Augmented uterine artery blood flow and oxygen delivery protect Andeans from altitude-associated reductions in fetal growth

Abstract

The effect of high altitude on reducing birth weight is markedly less in populations of high- (e.g., Andeans) relative to low-altitude origin (e.g., Europeans). Uterine artery (UA) blood flow is greater during pregnancy in Andeans than Europeans at high altitude; however, it is not clear whether such blood flow differences play a causal role in ancestry-associated variations in fetal growth. We tested the hypothesis that greater UA blood flow contributes to the protection of fetal growth afforded by Andean ancestry by comparing UA blood flow and fetal growth throughout pregnancy in 137 Andean or European residents of low (400 m; European n = 28, Andean n = 23) or high (3,100-4,100 m; European n = 51, Andean n = 35) altitude in Bolivia. Blood flow and fetal biometry were assessed by Doppler ultrasound, and maternal ancestry was confirmed, using a panel of 100 ancestry-informative genetic markers (AIMs). At low altitude, there were no ancestry-related differences in the pregnancy-associated rise in UA blood flow, fetal biometry, or birth weight. At high altitude, Andean infants weighed 253 g more than European infants after controlling for gestational age and other known influences. UA blood flow and O(2) delivery were twofold greater at 20 wk in Andean than European women at high altitude, and were paralleled by greater fetal size. Moreover, variation in the proportion of Indigenous American ancestry among individual women was positively associated with UA diameter, blood flow, O(2) delivery, and fetal head circumference. We concluded that greater UA blood flow protects against hypoxia-associated reductions in fetal growth, consistent with the hypothesis that genetic factors enabled Andeans to achieve a greater pregnancy-associated rise in UA blood flow and O(2) delivery than European women at high altitude.

Fig. 1.

Uterine artery (UA) blood flow increased with pregnancy in each ancestry group at low (A) or high (B) altitude. A: at low altitude, the pregnancy-associated rise in UA blood flow was equivalent between Andean and European women (interaction, ancestry × time = NS), and Europeans had slightly greater UA blood flow at 20 wk. B: at high altitude, the pregnancy-associated rise in UA blood flow tended to be greater in Andeans than Europeans, resulting in UA blood flows that were more than one-third larger at 20 or 36 wk in Andean women (both, P < 0.05). Comparing across altitudes, the Andean women had greater pregnancy-associated rise in UA blood flow, whereas the rise was unchanged in European subjects (time × ancestry × altitude, P < 0.05 and P = NS, respectively).

Fig. 2.

The change in UA blood flow measurements across time at low (A) and high (B) altitude. A: at low altitude, there was no difference between ancestry groups in the magnitude with which pregnancy increased UA blood flow. B: at high altitude, Andean compared with European women had more than a two-fold larger increase in UA blood flow from the nonpregnant state to week 20 or week 36 (both P < 0.05). There was no ancestry-associated difference in the magnitude to which UA blood flow increased from weeks 20 to 36 at either altitude.

Fig. 3.

The relationship between Indigenous American AIMs and UA diameter in Andean women at low (A) and high (B) altitude. A: at low altitude, UA diameter did not change with the percentage of Indigenous American AIMs among Andean women. B: at high altitude, Andean women with a higher proportion of Indigenous American AIMs had greater UA diameters.