Understanding pre-eclampsia and fetal growth restriction at high altitude: A narrative review

Pre-eclampsia (PE) and fetal growth restriction (FGR) are among the leading causes of maternal and perinatal morbidity and mortality worldwide. Both conditions are more frequent and severe at high altitudes due to physiological changes in oxygen availability and vascular adaptation. This narrative review explores the complex relationship between high-altitude pregnancy, the development of PE and FGR, and the underlying adaptive mechanisms that may influence maternal and fetal outcomes. We provide an updated synthesis of the current evidence regarding placental dysfunction, angiogenic imbalance, and oxidative stress in pregnancies at high altitude, highlighting the role of hypoxia-inducible factors, altered expression of sFlt-1 and PlGF, and their impact on trophoblast invasion and uteroplacental blood flow. The review also highlights genetic and physiological adaptations observed in permanent high-altitude populations that appear to mitigate these risks, including enhanced oxygen delivery, increased uterine artery diameter, and reduced placental vascular resistance. This review emphasizes the importance of considering geographic and environmental factors in pregnancy outcomes and calls for further research to better understand the mechanisms driving adverse outcomes at high altitude.