Fetal Anomalies and Pre-eclampsia Risk
The available evidence does not establish fetal anomalies as a recognized risk factor for pre-eclampsia development. While fetal growth restriction is acknowledged as a sign of pre-eclampsia after 20 weeks' gestation, structural fetal anomalies themselves are not listed among the established predisposing factors for this condition.
Evidence from Risk Assessment Guidelines
The most comprehensive risk stratification for pre-eclampsia comes from systematic reviews and meta-analyses that identified specific relative risks for developing the condition 1:
Established Risk Factors with Quantified Relative Risks:
- Antiphospholipid antibodies: RR 9.72 (95% CI 4.34-21.75) 1
- Previous pre-eclampsia: RR 7.19 (95% CI 5.85-8.83) 1
- Pre-existing diabetes: RR 3.56 (95% CI 2.54-4.99) 1
- Multiple pregnancy: RR 2.93 (95% CI 2.04-4.21) 1
- Nulliparity: RR 2.91 (95% CI 1.28-6.61) 1
- Family history of pre-eclampsia: RR 2.90 (95% CI 1.70-4.93) 1
- Maternal age ≥40 years: RR 1.68-1.96 1
- Elevated BMI at booking: RR 1.55 (95% CI 1.28-1.88) 1
Notably absent from this comprehensive list are fetal anomalies or congenital malformations 1.
Fetal Growth Restriction vs. Fetal Anomalies: A Critical Distinction
The guidelines do recognize fetal growth restriction as both a sign of pre-eclampsia and potentially part of the diagnostic criteria, but this is fundamentally different from structural fetal anomalies 1:
- Reduced fetal movements and small-for-gestational-age infants are listed as signs to monitor after 20 weeks' gestation 1
- The 2018 ISSHP guidelines note controversy about whether fetal growth restriction in the context of new-onset gestational hypertension should define pre-eclampsia, acknowledging that "pre-eclampsia is most commonly of itself a primary placental disorder" 1
- However, in chronic hypertension, fetal growth restriction "may be part of chronic hypertension per se and cannot be used as a diagnostic criterion for superimposed preeclampsia" 1
Pathophysiological Considerations
The pathophysiology of pre-eclampsia centers on placental dysfunction and maternal endothelial dysfunction, not fetal structural abnormalities 2, 3, 4:
- Pre-eclampsia results from abnormal placentation triggering maternal endothelial dysfunction through angiogenic imbalance 2
- Incomplete transformation of uteroplacental circulation leads to placental hypoxia and release of anti-angiogenic factors (sFlt-1, sEng) 2
- The placenta releases pathogenic factors into maternal circulation, causing widespread endothelial dysfunction affecting multiple organ systems 2
This mechanism does not implicate fetal structural anomalies as causative factors 2, 3, 4.
Clinical Implications for Risk Assessment
When assessing pre-eclampsia risk in early pregnancy, clinicians should focus on the validated risk factors 1:
Factors requiring specialist referral before 20 weeks:
- Previous pre-eclampsia 1
- Multiple pregnancy 1
- Pre-existing hypertension (diastolic BP ≥90 mmHg) 1
- Pre-existing renal disease or proteinuria 1
- Pre-existing diabetes 1
- Antiphospholipid antibodies 1
- Any two other predisposing factors 1
The presence of fetal anomalies detected on ultrasound should not, based on current evidence, alter pre-eclampsia risk stratification or monitoring protocols 1.
Important Caveats
While fetal anomalies are not established risk factors for pre-eclampsia, clinicians should remain vigilant because:
- Pre-eclampsia can develop in any pregnancy, even those without identified risk factors 1
- Women should be educated about symptoms of pre-eclampsia regardless of risk category 1
- Standard monitoring protocols after 20 weeks should detect pre-eclampsia development regardless of fetal status 1
The distinction between fetal growth restriction (which may indicate placental insufficiency and pre-eclampsia) and structural fetal anomalies (which do not predict maternal pre-eclampsia risk) is clinically important and should guide counseling and monitoring strategies 1.