Protected fetal growth in highland Andeans: The role of maternal antioxidant status and oxidative stress

Permanent high-altitude (HA) residence compromises fetal growth and increases the incidence of preeclampsia (PE). Highland ancestry groups (i.e. Andeans) experience a lesser degree of birth weight reduction than lowland ancestry groups (i.e. Europeans). Oxidative stress and reduced antioxidant capacity have been implicated in the maternal vascular dysfunction hallmark to PE and reduced fetal growth at low altitude (LA). Since hypoxia increases oxidative stress, we hypothesized (1) that altered redox status contributes to reduced fetal growth and PE at HA by causing endothelial damage and reducing uterine artery (UA) blood flow and (2) that enhanced antioxidant activity contributes to the protective effect of Andean ancestry. Studies (n=310) were conducted in non-pregnant (NP) or pregnant (20w, 36w) women of Andean or European ancestry residing at HA (3600--4100m, La Paz) or LA (400m, Santa Cruz) in Bolivia. Maternal oxidative stress (8-iso-PGF2alpha), antioxidant status (superoxide dismutase [SOD]; catalase) and UA blood flow were assessed at each time point. Fetal biometry was assessed by ultrasound at 20w and 36w. Erythrocyte SOD and catalase activity were quantified by spectrophotometry. Plasma 8-iso-PGF2alpha was measured by mass-spectrometry. Medical records were reviewed to obtain newborn information. At HA Andeans had greater UA blood flows at all time points, tended to be heavier at birth and to be SGA less often than Europeans. Catalase and SOD (36w) were lower during pregnancy in European than Andeans at HA. Catalase tended to be lower in Europeans who delivered SGA versus non-SGA infants (20w). SOD was lower in mothers of SGA infants in all women and at HA alone (20w). 8-iso-PGF2alpha reduced UA blood flow at HA in all women or in Europeans considered alone. Our data support the hypothesis that maternal antioxidant status has a protective effect on UA blood flow blood pressure and fetal growth at HA. Further, our results strongly suggest that augmented antioxidant activity contributes to the preservation of fetal growth at altitude in Andean populations.