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Multiple Births
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Section 2 of 8
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Background: The term multiple births is defined as more Follow-up
than one fetus being born of a pregnant woman. Since Miscellaneous
Bibliography
1970, prevalence of multiple births has been increasing
because of more widespread use of assisted reproductive Click for related
technologies to treat infertility. Multifetal pregnancies are images.
high-risk pregnancies with a number of associated fetal
and neonatal complications. Researchers have studied
twins in an attempt to separate the influence of genetic
and environmental factors on both fetal and postpartum Continuing
development. Education
CME available for
Pathophysiology: Multiple births include twins and this topic. Click
higher order multiples (eg, triplets, quadruplets). The 2 here to take this
types of twins are monozygotic and dizygotic. CME.

Two sperm fertilizing 2 ova produce dizygotic twins, which Patient Education
sometimes are called fraternal twins. Separate amnions,
chorions, and placentas are formed in dizygotic twins. The Click here for
placentas in dizygotic twins may fuse if the implantation patient education.
sites are proximate. The fused placentas can be
separated easily after birth.

Monozygotic twins develop when a single fertilized ovum

splits during the first 2 weeks after conception.
Monozygotic twins also are called identical twins. An early
splitting (ie, within the first 2 days after fertilization) of
monozygotic twins produces separate chorions and
amnions (dichorionic/diamniotic). These dichorionic twins
have different placentas that can be separate or fused.
Approximately 30% of monozygotic twins have
dichorionic/diamniotic placentas.

Later splitting (ie, during days 3-8 after fertilization) results

in monochorionic/diamniotic placentation. Approximately
70% of monozygotic twins are monochorionic/diamniotic.
If splitting occurs even later (ie, during days 9-12 after
fertilization), then monochorionic/monoamniotic
placentation occurs. Monochorionic/monoamniotic twins
are rare; only 1% of monozygotic twins have this form of
placentation. Monochorionic/monoamniotic twins have a
common placenta with vascular communications between
the 2 circulations. These twins can develop twin-to-twin
transfusion syndrome (TTTS). If twinning occurs beyond
12 days after fertilization, then the monozygotic pair only
partially split, resulting in conjoined twins.

Triplets can be monozygotic, dizygotic, or trizygotic.

Trizygotic triplets occur when 3 sperm fertilize 3 ova.
Dizygotic triplets develop from one set of monozygotic
cotriplets and a third cotriplet derived from a different
zygote. Finally, 2 consecutive zygotic splittings with 1 split
result in a vanished fetus and monozygotic triplets.

It is important to evaluate the placenta(s) after the birth of

all multifetal pregnancies in order to determine zygosity.

Frequency:

In the US: The birth rate of monozygotic twins is

constant worldwide (approximately 4 per 1000
births). In contrast, dizygotic twinning is associated
with multiple ovulation, and its frequency varies
among races within countries and is affected by
maternal age (increases from 3 in 1000 in women
younger than 20 years to 14 in 1000 in women
aged 35-40 years, declining thereafter) and parity.
In the United States, the overall prevalence of twins
is approximately 12 per 1000, and two thirds are
dizygotic. The birth rate of dizygotic twinning is
highest for African Americans (10-40 per 1000
births), followed by Caucasians (7-10 per 1000
births) and Asian Americans (3 per 1000 births).
The rate of higher order multiple births has also
increased recently, which has been attributed to in
vitro fertilization and embryo transfer. Naturally
occurring triplet births occur in approximately 1 per
7000-10,000 births; naturally occurring quadruplet
births occur in 1 per 600,000 births.

Internationally: The birth rate of monozygotic

twins is constant worldwide (approximately 4 per
1000 births). Birth rates of dizygotic twins vary by
race. The highest birth rate of dizygotic twinning
occurs in African nations, and the lowest birth rate
of dizygotic twinning occurs in Asia. The Yorubas of
Western Nigeria have a frequency of 45 twins per
1000 live births, and approximately 90 percent are
 dizygotic.

Mortality/Morbidity: Multifetal pregnancies are high-risk

pregnancies. The fetal mortality rate for twins is 4 times
the fetal mortality rate for single births. The neonatal
mortality rate for twins is 6 times more than the neonatal
mortality rate for single births. Higher order multiple births
have even greater mortality rates in comparison to twin
and single births.

A high prevalence of low-birth weight infants, due to

prematurity and intrauterine growth retardation (IUGR)
and their associated complications, contribute to this
problem. Twins have increased frequency of congenital
anomalies, placenta previa, abruptio placenta,
preeclampsia, cord accidents, and malpresentations, as
well as asphyxia/perinatal depression, group B
streptococcal (GBS) infections, hyaline membrane
disease, and TTTS.

Race: The frequency of naturally occurring twin births

varies by race. Black women have the highest birth rate of
twins, followed by Caucasian and Hispanic women. Asian
women have the lowest birth rate of twins. There is a
racial disparity in the United States between black and
Caucasian twin stillbirths. Risk of stillbirth is elevated in
black fetuses compared with white fetuses among twins
but not triplets.

Age: Maternal age has no effect on monozygotic twin

births. Advanced maternal age (>35 y) is associated with
increased risk of dizygotic twins. Prevalence of naturally
occurring twin births has increased recently because of
the trend to delay childbearing to later years.

CLINICAL Section 3 of 8

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History: Most multifetal pregnancies are diagnosed

prenatally. Maternal complaints of excessive weight gain,
hyperemesis gravidarum, and/or sensation of more than
one moving fetus; use of ovulation-inducing drugs; or
family history of dizygotic twins should alert caregivers to
the possibility of a multifetal pregnancy.

Physical: Women with multifetal pregnancies may have a

uterine size inconsistently large for dates and may
experience accelerated weight gain. On auscultation,
more than one fetal heart rate may be heard.

Causes: Risk factors for multifetal pregnancy can be

divided into natural and induced. Risk factors for natural
multifetal pregnancy include advanced maternal age,
family history of dizygotic twins, and race. Induced
multifetal pregnancies occur following infertility treatment
via the use of ovulation-inducing agents or gamete/zygote
transfer.

WORKUP Section 4 of 8

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Lab Studies:

CBC: In TTTS the donor twin is frequently anemic

at birth. The recipient twin is polycythemic at birth.

Calcium: Hypocalcemia is common in premature

infants, especially the donor twin in TTTS.

Glucose: Hypoglycemia is common in premature

infants, especially if TTTS is present.

Bilirubin: Hyperbilirubinemia may develop in

polycythemic infants from TTTS.

Imaging Studies:

Maternal ultrasonography confirms most multiple

gestation pregnancies.

Neonatal head ultrasound: Premature infants from

multifetal pregnancies are susceptible to
intraventricular hemorrhage and periventricular
leukomalacia.

TREATMENT Section 5 of 8

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Medical Care: Medical care of the woman with multiple gestation pregnancy is
beyond the scope of this chapter.

Medical care of infants from multiple gestation births depends on

complications.
 The usual method of delivery for higher order multiple births (eg, triplets,
quadruplets) is cesarean delivery. Cesarean delivery is also the usual
method of delivery for twins in the following situations:

o Breech/vertex presentation with the possibility of interlocking twins

o Monoamniotic twins
o Conjoined twins
o Congenital anomalies that threaten increased neonatal morbidity
in a twin
o Delayed interval delivery of remaining fetuses in multifetal
pregnancy at the border of viability is becoming more common.
Before 30 weeks of gestation, delayed delivery for 2 or more days
is associated with improved survival in the second twin.

Delivery room management of infants from multifetal pregnancies

requires adequate personnel skilled in neonatal resuscitation. Infants
from multifetal pregnancies are at increased risk of birth asphyxia and
respiratory distress syndrome (RDS). Such infants may require bag mask
ventilation and endotracheal intubation in the delivery room.
Partial exchange transfusion may be necessary in donor or recipient
twins from TTTS.

o Partial exchange transfusions are used to increase hemoglobin

concentrations in anemic donor twins while maintaining euvolemia.
Small aliquots (5-15 cc) of packed red blood cells (RBCs) are
infused (usually via an umbilical venous catheter) following
removal of an equal volume of the infant's blood until a desired
hemoglobin is attained. The transfused packed RBCs should be
appropriately cross-matched, cytomegalovirus (CMV) negative,
and irradiated.

o Partial exchange transfusions are used to decrease hemoglobin

concentrations in polycythemic recipient twins while maintaining
euvolemia. Small aliquots (5-10 cc) of fresh frozen plasma are
infused (usually via an umbilical venous catheter) following
removal of an equal volume of the infant's blood until a desired
hemoglobin is attained.

Consultations: A woman with multiple gestation pregnancy may benefit from a

consultation with a perinatologist. A neonatologist may be involved in the
postnatal care of multiple birth infants, particularly if the births are premature or
if congenital anomalies are present.

FOLLOW-UP Section 6 of 8

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Complications:
 Prematurity: Infants from multifetal pregnancies are more likely to be born
prematurely and to require neonatal intensive care. Approximately 50% of
twin deliveries occur before 37 weeks' gestation. The length of gestation
decreases inversely with the number of fetuses present. Infants from
multifetal pregnancies represent 20% of very low birth weight infants.

Hyaline membrane disease: Twins born at fewer than 35 weeks' gestation

are twice as likely to develop hyaline membrane disease (HMD) as single
birth infants born at fewer than 35 weeks' gestation are. Prevalence of
HMD is greater in monozygotic than in dizygotic twins. Concordance rate
for HMD (ie, both twins have HMD) is greater in monozygotic than in
dizygotic twins. If the twins are discordant for HMD, then the second twin
is more likely to develop HMD than the first twin.

Birth asphyxia/perinatal depression: Newborns from multiple gestation

pregnancies have an increased frequency of perinatal depression and
birth asphyxia from a variety of causes. Umbilical cord entanglement,
locked twins, a prolapsed umbilical cord, placenta previa, and uterine
rupture can occur and result in asphyxiation of an infant. Occurrence of
cerebral palsy is 6 times more common in twin births and 30 times more
common in triplet births than in single births.
Monochorionic/monoamniotic twins are at highest risk for cord
entanglement. The second-born twin is at greatest risk for birth
asphyxia/perinatal depression.

GBS infections: Early onset GBS infections in low birth weight infants are
nearly 5-fold greater than in average weight singletons.

Vanishing twin syndrome: Early ultrasound diagnosis has revealed that

as many as one half of all twin pregnancies result in the delivery of only a
single fetus. The second twin vanishes. Intrauterine demise of one twin
can result in neurologic sequelae in the surviving twin. Acute
exsanguination of the surviving twin into the relaxed circulation of the
deceased twin can result in intrauterine CNS ischemia.

Congenital anomalies/acardia/twin reversed arterial perfusion sequence:

Congenital anomalies more commonly develop in twins than in a single
fetus. CNS, cardiovascular, and GI defects occur with increased
frequency. Monozygotic twins have increased prevalence of deformations
secondary to intrauterine space constraints. Common deformations in
twins include limb defects, plagiocephaly, facial asymmetry, and torticollis.
Acardia is a rare anomaly unique to multiple gestation. In this condition,
one twin has an absent or rudimentary heart. Twin reversed arterial
perfusion (TRAP) sequence occurs when an acardiac twin receives all of
the blood supply from the normal "pump" twin. This only occurs in
monochorionic twins. Blood enters the acardiac twin in a reversed
perfusion manner. Blood enters this fetus via an umbilical artery and exits
via the umbilical vein. The excessive demands on the normal "pump" twin
can cause cardiac failure in that twin.
 Twin-to-twin transfusion syndrome: This syndrome occurs in
monochorionic/monoamniotic or monochorionic/diamniotic twins.
Vascular anastomoses in the monochorionic placenta result in transfusion
of blood from one twin (ie, donor) to the other twin (ie, recipient). One
classification scheme separates TTTS into severe, moderate, and mild
forms.
o Severe TTTS presents early in the second trimester (16-18 weeks'
gestation). A difference of more than 1.5 weeks' gestational size
between twins occurs. Severe TTTS has a 60-100% mortality rate.
Polyhydramnios develops in the sac of the recipient twin because
of volume overload and increased fetal urine output.
Oligohydramnios develops in the sac of the donor twin because of
hypovolemia and decreased urine output. Severe oligohydramnios
can result in the stuck twin phenomena in which the twin appears
in a fixed position against the uterine wall.
o Moderate TTTS develops later at 24-30 weeks' gestation. Although
a fetal size discrepancy of more than 1.5 weeks' gestation occurs,
polyhydramnios and oligohydramnios do not develop. The donor
twin becomes anemic, hypovolemic, and growth retarded. The
recipient twin becomes plethoric, hypervolemic, and macrosomic.
Either twin can develop hydrops fetalis.
o Mild TTTS develops slowly in the third trimester. Polyhydramnios
and oligohydramnios usually do not develop. Hemoglobin
concentrations differ by more than 5g/dL. Twin sizes differ by more
than 20%. Polycythemic twins can develop hyperviscosity
syndrome and hyperbilirubinemia after birth.

Conjoined twins: Incomplete late division of monozygotic twins produces

conjoined twins. Conjoined twins are connected at identical points and
are classified according to site of union.

o Thoracopagus - Joined at chest (40%)

o Xiphopagus/omphalopagus - Joined at abdomen (34%)
o Pygopagus - Joined at buttocks (18%)
o Ischiopagus - Joined at ischium (6%)
o Craniopagus - Joined at head (2%)

Intrauterine growth retardation: Birth weights of twins, triplets, etc. are

smaller than weights of corresponding singletons. However, when
combined, birth weights of twins are greater than weights of
corresponding singletons. Most of the deficit of birth weight occurs in the
final 8-11 weeks of pregnancy. Average birth weights are similar between
twins and singletons until 32 weeks of gestation. Average birth weights
are similar between triplets and singletons until 29 weeks of gestation.
Birth weight discrepancies of more than 20-25% are considered
discordant. Discordant birth weights occur in 10% of twins. The cause of
discordant birth weights among twins is the difference between each
twin's placental surface area or TTTS. Discordant birth weights among
triplets are more common than discordant birth weights between twins.
Approximately 30% of pregnancies with triplets have a birth weight
 discordance of more than 25%.

Prognosis:

The prognosis of infants born from multiple gestations depends upon the
complications that develop. Some studies have reported that the risks of
death, chronic lung disease, and grade III/IV intracranial hemorrhage
were similar in twins and singletons. Other studies have reported a higher
prevalence of complications such as necrotizing enterocolitis, retinopathy
of prematurity, and patent ductus arteriosus in infants from multiple
gestation versus singletons.

MISCELLANEOUS Section 7 of 8

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Medical/Legal Pitfalls:

Most problems that could result in medical legal action against the health
professional involve prenatal and intrapartum care issues.

Special Concerns:

Multiple births have significant economic implications. Twins and triplets

have more frequent and longer duration hospitalizations than singletons.
Multiple births contribute disproportionately to inpatient hospital costs in
the first 5 years of life.