Placental Dysfunction as a Common Pathway Linking Preeclampsia, Fetal Growth Restriction, and Preterm Birth: Current Evidence and Future Directions

Abstract

Preeclampsia, fetal growth restriction (FGR), and preterm birth remain major contributors to maternal and perinatal morbidity and mortality worldwide. Although these conditions are traditionally approached as distinct clinical entities, they frequently coexist and share overlapping risk factors, suggesting a common underlying pathophysiology. Increasing evidence indicates that placental dysfunction represents a central biological substrate linking these adverse pregnancy outcomes. Impaired placentation, inadequate spiral artery remodeling, and resultant uteroplacental hypoperfusion initiate a cascade of oxidative stress, angiogenic imbalance, immune dysregulation, and altered placental transport function. These placental disturbances precede clinical disease and shape both maternal and fetal manifestations across gestation. This narrative review synthesizes contemporary evidence supporting placental dysfunction as the shared mechanistic pathway underlying preeclampsia, FGR, and a substantial proportion of preterm births. Key histopathological, molecular, and imaging findings are reviewed, with particular emphasis on angiogenic signaling, Doppler velocimetry, and emerging biomarker-based approaches that reflect placental health. Differences between early- and late-onset disease phenotypes are discussed, highlighting how the timing and severity of placental insult influence clinical presentation and outcomes. The review also examines the implications of a placenta-centered framework for screening, surveillance, and timing of delivery. Recognition of these obstetric complications as manifestations of a common placental disease spectrum has important clinical implications. Integrating placenta-focused biomarkers and imaging into routine care offers an opportunity to improve risk stratification, personalize surveillance, and move toward earlier, prevention-oriented management. Future advances will depend on refining placenta-based phenotyping and translating mechanistic insights into equitable and clinically actionable strategies across diverse healthcare settings.