How does pre-eclampsia (PE) cause fetal growth restriction (FGR)?

How Pre-eclampsia Causes Fetal Growth Restriction

Pre-eclampsia causes fetal growth restriction through abnormal placental implantation and failed remodeling of spiral arteries, which leads to reduced uteroplacental perfusion and chronic placental insufficiency. 1

Primary Mechanism: Placental Malperfusion

The fundamental pathophysiology linking pre-eclampsia to FGR begins with defective placentation:

• Abnormal trophoblastic invasion of the maternal spiral arteries occurs in early pregnancy, preventing the normal transformation of these vessels into low-resistance, high-flow conduits 1
• This failure of spiral artery remodeling results in persistently high-resistance uteroplacental circulation, limiting oxygen and nutrient delivery to the developing fetus 1
• The placental disease manifests as variable degrees of placental malperfusion, which directly compromises fetal growth potential 2

Shared Pathophysiology with Important Distinctions

While pre-eclampsia and FGR share common origins in abnormal placentation, their relationship is complex and varies by gestational age:

• Early-onset disease (before 34 weeks) shows the strongest association, with 39-43% of early preterm FGR cases complicated by pre-eclampsia 3
• Late-onset disease demonstrates a much looser connection, with only 9-32% of late preterm FGR and 4-7% of term FGR associated with pre-eclampsia 3
• The implantation defect and vascular remodeling failure characteristic of pre-eclampsia are also present in isolated FGR and even in one-third of spontaneous preterm births 1

Critical Clinical Caveat

Reduced placental perfusion alone does not fully explain the maternal syndrome of pre-eclampsia. 1 Many pregnancies with FGR from uteroplacental insufficiency never develop pre-eclampsia, and conversely, some pre-eclamptic pregnancies have appropriately grown or even large fetuses 1. This suggests that maternal factors (genetic, behavioral, or environmental) must interact with the placental pathology to produce the full pre-eclamptic syndrome 1.

Endothelial Dysfunction as the Final Common Pathway

Beyond direct placental insufficiency, pre-eclampsia causes FGR through systemic maternal effects:

• The damaged placenta releases soluble factors into the maternal circulation that cause widespread vascular endothelial injury 2
• This endothelial dysfunction further compromises uteroplacental blood flow through vasoconstriction and reduced endothelial-mediated relaxation 1
• Reduced plasma volume from accelerated protein loss and abnormal coagulation activation compound the perfusion deficit 1

Heterogeneity of Mechanisms

Pre-eclampsia is not a single disorder but represents multiple pathways converging on a common endpoint 1:

• Term pre-eclampsia (the most common form) is not explained by abnormal placentation and has largely different mechanisms than early-onset disease 1
• Different placental and cardiovascular patterns distinguish isolated FGR from FGR with pre-eclampsia, with the latter showing more frequent placental vascular lesions 3
• Maternal cardiac output and peripheral vascular resistance patterns differ between late-onset FGR and pre-eclampsia 3

Clinical Implications for Surveillance

The mechanistic connection between pre-eclampsia and FGR has direct management implications:

• Umbilical artery Doppler assessment is essential for detecting worsening placental perfusion in FGR, with absent or reversed end-diastolic flow indicating severe compromise 1, 4
• Maternal hypertensive disease is present in 50-70% of early-onset FGR cases and represents one of the most important independent determinants of poor outcomes 1
• Women with early-onset FGR require close monitoring for development of hypertensive disorders, as maternal hypertension significantly shortens the interval to delivery and worsens neonatal outcomes 1