What are the short‑term and long‑term effects of fetal growth restriction (FGR) on the fetus and newborn?

Effects of Fetal Growth Restriction on the Fetus and Newborn

Fetal growth restriction (FGR) is a leading cause of perinatal morbidity and mortality, with affected fetuses facing doubled stillbirth rates, increased risk of severe acidosis at birth, low Apgar scores, NICU admissions, and long-term metabolic programming that increases cardiovascular and endocrine disease risk in adulthood. 1

Short-Term Perinatal Effects

Mortality Risks

• Stillbirth rates are approximately 1.5% for fetuses below the 10th percentile—twice the rate of normally growing fetuses. 1, 2
• For fetuses with weights below the 5th percentile, stillbirth rates escalate to 2.5%. 1, 2
• Preterm FGR compounds mortality risk dramatically, with 2- to 5-fold increased perinatal death rates compared to term FGR fetuses. 1, 3
• The worst outcomes occur in fetuses with estimated fetal weights below the 3rd percentile or those with fetal Doppler abnormalities. 1

Immediate Neonatal Complications

• Infants with birthweights below the 10th percentile are significantly more likely to experience severe acidosis at birth, low 5-minute Apgar scores, and require NICU admissions. 1, 2
• Acute neonatal complications include perinatal asphyxia, hypothermia, hypoglycemia, and polycythemia. 2
• These infants require interdisciplinary follow-up due to the constellation of immediate risks. 2

Severity-Based Risk Stratification

• Perinatal outcomes are largely dependent on FGR severity, with fetuses below the 3rd percentile facing the highest risk profile. 1
• The presence of abnormal umbilical artery Doppler findings (absent or reversed end-diastolic velocity) significantly worsens prognosis. 1
• Prematurity further compounds all adverse outcomes in FGR. 1

Long-Term Effects and Adult Disease

Metabolic Programming

• FGR is associated with metabolic programming that increases the risk of future development of metabolic syndrome and consequent cardiovascular and endocrine diseases. 1
• Suboptimal fetal growth leads to long-lasting physiological alterations that persist through childhood and into adulthood. 4
• These adaptations to poor oxygen and nutrient supply may be effective in the fetal period but become deleterious long-term through structural or functional alterations. 4

Specific Adult Chronic Diseases

• Epidemiologic studies demonstrate that FGR contributes to adult chronic diseases including cardiovascular disease, metabolic syndrome, and diabetes. 4
• Respiratory diseases and impaired lung function are associated with FGR. 4
• Chronic kidney disease risk is elevated in individuals with FGR history. 4

Neurodevelopmental Impact

• FGR is associated with adverse outcomes including neurodevelopmental delay. 1
• Long-term risks include neurodevelopmental handicaps that require ongoing monitoring. 2
• Neurodevelopmental impacts of placental disease occur before clinical decisions regarding delivery timing arise, emphasizing the importance of early recognition. 5

Pathophysiological Mechanisms

Placental Insufficiency

• Suboptimal perfusion of the maternal placental circulation is the most common cause of FGR, accounting for 25-30% of all cases. 1
• Uteroplacental insufficiency leads to chronic impairment of placental blood flow, resulting in decreased fetal renal perfusion, decreased fetal urine production, and oligohydramnios. 1
• As pregnancy progresses, increasing demands on the placenta for nutrient provision can outpace placental functional abilities, resulting in FGR. 1

Chromosomal and Structural Abnormalities

• Chromosomal disorders and congenital malformations are responsible for approximately 20% of FGR cases. 1
• Early-onset FGR (before 32 weeks) is particularly associated with fetal or chromosomal abnormalities, occurring in up to 20% of cases. 1, 3

Classification and Clinical Presentation

Early-Onset FGR (Before 32 Weeks)

• Early FGR is associated with substantial alterations in placental implantation with elevated hypoxia requiring cardiovascular adaptation. 6
• This form shows a characteristic sequence of responses evolving from the arterial circulation to the venous system and finally to biophysical abnormalities. 5
• Perinatal morbidity and mortality rates are high in early-onset FGR. 6

Late-Onset FGR (32 Weeks or Later)

• Late FGR presents with slight deficiencies in placentation leading to mild hypoxia and requiring little cardiovascular adaptation. 6
• This form presents with subtle Doppler and biophysical abnormalities, posing a diagnostic dilemma. 5
• Often unrecognized, term FGR contributes to a large proportion of adverse perinatal outcomes. 5
• Perinatal morbidity and mortality rates are lower than early-onset FGR but remain clinically significant. 6

Critical Clinical Pitfalls

A major pitfall is failing to distinguish between constitutionally small fetuses (who are healthy and not at risk) and true FGR with placental insufficiency. 1 While some small-for-gestational-age fetuses are constitutionally small and require only standard newborn care, others are affected by placental conditions leading to uteroplacental insufficiency and adverse outcomes. 1, 2

Another critical error is underestimating the impact of late-onset FGR at term, which often goes unrecognized despite contributing substantially to adverse perinatal outcomes. 5 The subtle presentation of late FGR requires heightened clinical vigilance and appropriate Doppler surveillance. 5