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 O₂ 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 O₂ 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 O₂ delivery. Fetal haemoglobin concentration was increased, decreased, and the fetal/curve was left-shifted at 3600 m. Fetuses receiving less O₂ extracted more (r² = 0.35, P < 0.0001). These adaptations resulted in similar fetal O₂ delivery and consumption across all four groups. Increased umbilical venous O₂ delivery correlated with increased fetal O₂ consumption per kg weight (r² = 0.50, P < 0.0001). Blood flow (r² = 0.16, P < 0.001) and O₂ delivery (r² = 0.17, P < 0.001) correlated with birth weight at 3600 m, but not at 400 m (r² = 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 O₂ extraction indicates that deficit in fetal oxygen delivery is unlikely to be causally associated with the altitude- and ancestry-related differences in fetal growth.