Clinical Strategies

f o r I m p ro v i n g t h e
Detection of Fetal
G ro w t h R e s t r i c t i o n
Jason Gardosi, MD, FRCOG

KEYWORDS
 Intrauterine growth restriction  Pregnancy
 Small for gestational age  Fetal surveillance

The single most important condition affecting the viable fetus is intrauterine growth
restriction, which in turn is associated with perinatal mortality, morbidity, and delayed
effects such as cerebral palsy and diseases in later life.1–3 IUGR is a common condi-
tion, affecting about 10% to 15% of the general maternity population.
Despite its importance and relatively high prevalence, IUGR detection is poor: in
routine maternity care, only about 25% of babies who are born IUGR are detected
as such antenatally,4 and in low-risk pregnancy, with lower levels of suspicion, detec-
tion rates as low as 15% have been reported.5
There are many reasons for this poor performance of maternity services, including,
insufficient means whereby to predict the at-risk pregnancy; lack of standardized,
evidence-based methods for screening and surveillance; and insufficient effort to
target investigations on the pregnancies where this matters.
Before dealing with these in turn, it is important to examine the definition of who is
actually growth restricted (ie, pathologically small). Usually, population norms are
being used to determine small for gestational age (SGA), which is then mistakenly
called ‘IUGR’. True IUGR associated with adverse outcome is then often not recog-
nized because of a failure to differentiate between constitutional and pathologic small-
ness. This can be avoided by defining growth restriction as the failure to reach the
individual growth potential.

DEFINING THE FETAL GROWTH POTENTIAL

This follows three basic principles.6,7 First, the growth standard needs to reflect
constitutional/physiologic variation due to maternal characteristics such as height
and pre-pregnancy or early pregnancy weight, as well as ethnic origin and birth order
(parity).8,9 Coefficients for each of these factors have been derived for maternity

West Midlands Perinatal Institute, Birmingham, B6 5RQ, UK

E-mail address: jason.gardosi@pi.nhs.uk

Clin Perinatol 38 (2011) 21–31

doi:10.1016/j.clp.2010.12.012 perinatology.theclinics.com
0095-5108/11/$ – see front matter Ó 2011 Published by Elsevier Inc.
22 Gardosi

populations in the United Kingdom,9 Australia10 New Zealand,11 France12 Spain,13 the
United States,14,15 and Sweden.16 International comparisons have demonstrated
many similarities in the growth potential that a baby of a standard mother can expect
to have in different countries10,14
Second, the standard has to exclude pathologic factors, such as smoking, hyper-
tensive diseases in pregnancy, or diabetes. The most common example is smoking,
known to affect birth weight in a dose-related relationship up to a deficit of around
250 g at term.9,17,18 Such factors should not affect the standard: rather than predicting
the birth weight that will be achieved, the growth potential defines the weight which the
baby should achieve if such pathologic factors were not present. Growth then can be
monitored against such an optimal standard, to increase the likelihood that IUGR is
detected if it does occur.
Third, preterm birth is also pathologic, and its association with IUGR is well
known.19–21 The weight distribution is negatively skewed, and birth weight is
lighter than fetal weight at the corresponding gestational age, derived from fetuses
that continue to grow toward a normal term delivery. The growth potential is
calculated by linking the predicted term optimal weight (TOW) to an intrauterine
proportionality curve based on Hadlock’s fetal growth standard22 to show the
weight that should be expected at each gestation week in an ‘optimal’ pregnancy,
the ‘gestation-related optimal weight curve’ (GROW).23 For populations with insuf-
ficiently detailed data to calculate individual growth potential, the term average
weight (TAW) can be entered into a software program that links it with the propor-
tionality equation to give an average fetal growth curve for that population,23 less
precise than TOW but still better than basing a growth curve on abnormal preterm
birth weight.

IDENTIFYING PATHOLOGY

The use of the growth potential identifies up to a third more cases than the original
SGA population,16 which are not recognized as SGA by conventional, population-
based birth weight percentiles. This unrecognized SGA group could, for example,
include SGA babies who were born preterm and not recognized as SGA by the
population-based neonatal weight standard,24 or they could include babies of large
mothers with birth weights that are within the population average, but small compared
with the customized growth potential.
Customixed birth weight standards have been demonstrated to be superior to
population-based standards in their associations with pregnancy complications
such as antepartum hemorrhage, preeclampsia, abnormal Doppler, or caesarean
section for fetal distress and adverse outcome including low 5-minute Apgar
score; need for neonatal resuscitation, admission, and prolonged stay in the
neonatal intensive care unit, adverse neurologic outcome, stillbirth, and neonatal
death.12,24–28
In Fig. 1, this principle is illustrated for neonatal deaths24; SGA determined by
customized growth potential is more strongly associated with neonatal deaths than
when population percentiles are used (square markers). A category (bottom of figure,
diamond markers: “Cust only SGA”) is identified, which is SGA by customized
percentiles only. This also is significantly linked to neonatal mortality, but is not
detected by the population standard. Another proportion of babies categorized as
SGA by the population standard were not SGA by the customized standard (see
Fig. 1 top, diamond markers: “Pop only SGA”), and these babies had no elevated
risk.24 Typically, these are small normal babies, designated as false-positive SGA
 Detection of Fetal Growth Restriction 23

Fig. 1. Neonatal deaths and small for gestational age (SGA) status by customized and pop-
ulation based percentiles. SGA was defined according to population-based percentiles (All
SGA by Pop) and SGA by customized centiles (All SGA by Cust) (square markers). Subgroups
are shown that are SGA by both methods (Pop and Cust SGA), by the population method
only (SGA Pop only), or by the customized method only (SGA by Cust only) (diamond
markers). Odds ratios and 95% confidence intervals are shown. (Reproduced from Gardosi
J, Francis A. Adverse pregnancy outcome and association with smallness for gestational
age by customised and population based birthweight percentiles. Am J Obstet Gynecol
2009;201:28, e6; with permission.)

by the population standard. They are also an important category to recognize, to

avoid unnecessary investigations and interventions.
The advantages of the customized growth potential concept become even more
evident when subgroups of maternal size and parity within the study population are
examined. A recent study compared customized with uncustomized fetal weight stan-
dards, and showed consistently, for each subgroup, that SGA defined by customized
growth reflected perinatal mortality risk substantially better than when SGA was
defined by an unadjusted fetal weight standard.16

CLINICAL APPLICATION

Antenatal detection of IUGR is an essential component of maternity care. First, it

informs the clinician and thence the mother that the pregnancy is at increased risk,
allowing considerations on the optimal timing for delivery. Depending on severity,
babies who are not fulfilling their growth potential have a 5- to 10-fold risk of dying
in utero.25
Second, the information is important as a prompt for further investigations such as
umbilical artery Doppler, which has been shown to reduce stillbirth and increase
preterm delivery without increasing neonatal mortality.29 In a large single-center retro-
spective study, antenatal detection of SGA was found to lead to significantly improved
outcome.30
Improvements in defining who is pathologically small has a positive effect on predic-
tion, surveillance and diagnosis of IUGR, which will each be examined in turn.
24 Gardosi

EARLY PREGNANCY PREDICTION

Current ability to predict which pregnancy will develop IUGR is limited. While low
PAPP-A or hCG in the first trimester31–33 or increased serum AFP, hCG, or inhibin-A
in the second trimester34–36 are associated with an increased risk of placenta-
related diseases and early onset preeclampsia and IUGR, predictive values do not
currently support routine use. Similarly, uterine artery Doppler can identify pregnan-
cies at risk37 but is not recommended for general application.38
Women with a past history of fetal growth restriction have a 50% increased risk of
growth restriction in the current pregnancy.39 However, IUGR is often misdiagnosed,
as constitutional factors are not taken into consideration. For example, the small baby
of a small mother might be falsely considered to have been IUGR, resulting in unnec-
essary investigations. Or the apparently well grown baby of a large mother may in fact
have been IUGR, but not detected as such unless customized percentiles are applied
when assessing the birth weight.
Obesity has been considered a protective factor for growth restriction,40 but such
findings are likely to be artifactual because of the use of unadjusted population stan-
dards. When SGA is defined by customized percentiles, obesity increases the risk of
SGA by 50%.25 Such relative smallness is pathologic: a large population-based
study25 reported that in obese women, higher perinatal mortality is associated with
higher rates of SGA, but only when SGA is defined by customized growth potential
(Fig. 2). Although obesity affects the accuracy of ultrasound biometry, it makes palpa-
tion and fundal height measurement even more difficult.41

Fig. 2. Perinatal mortality rate (PMR) and smallness for gestational age (SGA) by customized
(SGAcust) and population-based percentiles (SGApop), according to maternal body mass
index (BMI). Comparison test for difference of slopes: PMR versus SGAcust: P 5 .753; PMR
versus SGApop: P 5 .007. (Reproduced from Gardosi J, Clausson B, Francis A. The value of
customised centiles in assessing perinatal mortality risk associated with parity and maternal
size. BJOG 2009;116:1360; with permission.)
 Detection of Fetal Growth Restriction 25

Thus, against the background of currently limited capabilities to predict IUGR, the
application of customized growth potential improves the identification of which babies
are at risk and require increased surveillance.

ANTENATAL SURVEILLANCE

In the absence of good predictors, close surveillance during pregnancy is even more
important, and includes serial assessment of fetal growth by fundal height measure-
ment as a primary screening tool. Fundal height assessment has had variable results,
mainly because of lack of standardization. Furthermore, fundal height measurements
vary with individual maternity characteristics and also need to be adjusted or
customized.42 The customized chart displays a weight and a fundal height axis for
plotting the measurement, and the emphasis is on the slope or velocity of the growth
curve and whether it follows the predicted limits. In Fig. 3, charts for two mothers with
different characteristics are shown, with the resultant difference in curves illustrated by
the respective centiles of the same birthweight plotted on each.
A controlled study of serial fundal height measurements plotted on customized
charts, compared with clinical palpation, found significant improvement in detection
and reduced investigation, because the method was more likely to provide reassur-
ance when the measurement was normal.43
Thus here again the concept of growth potential results in improved detection and
increased cost-effectiveness because of a reduced number of investigations for
small–normal babies.

TARGETED INVESTIGATIONS AND DIAGNOSIS

Cochrane systematic reviews have suggested that umbilical artery Doppler in high-
risk pregnancy (hypertension or SGA) improves outcome, while routine Doppler in
low-risk pregnancies is not effective.29 Therefore, current best practice is to try to
identify the at-risk pregnancy that requires diagnostic investigation by umbilical artery
or other forms of Doppler studies.
Serial scans in the third trimester have not shown improved detection rates in
routine use,44 but are recommended in the high risk pregnancy, based either on
past history or on the basis of abnormal fundal height measurement.45,46 Therefore
ultrasound biometry is an essential part of the diagnostic pathway, and it is essential
that it is accurate. The preferred assessment is by calculating estimated fetal weight
through standard formulas suitable for the local population, and plotting the findings
on customized charts.45 Individual parameters such as biparietal diameter, head
circumference (HC), abdominal circumference (AC), and femur length (FL) cannot as
yet be customized, and their normal limits are based on the general population,
thereby missing cases that are smaller than their growth potential.
This problem is illustrated in Fig. 4, with an actual case from the West Midlands
confidential enquiries into perinatal deaths. A fetus suspected of IUGR on the basis
of a drop in fundal height measurements was referred for an ultrasound scan at
39 weeks. The individual parameters (HC 328 mm, AC 325 mm, FL 67 mm) were
plotted on standard ultrasound charts and showed in each case to be within normal
limits (see Fig. 4A). An estimated fetal weight was not plotted on the customized chart
but if it had been, it would have shown 2830 g, which was below the 10th percentile
adjusted for the mother’s characteristics (see Fig. 4B) and would have prompted
further investigations or delivery. Two days after the scan, the mother presented
with no fetal movements. Fetal death was diagnosed, and a normally formed male still-
born baby was delivered a day later, weighing 2810 g.
26 Gardosi
 Detection of Fetal Growth Restriction 27

Fig. 4. (A) Individual parameters (HC 328 mm, AC 325 mm, FL 67 mm) were plotted on stan-
dard ultrasound charts and showed in each case to be within normal limits. An estimated
fetal weight was not plotted on the customized chart but if it had been, it would have shown
2830 g, which was below the 10th percentile adjusted for the mother’s characteristics (B).
:

Fig. 3. Examples of customized charts using GROW (Gestation Related Optimal Weight soft-
ware vs 7.5.1, www.gestation.net.). The charts can be used to plot previous baby weights
and ultrasound estimated fetal weights in the current pregnancy (right Y axis) as well as fun-
dal height measurements for serial assessment (left Y axis). The horizontal axis shows the
day and month of the start of each week of gestation, calculated by the software on the
basis of the estimated date of confinement. The 3 curves on the chart are the 50th percentile
and the 10th and 90th percentile limits, representing the predicted range of optimal growth
for each pregnancy, after adjustment for maternal height, weight, parity and ethnic origin.
The pregnancy details are shown on the top left of the chart, with maternal height in cm,
and maternal weight in kg. The example shows two mothers, “Mrs Small” and “Mrs Large,”
with two different sets of characteristics. A previously born baby girl weighing 3000 g at
40.0 weeks is illustrated as being of average size (49th birthweight percentile) for Mrs Small
(Fig. 3A), but small for gestational age (SGA, 5th percentile) for Mrs Large (Fig. 3B).
28 Gardosi

Fig. 4. (continued)

AUDIT AND IMPROVEMENT OF PERFORMANCE

An important contributor to slow progress in improving perinatal outcome is a lack of

recognition and appreciation of the importance of IUGR. In addition, classification
systems for stillbirths and perinatal mortality have until recently returned a high
proportion (two-thirds or more) of stillbirths as being ‘unexplained’, and by implication
unavoidable. However, the application of customized percentiles allows the inclusion
of a category for IUGR, defined as a birth weight below the 10th customized percen-
tile. While the 5th and 3rd percentile cut-offs are even more strongly linked with
adverse outcome, the 10th percentile has a higher etiologic fraction for stillbirth16
and is closer to the optimal point (8th) in the receiver operator curve for predicting peri-
natal morbidity.47
Applying such principles in a new classification system (“Relevant Condition at
Death”–ReCoDe) showed that over 40% of stillbirths from 24 weeks, and over
50% when congenital anomalies are excluded, have had preceding IUGR.48 This
results also in a substantial reduction of the proportion of stillbirths categorized
as unexplained, to only about 16%.48,49 In a cohort of stillbirths that remained
unexplained even after postmortem and other investigations, over half were iden-
tified as IUGR when customized percentiles are applied.50
Linked to this, there is usually no system in place to audit and monitor how well
the health service performs in the task of identifying IUGR. In the West Midlands,
a region with a population of 5 million and annual births of 70,000, antenatal
detection of IUGR was recently agreed as a key performance indicator of the
effectiveness of maternity services, to be collected in all pregnancies. Analyses
of the impact are to follow, but within the first year, there are already
 Detection of Fetal Growth Restriction 29

improvements apparent in detection rates, which is likely to be due to an

increased attention being paid to the importance of this condition, as well as
increased training and standardized protocols.

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