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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...

Elevated hemoglobin concentrations have been reported for high-altitude sojourners and Andean high-altitude natives since early in the 20th century. Thus, reports that have appeared since the 1970s describing relatively low hemoglobin concentration among Tibetan high-altitude natives were unexpected. These suggested a hypothesis of population differences in hematological response to high-altitude hypoxia. A case of quantitatively different responses to one environmental stress would offer an opportunity to study the broad evolutionary question of the origin of adaptations. However, many factors may confound population comparisons. The present study was designed to test the null hypothesis of no difference in mean hemoglobin concentration of Tibetan and Aymara native residents at 3,800-4,065 meters by using healthy samples that were screened for iron deficiency, abnormal hemoglobins, and thalassemias, recruited and assessed using the same techniques. The hypothesis was rejected, because Tibetan males had a significantly lower mean hemoglobin concentration of 15.6 gm/dl compared with 19.2 gm/dl for Aymara males, and Tibetan females had a mean hemoglobin concentration of 14.2 gm/dl compared with 17.8 gm/dl for Aymara females. The Tibetan hemoglobin distribution closely resembled that from a comparable, sea-level sample from the United States, whereas the Aymara distribution was shifted toward 3-4 gm/dl higher values. Genetic factors accounted for a very high proportion of the phenotypic variance in hemoglobin concentration in both samples (0.86 in the Tibetan sample and 0.87 in the Aymara sample). The presence of significant genetic variance means that there is the potential for natural selection and genetic adaptation of hemoglobin concentration in Tibetan and Aymara high-altitude populations.

Chest depth, chest width, forced vital capacity (FVC), and forced expiratory volume (FEV1) were measured in 170 adult males differing by ancestral (genetic) and developmental exposure to high altitude (HA). A complete migrant study design was used to study HA natives (Aymara/Quechua ancestry, n = 88) and low altitude (LA) natives (European/North American ancestry, n = 82) at both altitude (La Paz, Bolivia, 3,600 m) and near sea level (Santa Cruz, Bolivia, 420 m). HAN and LAN migrant groups were classified as: Nth generation migrants, born and raised in a non‐native environment; child migrants who migrated during the period of growth and maturation (0–18 yrs); and adult migrants who migrated after 18 years of age. Chest depth, FVC, and FEV1 measures were larger with increasing developmental exposure in both HAN migrants at LA and LAN migrants at HA. Developmental responses were similar between HAN and LAN groups. FVC and FEV1 measures were larger in HANs vs LANs born and raised at HA to suggest a genetic effect, but were similar in HANs and LANs born and raised at LA. The similarity of HAN and LAN groups at LA suggests that the genetic potential for larger lung volumes at HA depends upon developmental exposure to HA. Additional data for females (HANs at HA, n = 20, and LAN adult migrants to HA, n = 17) show similar differences as those shown between male HAN and LAN groups. Am. J. Hum. Biol. 11:383–395, 1999. © 1999 Wiley‐Liss, Inc.

Vital capacity and residual lung volume (in terms of 1/min or ml/m 2 of body surface area) of 357 subjects (205 males, 152 females) was evaluated in La Paz, Bolivia, situated at 3,750 m. The sample included: (1) 37 high altitude rural natives (all male), (2) 125 high altitude urban natives