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OBSTETRICS
Intrauterine growth restriction: new concepts in antenatal
surveillance, diagnosis, and management
Francesc Figueras, MD, PhD; Jason Gardosi, MD, FRCOG
tial assessment as well as the baseline for evidence, that 1 cm fundal height should The high heterogeneity between stud-
subsequent measurements, which are in- equal 1 week of gestation and the defini- ies does not allow the calculation of
terpreted on the basis of the slope or ve- tion of normal as fundal height 2 or pooled values. The largest study,88 from
locity of growth. Indications for referral 3 cm of gestational age. But as with birth- the United Kingdom, included 3616
for further investigations include cases in weight and ultrasound growth, one size low-risk women on whom a third-tri-
which the first fundal height measure- does not fit all, and different-sized moth- mester (28-36 weeks) ultrasound was
ment is below the 10th centile or consec- ers have different normal fundal height performed with abdominal circumfer-
utive measurements suggest static or growth curves.80 As a serial assessment, ence measurement. Sensitivity for birth-
slow growth, meaning that the serial the emphasis with fundal height mea- weight less than the 10th centile was
measurements do not follow the ex- surement is on the slope of the curve. Re- 48%, with a false-positive rate of 7%.
pected slope of the growth curve. An au- ferral guidelines for further investigation Lindqvist and Molin26 introduced a pol-
dit on the population in the catchment by ultrasound biometry and Doppler in- icy of a routine scan at 32 weeks and ob-
area of a referral hospital in the West clude a single fundal height measurement served a detection rate of 54% for SGA
Midlands (UK) showed that the detec- which plots below the 10th customized (defined as birthweight deviation of at
tion rates for SGA fetuses are improved if centile, and serial measurements which least 22% from the mean, equivalent to
referral recommendations are fully ad- cross centiles (ie, are slower than the pre- the third centile). Hedriana and Moore89
hered to, highlighting the need for a con- dicted growth velocity).79 compared serial vs single scan in low-risk
tinuous program of education and A controlled study of 1200 patients women between 28 and 42 weeks and
training.69 compared measurement and plotting of found that multiple ultrasonographic
Not all pregnancies are suitable for fundal height on customized growth examinations provided little improve-
primary surveillance by fundal height charts against routine clinical assessment ment in the prediction of birthweight
measurement and require ultrasound bi- by palpation and found that it resulted in compared with a single observation.
ometry instead. In most instances, these a significant increase in antenatal detec- McKenna et al90 tested randomly a pol-
pregnancies fall into the following cate- icy of 2 scans at 30 and 36 weeks and
tion of SGA babies from 29% to 54%.81
gories: (1) fundal height measurement observed that fewer babies were born
Furthermore, there was a significant re-
unsuitable (eg, due to fibroids, high ma- SGA as a result of increased intervention
duction of false-positive rates (ie, small-
ternal body mass index) or (2) preg- in the study group, although no data
normal babies being referred unneces-
nancy considered high risk (eg, due to were given on actual detection rates.
sarily for investigation). The study was
previous history of SGA). The impact of routine third-trimester
not powered to assess the effect on peri-
Fundal height measurement is more of ultrasound on perinatal outcome is also
natal mortality, and there is a paucity of
a surveillance than a screening tool be- unclear. Seven trials83,85,86,91-94 have
prospective trials large enough to be able
cause its strength lies in serial assess- been included in a recently updated
ment. However, most clinicians are not to assess the effect on hard outcome metaanalysis95 that showed that routine
formally taught how to measure fundal measures. However, the antenatal iden- late pregnancy ultrasound in low-risk or
height and use a variety of different tification of IUGR is already of proven unselected populations does not confer
methods. This reduces accuracy and in- benefit in itself and allows further inves- benefit on mother or baby. Furthermore,
creases interobserver variation. Not sur- tigations and interventions that are it may be associated with a small increase
prisingly, the evidence on fundal height known to improve outcome. Serial mea- in cesarean section rates.
assessment is mixed, with some studies surement of fundal height and plotting However, it could be argued that the
reporting that it is a good predictor for on customized growth charts are recom- results of this metaanalysis have limited
IUGR,70-73 whereas others fail to find mended by the Royal College of Obste- validity for contemporary practice be-
much benefit.74-78 tricians and Gynaecologists guidelines.82 cause it included studies that used out-
A recent review has summarized the dated surrogates of fetal growth such
efforts being made to standardize this Routine/intermittent third-trimester ul- as biparietal diameter measurement83
tool to improve its reliability and effec- trasound biometry. The effectiveness of or protocols in which the diagnosis of
tiveness.79 The name symphysis-fundus third-trimester ultrasound biometry IUGR was not followed by a change in
height is in fact misleading because the pre- for the diagnosis of growth restriction management. A Swedish population-
ferred direction of measurement is from and its impact on perinatal outcome is based study96 compared the perinatal
the variable (the fundus) to the fixed point uncertain. Sensitivity of abdominal outcome of 56,371 unselected women in
(the top of the symphysis). The measure- circumference for detecting a birth- whom routine third-trimester ultra-
ment should be along the fetal axis, with no weight less than the 10th centile ranges sound was performed with the outcome
correction of the fundus to the midline, us- from 48% to 87%, with specificity from of 153,355 women with no such screen-
ing a nonelastic tape. 69% to 85%.83-88 For estimated fetal ing. No differences in perinatal mortality
One of the main problems has been weight, sensitivities of 25-100% have or early neonatal morbidity were found.
the assumption that has crept into com- been reported, with a specificity of There is currently therefore insuffi-
mon clinical practice, without any good 69-97%.84,87-89 cient evidence to support routine third-
of chronic placental embolization, the progressively abnormal because of in- late-onset IUGR cases, which needs fur-
obliteration of more than 50% of the pla- creasing hypoxemia and/or hypoxia, the ther investigation in randomized trials.
cental vessels is required before absent or latter correlates with acute changes oc-
Amniotic fluid. A metaanalysis132 of 18
reversed end-diastolic velocities appear. curring in advanced stages of fetal com-
randomized studies demonstrated that
There is good evidence that umbilical promise, characterized by severe hyp-
an amniotic fluid index of less than 5 is
Doppler ultrasound use in these preg- oxia and metabolic acidosis, and usually
associated with abnormal 5 minute Ap-
nancies improves a number of obstetric precedes fetal death by a few days. Be-
gar score but failed to demonstrate an
care outcomes and reduces perinatal cause a fixed sequence of fetal deteriora-
association with acidosis.
deaths.108 tion does not exist, integration of several
Longitudinal studies in early-onset
Whereas abnormal umbilical artery well-being tests into comprehensive
IUGR fetuses have shown that the am-
Doppler is associated with adverse peri- management protocols is required.
niotic fluid index progressively de-
natal and neurodevelopmental out-
creases.129,130 Amniotic fluid volume is
come,109-112 small fetuses with normal
Chronic tests believed to be a chronic parameter. In
umbilical artery Doppler are considered
Umbilical artery. Absent or reversed fact, among the components of biophys-
to represent one end of the normal-size
end-diastolic velocities are mostly found ical profile, it is the only one that is not
spectrum, and the importance of manag-
in early-onset IUGR, and these patterns considered acute. One week before acute
ing them as completely differently from
deterioration, 20-30% of cases have
true IUGR babies has been stressed.113,114 have been reported to be present on
average 1 week before the acute deterio- oligohydramnios.129,130
This may not be true for late-onset cases, in
which a substantial proportion of cases ration.128 Up to 40% of fetuses with
with a normal umbilical artery may have acidosis show this umbilical flow pat- Acute markers
true growth restriction, and are at risk of tern.128 Despite the fact that an associa- Ductus venosus (DV). Early studies on
adverse perinatal outcome.109,110,115,116 tion exists between the presence of IUGR fetuses demonstrated a good cor-
reversed end-diastolic flow in the umbil- relation of abnormal DV waveform with
Other Doppler parameters ical artery and adverse perinatal out- acidemia at cordocentesis,133 and this
Because the identification of late-onset come (with a sensitivity and specificity of Doppler sign is considered a surrogate
SGA fetuses with mild forms of growth about 60%), it is not clear whether this parameter of the fetal base-acid status.
restriction cannot only be relied on by association is confounded by prematu- The progression of this parameter is
umbilical artery Doppler, other vascular rity. More recent series129 of severely shown in Figure 6. Absent-reversed ve-
territories have been proposed. Abnor- compromised IUGR fetuses suggest that locities during atrial contraction are asso-
mal uterine artery Doppler is compara- such a finding has value independently ciated with perinatal mortality indepen-
ble with umbilical artery Doppler as a of gestational age in the prediction of dently of the gestational age at delivery,134
predictor of adverse outcome in growth- perinatal morbidity and mortality. with a risk ranging from 60% to 100% in
restricted fetuses.116-118 Up to 20% of fetuses with early-onset IUGR.135 How-
Middle cerebral artery. Longitudinal ever, its sensitivity for perinatal death is still
SGA fetuses have reduced resistance in studies on deteriorating early-onset
the middle cerebral artery (MCA), and 40-70%.134,136,137
IUGR fetuses have reported that the pul- Longitudinal studies have demon-
this sign is also associated with poorer
satility index in the MCA progressively strated that DV flow waveforms become
perinatal outcome116-119 and subopti-
becomes abnormal.130 Figure 5 shows abnormal only in advanced stages of fetal
mal neurodevelopmental development
the progression of this parameter. Up to compromise.128-131 Whereas in about
at 2 years of age.120 Umbilical and cere-
80% of fetuses have vasodilatation 2 50% of cases abnormal DV precedes the
bral Doppler can be combined in the ce-
weeks before the acute deterioration,128 loss of short-term variability in the fetal
rebroplacental ratio. This ratio has been
although other series have found this fig- heart rate,130 in about 90% of cases it be-
demonstrated in animal121 and clini-
ure to be less than 50%.129 Preliminary comes abnormal only 48-72 hours be-
cal122 models to be more sensitive to
hypoxia than its individual components
findings of an acute loss of the MCA va- fore the biophysical profile.131 Debate
sodilatation in advanced stages of fetal exists regarding the advantages of DV
and correlates better with adverse
compromise have not been confirmed in Doppler investigation over biophysical
outcome.123
more recent series,128-131 and therefore profile. However, observational stud-
Assessment of the IUGR fetus this sign does not seems to be clinically ies138 suggest the integration of both DV
Because no treatment has been demon- relevant for management purposes in Doppler investigation and biophysical
strated to be of benefit for FGR,124-127 early-onset cases. In late-onset IUGR, profile in the management of preterm
the assessment of fetal well-being and there is observational evidence116,119 IUGR because these strategies seem to
timely delivery remains as the main that MCA vasodilatation is associated stratify IUGR fetuses into risk categories
strategy for management. Fetal well-be- with adverse outcome independently of more effectively. An ongoing random-
ing tests could be classified as chronic or the umbilical artery. This suggests a role ized clinical trial (Trial of umbilical and
acute. Whereas, the former becomes of MCA Doppler for fetal monitoring in fetal flow in Europe, TRUFFLE) is aimed
FIGURE 5 FIGURE 6
Color Doppler assessment of the middle cerebral artery Insonation of the ductus
venosus with color Doppler
A
A
E
C
there is no evidence to support the use of pears to be independently reflected by Improved definition of the intrauter-
traditional fetal heart rate monitoring or both tests, further studies are required to ine standard for IUGR by the use of the
nonstress tests in IUGR fetuses. How- prove the usefulness of combining both fetal growth potential allows a more dis-
ever, these studies were conducted in the testing modalities. cerning assessment. A baby with an EFW
early 1980s, and the control group had Longitudinal series131 have demon- below the 10th customized centile has a
no fetal well-being assessment or out- strated that except for amniotic fluid vol- significantly elevated risk of morbidity,
dated techniques such as biochemical ume and the fetal heart rate, the other even in the absence of an abnormal um-
tests. components (tone, breathing, and body bilical artery Doppler.110 Added into the
Computerized FHR has provided new movements) of the biophysical profile equation is the awareness that leaving
insight into the pathophysiology of become abnormal only in advanced pregnancies with IUGR to deliver at term
IUGR. Short-term variability closely stages of fetal compromise. In fact, in may also lead to perinatal morbidity and
correlates with acidosis and severe hyp- about 90% of cases, the biophysical pro- delayed effects such as cerebral palsy.2
oxia as demonstrated by cord blood file becomes abnormal only 48-72 hours Therefore, current best practice would
sampling at the time of a cesarean sec- after the ductus venosus.131 indicate that from the time fetal pulmo-
tion.141 Whereas Bracero et al142 demon- nary maturity can be inferred, there is
strated no significant differences in peri- Timing of delivery little to be gained by allowing a preg-
natal outcome between visual and IUGR is one of the most common preg- nancy to continue if good fetal growth
computerized FHR, more recent longi- nancy complications and substantially cannot be demonstrated. However, each
tudinal series have pointed to a potential increases the prospective risk of adverse case needs to be carefully assessed and
role as an acute marker.130 Short-term outcome. Yet according to pregnancy individually considered, in consultation
variability becomes abnormal, coincid- audits, most instances of IUGR are not with the parents. f
ing with the DV: whereas in about half of detected as such antenatally. Modern
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