Where the O2 goes to: preservation of human fetal oxygen delivery and consumption at high altitude.

Fetal growth is decreased at high altitude (> 2700 m). We hypothesized that variation in fetal O(2) delivery might account for both the altitude effect and the relative preservation of fetal growth in multigenerational natives to high altitude. Participants were 168 women of European or Andean ancestry living at 3600 m or 400 m. Ancestry was genetically confirmed. Umbilical vein blood flow was measured using ultrasound and Doppler. Cord blood samples permitted calculation of fetal O(2) delivery and consumption. Andean fetuses had greater blood flow and oxygen delivery than Europeans and weighed more at birth, regardless of altitude (+208 g, P < 0.0001). Fetal blood flow was decreased at 3600 m (P < 0.0001); the decrement was similar in both ancestry groups. Altitude-associated decrease in birth weight was greater in Europeans (-417 g) than Andeans (-228 g, P < 0.005). Birth weight at 3600 m was > 200 g lower for Europeans at any given level of blood flow or O(2) delivery. Fetal haemoglobin concentration was increased, decreased, and the fetal / curve was left-shifted at 3600 m. Fetuses receiving less O(2) extracted more (r(2) = 0.35, P < 0.0001). These adaptations resulted in similar fetal O(2) delivery and consumption across all four groups. Increased umbilical venous O(2) delivery correlated with increased fetal O(2) consumption per kg weight (r(2) = 0.50, P < 0.0001). Blood flow (r(2) = 0.16, P < 0.001) and O(2) delivery (r(2) = 0.17, P < 0.001) correlated with birth weight at 3600 m, but not at 400 m (r(2) = 0.04, and 0.03, respectively). We concluded that the most pronounced difference at high altitude is reduced fetal blood flow, but fetal haematological adaptation and fetal capacity to increase O(2) extraction indicates that deficit in fetal oxygen delivery is unlikely to be causally associated with the altitude- and ancestry-related differences in fetal growth.

Maternal oxygen delivery is not related to altitude- and ancestry-associated differences in human fetal growth.

Fetal growth is reduced at high altitude, but the decrease is less among long-resident populations. We hypothesized that greater maternal uteroplacental O(2) delivery would explain increased fetal growth in Andean natives versus European migrants to high altitude. O(2) delivery was measured with ultrasound, Doppler and haematological techniques. Participants (n=180) were pregnant women of self-professed European or Andean ancestry living at 3600 m or 400 m in Bolivia. Ancestry was quantified using ancestry-informative single nucleotide polymorphism. The altitude-associated decrement in birth weight was 418 g in European versus 236 g in Andean women (P<0.005). Altitude was associated with decreased uterine artery diameter, volumetric blood flow and O(2) delivery regardless of ancestry. But the hypothesis was rejected as O(2) delivery was similar between ancestry groups at their respective altitudes of residence. Instead, Andean neonates were larger and heavier per unit of O(2) delivery, regardless of altitude (P<0.001). European admixture among Andeans was negatively correlated with birth weight at both altitudes (P<0.01), but admixture was not related to any of the O(2) transport variables. Genetically mediated differences in maternal O(2) delivery are thus unlikely to explain the Andean advantage in fetal growth. Of the other independent variables, only placental weight and gestational age explained significant variation in birth weight. Thus greater placental efficiency in O(2) and nutrient transport, and/or greater fetal efficiency in substrate utilization may contribute to ancestry- and altitude-related differences in fetal growth. Uterine artery O(2) delivery in these pregnancies was 99 +/- 3 ml min(-1), approximately 5-fold greater than near-term fetal O(2) consumption. Deficits in maternal O(2) transport in third trimester normal pregnancy are unlikely to be causally associated with variation in fetal growth.