High-altitude pregnancy adaptation: evidence from a Himalayan population in Leh.

Leh, Ladakh, is situated at an altitude of more than 3500 metres above sea level (masl) and serves as a natural hypoxic environment for studying the effects of a low-oxygen environment on pregnancy. Over a 10 year collaboration, pregnant women in Leh were recruited and studied, alongside their partners and offspring at birth. The aim was to better elucidate underlying mechanisms that might both protect from, as well as predispose to, poor fetal growth. Phenotypic data were analysed alongside genomic data generated by the Infinium™ Global Screening Array-24 BeadChip. Patient records from low-altitude sites (Bylakuppe 850 m a.s.l) and Delhi (200 m) were compared with data from Leh. A cohort of 318 pregnant women in Ladakh were studied, with an average birthweight for those born at term of 3.15 kg. Compared with women who delivered an appropriate for gestational age (AGA) baby in Leh, those who delivered a small for gestational age (SGA) (<10th birth weight centile) were statistically older and lighter and had smaller maternal uterine artery diameters at 18-22 weeks of gestation. This difference was not maintained between AGA and SGA babies at low altitude in the Delhi cohort. Genetic analysis of Ladakh babies suggested a genetic history most closely related to neighbouring Tibeto-Burman-speaking populations and birth weight analysis replicated previous identified SNPs related to metabolic, skeletal and height genes, offering novel avenues of investigation.This article is part of the discussion meeting issue 'Pregnancy at high altitude: the challenge of hypoxia'.