Cause of fetal growth restriction during high-altitude pregnancy

High-altitude pregnancy increases the incidence of fetal growth restriction and reduces birth weight. This poses a significant clinical challenge as both are linked to adverse health outcomes, including raised infant mortality and the development of the metabolic syndrome in later life. While this reduction in birth weight is mostly understood to be driven by the hypobaric hypoxia of high altitude, the causative mechanism is unclear. Moreover, it is now recognized that highland ancestry confers protection against this reduction in birth weight. Here, we analyze the evidence that pregnancy at high altitude reduces birth weight and that highland ancestry confers protection, discussing mechanisms contributing to both effects. [Display omitted] •Birth weight decreases by 90.95g for every 1000m increase in altitude•Highland ancestry decreases the birth weight reduction at altitude by half•Fetal hypoglycaemia and hypoinsulinaemia are important in FGR at high altitude•Uterine artery and placental metabolic adaptations protect against FGR at altitude Female reproductive endocrinology; Reproductive medicine; Women's health