Fetal growth restriction
3 keys to successful management
A rational strategy for antepartum identification, close fetal surveillance, and individualized intervention is based on meta-analyses, Cochrane reviews, and current standards of care.
KEYS TO SUCCESS
- Antepartum recognition of fetal growth restriction is essential for proper surveillance and management.
- Because growth-restricted fetuses are at risk for adverse outcomes in utero, fetal surveillance is vital for timely recognition and intervention.
- Once growth restriction is identified, management should be individualized to ensure optimal gestational development and safe delivery.
Not only is fetal growth restriction (FGR) associated with perinatal mortality and morbidity, but it may be linked to adverse consequences in adulthood.1 Its many causes involve diverse pathological processes; thus, it should not be considered a single disease. Many aspects remain unclear, a substantial number of affected infants are not identified before birth, and effective antepartum prevention and treatment remain elusive.
Fortunately, managing FGR has hopeful aspects. Meaningful recent advances elucidate its etiologic and pathophysiologic mechanisms and help clarify diagnosis and management.
This article offers an up-to-date, evidence-based approach and includes guidelines on 3 keys to success: antepartum recognition, fetal surveillance, and antepartum and intrapartum management. These guidelines are not intended as a strict protocol, since the clinical course of FGR is highly variable, but as the starting point for individualized care.
An amorphous entity: FGR terminology
Fetal growth restriction implies failure to realize genetically determined growth potential. Terms include fetal growth restriction, intrauterine growth restriction, and small for gestational age (SGA). The pejorative term growth retardation is obsolete.
Traditionally, FGR refers to prenatally identified fetal growth deficiency, whereas SGA refers to suboptimal birth weight for the gestational age. However, some small fetuses are merely constitutionally small, not growth-restricted. Conversely, not all growth-restricted fetuses are small in size or weight for gestational age. Yet defining these groups is difficult, as the tools are imprecise and controversial.
This article uses these definitions:
Fetal growth restriction identified in the antepartum period refers to a fetus with sonographically measured fetal dimensions, particularly abdominal circumference or estimated weight, below an age-specific threshold, typically the 10th percentile.
Fetal growth restriction identified at birth is birth weight below the 10th percentile for gestational age, or SGA. Unfortunately, this definition may fail to identify some fetuses that are truly growth-restricted. Alternative, more sensitive definitions, such as the Ponderal index or birth weight ratio, are used primarily in research.
Consequences of FGR
Perinatal outcomes. Perinatal morbidities include prematurity, oligohydramnios, nonreassuring fetal heart rate patterns with a higher incidence of cesarean delivery, birth asphyxia, low Apgar score, neonatal hypoglycemia, hypocalcemia, polycythemia, hyperbilirubinemia, hypothermia, apnea, seizure disorders, and infection.
Fetal and neonatal mortality is significantly increased. Perinatal mortality is influenced by many factors, including severity of growth restriction, timing of onset, gestational age, and cause of growth restriction. The lower the birth-weight percentile for gestational age, the higher the mortality rate.
Effects in infancy. Although many SGA infants “catch up” growth in infancy, the pattern varies. Height and weight catch-up growth of preterm FGR infants lags behind that of preterm infants that are appropriate for gestational age (AGA) at birth.2 Those with early-onset or severe growth deficit continue to lag behind in postnatal growth. Although recent studies indicate that rapid postnatal growth in SGA infants may lead to increased risk of chronic diseases, including type 2 diabetes, others have found tangible short-term benefits of less frequent morbidity and mortality in infancy.3
FGR has been linked to a spectrum of neurodevelopmental risks, including subtle behavioral abnormalities, immature sleep patterns, decreased visual fixation, decreased general activity, altered early mother-infant interaction, altered motor skills, and hyperactivity.4,5 Infants born SGA at 32 to 42 weeks were 4 to 6 times more likely to have cerebral palsy, yet those whose birth weight was above the 97th percentile also had increased risk. It remains uncertain whether deviant growth is the cause or a consequence of this disability.6
Long-term effects. Lifetime sequelae of early nutritional deprivation have been demonstrated in animals.7 Moreover, epidemiological evidence suggesting an association between SGA at birth or infancy and increased risk of abnormal blood lipid values, diabetes, hypertension, and ischemic heart disease in adult life led Barker and associates to propose the fetal origins hypothesis.1
1. Antepartum recognitionDetermine gestational age
A reliable estimate of gestational age is central to identification of fetal growth compromise in utero or at birth. In pregnancies at risk for fetal growth restriction, gestational age should be established early, preferably in the first trimester.
The method of determining gestational age influences the observed frequency of FGR and SGA births. Estimates are more accurate when based on early ultrasound biometry than on menstrual history. The latter, if well documented, regular, and ovulatory, may be reliable if it differs by no more than 1 week from the sonographic gestational age. Otherwise, early-pregnancy, ultrasoundbased age is more accurate.
Screening for FGR
Screening can be done clinically or by special investigation. The following methods are used, some of which remain experimental:
- assessment of historical clinical risks
- clinical evaluation of fetal and uterine size
- ultrasound fetal biometry
- umbilical arterial and uterine arterial
Clinical risk assessment. Evaluate all gravidas for risk factors (TABLE 1). If a woman is determined to be at heightened risk, take appropriate steps to diagnose FGR as early as possible.
Clinical evaluation of fetal and uterine size. Clinical assessment of fetal growth includes estimating fetal size by traditional obstetrical manual examination and by measuring the uterine fundal height.
- Abdominal palpation is inadequate to identify the fetus at increased risk of growth restriction, missing 74% of cases.8
- Serial measurements of the uterine fundal height, however, may be more reliable.9 This method consists of measuring fundal height from the symphysis pubis using a nonstretchable tape measure and assessing the results against a gestational age-specific nomogram. Limitations include significant interobserver differences and varying effects of maternal weight, parity, and fetal sex. A randomized trial of the method did not demonstrate any benefits, and a subsequent Cochrane review of the same study considered the evidence insufficient for any recommendations.10,11
Nevertheless, clinical assessment of uterine and fetal size is an essential, inexpensive component of prenatal care and a simple screening tool for identifying mothers who would benefit from further, more definitive sonographic investigation.
Routine ultrasound biometry. The potential benefits of accurately determined gestational age, and recognition of fetal malformations and multiple gestation, via earlyor mid-pregnancy ultrasound are well recognized and justify widespread use.
Routine scanning increases detection of SGA infants.12 A population-based cohort study13 involving over 16,000 singleton pregnancies found that fetuses smaller than expected at mid-second trimester ultrasound (discrepancy exceeding 14 days) were at increased risk for adverse outcomes, including perinatal mortality and SGA.
Unfortunately, these findings have not led to improved outcomes. A high false-positive rate remains a major concern. A prospective observational study14 found that routine ultrasound did not identify most cases of FGR, but resulted in a fivefold increase in iatrogenic premature delivery and significantly increased neonatal intensive care admissions.
- The Routine Antenatal Diagnostic Imaging with Ultrasound (RADIUS) trial15 randomized 15,000 low-risk gravidas to routine ultrasound imaging (at 15 to 22 weeks and again at 31 to 35 weeks) or to ultrasound only when indicated. The groups had similar rates of adverse perinatal outcome, distribution of birth weights, and preterm delivery. The trial’s weaknesses include selection criteria for low risk that excluded most pregnancies, inappropriate perinatal-outcome parameters, and suboptimal ultrasonographer expertise.
- A recent Cochrane review16 of 7 trials involving more than 25,000 women failed to demonstrate any improvements in perinatal mortality and morbidity with routine ultrasound, or any difference in antenatal, obstetric, and neonatal interventions.
Estimated fetal weight may differ from actual weight by as much as 20%.
We also lack evidence regarding longterm outcomes such as neurodevelopment.
Umbilical arterial Doppler. A meta-analysis17 of 4 randomized trials in unselected or low-risk pregnancies with a total population of 11,375 women found no effect of screening Doppler umbilical artery velocimetry on perinatal death, stillbirth, antenatal hospitalization, obstetric outcome, or perinatal morbidity.
A subsequent meta-analysis18 of 5 trials of routine Doppler ultrasound in unselected and low-risk pregnancies with a total population of more than 14,000 women also found no benefit for mother or infant.
We lack evidence on long-term outcomes.
Uterine arterial Doppler screening. Increased pulsatility of the uterine arterial Doppler waveform, persistence of the notch, and a significant difference between right and left uterine arteries have been associated with FGR, pregnancy-induced hypertension, and adverse perinatal outcome. A review19 of 15 studies of routine uterine Doppler in unselected populations showed considerable heterogeneity, but indicated that increased impedance in the uterine arteries identifies about 20% of those who develop FGR, with a positive likelihood ratio of 3.5.
We lack exclusive randomized trials of routine uterine Doppler sonography in unselected and low-risk pregnancies. However, 2 studies done in conjunction with umbilical arterial Doppler found no impact on outcome, and a recent Cochrane review18 found insufficient evidence to support routine uterine Doppler for FGR screening.
Antiphospholipid antibody syndrome
Diabetes with vasculopathy
Cyanotic heart disease
Substance abuse (eg, alcohol, heroine, cocaine)
Confined placental mosaic
Unexplained elevated alpha-fetoprotein
Infection (eg, rubella, cytomegalovirus, herpes, malaria, toxoplasmosis)
Malformations (eg, gastroschisis, omphalocele, diaphragmatic hernia, congenital heart defect)
Genetic disorders (eg, trisomy 13, 18, and 21; triploidy; some cases of Turner’s syndrome)
Identifying FGR in utero
Antepartum diagnosis is based on sonographic measurement of various fetal dimensions.
Abdominal circumference and estimated fetal weight. A review20 of 60 studies found that abdominal circumference (AC) and sonographically estimated fetal weight (EFW) were the best predictors of birth weight below the 10th percentile in high-risk pregnancies. AC below the 10th percentile had sensitivities ranging from 72.9% to 94.5%, false-positive rates of 16.2% to 49.4%, and a common odds ratio of 18.4. An EFW below the 10th percentile had a common odds ratio of 39.1, which was the highest among all the biometric measurements. Its sensitivity ranged from 33.3% to 89.2%, and false-positive rates ranged from 9.1% to 46.3%.
The proportionality of fetal dimensions, such as the head/abdominal ratio, was not a good predictor, although it is routinely generated in ultrasound biometry.
Ultrasound estimation of fetal weight is based on a combination of 2 or 3 biometric measurements of the fetus, including the biparietal diameter (BPD) or the head circumference (HC), AC, and femur length (FL). Several formulae yield varying estimations of weight. Thus, a fetus identified as growth-restricted by 1 formula may not be so diagnosed by another. For this reason, it is prudent to be consistent in their use. EFW generated from measurements of the head (BPD or HC), AC, and FL is most reliable.21
The EFW also is expressed as the percentile for the gestational age.
Limitations of ultrasound estimation.
The optimal process of translating dimensional measurements into fetal body mass for both health and disease remains unknown. This leads to inaccurate assumptions and erroneous weight projections.
Inaccuracies also result from variations in measurement. In addition, the estimation is less accurate in the lower and upper ranges of fetal weight distribution and in the presence of oligohydramnios. As a result, estimated weight may differ from actual weight by as much as 20%, with greater margins of error at the lower and upper extremes.
Guidelines for screening and diagnosis
Assess all pregnancies for risk factors and determine the gestational age in early pregnancy, especially in women at higher risk of FGR. If the patient has substantial clinical risks or there is suspicion of growth restriction, fetal ultrasound biometry is recommended. Diagnosis of FGR is based on fetal sonographic measurements, especially AC; estimated fetal weight derived from BPD or HC, AC and FL; and longitudinal progression of fetal growth.
Current evidence suggests the use of a 10th percentile diagnostic threshold for these measurements. Follow the biometric parameters longitudinally, repeating the measurement every 2 to 4 weeks. More frequent examination is unreliable.