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Growth-restricted fetuses pose many clinical conundrums: How to identify them? How to distinguish the small and normal from the small and abnormal? How to manage them?
Committee on Practice Bulletins - Obstetrics
ACOG Practice Bulletin Number 134: Fetal Growth Restriction, May 2013 (Replaces Practice Bulletin Number 12, January 2000). Obstet Gynecol. 2013; 121: 1122-1133. Full text of ACOG Practice Bulletin is available to ACOG members at http://www.acog.org/Resources_And_Publications/Practice_Bulletins/committee_on_practice_bulletins_--_Obstetrics/Fetal_Growth_Restriction
Fetal Growth Restriction
Fetal growth restriction, also known as intrauterine growth restriction, is a common complication of pregnancy that has been associated with a variety of adverse perinatal outcomes. There is a lack of consensus regarding terminology, etiology, and diagnostic criteria for fetal growth restriction, with uncertainty surrounding the optimal management and timing of delivery for the growth-restricted fetus. An additional challenge is the difficulty in differentiating between the fetus that is constitutionally small and fulfilling its growth potential and the small fetus that is not fulfilling its growth potential because of an underlying pathologic condition. The purpose of this document is to review the topic of fetal growth restriction with a focus on terminology, etiology, diagnostic and surveillance tools, and guidance for management and timing of delivery.
Used with permission. Copyright the American College of Obstetricians and Gynecologists.
By Joshua A. Copel, MD
Dr. Copel is a professor of obstetrics, gynecology, reproductive sciences, and pediatrics at Yale University School of Medicine, New Haven, Connecticut. He is also a member of the Contemporary OB/GYN editorial board.
Growth-restricted fetuses pose many clinical conundrums: How to identify them? How to distinguish the small and normal from the small and abnormal? How to manage them? Once ultrasound weight projection tables became available more than 30 years ago, a major goal of prenatal care became how to prevent the morbidity and mortality of what was dubbed the growth-restricted fetus. The term “growth restriction” replaced “growth retardation” because of the negative prognostic connotations of the word “retardation.”
Risk factors for fetal growth restriction are usually categorized as maternal, fetal, and placental. Only a few of these factors are readily modifiable, most notably substance abuse. Some risk factors, such as congenital infections, may be avoidable to a certain degree, whereas others fall into that more difficult category including exposures to medications that are important for maternal health. Frustratingly, controlling maternal diseases such as lupus and hypertension does not always improve birthweights.
Periodically reviewing our state of knowledge about fetal growth restriction (FGR) is important. ACOG Practice Bulletin (PB) 134 reviews the etiologies of FGR and screening strategies for it, and addresses pertinent clinical questions.
In PB 134, FGR and small-for-gestational-age (SGA) are distinguished by the time of identification. FGR is defined as the fetus with estimated weight below the 10th percentile, whereas SGA refers to newborns with weights below the 10th percentile for gestational age. This review will use those definitions, although SGA may be better used for fetuses thought to be constitutionally small and FGR for those with suspected pathology, usually as identified by abnormal Doppler findings.
Maternal conditions including hypertension and antiphospholipid antibody syndrome are considered strong risk factors for FGR. Importantly, PB 134 reminds us that the hereditary thrombophilias such as factor V Leiden, the prothrombin G20210A mutation, and methylenetetrahydrofolate reductase gene mutations have not consistently been associated with FGR.
Pregnant women with small fetuses often ask about the adequacy of their nutrition. However, even famine-level caloric intake (600–900 kcal/day) has only a modest effect on birth weight.1 Conversely, increased caloric intake is very unlikely to alter the growth of an FGR fetus.
Viral titers often are recommended for assessment of FGR, although viral infections cause a small fraction of reported cases. Depending on maternal history and other findings such as intracranial or peritoneal calcifications, viral testing may be useful. Most infectious-mediated FGR worldwide is caused by malaria.
Chromosomal malformation can cause FGR, especially trisomies 13 and 18, so in the presence of FGR with malformations, and often associated polyhydramnios, it is prudent to offer invasive testing. Although not addressed in the PB, I discourage maternal cell-free fetal DNA testing in this circumstance because it does not offer microarray analysis. It is also becoming clear that copy number variants (eg, microdeletions and microduplications) are associated with FGR.
Among placental anomalies, a single umbilical artery has recently been more convincingly shown to be associated with FGR. Consequently, although not addressed in the PB, I recommend a growth check at 32 weeks for affected pregnancies, with no further testing if it is normal. A similar recommendation can be made for velamentous and perhaps even marginal cord insertions.
Should all patients have a screening “growth scan” in the third trimester? Should we adopt first- or second-trimester uterine artery Doppler velocimetry or use serum analytes for this purpose? The PB is quite clear that the basic screening modality is fundal height measurements and that there is no evidence of value for a routine growth scan in normal pregnancies.
Maternal obesity or the presence of large uterine myomas, if they make fundal height measurement difficult, can be indications for serial sonograms for fetal size estimation.
There is little benefit to uterine artery Doppler in the first trimester because it has a high false-positive rate and there is no evidence of improved outcomes with its use. Evidence of the association between FGR and low Pregnancy Associated Plasma Protein A (PAPP-A) in the first trimester or high serum alpha-fetoprotein in the second trimester is sufficient to check a third-trimester growth scan in affected pregnancies, but I would not order these tests to predict FGR alone.
The major advance of the past 20 years in mangement of FGR has been the incorporation of umbilical artery Doppler velocimetry. Doppler does not work as a screening test because there are many etiologies of FGR that do not result in aberrant umbilical artery flow. However, there is a utility to Doppler flow studies in the setting of demonstrable FGR. Abnormal results, especially absent or reversed end-diastolic flow, can be used to modify frequency of fetal surveillance with other traditional tests (ie NST, BPP) with improved perinatal survival.
Although PB 134 categorizes the value of Doppler investigation of other vessels such as the middle cerebral artery and ductus venosus as uncertain, many experts use these tests to supplement the information obtained from the umbilical artery.
NEXT: MANAGEMENT AND DELIVERY
Finally there is the thorniest question of all: when to deliver. The growth-restricted preterm fetus is the most challenging. In the case of the periviable fetus, it is important to take parental wishes into account, and multiple variables can affect prognosis, including weight and gestational age.
PB 134 reviews data from several large studies looking at expectant versus aggressive management at different gestational ages. Both the GRIT study (<34 weeks’ gestation) and the DIGITAT trial (>36 weeks) show no benefit or harm for immediate delivery, leaving a major clinical quandary.2,3
PB 134 concludes with a rational standardized approach to this issue. It is worth quoting directly:
Delivery at 38 0/7–39 6/7 weeks of gestation in cases of isolated [FGR] and 2) delivery at 34 0/7–37 6/7 weeks of gestation in cases of FGR with additional risk factors for adverse outcome (eg, oligohydramnios, abnormal umbilical artery Doppler velocimetry results, maternal risk factors, or co-morbidities).
When delivery for FGR is anticipated before 34 weeks of gestation, the delivery should be planned at a center with a neonatal intensive care unit and, ideally, after consultation with a maternal–fetal specialist. Antenatal corticosteroids should be administered before delivery because they are associated with improved preterm neonatal outcomes. For cases in which delivery occurs before 32 weeks of gestation, magnesium sulfate should be considered for fetal and neonatal neuroprotection in accordance with one of the accepted published protocols.
1. Smith CA. Effects of maternal under nutrition upon the newborn infant in Holland (1944–1945). J Pediatr. 1947;30:229–243.
2. A randomised trial of timed delivery for the compromised preterm fetus: short term outcomes and Bayesian interpretation. GRIT Study Group. BJOG. 2003;110:27–32.
3. Boers KE, Vijgen SM, Bijlenga D, van der Post JA, Bekedam DJ, Kwee A, et al. Induction versus expectant monitoring for intrauterine growth restriction at term: randomised equivalence trial (DIGITAT). DIGITAT Study Group. BMJ. 2010;341:c7087.