cerebral
dysfunctions originate from the intrauterine, rather than the perinatal or postnatal period [25, 83, 84]. Major
developmental events, such as establishment of the neural connections in different regions of the brain are
accompanied by the appearance of new patterns of fetal activities or by the transformation of existing patterns [34].
Fetal hypoxia, infections or maternal stress can also interfere with fetal neurodevelopment and leave long-term and
profound consequences on brain structure and function.
Observation of the fetal bahavior provides a direct assessment of the CNS [85]. There are published data that fetuses
with abnormalities of the CNS reveal unusual behavioral patterns compared to those without these circumstances and
that normal fetal bahavior reflects normal CNS functioning [86]. Accordingly, abnormal behavior seems to indicate
faulty formation of the CNS (Power point slide 30, 31, see Appendix).
Visser and co-workers, in the study of anencephalic fetuses, demonstrated that, in early life, normal fetal movements
can be present with only a motor neurons present [87]. The quality of observed movements, however, differed
dramatically compared to that of controls. Similarly, in case with Fanconi anemia, De Vries and colleagues described
qualitatively abnormal fetal motor behavior when mother reported strong fetal kicking at 15 weeks of gestation [88].
Figure 22: Fetal (4DUS) and neonatal facial expression.

De Vries evaluated the literature on fetuses determined to be at high risk for motor anomalies, particularly congenital
ones, by means of real-time 2D sonography [89]. The study revealed that fetal motor activity can be affected in
quantitative and qualitative way, depending on the underlying disorder [89]. The same group stated detailed high risk
factors that can lead to complications followed by abnormalities of fetal movement [90]. Risk does not necessarily
mean that a problem will occur, but it indicated extra vigilance. Although there is considerable overlap in this
approach, it has the advantage of ensuring that both maternal and fetal are taken into account. A healthy mother may
develop problems during the pregnancy and individual pregnancy may proceed uneventfully despite the presence of
a significant past medical or obstetric history. However, terminating a pregnancy as high risk may lead to
unnecessary anxiety when the outcome is ultimately uneventful [90]. Awareness of changing risk, and the potential
for significant neurodevelopmental problem, is an underlying principle of perinatal medicine. Unfortunate
neurological outcomes often result from a delay in recognizing or responding to CNS developing risk [91].
A delay of the appearance of fetal movement patterns by 1-2 weeks has been found in generally well controlled
studies in women with type 1 diabetes mellitus [92]. Abnormal movement patterns have been found in fetuses with
severe abnormalities, e.g. anencephaly and growth restriction [93, 94]. The abnormal movement patterns are
indicative of altered brain and muscular development and are most commonly due to changes in the quality of
movements. Delayed behavioral state development has been found in growth restricted fetuses and in fetuses with
insulin-dependent diabetes mellitus [95,96]. Zagreb group assessed by 4D sonography the neurobehavior of 50
growth restricted fetuses in the third trimester of the pregnancy [97]. They noted the tendency that IUGR fetuses
have less behavioral activity than normal fetuses in all observed patterns.
Ahmed and co workers investigated fetal behavior and structural abnormalities in high risk fetuses with 4D
sonography [91]. They ilustrated behavior in eight high risk fetuses. In anencephalic case they observed almost
absent movements in the lower extremity (Fig. 23) (Power point slide 30, see Appendix). General movements in
the first trimester showed a lack of positional changes, high volume and hypertonia with reduced participating body
parts. They noticed no facial expressions during the second and the third trimester. All the frequencies of the
movement patterns were decreased compared with normal longitudinal parameters in all trimesters.
In the case of fetus with a congenital diaphragmatic hernia there was no difference in the data frequency compared to
normal longitudinal parameters. In the case of the fetus with cephalocele all movement patterns appeared. Almost all
frequencies of the movement patterns had decreased compared to normal longitudinal parameter in the first trimester.
In the fetus with homocystinuria movements of the upper extremities appeared spontaneously with decreased tonus.
Movement patterns of the head were also hypotonia but demonstrated variety in directions. The frequency of
movement patterns was normal compared to longitudinal parameters in the first trimester. Fetus with Meckel-Gruber
syndrome showed hypotonic movement patterns of the head with lack in variability. Movements of hand to body
parts were could not be observed. Movement of the lower extremities emerged spontaneously with hypotonia. In
fetus with prune-belly syndrome there was no difference in the frequency data compared to longitudinal standard
parameters, as well as in fetus with hydrotorax. In fetus with achondrogenesis no specific hand to body movements
could be observed. There was no variation of the positional changes of body movements with a lack of intensity and
discontinuous sequence of arm and leg movements, although their onset was still spontaneous and smooth. All
obtained frequency movement parameters were decreased compared to normal longitudinal parameters [91].
Figure 23: 4D US image sequences of an anencephalic fetus in the third trimesters of pregnancy (at 30 weeks of gestation).
10. NEW SCORING SYSTEM
A variety of pathologies can disrupt fetal development leading to alteration of fetal behavioral patterns. If behavioral
analysis is to have a role in the routine clinical environment, then normal standard parameters and objective methods
need to be developed [20, 25].
Current data suggest that 60-70% of neurodevelopmental disabilities are caused during the prenatal period. Efforts to
prevent cerebral palsy will require focusing on factors and events during pregnancy. Identification of changes in movement
patterns over gestation and postnataly may assist in explicating the role of some of these factors and events [14].
It has been proved that assessment of general movements in high-risk newborns has significantly better predictive
value for later neurological development than classical neurological examination [98-100]. Assessment of neonatal
behavior is a better method for early detection of cerebral palsy than neurological examination alone since almost
70% of causes of cerebral palsy occur prenataly [101]. It is still unclear whether there are any changes specific for
cerebral palsy in the developing brain, and whether they can be detected early enough either by sophisticated
methods of basic sciences or by simple methods of clinical sciences to predict the developmental outcome [81,102].
Fetal motor activities seem to indicate typical features as regards regulatory behaviors in the first month, and they are the
starting point for individual differences in reactivity and regulation in infancy [74, 76]. Furthermore, fetal exposure to
stress or even several maternal stresses can also interfere with fetal neurodevelopment and leave long-term and profound
consequences on brain structure and function. A variety of neurophychiatric diseases are today considered to originate at
least from prenatal incidents. In most of these conditions, there is no reliable parameter for detection or prevention of
cerebral lesions. On the other hand, the severity of consequences indicates the need to develop any strategy that would
enable the early detection of cerebral lesions or indicators that the lesions may occur [20, 25].
Cerebral palsy is the most common chronic motor disability in childhood. The worldwide prevalence ranges from 2-2.5
per 1000 live-births and the incidence did not change since 1951 [103]. Cerebral palsy is an “umbrella” term for disorders
of development, movements and posture, resulting in limitations of activity due to non-progressive impairment of
developing brain [104]. Cerebral palsy does not result from a single event but rather from a sequence of interdependent
adverse events [105]. This time frame evolving adverse events should be taken into account when considering the
possibility of cerebral palsy diagnosis in infants [104,105]. Because the ethiology of cerebral palsy is mostly shifted
towards the prenatal period, attempts were made to diagnose neurological impairment in the prenatal period [106-110].
Periventricular white- matter injury is now the most common cause of brain injury in preterm infants and the leading
cause of chronic neurological morbidity and cerebral palsy. Standardized methods of clinical neurological assessment
from the neonatal period onwards were developed in order to identify three grades of neurological impairment: severe,
moderate and mild. The clinical identification of severely affected patients is less problematic than the identification of
moderately and mildly affected infants. Cranial ultrasound, magnetic resonance imaging, magnetic resonance
spectroscopy and diffusion weighted imaging are helpful in very low birth weight premature and in term infants with
encephalopathy [104]. According to Prechtl and co-workers, any fetal brain damage will interfere with the endogenous
motor activity [111-113]. Therefore, spontaneous movements, as an expression of neural activity, could be used as a
market for fetal brain status [111].Consequently, observation of the unstimulated fetus should contribute to the
assessment of CNS function [21,112]. Movement patterns could be described in terms of complexity, variability and
fluency [113]. General movements include the consideration of body movements spreading in variable sequences with a
gradual beginning and end. General movements can be finally classified as normal-optimal, normal suboptimal, and
abnormal [114]. Assessment of general movements is based on the concept of ontogenetic adaptation corresponding to
the development of human organism, which during each developmental stage is adapted to the internal and external
requirements [115-118]. Prechtl stated that spontaneous motility, as the expression of spontaneous neural activity, is a
marker of the brain proper or disturbed function [113,119].
In the recent study the Zagreb group attempted to produce a new scoring system for fetal neurobehavior based on
prenatal assessment by 3D/4D sonography, KANET (Kurjak Antenatal Neurological test) [120]. Parameters that
were analyzed were the product of multicentric studies conducted during several years which resulted with the most
significant parameters for the assessment of fetal neurological development (Table 2, 3) [20, 25]. There is a
similarity between neonatal optimality test of Amiel-Tison and that new scoring system for the assessment of
neurological status in fetuses [115]. One of the differences was that the analytical criteria of typical passive and
active tone in the neonate cannot be elicited in the fetus: head anteflexion versus retroflexion, ventral versus dorsal
incurvations in the axis, both being of the most importance postnatally to confirm CNS optimality.
Table 2: Neurological scoring test for fetus. Observed characteristic movements are presented in the Power point slides 13-29,
see Appendix.
Sign Score Sign Score

0 1 2
Isolated head anteflexion Abrupt Small range Variable in full range,

(0 - 3 times of many alternation (> 3
movements) times of movements)
Cranial sutures and head Overlapping of cranial Normal cranial Normal cranial sutures
circumference Sutures sutures with with normal measurement
measurement of of HC according to GA
HC below or above the normal
limit (-2 SD) according to GA
Isolated eye blinking Not present Not fluent Fluency
(1 - 5 times of (> 5 times of blinking)
blinking)
Facial alteration (grimace or Not present Not fluent Fluency

tongue expulsion) (1 - 5 times of (> 5 times of alteration)
alteration)
Mouth opening Not present Not fluent Fluency

(yawning or mouthing) (1 - 3 times of (> 3 times of alteration)
alteration)
Isolated hand movement Cramped Poor repertoire Variable and complex
Isolated leg movement Cramped Poor repertoire Variable and complex
Hand to face movements Abrupt Small range (0 - 5 times of Variable in full range,
movement) many alternation (> 6
times of movements)
Fingers movements Unilateral or bilateral Cramped invariable Smooth and complex,

clenched fist, finger movements variable finger movements
(neurological thumb)
Gestalt perception of GMs Definitely abnormal Borderline Normal

Total score
To produce the new scoring test KANET, the Zagreb group identified severely brain damaged infants and those with
optimal neurological findings by comparing fetal with neonatal findings. In the group of 100 low-risk pregnancies
they retrospectively applied new scoring system. After delivery, postnatal neurological assessment (ATNAT) was
performed and all neonates assessed as normal reached a score between 14 and 20, which was assumed to be a score
of optimal neurological development [115,120]. KANET scoring system was applied in the group of 120 high risk
pregnancies in which, based on postnatal neurological findings, three subgroups of newborns were found: normal,
mildly or moderately abnormal and abnormal. Based on this, a neurological scoring system has been proposed. All
normal fetuses reached a score in the range from 14 to 20. Ten fetuses who were postnatally described as mildly or
moderately abnormal achieved prenatal score of 5 to 13 prenatally, while another ten fetuses postnatally assigned as
neurologically abnormal had a prenatal score from 0-5. Among this group four had alobar holoprosencephally, one
had severe hypertensive hydrocephaly, one had tanatophoric dysplasia and four fetuses had multiple malformations.
This was a preliminary study which will continue in several collaborative centres. It is hoped that the future database
formed using this new score for fetal neurological assessment will help in distinguishing fetal brain and
neurodevelopmental alternations due to the early brain impairment occurring in utero. Study of a large population
will hopefully validate the value of the new test as a predictive marker for fetal neurodevelopmental outcome in both
low and high-risk populations.
Table 3: Interpretation of total score
TOTAL SCORE INTERPRETATION

0-5 Abnormal
6-13 Borderline
14-20 Normal
11. CONCLUSION
The study of fetal behaviour, behaviour-related phenomena and fetal reflexes provided us with a great possibility of
understanding the hidden function of the development pathway of the fetal CNS and the potentialities of originating
a neurological investigation in utero. An evolving challenge for the medical profession is to better define normal and
abnormal fetal neurological function in utero so we can better predict antenatally which foetuses are at risk for
adverse neurological outcomes irrespective of intrapartum management. There are many functional neurological
abnormalities such as cerebral palsy whose causes are poorly understood. It is hoped that introduction of 4DUS with
more sophisticated analysis software might help in discovering neurological tests for the fetus. Knowing that the
incidence of feta behavioral patterns fairly correlates with the gestational age, and also correlates with structural
development of the CNS and that the quality of fetal movements reveals the integrity of the CNS, this technique
might facilitate the development of a diagnostic strategy for early detection of cerebral dysfunctions. Preliminary
study of antenatal test has been proposed. It is hoped that the future data base using that new score for a fetal
neurological assessment will help in distinguishing fetal brain and neurodevelopmental alterations due to the early
impairment in utero. There is an urgent need for multicentric studies with improved speed of 4D sonography. In the
meantime, new tests should be neither overestimated nor underestimated.
12. SUPPORTIVE MATERIAL
Power point presentation containing slides described in the text (see Appendix).
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Appendix
8 weeks: First Specific Body Movement Pattern Head And Rump- Sideways Bending With Small Speed
Amplitude Every 2 Min
9 weeks: side bending, arm and leg movements
10 weeks, isolated arm movement

Isolated arm movement
Isolated leg movement
10 weeks: hand to head movements

12 weeks: hand, leg and fist movements
Anteflexion
Stretching
Retroflexion
Rotation
Startle
Hand to face movement
Hand to head movement
Hand to mouth movement

Hand and finger movements
Face and smile
Smiling
Smiling, tongue expulsion
Tongue expulsion
Crying
Eyeblinking
Eyelids opening
Mouthing
Swallowing
Yawning
Yawning
Head retroflexion
Mouthing
Anencephaly
Acrania

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List of Contributors iii

1. Normal Fetal Anatomy and Development 1

Part 1. First Trimestre Anomalies 12

Part 2. Second Trimester: Cephalic Pole Malformations 49

Part 3. Second Trimester: Skeletal Disorders, Thoracic, Abdominal, Kidney and

3. Fetal Central Nervous System 118

4. Fetal 3D/4D Cardiovascular Imaging 133

5. Fetal Weight Estimation and Organ Volume Measurement by Three-Dimensional

7. Assessment of Fetal Behaviour by 3D and 4D Sonography 212

I wish this book a good success.

Dr. Alfred Kratochwil

Toshiyuki Hata, M.D., Ph.D.

Fernando Bonilla-Musoles Department of Obstetrics and Gynecology, Valencia School of Medicine,

Franciso Raga Universities of Valencia, Salvador de Bahia, Panamá City, Panamá

Newton Osborne3 Universities of Valencia, Salvador de Bahia, Panamá City, Panamá

Esperanza Villalaiz Universities of Valencia, Salvador de Bahia, Panamá City, Panamá

Fernanda Machado Universities of Valencia, Salvador de Bahia, Panamá City, Panamá

Toshiyuki Hata Department of Perinatology and Gynecology, Kagawa University, School of

Luis T. Mercé Department of Obstetrics and Gynaecology, International Ruber Hospital,

María J. Barco Bolonia Gynaecological Medical Center, Zaragoza, Spain

Guillermo Azumendi Prenatal Diagnosis, Ultrasound Unit Centro Gutenberg, Malaga

2. THREE-DIMENSIONAL ULTRASOUND OF THE GESTATIONAL SAC AND THE YOLK SAC

3. THREE-DIMENSIONAL ULTRASOUND OF THE EMBRYO AND THE FETUS

3.2. Fetal Extremities

3.3. Fetal Trunk

3.4. Fetal Face

(A) (B) (C) (D)

Part 1- First Trimestre Anomalies

 A third scanning between weeks 28 and 32 is only a recommendation.

 Transvaginal sonography [3, 36,38,39]

 Transabdominal sonography [33,40,42]

 Doppler scanning [1]

DETECTION OF MALFORMATIONS IN THE FIRST TRIMESTER

 It is necessary to diagnose malformations as early as possible because in practically all of Europe

 It is therefore important to perform morphologic ultrasonography between weeks 18 and 24 of

EMBRYONIC ULTRASOUND TIMETABLE

The first ultrasound survey has the following basic goals:

 Determine and document the number of gestational sacs.

 Document the presence or absence of an embryo.

 Document presence or absence of cardiac activity.

 Rule out ectopic pregnancy.

 Whether the progress of gestation is normal or abnormal.

 Presence of anomalies or malformations in the embryo or its adnexal structures.

 Whether there is fetal growth restriction.

 Evidence to suggest loss of fetal wellbeing.

Weekly Embryo Timetable

 It is always round or oval

 It measures 3 mm initially and grows 1.15 mm/day

 It is the first embryonic structure to appear on day 32 ± 1.

 It is 3 mm on week 5 and 6 to 7 mm on week 10.

 It is always round, has a homogeneous surface, and is echonegative.

 The first vascularity appears on its surface.

 It is responsible for transport and metabolism of the embryo.

 It is involved in abdominal wall closure.

 It is responsible for embryonic immune response.

 It creates the surface tension of the amnios.

Table 1: Normal and abnormal characteristics of the yolk sac

Characteristic Normal Pathologic

 The cephalic and caudal poles of the embryo are visible.

o Lower limb buds appear followed by upper limb buds.

o The medullary canal can be seen on the dorsum.