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This Article Full Text Full Text (PDF) All Versions of this Article: 295/3/R906    most recent 00164.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Julian, C. G. Articles by Moore, L. G. PubMed PubMed Citation Articles by Julian, C. G. Articles by Moore, L. G.

DEVELOPMENTAL PHYSIOLOGY AND PREGNANCY

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

¹Altitude Research Center, Department of Surgery, Division of Emergency Medicine, ²Department of Health and Behavioral Sciences, ³Department of Obstetrics and Gynecology, University of Colorado Denver, Aurora, Colorado

Submitted 4 March 2008 ; accepted in final form 10 June 2008

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; 1600 m, n = 18) or high altitude (HA; 3100 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 (). 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.

fetal growth restriction; hypoxia; small-for-gestational age; uteroplacental oxygen delivery; pregnancy