Background: We present a cohort of ca. 25,000 birth records from Bolivia of men and women who are currently adults. We used this cohort to test the hypothesis that high altitude reduces birth weight and that highland ancestry confers graduated protection against this effect. Methods: Birth records were obtained from obstetric clinics and hospitals in La Paz (3,600 m) and Santa Cruz (420 m). Only singleton, healthy term (>37 wk) pregnancies of nonsmoking mothers were included. Andean, Mestizo, or European ancestry was determined by validated analysis of parental surnames. results: High altitude reduced body weight (3,396 ± 3 vs. 3,090 ± 6 g) and length (50.8 ± 0 vs. 48.7 ± 0 cm) at birth (P < 0.001). Highland ancestry partially protected against the effects of high altitude on birth weight (Andean = 3,148 ± 15 g; Mestizo = 3,081 ± 6 g; and European = 2,957 ± 32 g; trend P < 0.001) but not on birth length. The effects of high-altitude pregnancy on birth size were similar for male and female babies. conclusion: High altitude reduces birth weight and highland native ancestry confers graduated protection. Given previous studies linking reduced birth weight with increased risk of cardiovascular disease, further study is warranted to test whether adults from high-altitude pregnancy are at increased risk of developing cardiovascular disease.i n addition to the interaction between our genetic makeup and traditional lifestyle risk factors, such as smoking and obesity, it is now accepted that the quality of the environment in prenatal life programs cardiovascular health and the risk of developing heart disease (1). Overwhelming evidence derived from human studies dating back more than two decades and encompassing six continents now links development under suboptimal intrauterine conditions with low birth weight and increased rates of coronary heart disease and the metabolic syndrome (2-8). Epidemiologic studies relating the type of suboptimal intrauterine condition with physiological dysfunction in later life have largely focused on human populations undergoing alterations in maternal nutrition or on human pregnancy affected by maternal psychological stress or by exposure to stress hormones (9-11). This focus on the nutrient supply to the fetus or on maternofetal stress in humans is supported by a large number of investigations in experimental animal models demonstrating that cardiovascular dysfunction in adulthood can be programmed in pregnancy by inappropriate nutrition or by exposure to glucocorticoid excess (1,12,13).In addition to the alterations in maternal nutrition and maternal stress, fetal hypoxia is one of the most common suboptimal conditions in complicated pregnancy. More than 140 million people live at altitudes >2,500 m where lowered oxygen availability has been shown to reduce fetal growth and birth weight, thus comprising the largest single human group at risk for fetal growth restriction. Of note, multigenerational highaltitude populations demonstrate protection against the effects of high-altitude hypoxi...