Pinky Ronen, M.D.
INITIAL DIAGNOSTIC EVALUATION: Diagnosis of fetal growth restriction FGR is based upon sonographic estimation of fetal weight. A complete history and physical examination is performed to look for maternal disorders associated with impaired fetal growth (eg, alcohol or tobacco use, maternal vascular disease, antiphospholipid syndrome). In addition, obstetrical imaging and laboratory evaluations are performed to look for fetal or placental etiologies.
Fetal survey — A detailed fetal anatomic survey is recommended in all cases since major congenital anomalies are frequently associated with failure to maintain normal fetal growth. Approximately 10 percent of FGR is accompanied by congenital anomalies. Some anomalies associated with FGR include omphalocele, diaphragmatic hernia, skeletal dysplasia, and some congenital heart defects.
Karyotype — Fetal karyotyping is suggested when FGR is early onset and symmetric (second trimester), severe (<3rd percentile), or accompanied by polyhydramnios (suggestive of trisomy 18) or structural anomalies
Infection — When there is a clinical suspicion of viral infection (eg, maternal or fetal signs/symptoms of cytomegalovirus, rubella, varicella), maternal serum should be examined for evidence of infection. Specific amniotic fluid viral DNA testing can also be performed, when indicated.
If the fetus is small, but anatomically normal with an appropriate amniotic fluid volume and growth rate, the outcome will usually be a normal, constitutionally small neonate. It is imperative to distinguish between the constitutionally small fetus and the fetus with pathologic growth restriction so that appropriate interventions can be implemented. In this regard, it is important to recognize ethnic and geographic differences in growth potential.
Antepartum fetal assessment — The optimal approach to monitoring the fetus with suspected growth restriction has not been established. Serial ultrasound evaluation of fetal growth, fetal behavior (BPP), and impedance to blood flow in fetal arterial and venous vessels (Doppler velocimetry) form the cornerstone of evaluation of the fetal condition and decision making. The purpose is to try to identify those fetuses who are at highest risk of in utero demise and neonatal morbidity, and thus may benefit from intervention by preterm delivery.
Serial fetal weight assessment — Fetal weight estimates are calculated using various published equations and formulae. The computed weight is then plotted on a population-based or customized growth curve, which allows the clinician to determine when the estimated weight is below the 10th percentile and to follow growth velocity. Serial sonograms are typically obtained at two- to four-week intervals; persistent growth deficiency in multiple examinations over many weeks strengthens the likelihood of FGR. Conversely, normal growth velocity in a small fetus suggests a constitutionally small but normal fetus.
Doppler velocimetry — Doppler velocimetry of the umbilical artery is recommended as the primary surveillance tool for monitoring pregnancies in which FGR is suspected. It has been well established by numerous randomized trials that the use of this tool can significantly reduce perinatal death, as well as unnecessary induction of labor in the preterm growth restricted fetus.
Doppler velocimetry is a good tool for fetal assessment in FGR when the etiology is placental dysfunction related to progressive obliteration of the villous vasculature. As placental dysfunction worsens, umbilical artery blood flow resistance increases and transfer of substrates, oxygen, and fetal waste products becomes increasingly impaired.
Umbilical artery — An increase in umbilical artery resistance leading to reduced end diastolic flow is consistently seen when 30 percent of the villous vasculature ceases to function. Normal or reduced end diastolic flow is rarely associated with significant perinatal morbidity or mortality and is strong evidence of fetal well-being, thus provides support for delaying delivery when it is important to achieve further fetal maturity. Absent or reversed end-diastolic flow in the umbilical artery occurs when 60 to 70 percent of the villous vasculature is obliterated and is evidence of poor fetal condition. These fetuses eventually show the metabolic and biophysical consequences of worsening hypoxia, including acidosis, loss of heart rate variability, and loss of fetal movement, breathing, and tone.
Middle cerebral artery — Vasodilation and high diastolic flow in the middle cerebral artery reflect compensatory cerebral vasodilatation (brain-sparing effect) secondary to fetal hypoxia and result in a reduced pulsatility index (MCA-PI).
Ductus venosus — With progressively increasing umbilical arterial resistance, fetal cardiac performance can become impaired and central venous pressure increases, resulting in reduced diastolic flow in the ductus venosus and other large veins.
Biophysical profile — The biophysical profile (BPP) is a useful method for monitoring the fetus because it provides an evaluation of multiple acute and chronic fetal physiologic parameters, is relatively easy to perform, and is a reliable test of fetal well-being (fetal death within one week of a normal test score is rare). Amniotic fluid assessment is a component of the BPP or modified BPP. Chronic placental insufficiency results in both FGR and oligohydramnios and observational studies have reported that pregnancies complicated by FGR and oligohydramnios have a modestly increased risk of perinatal mortality. Conversely, normal amniotic fluid volume is infrequently associated with either FGR or fetal demise.
The BPP is typically obtained once or twice per week; however, more frequent testing, as often as daily, is indicated for fetuses at highest risk, including, but not limited to, severe FGR (less than the fifth percentile), severe oligohydramnios, absent or reversed umbilical artery flow on Doppler velocimetry, or equivocal BPP score (ie, 6/10). Very preterm, severely growth restricted fetuses can deteriorate rapidly; they should be monitored closely using multiple modalities if delivery is to be delayed [17,27].
Outpatient versus inpatient monitoring — Women with pregnancies complicated by FGR are usually evaluated and monitored as outpatients. There are no data on which to base indications for hospitalization.
Frequency of fetal surveillance — The frequency of fetal surveillance is based upon the severity of findings and whether the examinations are being done to monitor fetal well-being, which requires relatively frequent assessment, or fetal growth, which is assessed over intervals of two to four weeks.
The Society for Maternal-Fetal Medicine publications committee suggests umbilical artery Doppler studies every one to two weeks initially, and if normal, the interval can be decreased. In general, when umbilical artery end diastolic flow is present and stable, we follow the fetus with weekly Doppler evaluation to determine the pattern of progression. The BPP is used either once weekly as an interval test between Doppler examinations or twice weekly, with one test at the time of the Doppler examination; there are no data to support one approach over the other. One trial reported that growth restricted fetuses with normal umbilical artery Doppler impedance could be safely evaluated (and with fewer interventions) with fortnightly, rather than twice weekly, surveillance.
Weekly Doppler should be complemented by twice weekly BPP or another combination of two antenatal tests (nonstress test and modified BPP or BPP) when FGR is complicated by oligohydramnios, preeclampsia, deceleration of fetal growth, increasing umbilical Dopper index, or other complications, even when umbilical artery end diastolic flow is present.
Absent or reversed end diastolic flow in the umbilical artery is potentially a sign of impending fetal cardiovascular and metabolic deterioration. If either of these abnormal patterns is present and the fetus is not immediately delivered because of extreme prematurity, then daily BPP and Doppler are recommended. The absence of abnormal flow patterns in the ductus venosus may be used to support the decision to extend such a pregnancy, and may enable the pregnancy to be prolonged for as long as two weeks.
Antenatal steroids — The efficacy of antenatal steroids for reducing neonatal morbidity and mortality in the preterm growth restricted neonate remains controversial. Until more information is available, it is appropriate to administer a course of antenatal steroids in case preterm delivery occurs. Multiple series have found that both spontaneous and indicated preterm delivery are more common in growth restricted fetuses.
Ideally, one course of steroids is given between 24 and 34 weeks of gestation in the week before delivery is expected.
Medical interventions — There is little evidence that any maternal antenatal treatment enhances fetal growth in growth restricted fetuses. Numerous approaches have been tried in small randomized trials, including nutritional supplementation, maternal oxygen therapy, and interventions to improve blood flow to the placenta, such as plasma volume expansion, low dose aspirin, heparin, bed rest, and beta-mimetics, calcium channel blockers, or sildenafil. None have consistently been shown to be of value. In smokers, an intensive smoking cessation program might be of value, and has other pregnancy and health benefits.
Short-term, maternal hyperoxia may improve fetal acid base status at the time of delivery. Although its long-term use has been reported to lower perinatal mortality compared to controls, the differences may be due to more advanced gestational age in the oxygen-treated group . Antihypertensive therapy of hypertensive gravidas does not improve fetal growth [52-54].
TIMING OF DELIVERY
General principles — There is little consensus about the optimal timing of delivery of the high risk preterm growth restricted fetus. There is consensus that the growth restricted fetus should be delivered if the risk of fetal death, as determined by antepartum monitoring tests, exceeds the risk of neonatal death, which is highly dependent on gestational age.
Remote from term — In growth restricted fetuses remote from term (<34 weeks of gestation), evidence of normal umbilical artery flow by Doppler velocimetry is reassuring with regard to immediate fetal outcome; prolongation of pregnancy to gain further fetal maturity is reasonable in these cases. Between 26 and 29 weeks of gestation, each day in utero has been estimated to improve survival by 1 to 2 percent. Morbidity and mortality remain relatively high under 32 weeks of gestation .
On the other hand, absence and particularly reversal of flow are ominous findings; the high risk of fetal demise with expectant management in these cases can exceed the risks associated with preterm delivery. We would immediately deliver any pregnancy ≥32 weeks with reversed flow and ≥34 weeks with absent flow, but would try to delay delivery in those under 32 weeks with reversed flow and those under 34 weeks with absent flow.
Late preterm and term — Delivery of the late preterm (34 to 366/7ths weeks) or early term (370/7ths to 376/7ths weeks) growth restricted fetus is recommended if there are additional risk factors for adverse outcome, such as maternal medical/obstetrical disorders, arrest of growth over a three- to four-week interval, and/or absence or reversal of Doppler flow in the umbilical artery. At this gestational age range, the risks of preterm birth are relatively low, and thus outweighed by the risks estimated to be associated with these variables. However, the patient’s specific clinical situation must be assessed and management individualized.