Fetal growth and spontaneous preterm birth in high-altitude pregnancy: A systematic review, meta-analysis, and meta-regression

Objective To understand the relationship between birth weight and altitude to improve health outcomes in high-altitude populations, to systematically assess the impact of altitude on the likelihood of low birth weight (LBW), small for gestational age (SGA), and spontaneous preterm birth (sPTB), and to estimate the magnitude of reduced birth weight associated with altitude. Methods PubMed, OvidEMBASE, Cochrane Library, Medline, Web of Science, and clinicaltrials.gov were searched (from inception to November 11, 2020). Observational, cohort, or case-control studies were included if they reported a high altitude (>2500 m) and appropriate control population. Results Of 2524 studies identified, 59 were included (n = 1 604 770 pregnancies). Data were abstracted according to PRISMA guidelines, and were pooled using random-effects models. There are greater odds of LBW (odds ratio [OR] 1.47, 95% confidence interval [CI] 1.33-1.62, P < 0.001), SGA (OR 1.88, 95% CI 1.08-3.28, P = 0.026), and sPTB (OR 1.23, 95% CI 1.04-1.47, P = 0.016) in high- versus low-altitude pregnancies. Birth weight decreases by 54.7 g (+/- 13.0 g, P < 0.0001) per 1000 m increase in altitude. Average gestational age at delivery was not significantly different. Conclusion Globally, the likelihood of adverse perinatal outcomes, including LBW, SGA, and sPTB, increases in high-altitude pregnancies. There is an inverse relationship between birth weight and altitude. These findings have important implications for the increasing global population living at altitudes above 2500 m.