Determinants of blood oxygenation during pregnancy in Andean and European residents of high altitude

Abstract

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...

Physiological adaptation of maternal plasma volume during pregnancy: a systematic review and meta-analysis

“…Vargas (2007) 40 Whittaker (1996) 38 Whittaker (1993) 37 Abudu (1988) 30 Abudu (1985) 14 Rajalakshmi (1985) 32 Bruinse (1985) 44 Hunyor (1982) 46 Pirani (1973) 7 Pirani (1973) 7 Blanche Butler (1968) 34 Hytten (1963) 5 Paintin (1962) 27 Berlin (1953) 39 Whittaker (1996) 38 Whittaker (1993) 37 Bruinse (1985) 44 Rajalakshmi (1985) 32 Abudu (1985) 14 Gibson (1973) 47 Pirani (1973) 7 Blekta (1970) 35 Blanche Butler (1968) 34 Rovinsky (1965) 51 Hytten (1963) 5 Hytten (1963) 5 Berlin (1953) 39 Berlin (1953) Only first author of each study is given. Some studies appear more than once within a gestational-age interval because they provided data for different gestational weeks within that interval.…”

Graduated effects of high-altitude hypoxia and highland ancestry on birth size

“…This rationale stemmed from previous studies in which we were not able to accurately predict non-Andean ancestry using Hispanic surnames. More specifically, in some cases, even women with two non-Andean, Hispanic surnames (e.g., Garcia) were found to be 100% Amerindian according to ancestry informative genetic markers (39). By contrast, Andean surname frequency (e.g., Condori, Mamani, or Huanca) is strongly correlated with high altitude in Bolivia (39,40).…”

“…Infant ancestry was classified retrospectively using parental surnames with a methodology validated by gene markers, as described elsewhere (39). Surnames were classified as "Andean" if they were of Aymara or Quechua origin, "Foreign" if they were non-Andean and nonHispanic, and "Mestizo" for all other cases.…”

Lower uterine artery blood flow and higher endothelin relative to nitric oxide metabolite levels are associated with reductions in birth weight at high altitude

“…Previously we have shown that uterine artery (UA) diameter and blood flow are lower near term in women residing at high (3,100 m; 10,170 ft, Leadville) compared with low altitude (1,600 m; 5,280 ft, Denver) in Colorado (36). Greater maternal arterial oxygen content and/or UA blood flow, both of which are determinants of uteroplacental oxygen delivery, are associated with protection from SGA at high altitude (20,28,32,35,36). The frequency of preeclampsia, another condition in which UA blood flow is reduced, also increases with altitude and is responsible for approximately one-half of the altitude-associated reduction in birth weight, further demonstrating the importance of adequate UA blood flow to fetal growth at high altitude (13,15).…”