Residency · Residency · Obstetrics Gynecology

Intrauterine Growth Restriction

Definitions

Small for gestational age (SGA) refers to an estimated fetal weight (EFW) or birth weight below the 10th percentile for gestational age. Fetal growth restriction (FGR, also called IUGR) is SGA accompanied by evidence of pathologic growth restriction, such as abnormal Doppler studies, a declining growth trajectory, or an identifiable underlying etiology. Not all SGA fetuses are growth restricted; some are constitutionally small but healthy. Severe FGR is defined as an EFW below the 3rd percentile.

Etiology

Maternal Causes

Hypertensive disorders, including preeclampsia and chronic hypertension, are the most common maternal cause of growth restriction. Other maternal conditions that impair fetal growth include autoimmune diseases (systemic lupus erythematosus and antiphospholipid syndrome), chronic renal disease, pregestational diabetes with vascular disease, severe malnutrition, substance use (smoking, alcohol, cocaine), thrombophilias, and advanced maternal age.

Placental Causes

Placental insufficiency from abnormal placentation, placental infarction, or abruption is a major mechanism. Additional placental causes include confined placental mosaicism, placental tumors such as chorioangioma, velamentous cord insertion, and single umbilical artery.

Fetal Causes

Chromosomal abnormalities (trisomy 13, 18, and 21, triploidy, and Turner syndrome) are important fetal causes. Congenital anomalies, particularly cardiac defects, can impair growth. Congenital infections contribute to growth restriction, with cytomegalovirus being the most common infectious cause, followed by toxoplasmosis, rubella, and syphilis. Multiple gestation is another well-recognized fetal cause.

Classification by Growth Pattern

Symmetric (early-onset, proportional) growth restriction involves proportional reduction in head circumference, abdominal circumference, and femur length. It suggests an early insult such as a chromosomal abnormality, congenital infection, or severe early-onset placental disease and represents approximately 20 to 30% of IUGR cases. Asymmetric (late-onset) growth restriction is characterized by head-sparing with a disproportionately small abdomen, reflecting decreased liver glycogen stores and subcutaneous fat. This pattern reflects placental insufficiency with redistribution of blood flow to the brain ("brain-sparing") and accounts for approximately 70 to 80% of cases.

<image>Diagram comparing symmetric versus asymmetric intrauterine growth restriction, showing a symmetric IUGR fetus with proportionally reduced head circumference, abdominal circumference, and femur length versus an asymmetric IUGR fetus with preserved head circumference but reduced abdominal circumference</image>

Screening and Diagnosis

Screening

Fundal height measurement at each prenatal visit after 24 weeks serves as the primary screening method. A discrepancy of more than 3 cm from the expected gestational age warrants ultrasound evaluation. However, fundal height has limited sensitivity and specificity, and many cases of IUGR are missed by this method alone.

Ultrasound Diagnosis

Diagnosis is made when the EFW falls below the 10th percentile based on biometry (biparietal diameter, head circumference, abdominal circumference, and femur length). Abdominal circumference is the most sensitive single parameter for detecting growth restriction. Measurements are plotted on population-based or customized growth charts. Serial growth ultrasound every 2 to 4 weeks is essential to assess the growth trajectory, as declining percentiles are more concerning than a single measurement below the 10th percentile, which may simply reflect a constitutionally small fetus.

Initial Workup When IUGR Diagnosed

A detailed anatomy survey should be performed to evaluate for structural anomalies. Umbilical artery Doppler assessment is obtained. Additional evaluation to consider includes genetic testing (amniocentesis for karyotype and microarray, especially in early-onset or symmetric IUGR), infection screening (CMV IgG/IgM, toxoplasmosis, syphilis), preeclampsia evaluation (blood pressure, proteinuria, laboratory studies), antiphospholipid antibody testing if not previously performed, and uterine artery Doppler, where abnormal notching suggests uteroplacental insufficiency.

Doppler Surveillance

Umbilical Artery (UA) Doppler

Umbilical artery Doppler reflects placental vascular resistance. Normal flow shows low-resistance forward flow throughout the cardiac cycle. An elevated systolic-to-diastolic (S/D) ratio above the 95th percentile indicates increased placental resistance. Absent end-diastolic flow (AEDF) represents significant placental disease with an associated perinatal mortality of approximately 40% if undelivered. Reversed end-diastolic flow (REDF) is a critical finding associated with high mortality risk, and delivery is usually indicated if the fetus is viable.

Middle Cerebral Artery (MCA) Doppler

The MCA Doppler assesses fetal brain perfusion. A low MCA pulsatility index (below the 5th percentile) indicates cerebral vasodilation, the so-called brain-sparing effect. The cerebroplacental ratio (CPR), calculated as MCA PI divided by UA PI, is a useful integrated measure. A CPR below 1.0 or below the 5th percentile indicates redistribution and increased risk of adverse outcome. The CPR is particularly useful in late-onset FGR, where the umbilical artery Doppler may still be normal.

Ductus Venosus (DV) Doppler

Ductus venosus Doppler reflects cardiac function and central venous pressure. An absent or reversed a-wave indicates cardiac decompensation and is the strongest predictor of imminent fetal death in early-onset IUGR. It serves as a key determinant for delivery timing at previable and periviable gestational ages.

Surveillance Frequency

When umbilical artery Doppler is normal, assessment is repeated every 1 to 2 weeks with weekly nonstress testing or biophysical profile. An elevated UA S/D ratio warrants evaluation every 3 to 7 days with twice-weekly NST or BPP. AEDF requires assessment every 1 to 3 days, inpatient monitoring is recommended, and ductus venosus Doppler is added. REDF necessitates daily or more frequent assessment with preparation for delivery.

<image>Series of umbilical artery Doppler waveforms showing progression from normal flow with positive end-diastolic flow, to elevated S/D ratio, to absent end-diastolic flow (AEDF), and finally to reversed end-diastolic flow (REDF), illustrating increasing placental resistance and disease severity</image>

Distinguishing Early-Onset from Late-Onset IUGR

Early-Onset IUGR (< 32 weeks)

Early-onset IUGR is usually caused by severe placental insufficiency. Abnormal umbilical artery Doppler is common, and progressive Doppler deterioration follows a predictable sequence: elevated S/D ratio, then AEDF, then REDF, then abnormal ductus venosus, and finally hydrops. This sequence may unfold over days to weeks. The central challenge is balancing the risks of prematurity against the risks of continued in utero deterioration. Early-onset IUGR carries higher morbidity and mortality.

Late-Onset IUGR (>= 32 weeks)

Late-onset IUGR is more common than early-onset disease. Umbilical artery Doppler may remain normal, and MCA and CPR abnormalities are more useful for identifying at-risk fetuses. A concerning feature of late-onset IUGR is the risk of sudden fetal death without preceding Doppler deterioration. Overall mortality is lower than in early-onset disease, but the risk of stillbirth remains elevated compared to appropriately grown fetuses.

Delivery Timing

Based on Gestational Age and Doppler Findings

When umbilical artery Doppler is normal and the finding is isolated SGA, delivery is planned at 37 to 38 weeks with close fetal surveillance. An elevated UA S/D ratio with positive end-diastolic flow warrants delivery at 37 weeks. AEDF calls for delivery at 34 weeks after corticosteroids, earlier if the ductus venosus is abnormal or fetal testing is non-reassuring. REDF prompts delivery at 32 weeks after corticosteroids, earlier if the ductus venosus is abnormal. An abnormal ductus venosus with absent or reversed a-wave triggers delivery regardless of gestational age if the fetus is viable, typically at 26 weeks or later after corticosteroids. Abnormal NST or a BPP of 4 or below warrants delivery regardless of Doppler findings.

Mode of Delivery

Vaginal delivery can be attempted if fetal status is reassuring, but continuous fetal monitoring during labor is mandatory. There should be a low threshold for cesarean delivery because IUGR fetuses have diminished reserve and tolerate labor poorly. In the setting of AEDF or REDF, cesarean delivery should be considered given the poor tolerance of labor in these fetuses.

Antenatal Corticosteroids

Betamethasone should be administered at standard dosing if delivery is anticipated before 34 weeks. Late preterm steroids between 34 and 36 weeks 6 days may be considered per institutional protocol.

Prevention and Recurrence

There is no proven treatment to reverse established IUGR. Bed rest, maternal supplementation, and plasma volume expansion have not demonstrated benefit. Low-dose aspirin (81 mg starting at 12 to 16 weeks) may reduce the risk in subsequent pregnancies if the prior IUGR was associated with preeclampsia. Smoking cessation and treatment of underlying maternal conditions are important modifiable factors. The recurrence risk is 20 to 25% in subsequent pregnancies. Enhanced surveillance in future pregnancies includes uterine artery Doppler at 20 to 24 weeks and serial growth ultrasound beginning at 24 weeks.

Clinical Pearls

Not all small babies are growth restricted. It is essential to distinguish constitutionally small fetuses with normal Dopplers and a consistent growth trajectory from those with pathologic growth restriction.

Abdominal circumference is the earliest and most sensitive ultrasound parameter to decline in IUGR.

Umbilical artery Doppler is the primary surveillance tool in early-onset IUGR, while MCA and CPR are more informative in late-onset IUGR.

Reversed end-diastolic flow in the umbilical artery is a pre-terminal finding, and delivery should not be delayed.

Ductus venosus Doppler with an absent or reversed a-wave is the strongest predictor of imminent fetal death and is the trigger for delivery in previable and periviable IUGR.

IUGR fetuses have poor metabolic reserve. They tolerate the stress of labor poorly and have higher rates of intrapartum fetal distress.

Always consider chromosomal and infectious etiologies in early-onset symmetric IUGR. Amniocentesis for microarray and CMV PCR should be offered.

References

• ACOG Practice Bulletin No. 204: Fetal Growth Restriction (2019, reaffirmed 2022)
• SMFM Consult Series No. 52: Diagnosis and Management of Fetal Growth Restriction (2020)
• Lees CC et al. TRUFFLE study: a randomized trial of timing of delivery in fetal growth restriction. Lancet. 2015;385:2162-2170
• Figueras F, Gratacos E. Update on the diagnosis and classification of fetal growth restriction. Clin Obstet Gynecol. 2014;57:735-749
• Baschat AA. Neurodevelopment following fetal growth restriction and its relationship with antepartum parameters of placental dysfunction. Ultrasound Obstet Gynecol. 2011;37:501-514

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