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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.
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 C. G. Julian, M. J. Wilson, M. Lopez, H. Yamashiro, W. Tellez, A. Rodriguez, A. W. Bigham, M. D. Shriver, C. Rodriguez, E. Vargas, et al. Augmented uterine artery blood flow and oxygen delivery protect Andeans from altitude-associated reductions in fetal growth Am J Physiol Regulatory Integrative Comp Physiol, May 1, 2009; 296(5): R1564 - R1575. [Abstract] [Full Text] [PDF]
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