Submitted on March 4, 2008
Accepted on June 10, 2008
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 Julian1*, Henry L. Galan2, Megan Wilson3, Wendy DeSilva4, Darleen Cioffi-Ragan2, Joel Schwartz2, and Lorna G. Moore1
1 Dept of Surgery, Division of Emergency Medicine, Altitude Research Center, University of Colorado Denver, Aurora, Colorado, United States; Health and Behavioral Sciences, University of Colorado Denver, Denver, Colorado, United States
2 Obstetrics & Gynecology, University of Colorado Denver, Aurora, Colorado, United States
3 Health and Behavioral Sciences, University of Colorado Denver, Denver, Colorado, United States
4 Dept of Surgery, Division of Emergency Medicine, Altitude Research Center, University of Colorado Denver, Aurora, Colorado, United States
* To whom correspondence should be addressed. E-mail: colleen.julian{at}uchsc.edu.
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, 1600m, n=18) or high altitude (HA, 3100m, n=25) were studied during pregnancy (20w, 30w, 36w) and 4mo postpartum (PP) using Doppler ultrasound. At each study endothelin (ET-1), nitric oxide metabolites (NOx), 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 to LA. HA was associated with lower UA diameter (p<0.01) and blood flow (p<0.05). Altitude did not affect ET-1, sFlt-1 or PlGF however ET-1/NOx was greater and NOx lower during pregnancy and PP at HA vs. LA. ET-1/NOx was negatively associated with birth weight (20w, p<0.01; 36w, p=0.05) at LA and HA combined. At HA UA blood flow (30w) was positively associated with birth weight (
). UA blood flow and ET-1/NOx levels accounted for 45% (20w) and 32% (30w) of birth weight variation at LA and HA combined, due primarily to effects at HA. We concluded that elevated ET-1/NOx and altered determinants of uteroplacental blood flow occur prior to altitude-associated reductions in fetal growth, and therefore are likely a cause rather than a consequence of smaller fetal size.
