Understanding Physiological Adaptations of Pregnancy to the Chronic Hypoxia of High Altitude to Inform Obstetrical and Neonatal Care

The chronic hypoxia experienced by high-altitude residents profoundly impacts pregnancy, influencing maternal health, placental function, and the growth and development of the fetus. Exposure to chronic hypoxia during pregnancy increases the risk of complications like preeclampsia and fetal growth restriction and has lasting effects on offspring, extending from infancy to adulthood. Understanding how chronic hypoxia alters physiological adaptations to pregnancy and pregnancy outcomes is essential for high-altitude populations and for gaining broader insights into the mechanisms underlying reduced fetoplacental oxygenation in complicated pregnancy at sea level. This review summarizes current knowledge on physiological adaptations during pregnancy under hypoxic conditions. We describe key studies on the effects of high altitude and chronic hypoxia on pregnancy, and examine the maternal, placental, fetal, and long-term physiological consequences. Finally, we review preclinical and clinical studies aimed at identifying interventions that could prevent or alleviate the adverse effects of chronic hypoxia on pregnancy outcomes and beyond.