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1. Chapter 11
Fetal Growth Disorders
TATIANA STANISIC CHOU • JULIANNE S. TOOHEY
K E Y U P D AT E S
1 Thrombophilias may be associated with intrauterine growth restriction (IUGR).
2 Multiple-dose steroids have been associated with growth restriction.
3 Customized growth curves should be employed when possible to allay bias in the
population.
4 Doppler velocimetry has been found to be a predictor of adverse perinatal
outcome.
5 In an attempt to identify a fetus in distress prior to the severe consequences of
hypoxemia or acidemia, the ductus venosus has been investigated because of its
rapid blood flow.
6 Several studies of long-term outcomes in IUGR infants reveal an association
between lower IQ and an increase in emotional and behavioral issues. Long-term
outcomes of IUGR fetuses are associated with decreased IQ as well as emotional
and behavioral issues.
7 An increased incidence of the metabolic syndrome with type 2 diabetes, obesity,
cardiovascular disease, and hypertension in adult life has been associated with IUGR.
Intrauterine Growth Restriction age, or SGA) with the understanding that not all SGA
infants are pathologically growth restricted and may in
BACKGROUND fact be constitutionally small. Similarly, not all fetuses
• Intrauterine growth restriction (IUGR) refers to the that have failed to achieve their growth potential fall
condition of a fetus unable to achieve its genetically under the 10th percentile for the gestational age.
determined potential size. This definition would • Can be associated with maternal, fetal, or placental
exclude constitutionally small fetuses that would not causes.
be at risk for adverse outcome; however, often this
cannot be determined absolutely until after delivery. In SYMMETRICAL AND ASYMMETRICAL
addition, there is a subset of fetuses that are intrinsically • Symmetrical IUGR occurs during the first few months
small and for whom intervention will not affect of gestation and is caused by the failure of one or more
outcome such as in Trisomy 18. The clinical challenge cell cycles leaving all organ systems equally smaller in
is to identify a fetus that is at risk for poor outcome size.
with the hope that modification of risk factors and • Asymmetrical IUGR occurs in the second half of the
appropriate interventions will improve such outcomes. pregnancy and is associated with malnutrition and
We also would like to identify small but otherwise hypoxemia of the fetus.
healthy fetuses in order to avoid unnecessary and
inadvisable interventions. CLASSIFICATIONS
• Incidence rate of IUGR in singleton fetuses is 3% • Constitutionally small fetus measurements are
to 7% (Romo et al, 2009) and 15% to 25% in twins symmetrical with normal amniotic fluid.
(McCormick et al, 1985). • Chromosomal and structural abnormalities, often
• Correct diagnosis requires accurate dating, which can symmetrical measurements with aberrations of the
be difficult and is frequently inaccurate. amniotic fluid volume.
• Ethnicity and racial considerations affect the expected • Substrate deficiencies and placental insufficiency,
growth rate of a fetus, which complicates population- usually asymmetrical growth restriction with associated
based growth curves. oligohydramnios.
DEFINITION ETIOLOGIES
• Estimated fetal weight measured as less than 10th • Fetal causes. Include genetic disorders such as
percentile for the gestational age (small for gestational chromosomal and structural abnormalities.
97

2. 98 Section 4 | The Third Trimester and Late Pregnancy Complications
• Maternal causes. Include conditions such as Studies have shown that compared to symmetric twins,
hypertension, renal disease, restrictive lung disease, asymmetric discordant twins are at higher risk for
Class F or greater diabetes, cyanotic heart disease, adverse outcomes (Dashe et al, 2000). However, each
antiphospholipid syndrome, collagen-vascular disease, dichorionic twin must be assessed individually, as each
and hemoglobinopathies, which could lead to fetal fetus follows its own growth velocity curve. Normal
hypoxemia, vasoconstriction, or decreased fetal growth velocity in each twin is of greater importance
perfusion leading to IUGR. Clinical maternal vascular than a discordant measurement between the two
disease and the presumed decrease in uteroplacental fetuses. Monochorionic twins must be evaluated in light
perfusion can account for 30% of growth-restricted of possible vascular anastomoses. Severe IUGR can be
infants. seen as part of the twin-twin transfusion syndrome.
Early diagnosis is essential in order to manage
U P D AT E # 1
complications related to this condition.
• Primary placental disease can also be related to IUGR
Thrombophilias have shown some correlation with IUGR. Meta- often leading to impaired perfusion because of
analysis (Howley et al, 2005) found an association with factor V
Leiden and prothrombin gene mutation; however, more recent
conditions such as placenta previa, hemangiomas,
studies show no relationship. abruption, or infarcts. IUGR without other
abnormalities is usually associated with a small placenta
with diminished diffusing capacity. Abnormal cord
• Other possible causes. Exposure to teratogens, insertions such as velamentous and marginal cord
malnutrition (less than 1500 kcal/day), smoking, or insertions are other causes of IUGR.
substance abuse (fetal alcohol syndrome strongly
correlates with IUGR). Maternal cigarette smoking SCREENING
decreases birth weight approximately 135 to 300 gm, • Lagging fundal height noted during prenatal exam is
the fetus being symmetrically smaller. If smoking typically the first indication but is often inaccurate and
is discontinued prior to the third trimester, the should only be used for screening.
deleterious effect on birth weight is reduced. Prolonged • Essentially, all pregnant women will be screened by
use of some medications, including steroids, Dilantin measuring fundal height when receiving prenatal care.
and Coumadin, has also been associated with growth which at 32 to 34 weeks’ gestational age provides 96%
restriction in the fetus. Uterine abnormalities such as specificity and 70% to 85% sensitivity (Leeson et al, 1997).
fibroids or bicornuate or separated uteri are also a cause • Those women with previous IUGR pregnancies should
of IUGR as is prolonged exposure to high altitudes. be screened by ultrasound because of their increased
risk. The recurrence rate for IUGR in a previous
U P D AT E # 2 pregnancy is nearly 20% (Berghella et al, 2007).
Steroids have been used to improve fetal morbidity and
mortality by advancing fetal lung maturity in preterm births. U P D AT E # 3
The practice of repeated dosing became commonplace in the The use of population-based growth curves has been the
United States despite a lack of evidence for its necessity. Studies standard. However, there is currently much discussion of
have shown that the group receiving repeat courses of beta- customized growth curves to allay bias in the population. Some
methasone, specifically four or more doses, had a birth weight portion of the variability in fetal birth weight can be attributed to
reduction of 95 g (Wapner et al, 2006), which was not seen fetal and maternal factors including gender of the fetus,
in the group receiving zero to three doses. Repeated steroid ethnicity, maternal body habitus, age, and education. Studies
dosing more commonly resulted in birth weight below the 5th (Gardosi et al, 2009) have found that 33% of the babies
and 10th percentiles for gestational age. This study also failed identified as IUGR by the customized curve were not recognized
to show any benefit to repeated dosing compared to placebo. by the population-based curve, and 26% of those were born
A single rescue course of steroids given prior to 33 weeks was prematurely. Additionally, 17.2% of those found to be IUGR by
shown to improve outcome without increased short-term risk the population-based curve were within normal growth patterns
(Garite et al, 2009). by the customized standards and were born without any of the
studied adverse outcomes. Multicenter investigations sponsored
by the National Institute of Child Health and Development
• Infections including viruses such as fetal rubella, (NICHD) and the World Health Organization (WHO) are under
Cytomegalovirus, and varicella are a cause for intrauterine way to address these issues sonographically.
growth restriction. Additionally protozoal infections such as
Toxoplasma gondii and Toxoplasma cruzi as well as syphilis
are other possible causes. Bacterial infections are not shown DIAGNOSIS
to cause IUGR. • Estimated fetal weight by ultrasound
• Multiple gestations are associated with an increased • Head-to-abdomen or femur-to-abdomen ratios
risk for intrauterine growth restriction as well as a • Growth velocity tracked over time
progressive decrease in fetal and placental weight as • Evaluation of amniotic fluid
the number of offspring increases. IUGR can be seen
in both monochorionic and dichorionic twins. Twins EVALUATION
are considered discordant when there is greater than • Detailed anatomic survey
20% difference in growth. There is no established • Consideration for fetal karyotyping
standard for what amount of discordance is significant. • TORCH titers if viral infection is suspected

3. Chapter 11 | Fetal Growth Disorders 99
• Consider amniotic viral DNA testing meta-analysis in 1997 that found three interventions
• Consider a thrombophilia workup, though this is improving fetal growth. These included strategies to
controversial decrease smoking, providing nutritional supplements
for undernourished women, and treating malaria
FETAL EVALUATION when this was found to be the etiology for the growth
• Nonstress testing (NST) restriction.
• Biophysical profile (BPP) • Pollack and colleagues reported in 1997 on in-hospital
• Contraction stress test bed rest and found no improvement in fetal condition.
• Serial ultrasound exams for growth velocity every 2 to • The only treatment that has improved neonatal
4 weeks outcome is administration of steroids when premature
• Doppler velocimetry delivery is anticipated. Bernstein reported similar
benefits in the growth-restricted infant compared to its
U P D AT E # 4
normally grown counterpart.
• Recent reports have noted that there may be a subset
Doppler velocimetry was found to be the best predictor of of particularly at-risk fetuses. In 2004, Simchen et al.
adverse perinatal outcome in IUGR (Gonzalez et al, 2007). Indi-
ces used for Doppler evaluation include systolic/diastolic ratio,
noted that after administration of steroids in a group
the resistance index (systolic velocity—diastolic velocity/systolic of chromosomally normal IUGR fetuses with either
velocity) and the pulsatility index (systolic velocity—diastolic absent or reverse diastolic flow, 45% had a transient
velocity/mean velocity) (Hoffman et al, 2009). improvement in the Doppler waveform. This group had
significantly better outcomes than the group that had
no improvement.
• Umbilical artery. Providing an early sign of IUGR, • Despite the theoretic benefits of aspirin to treat or
umbilical artery Doppler indicates vascular blockage at prevent IUGR, studies are conflicting, and as such the
the placenta by measuring the systolic/diastolic ratio. role of aspirin is undetermined.
As more of the vasculature is affected, the end diastolic
flow decreases until it is eventually absent or reversed, MANAGEMENT
which is an indication of fetal vascular distress with a • Once IUGR is diagnosed, serial exams should
potentially fatal outcome (Hoffman et al, 2009). be conducted including non-stress test (NST),
• Middle cerebral artery. Once umbilical artery blood biophysical profile (BPP), and ultrasound to
flow is found to be abnormal, the middle cerebral follow the development of the fetus and track its
artery is examined to look for brain sparing resulting condition. Steroids are given when preterm delivery is
from blood shunting to the brain in the condition of anticipated.
hypoxemia or hypercapnia. In 2008, Mari and Hanif • Timing of delivery depends on several factors:
found that the middle cerebral artery peak systolic • Abnormal fetus. Timing depends on etiology and
velocity consistently showed an increase in blood desire to intervene.
velocity and then a decrease immediately prior to fetal • Placental insufficiency. Depends on growth velocity,
demise. gestational age, fetal status, and lung maturity.
• Term or near term. Deliver for preeclampsia, for no
U P D AT E # 5 growth over 2 to 4 weeks, for BPP of 6 or less, and for
In an attempt to identify a fetus in distress prior to the severe absent end or reverse diastolic blood flow.
consequences of hypoxemia or acidemia, the ductus venosus • Remote from term. Individualization is made based on
has been investigated because of its rapid blood flow. Using gestational age and fetal status.
color and duplex Doppler to identify abnormal blood flow or • Constitutionally small fetus. If a fetus has normal
reversed or absent end-diastolic flow has been suggested as growth velocity on serial ultrasounds, symmetrical
an indicator for delivery; however, this remains in debate (Mari measurements, no abnormalities, and normal
et al, 2008). Mari and Picconi have argued against using ductus amniotic fluid volume, expectant management can be
venosus reverse flow (DVRF) for delivery indications prior to employed.
32 weeks’ gestation, noting that acidemia is uncommon in DVRF
fetuses and each week of gestation between 25 and 29 weeks OUTCOME
s
­ ignificantly decreases mortality.
• IUGR is associated with an increase in fetal
morbidity and mortality, including the need for
• Staging (Mari et al, 2008). induction, fetal compromise during labor, cesarean
• Stage I: Normal NST and umbilical artery Doppler section, iatrogenic prematurity, and stillbirth. Gardiosi
show no hypoxemia or fetal acidosis. and colleagues noted in 1998 that nearly 40% of
• Stage II: Normal NST and abnormal umbilical artery stillbirths with no abnormalities were small for
Doppler found 5% rate of hypoxia or acidosis. gestational age.
• Stage III: Abnormal NST and umbilical artery • Morbidity for neonates with IUGR includes increased
Doppler found a rate of 60% hypoxia or acidosis. rates of thrombocytopenia, temperature instability,
necrotizing enterocolitis, and renal failure.
TREATMENT • Considerations for long-term outcome of these
• There has been limited success in treating fetal growth infants include developmental, academic and
restriction. Gulmezoglu and colleagues reported a physical growth.

4. 100 Section 4 | The Third Trimester and Late Pregnancy Complications
IUGR Screening
U P D AT E # 6
Berghella V: Prevention of recurrent fetal growth restriction, Obstet Gynecol
Evaluating several published studies of long-term outcomes of 110(4):904–912, 2007.
IUGR infants, the Perinatal Outcome and Later Implications of Leeson S, Aziz N: Customised fetal growth assessment, Br J Obstet Gynaecol
Intrauterine Growth Restriction publication (Pallotto et al, 2006) 104(6): 648–651, 1997.
noted several long-term complications for these children. Studies
of the IQ of IUGR infants and their average-sized controls have IUGR Fetal Evaluation
generally found an association between IQ and IUGR resulting in Gardosi J, Francis A: Adverse pregnancy outcome and association with
a four- to eight-point decrease in IUGR infants. Abnormal Doppler small for gestational age birthweight by customized and population-based
studies in IUGR have also been associated with impaired cognitive percentiles, Am J Obstet Gynecol 201(1), 2009. 28.e1–8.
Gonzalez J, Stamilio D, Ural S, et al: Relationship between abnormal fetal
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testing and adverse perinatal outcomes in intrauterine growth restriction,
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Hoffman C, Galan H: Assessing the at-risk fetus: Doppler ultrasound, Curr
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