A fetus with an estimated weight or abdominal circumference below the 10th percentile for its gestational age, as determined by ultrasound, is referred to as a small for gestational age infant (SGA). However, not all SGA cases indicate pathological growth restriction. Certain SGAs are constitutionally small but healthy, with no structural abnormalities, functional impairments, or evidence of intrauterine hypoxia, apart from smaller body size and weight. Fetal growth restriction (FGR) refers to a failure of the fetus to reach its genetic growth potential due to pathological factors, such as maternal, fetal, or placental conditions. FGR often manifests as an estimated fetal weight (EFW) or abdominal circumference (AC) below the 10th percentile for gestational age, though some affected fetuses may have normal EFWs (10th–90th percentile) or even weights exceeding the 90th percentile. Severe FGR is characterized as an EFW or AC below the 3rd percentile or as cases accompanied by abnormal blood flow. Severe FGR is associated with a heightened risk of adverse pregnancy outcomes and is a critical focus for prenatal screening, diagnosis, and management.
Etiology
FGR is caused by a range of factors, primarily categorized as maternal, fetal, or placental/umbilical cord-related.
Maternal Factors
Nutritional Factors
Conditions such as maternal dietary imbalances, hyperemesis gravidarum, or insufficient protein, vitamin, and trace element intake can result in inadequate nutritional supply to the fetus, leading to FGR.
Pregnancy Complications and Comorbidities
Common complications, such as hypertensive disorders during pregnancy, multiple gestation, placental abruption, post-term pregnancy, or intrahepatic cholestasis of pregnancy, and comorbidities, such as heart disease, nephritis, anemia, antiphospholipid syndrome, hyperthyroidism, or autoimmune diseases, can reduce placental perfusion, thereby affecting fetal growth.
Other Factors
Fetal growth may be influenced by maternal age, geographic location, body weight, height, and socioeconomic status. Other contributors include multiple pregnancies, intrauterine infections, uterine abnormalities, smoking, drug abuse, heavy alcohol consumption, maternal exposure to radiation or toxic substances, and the use of certain medications during pregnancy (e.g., phenytoin or warfarin).
Fetal Factors
Certain fetal genetic conditions, including chromosomal disorders, genomic disorders, and single-gene diseases, may present clinically as FGR. Among fetuses with congenital structural abnormalities, 20–30% also exhibit FGR. The likelihood of FGR increases with the presence of multiple congenital anomalies.
Placental and Umbilical Cord Factors
Various placental abnormalities, including circumvallate placenta, accessory lobe placenta, small placenta, or placental vascular tumors, may reduce uteroplacental blood flow. Umbilical cord abnormalities, such as a single umbilical artery, excessively long or thin umbilical cords (especially near the insertion site), umbilical cord torsion, or knots, can impair fetal blood supply and contribute to FGR.
Diagnosis
Diagnosing FGR involves verifying the gestational age, conducting ultrasound assessments, and identifying underlying pathological factors.
Verification of Gestational Age
Gestational age determination considers the maternal menstrual history, details of assisted reproductive technologies used, and first- and second-trimester ultrasound findings to evaluate whether corrections are needed for the estimated due date.
Ultrasonographic Assessment of Fetal Growth
Biometric parameters, including biparietal diameter (BPD), head circumference (HC), abdominal circumference (AC), and femur length (FL), are measured. Appropriate fetal growth curves are used to estimate fetal weight (EFW). A diagnosis of SGA is made when EFW or AC is below the 10th percentile for the corresponding gestational age.
Identification of Pathological Causes of SGA
The differential diagnosis between SGA and FGR involves determining underlying pathological factors. FGR is established when an identifiable pathological origin exists.
Maternal Factor Evaluation
A detailed review of the maternal medical history, including pre-existing conditions (e.g., cyanotic congenital heart disease, chronic kidney disease, chronic hypertension, diabetes) and pregnancy complications (e.g., preeclampsia, intrahepatic cholestasis of pregnancy), is critical. Suspected uteroplacental perfusion abnormalities may warrant autoimmune screening to exclude conditions such as antiphospholipid syndrome.
Fetal Factor Evaluation
A detailed anatomical ultrasound is suggested to assess for fetal structural abnormalities. When necessary, invasive prenatal diagnostic methods, such as fetal cell or DNA sampling, enable genetic analyses. Chromosomal disorders and genomic disorders can be evaluated using karyotyping and chromosomal microarray analysis, while single-gene disorders may require whole exome sequencing (WES).
Placental and Umbilical Cord Factor Evaluation
Ultrasound evaluations of fetal appendages, including the placenta and umbilical cord, are recommended to identify abnormalities related to FGR. Factors such as abnormal placental morphology (e.g., circumvallate placenta, accessory lobe placenta), placental chorioangiomas, single umbilical artery, velamentous or marginal cord insertion, and umbilical cord edema may indicate placental or umbilical cord involvement in FGR.
Other Factor Evaluation
For high-risk populations with potential TORCH infections or abnormal ultrasound findings across multiple parameters suggestive of TORCH-related anomalies, TORCH screening is advised.
Management
The management of fetal growth restriction (FGR) primarily focuses on enhanced fetal surveillance and determining the appropriate timing for delivery.
General Management
Currently, there is no evidence that universal interventions such as nutritional supplementation, oxygen administration, hospitalization, or use of low-molecular-weight heparin improve fetal growth or intrauterine well-being in pregnancies affected by FGR. For cases directly attributed to maternal malnutrition, targeted nutritional interventions may improve outcomes. For FGR caused by pregnancy-related complications or comorbidities, appropriate treatment of the underlying condition is required.
Fetal Surveillance
In confirmed FGR, dynamic ultrasound evaluations to assess fetal growth trends are recommended every 2–3 weeks, along with comprehensive monitoring of fetal well-being using ultrasound, electronic fetal monitoring, and other tools. Specific assessments include the following:
Umbilical Artery Doppler Waveform
Decreased end-diastolic blood flow in the umbilical artery often indicates increased vascular resistance in FGR fetuses, with the pulsatility index reflecting placental vascular resistance. Worsening conditions can lead to absent or reversed end-diastolic flow in the umbilical artery.
Middle Cerebral Artery (MCA) Doppler Waveform: MCA Doppler waveforms typically exhibit higher resistance in cerebral circulation compared to the umbilical artery in normally growing fetuses. In FGR, placental insufficiency leading to fetal hypoxia can trigger blood flow redistribution toward vital organs such as the brain, heart, and adrenal glands, reducing cerebral vascular resistance (termed "brain-sparing effect"). A low MCA pulsatility index may reflect this compensatory redistribution due to hypoxia. While MCA Doppler findings can predict adverse perinatal outcomes in high-risk fetuses, evidence supporting its sole use to determine the timing of delivery is limited.
Fetal Venous Doppler Waveform
Acidosis-induced cardiac dysfunction in FGR fetuses can be assessed through venous Doppler studies, which provide insight into fetal ventricular function. Acidotic states increase cardiac preload and afterload (resulting from placental vascular abnormalities), which may manifest as absent or reversed a-wave flow at the ductus venosus or pulsations in the umbilical vein.
Non-Stress Test (NST) and Electronic Fetal Heart Monitoring: Chronic uteroplacental insufficiency leads to norepinephrine-mediated sympathetic dominance, replacing vagal influence. This results in reductions in fetal heart rate variability and episodes of tachycardia. Short-term variability in fetal heart rate is an effective indicator of fetal intrauterine health.
Biophysical Profile (BPP)
The biophysical profile assesses fetal breathing, movements, tone, and amniotic fluid volume. Scores have predictive value for adverse perinatal outcomes.
Amniotic Fluid Volume
Following FGR diagnosis, amniotic fluid index or maximum vertical pocket depth should be assessed using ultrasound. Ongoing monitoring of amniotic fluid levels is essential. Oligohydramnios or anhydramnios in FGR fetuses is indicative of worsening placental function and may suggest fetal hypoxia or acidosis.
Timing and Mode of Delivery
Timing of Delivery
When fetal condition and placental function are stable, pregnancies without maternal complications or comorbidities may reach full term under close monitoring. For FGR pregnancies at or beyond 37 weeks of gestation, consideration should be given to delivery. During the expectant management period, a combination of tools such as Doppler ultrasound, fetal heart monitoring, amniotic fluid volume assessment, and biophysical profiles is employed to evaluate intrauterine health comprehensively. Decisions regarding delivery timing should balance the potential benefits of extended gestation against the risks associated with continuing pregnancy.
For cases of FGR with abnormal Doppler findings, close monitoring is necessary. When absent end-diastolic flow in the umbilical artery is observed, continuation of pregnancy beyond 34 weeks is generally not advised. Reversed end-diastolic flow warrants limiting gestation to no later than 32 weeks. Should absent or reversed end-diastolic flow occur prior to 32 weeks, accompanied by ductus venosus abnormalities, delivery may be considered after fetal lung maturation has been induced. For pregnancies under 34 weeks of gestation, magnesium sulfate may be administered for fetal neuroprotection, and delivery is recommended after completing antenatal corticosteroids to promote fetal lung maturity. In settings with limited neonatal intensive care capabilities, in-utero transfer to a higher-level facility may be appropriate.
Mode of Delivery
FGR fetuses exhibit limited tolerance to hypoxia, with reduced fetal and placental reserves making them susceptible to intrapartum hypoxic events caused by uterine contractions. These factors justify more relaxed criteria for cesarean delivery in FGR pregnancies.
Vaginal Delivery
For FGR pregnancies entering spontaneous labor, early hospital admission and enhanced fetal heart monitoring are advised. Contraindications for vaginal delivery should be excluded. Cervical readiness and amniotic fluid levels should guide decisions regarding labor induction and the method of induction.
Cesarean Delivery
FGR alone is not an absolute indication for cesarean delivery. However, with severe fetal compromise, unfavorable conditions for vaginal delivery, or indications for cesarean unrelated to FGR, surgical delivery is appropriate.
Prevention
For individuals with a history of FGR or preeclampsia, the use of low-dose aspirin from 11 to 13+6 weeks of gestation until 36 weeks may reduce the risk of recurrent FGR. For FGR cases caused by maternal factors, addressing underlying conditions such as smoking, alcohol, or drug use can minimize the risk. Prophylactic aspirin in high-risk populations for preeclampsia not only reduces preeclampsia risk but also helps prevent FGR.