Multigenerational (Andean) compared with shorter-term (European) high-altitude residents exhibit less hypoxia-associated reductions in birth weight. Because differences in arterial O(2) content are not responsible, we asked whether greater pregnancy-associated increases in uterine artery (UA) blood flow and O(2) delivery were involved. Serial studies were conducted in 42 Andean and 26 European residents of La Paz, Bolivia (3600 m) at weeks 20, 30, 36 of pregnancy and 4 mo postpartum using Doppler ultrasound. There were no differences postpartum but Andean vs. European women had greater UA diameter (0.65 +/- 0.01 vs. 0.56 +/- 0.01 cm), cross-sectional area (33.1 +/- 0.97 vs. 24.7 +/- 1.18 mm(2)), and blood flow at week 36 (743 +/- 87 vs. 474 +/- 36 ml/min) (all P < 0.05) and thus 1.6-fold greater uteroplacental O(2) delivery near term (126.82 +/- 18.47 vs. 80.33 +/- 8.69 ml O(2).ml blood(-1).min(-1), P < 0.05). Andeans had greater common iliac (CI) flow and lower external iliac relative to CI flow (0.52 +/- 0.11 vs. 0.95 +/- 0.14, P < 0.05) than Europeans at week 36. After adjusting for gestational age, maternal height, and parity, Andean babies weighed 209 g more than the Europeans. Greater UA cross-sectional area at week 30 related positively to birth weight in Andeans (r = +0.39) but negatively in Europeans (r = -0.37) (both P < 0.01). We concluded that a greater pregnancy-associated increase in UA diameter raised UA blood flow and uteroplacental O(2) delivery in the Andeans and contributed to their ability to maintain normal fetal growth under conditions of high-altitude hypoxia. These data implicate the involvement of genetic factors in protecting multigenerational populations from hypoxia-associated reductions in fetal growth, but future studies are required for confirmation and identification of the specific genes involved.

High altitude decreases birth weight, but this effect is diminished in long vs. short-resident, high-altitude populations. We asked whether women from long vs. short-resident, high-altitude populations had higher arterial oxygenation levels by comparing 42 Andean and 26 European residents of La Paz, Bolivia (3,600 m), serially during pregnancy (weeks 20, 30, and 36) and again 4 mo postpartum. Pregnancy raised hypoxic ventilatory sensitivity threefold, resting ventilation (V E), and arterial O2 saturation (SaO 2 ) in both groups. Ancestry, as identified using 81 genetic markers, correlated with respiratory pattern, such that greater Andean ancestry was associated with higher respiratory frequency and lower tidal volume. Pregnancy increased total blood and plasma volume ϳ40% in both groups without changing red blood cell mass relative to body weight; hence, hemoglobin fell. The hemoglobin decline was compensated for by the rise in V E and SaO 2 with the result that arterial O2 content (Ca O 2 ) was maintained near nonpregnant levels in both groups. Birth weights were similar for all Andean and European babies, but after adjusting for variation in gestational age, maternal height and parity, Andeans weighed 209 g more than Europeans. Babies with heavier birth weights and greater ponderal indices were born to Andean women with higher V E during pregnancy. We concluded that while maternal V E and arterial oxygenation were important, some factor other than higher Ca O 2 was responsible for protecting Andeans from altitude-associated reductions in fetal growth.hypoxia; ventilation; ventilatory control; infant birth weight; fetal growth; genetics of birth weight; human adaptation; respiratory pattern RESIDENCE AT HIGH ALTITUDE (Ͼ8,000 ft, 2,500 m) exerts among the most powerful effects on birth weight with values falling, on average, 121 g per 1,000 m in Colorado high-altitude (Ͼ2,500 m, 8,000 ft) residents (15). This effect is due primarily to a slowing of fetal growth, not shortened gestation, and is greater than the effects of parity, the number of prenatal visits, or moderate maternal smoking on birth weight. Existing data indicate that the birth weight fall is not due to socioeconomic or other known risk factors (6, 15), but rather to the effects of hypoxia itself.Some 140 million persons live at high altitude, making them the largest single group at risk of low birth weight (16). While birth weight declines in all populations studied to date, the magnitude of fall varies, being least in long-and greatest in short-resident groups. For example, across a 2,700 -4,700 m (8,900 -15,500 ft) altitude range, birth weight decreases three times as much in Han ("Chinese") compared with Tibetans (24). In La Paz, Bolivia, at 3,600 m (11,880 ft), women of indigenous (Aymára or Quechua) ancestry give birth to heavier weight infants than European women, regardless of whether the data are adjusted for differences in maternal body size, nutrition, or the mother's own altitude of birth and development (9).On the basis of our previo...