High-altitude population neonatal and maternal phenotypes associated with birthweight protection

Padma Dolma,David J Williams,P T Angchuk,Sara L Hillman,Hugh E Montgomery,Dalvir Kular,Vatsla Dadhwal,Vandana Jain

doi:10.1038/s41390-021-01593-5

Abstract

BackgroundStates which reduce foetal oxygen delivery are associated with impaired intrauterine growth. Hypoxia results when barometric pressure falls with ascent to altitude, and with it the partial pressure of inspired oxygen (‘hypobaric hypoxia’). birthweight is reduced when native lowlanders gestate at such high altitude (HA)—an effect mitigated in native (millennia) HA populations. Studying HA populations offer a route to explore the mechanisms by which hypoxia impacts foetal growth.MethodsBetween February 2017 and January 2019, we prospectively studied 316 pregnant women, in Leh, Ladakh (altitude 3524 m, where oxygen partial pressure is reduced by 1/3) and 101 pregnant women living in Delhi (low altitude, 216 m above sea level).ResultsOf Ladakhi HA newborns, 14% were small for gestational age (<10th birthweight centile) vs 19% of newborn at low altitude. At HA, increased maternal body mass index, age, and uterine artery (UtA) diameter were positively associated with growth >10th weight centile.ConclusionsThis study showed that Ladakhi offspring birthweight is relatively spared from the expected adverse HA effects. Furthermore, maternal body composition and greater UtA size may be physiological HA adaptations and warrant further study, as they offer potential mechanisms to overcome hypoxia-related growth issues.ImpactReduced foetal oxygen delivery seen in native lowlanders who gestate at HA causes foetal growth restriction—an effect thought to be mitigated in native HA populations.We found that greater maternal body mass and UtA diameter were associated with increased offspring birthweight in a (Ladakh) HA population.This supports a role for them as physiological mediators of adaptation and provides insights into potential mechanisms that may treat hypoxia-related growth issues.

Highlights

Birthweight is an important determinant of foetal and infant survival.[1,2,3,4] Small newborns are vulnerable to morbidity and mortality.[5,6,7] Conditions which reduce foetal oxygen delivery are associated with lower birthweight.[8]Exploring the pathogenesis of this impact in disease states is difficult
● We found that greater maternal body mass and uterine artery (UtA) diameter were associated with increased offspring birthweight in a (Ladakh) high altitude (HA) population
One approach is to study otherwise healthy individuals exposed to the environmental hypoxia, which results from residency at high altitude (HA; ‘hypobaric hypoxia’), among whom birthweight is reduced by 100 g per 1000 m ascent beyond 1500 m

Summary

Introduction

Birthweight is an important determinant of foetal and infant survival.[1,2,3,4] Small newborns are vulnerable to morbidity and mortality.[5,6,7] Conditions which reduce foetal oxygen delivery (such as significant maternal cardiac disease) are associated with lower birthweight.[8]Exploring the pathogenesis of this impact in disease states is difficult. One approach is to study otherwise healthy individuals exposed to the environmental hypoxia, which results from residency at high altitude (HA; ‘hypobaric hypoxia’), among whom birthweight is reduced by 100 g per 1000 m ascent beyond 1500 m.9–12. Such impacts are seen especially amongst native lowlanders. Birthweight is reduced when native lowlanders gestate at such high altitude (HA)—an effect mitigated in native (millennia) HA populations. Studying HA populations offer a route to explore the mechanisms by which hypoxia impacts foetal growth. RESULTS: Of Ladakhi HA newborns, 14% were small for gestational age (

Methods

Results

Conclusion