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The Management of Large and Small for

Gestational Age Fetuses


Philip Steer

The major influence on birth weight is gestational age. At any given week of gestation, however, size
varies enormously. There is no specific cut-off that separates abnormally large or small babies for
gestational age from normal. Instead, function alters as a continuum across the weight distribution.
Small babies are prone to hypoxia, acidosis, and stillbirth. Large babies on the other hand are
associated with prolonged labor and mechanical problems. The optimum size for fetal survival is 1
to 1.5 standard deviations above the mean, whereas cesarean section rates are lowest when the fetal
weight is 0.5 to 1.5 standard deviations below the mean. Antenatal detection of both very small and
very large babies is difficult and imprecise. Expectant management is therefore preferable unless
there are very specific indications for emergency or operative delivery.
© 2004 Elsevier Inc. All rights reserved.

he management of babies that are large or cases in each step becomes small, approximately
T small for gestational age presents many
problems, not the least of which is that size at
100 or less.
Figure 2 illustrates that the lowest perinatal
birth is a continuum without precise cut-offs mortality occurs when the birth weight is 1.0 to
delineating normal from abnormal. This can be 1.5 standard deviations (SD) above the mean (1
illustrated using data from the North West SD above the mean is approximately the 84th
Thames regional database (containing data on percentile, 2 SD is approximately the 98th cen-
all pregnancies booked into 15 maternity units tile). It can also be seen that perinatal mortality
in the North West Thames Region of London increases steadily away from this central group,
between 1988-1998 inclusive). The database in- without any clear cut-off at a particular SDS. As
cludes 497,105 pregnancies, of which 439,689 babies are smaller for gestational age, their peri-
progressed far enough in pregnancy to have a natal mortality increases, reaching 100% at 5.5
birth weight recorded. Data were entered by standard deviations from the mean. Larger ba-
trained clerks or midwives with on-line valida- bies also have a higher perinatal mortality, but
tion and prompting, and standard definitions after a standard deviation of 2.5, the numbers of
for a range of clinical measurements. The qual- perinatal deaths are too small to be meaningful.
ity of data collected has been shown to be high.1
The overall perinatal mortality rate was 2.63 per
For the purposes of this paper, I have analyzed
thousand, of which the greater proportion was
data from 137,114 White European women in
made up of stillbirths. Antepartum stillbirths ac-
their first registrable pregnancy, and gestational
counted for 1.46 per thousand, intrapartum still-
age at delivery of 37 weeks or more. This avoids
births 0.39 per thousand, and indeterminate
the complication of ethnic differences, and the
stillbirths 0.15 per thousand. The pattern of still-
effect of preterm delivery. For each week of
births mirrored that of overall perinatal mortal-
gestational age, the mean and the standard de-
viation of birth weight was calculated for boys
and girls, and then the birth weight of each baby
From the Division of Paediatrics, Obstetrics, and Gynecology, De-
expressed as a positive or negative standard de-
partment of Obstetrics and Gynaecology, Imperial College, London,
viation from the mean according to gender UK.
(standard deviation score, SDS). Address reprint requests to Philip Steer, BSc, MB, BS, MD, FRCOG,
Figure 1 illustrates the distribution of birth Academic Department of Obstetrics and Gynaecology, Chelsea and
weight by standard deviation scores, in steps of Westminster Hospital, 369 Fulham Rd, London SW10 9 NH, UK;
e-mail: p.steer@imperial.ac.uk.
0.5 of a standard deviation. It can be seen that © 2004 Elsevier Inc. All rights reserved.
outside a standard deviation of 3 (which in- 0146-0005/04/2801-0007$30.00/0
cludes 99.73% of the population) the number of doi:10.1053/j.semperi.2003.10.013

Seminars in Perinatology, Vol 28, No 1 (February), 2004: pp 59-66 59


60 Philip Steer

Figure 1. Distribution of birth weight by standard


deviation score (log scale of actual numbers of preg-
nancies analyzed).

Figure 3. The percentage of abnormal fetal heart


ity, whereas that of neonatal deaths showed a less rate patterns in labor according to standard deviation
clear relationship with SDS. score of birth weight.
The main contribution to hypoxic dysfunc-
tion during labor is from babies that are small
small babies relating more to hypoxemia and
for gestational age. Figure 3 illustrates the
acidosis (Figs 6 and 7), while those in the large
higher proportion of abnormal fetal heart rate
babies relate more to trauma, associated with a
patterns during labor associated with being
higher rates of emergency cesarean section
small, compared with average or large babies. A
(Fig 8).
similar pattern is seen with meconium staining
The fact that the dysfunction associated with
of the amniotic fluid during labor (Fig 4), al-
being large or small is a continuum accounts for
though there is a slight increase with large ba-
the failure of consensus on what limits should be
bies. Once again, there is no specific cut-off of
used to define large or small babies for gesta-
SDS that delineates normal from abnormal. On
tional age; the 10th, 5th or 3rd centile, or 2SD,
the other hand, the proportion of babies taken
have all been used to define small for gestational
to the special care baby unit after birth rises
age. Indeed, it can be argued that while size
sharply away from the mean, for both small and
matters, function matters even more.2 Work
large babies (Fig 5). This probably reflects dif-
from our group has shown previously that failure
ferent problems in the 2 groups, those in the

Figure 4. The percentage of meconium staining of


Figure 2. Perinatal mortality (percent, log scale) ac- the amniotic fluid according to standard deviation
cording to standard deviation score of birth weight. score of birth weight.
Large and Small for GA Fetuses 61

Figure 5. Percentage of babies transferred to the Figure 7. Mean Apgar score (⫾ 95% confidence lim-
special care baby unit following birth according to its) at 5 minutes by standard deviation score of birth
standard deviation score of birth weight. weight.

of growth during gestation is a better predictor large babies irrespective of the aetiology of their
of peripartum and neonatal dysfunction than macrosomia. Measures of size that take into ac-
size per se.3 Many small babies are constitution- count maternal dimensions have advantages
ally small (“healthy small”4), while some babies (see Gardosi, this issue), but even then, correc-
that are failing to achieve their growth potential tion for severe maternal underweight for exam-
are above the 10 centile.5 These latter babies can ple may result in false reassurance.
be termed “normal weight growth restricted.”
Large babies on the other hand may be consti- Implications for Management
tutionally large, or large because their mother is
overweight or diabetic. The implications, such as Small Babies
neonatal hypoglycemia, are greater in the latter Antenatal detection of babies that are small for
group, although mechanical problems in labor gestational age is currently neither easy nor ef-
such as shoulder dystocia are common in all fective. Ideally, and to be most cost-effective,
screening on a population basis should be prac-
tical using history and clinical examination. The
single most effective indicator of a high risk of a
small for dates baby is a small baby in a previous

Figure 6. Mean lowest pH in labor (⫾ 95% confi-


dence limits) by standard deviation score of birth Figure 8. Percent delivered by emergency caesarean
weight. section by standard deviation score of birth weight.
62 Philip Steer

weight (Fig 9). Even more striking is the lack of


an increased elective cesarean section rate with
such small babies, in contrast to the increased
elective cesarean section rate for large babies
(Fig 10).
How should we manage babies that are diag-
nosed as being very small, either serendipitously
or on the basis of risk factors? Ideally, we should
use a therapy to improve intrauterine fetal
growth. Unfortunately, although many therapies
such as bed rest in hospital,10 maternal nutrient
supplementation,11 maternal oxygen administra-
tion,12 plasma volume expansion,13 and the use
of beta mimetics14 or calcium channel blockers15
to reduce uterine tone and thereby encourage
Figure 9. Number of ultrasound scans per pregnancy placental blood flow have been advocated, re-
according to standard deviation score of birth weight. sults either show no benefit or insufficient evi-
dence of benefit for them to be recommended
at the present time. The only practical approach
pregnancy (30% recurrence risk), and yet obvi- is therefore timely delivery of the fetus. The
ously this history is not available for women in scheme that we use at the Chelsea and Westmin-
their first pregnancy. Other factors predisposing ster hospital is illustrated in Figure 11; such
to intrauterine growth restriction include mater- schemes are widely used.16 The use of Doppler
nal malnutrition (low body mass index), and examination of umbilical artery blood flow as a
smoking. However, most of these historical fea- screen for uteroplacental dysfunction is well es-
tures carry a relative risk of smallness of only 1.3 tablished,17 and probably effective at reducing
to 1.8 times and are therefore not specific stillbirth.18 Some regard absent or reversed end
enough to allow targeted screening. The only diastolic flow as a sufficient indication for deliv-
clinical examination relevant to detecting small ery, even in preterm infants.4 Others, however,
for gestational age babies is symphysis-fundal prefer to rely on analysis of the fetal heart rate
height measurement. A recent Cochrane collab- pattern. The growth restriction intervention trial
oration review6 of such measurements found (GRIT)19 was designed to investigate the opti-
only one reliable randomised trial, which did mum timing of delivery for babies known to be
not show a useful pickup rate.7 The predictive small, and with abnormal Doppler blood velocity
accuracy of third trimester ultrasound for the waveforms. It was a Bayesian trial, which means
detection of intrauterine growth restriction has that it was designed to take into account differ-
been studied extensively, and the abdominal cir- ences in the threshold of different clinicians to
cumference has been found to be the single
most effective measurement to use.8 However,
the same studies have shown that there is both a
significant false negative, and a large false-posi-
tive rate. The Cochrane review of routine third
trimester ultrasound screening for fetal growth
in low-risk populations came to the conclusion
that it was not effective.9
The North Thames database also suggests
that antenatal detection of significantly “small
for dates” fetuses is poor. The number of ante-
natal scans per pregnancy increases from an
average of 2 per pregnancy for normal weight
babies, to only 3 per pregnancy even for babies Figure 10. Percent emergency caesarean section by
that are 3 standard deviations below mean birth standard deviation score of birth weight.
Large and Small for GA Fetuses 63

The overall effect was therefore a slightly lower


death rate prior to discharge in the delayed
group (27/291, 9% v 29/296, 10%, including
late neonatal deaths) although this difference
did not reach statistical significance. Although
the average randomization to delivery time was
only 4 days longer in the delayed group, none-
theless, if one includes the effect of the higher
stillbirth rate and the lower neonatal mortality, it
is likely that there was a significant cost benefit
to the delayed delivery policy. This is because
antenatal care is much cheaper than neonatal
intensive care per day. However, the detailed
cost analysis of this study has yet to be reported.
The trial is continuing with the follow-up of the
babies in the 2 groups, and because it is a Bayes-
ian trial, interim results are available. At the time
of writing, Griffiths assessments (a measure of
sensory, motor, and intellectual performance) at
approximately 2 years of age show a slight ad-
vantage in the score for the delayed delivery
group in babies born at 24 to 30 weeks’ gesta-
tional age. The median 2-year score is identical
for babies born at 31 weeks’ gestational age or
more. The full results must be awaited before we
will be able to tell whether this advantage is
significant. Nonetheless, it does appear that
even when the umbilical artery Doppler is ab-
normal, it is reasonable to wait to deliver until
the fetal heart rate pattern becomes abnormal.
Moreover, early evidence of hypoxemia on the
fetal heart rate tracing does not appear to indi-
cate irreversible hypoxic damage. In terms of
accuracy, consistency, and reliability, there may
well be advantages to using online computerized
Figure 11. Scheme for antepartum fetal monitoring. fetal heart rate analysis, such as that provided by
the Sonicaid 8,000 system (Oxford Instruments
delivery at various gestations, depending on Medical LTD, UK).20,21 More sophisticated mea-
whether umbilical artery Doppler showed re- sures of blood flow and distribution are dis-
duced, absent, or reversed end diastolic flow. cussed elsewhere in this issue, but it will be
When the clinicians reached the point at which necessary to conduct further prospective studies
they were unsure whether to deliver now, or to before one can judge whether such sophistica-
deliver later, the patient was randomised either tion results in improved outcome. Until such
to “deliver now” (meaning within 48 hours to studies are conducted, it seems reasonable to
permit completion of the steroids course), or to continue with the policy as laid out in Figure 11.
“delay delivery” (meaning until delivery was in- Once the decision to deliver has been taken,
dicated using other tests, commonly analysis of it is necessary to consider the mode of delivery.
the fetal heart rate pattern). As might have been This will depend on the gestational age of the
expected, there was a higher stillbirth rate in the fetus, and the ripeness of the cervix. Even if the
delayed group (9/291 v 2/296), but this was indication for delivery is an abnormal cardioto-
balanced by a higher neonatal death rate in the cogram, if the cervix is favourable induction of
immediate delivery group (23/296 v 12/291). labor should be considered because experience
64 Philip Steer

shows that in at least 50% of cases the fetal heart livery. There is no simple answer to this di-
rate pattern returns to normal once labor be- lemma, which has to be addressed by close con-
gins. This is presumably because of increased sultation with the parents and neonatologists.
sympathetic drive causing redistribution of A small but significant proportion of intra-
blood flow in the fetus toward the vital organs uterine growth restriction is caused by infection
such as the brain and the heart, resulting in with cytomegalovirus, which is very difficult to
improved oxygenation. However, if there is evi- detect antenatally; it is usually diagnosed by cul-
dence of marked hypoxaemia, suggestive of al- ture of the virus from the urine of the newborn
ready established acidosis, delivery by cesarean baby. Rubella is also a significant cause but is
section is probably safer because the tolerance of usually clinically more obvious because of the
the growth restricted fetus to further hypoxia maternal rash which occurs. Abnormalities of
during labor is limited.22,23 Some have suggested growth associated with maternal use of “recre-
that the addition of intrapartum hypoxemia to ational drugs” (such as cocaine, heroin, and al-
restricted antepartum cardiac output may signif- cohol) and medically prescribed drugs such as
icantly increase sequelae such as necrotizing en- anticonvulsants and Warfarin should also be
terocolitis,24 although others have found little or considered and managed appropriately.
no effect.25,26
It should also always be borne in mind that
the aetiology of intrauterine growth restriction Large Babies
may not be simply uteroplacental insufficiency.
Any small baby should be screened carefully for As shown in Figures 1 to 10, the risk to the large
congenital abnormalities, including aneuploidy. for gestational age baby is not so much antepar-
This involves detailed and systematic ultrasound tum hypoxaemia and acidosis as the problem of
examination, and chromosomal analysis from prolonged labor and intrapartum trauma. The
amniocentesis and cordocentesis may also be majority of macrosomic babies are not associ-
necessary. About 1 in 5 very small babies will ated with diabetes, but with large mothers. Thus,
prove to have congenital abnormalities, and this within the North West Thames database cohort
proportion is higher if growth failure is detected as defined above for this study, macrosomia (de-
before 26 weeks, or there is associated polyhy- fined arbitrarily as a birth weight ⬎ ⫽ 4 kg)
dramnios.4 This is because growth restriction occurred in 9.5% of 123,681 women with normal
associated with uteroplacental insufficiency in- carbohydrate tolerance during pregnancy,
creases in incidence as pregnancy progresses. It 15.8% of 766 women with gestational diabetes,
is uncommon before 26 weeks’ gestation, and is and 23.4% of 312 women with established dia-
usually associated with oligohydramnios because betes. However, macrosomia associated with di-
of the reduced renal perfusion in growth re- abetes accounted for only 1.6% of all babies
stricted babies. Management of growth re- weighing 4 kg or more. In contrast, the risk of
stricted babies with aneuploidy, particularly tri- macrosomia rose from 4.8% in underweight
somy 21, can pose ethical problems. Parents may women (body mass index [BMI] ⬍ 20, n ⫽
feel ambivalent about emergency delivery by ce- 8,040), to 8.1% in women with a normal BMI (20
sarean section for a Down’s fetus with failure of to 24.9, n ⫽ 61,260), 12% in overweight women
growth, or an abnormal fetal heart rate tracing. (BMI 25 to 29.9, n ⫽ 27,687) and 15.6% in obese
However, such babies may not necessarily die women (BMI 30 or more, n ⫽ 9,156). However,
without emergency delivery, and expectant man- unlike diabetes, overweight was associated with
agement can therefore result in a baby with 32.9% of macrosomia, and obesity with 14.1%.
impaired intellectual potential being further Thus, almost half of all macrosomia occurred in
compromised by hypoxic ischemic damage. An- women who were overweight or obese. More-
other area of ethical difficulty is the manage- over, these macrosomic babies were more than
ment of multiple pregnancy, where one or more twice as likely to be delivered by emergency ce-
of the fetuses is growth restricted, and the re- sarean section as babies weighing less than 4 kg
mainder are growing normally. To rescue the (21% v10.3%). Unfortunately, it is in obese
growth restricted baby will place the normally mothers that fetal weight assessment is most dif-
grown fetus at increased risk from preterm de- ficult, both clinically and by ultrasound, and
Large and Small for GA Fetuses 65

both large and small babies are likely to go accuracy deteriorates away from the mean value
undetected. with a tendency toward the mean. Thus, there is
One of the most feared causes of intrapartum a tendency to overestimate the weight of small
trauma is shoulder dystocia. Most papers have babies and underestimate the weight of large
reported that fetal macrosomia is the principal ones. For example, in one study, in diabetic
risk factor for shoulder dystocia.27-33 However, patients, 26.3 % of the birth weights were under-
our ability to detect macrosomia antenatally is estimated by more than 15 %, compared to 5.4%
limited and none of these studies recommended in a nondiabetic control group.38 In another
routine abdominal delivery for suspected mac- study, the mean error in diabetic patients was
rosomia. In one study of 4,480 births,30 in which 265g, with the error being over 500g in almost
the overall frequency of shoulder dystocia was 10%.39 Even in diabetics, maternal weight rather
2% (90 cases), the majority of cases (93%, 83 than glycemic control is one of the most useful
cases) occurred in infants weighing less than predictors.40 The topic of route of delivery of
4,500g. In a detailed study of cost effectiveness, macrosomic fetuses in diabetic pregnancies has
Rouse et al34 concluded that “For the 97% of recently been fully reviewed in this Journal by
pregnant women who are not diabetic, a policy Conway.41
of elective cesarean delivery for ultrasonographi-
cally diagnosed fetal macrosomia is medically
and economically unsound. In pregnancies com- Summary
plicated by diabetes, such a policy appears to be
The management of small for dates and large
more tenable, although the merits of such an
for dates fetuses is complicated by the fact that
approach are debatable.”
they exist as part of a continuum, with no clear
If elective cesarean section is not justified,
distinction between pathology and normality.
what about induction of labor before the due
Accordingly, management decisions must be
date? Attempting to deliver the baby vaginally
based not only on the estimated fetal weight for
before it gets too large is a logical approach.
gestational age, but also on functional criteria
However, even the most recent studies do not
such as changes in growth velocity, and mea-
show any advantage to induction before the due
sures of fetal wellbeing including components of
date.35 Moreover, a recent systematic review of 9
the biophysical profile. The mode of delivery will
observational studies and 2 randomized trials of
depend on a balance being struck between fetal
labor induction for suspected fetal macrosomia
and maternal risk, the facilities available for
has shown that such a policy results in an in-
monitoring labor, and the wishes of the parents.
creased cesarean delivery rate without improv-
ing perinatal outcomes.36 It appears that the
benefits of the baby being smaller are vitiated by References
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