Lower uterine artery blood flow and higher endothelin relative to nitric oxide metabolite levels are associated with reductions in birth weight at high altitude - PubMed (original) (raw)

Lower uterine artery blood flow and higher endothelin relative to nitric oxide metabolite levels are associated with reductions in birth weight at high altitude

Colleen Glyde Julian et al. Am J Physiol Regul Integr Comp Physiol. 2008 Sep.

Abstract

Reduced uteroplacental blood flow is hypothesized to play a key role in altitude-associated fetal growth restriction. It is unknown whether reduced blood flow is a cause or consequence of reduced fetal size. We asked whether determinants of uteroplacental blood flow were altered prior to reduced fetal growth and whether vasoactive and/or angiogenic factors were involved. Women residing at low (LA; 1,600 m, n = 18) or high altitude (HA; 3,100 m, n = 25) were studied during pregnancy (20, 30, and 36 wk) and 4 mo postpartum (PP) using Doppler ultrasound. In each study, endothelin (ET-1), nitric oxide metabolites (NO(x)), soluble fms-like tyrosine kinase (sFlt-1) and placental growth factor (PlGF) levels were quantified. At HA, birth weights were lower (P < 0.01) and small-for-gestational age was more common (P < 0.05) compared with LA. HA was associated with lower uterine artery (UA) diameter (P < 0.01) and blood flow (P < 0.05). Altitude did not affect ET-1, sFlt-1 or PlGF; however, ET-1/NO(x) was greater and NO(x) lower during pregnancy and PP at HA vs. LA. ET-1/NO(x) was negatively associated with birth weight (20 wk, P < 0.01; 36 wk, P = 0.05) at LA and HA combined. At HA, UA blood flow (30 wk) was positively associated with birth weight (dagger). UA blood flow and ET-1/NO(x) levels accounted for 45% (20 wk) and 32% (30 wk) of birth weight variation at LA and HA combined, primarily attributed to effects at HA. We concluded that elevated ET-1/NO(x) and altered determinants of uteroplacental blood flow occur prior to altitude-associated reductions in fetal growth, and therefore, they are likely a cause rather than a consequence of smaller fetal size.

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Figures

Fig. 1.

Fig. 1.

Level of endothelin (ET-1) relative to nitric oxide metabolites (NO_x_) in the maternal circulation were elevated in the nonpregnant state, as well as at all times of measure during pregnancy.

Fig. 2.

Fig. 2.

Uterine artery (UA) blood flow at 30 wk of pregnancy was unassociated with birth weight at low altitude (left). In contrast, at high altitude, women with greater UA blood flow at 30 wk tended to deliver infants of heavier birth weight (right).

Fig. 3.

Fig. 3.

Women with higher ET-1 relative to nitric oxide metabolites (NO_x_) at 20 (left, P < 0.01) or 36 wk (right, P = 0.05) delivered infants of lower birth weight at both altitudes combined.

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