title: Lower uterine artery blood flow and higher endothelin relative to nitric oxide metabolite levels are associated with reductions in birth weight at high altitude.
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.
authors.affiliation: Altitude Research Center, Dept. of Surgery, Division of Emergency Medicine, Univ. of Colorado Denver, 12469 East 17th Place, Bldg. 400, Aurora, Colorado 80045, USA. colleen.julian@uchsc.edu
authors.forename: Colleen Glyde
authors.initials: CG
authors.lastname: Julian
authors.forename: Henry L
authors.initials: HL
authors.lastname: Galan
authors.forename: Megan J
authors.initials: MJ
authors.lastname: Wilson
authors.forename: Wendy
authors.initials: W
authors.lastname: Desilva
authors.forename: Darleen
authors.initials: D
authors.lastname: Cioffi-Ragan
authors.forename: Joel
authors.initials: J
authors.lastname: Schwartz
authors.forename: Lorna G
authors.initials: LG
authors.lastname: Moore
mesh_terms: D000328:Adult; D000531:Altitude; D001724:Birth Weight / Q000502:physiology*; D003120:Colorado; D019332:Endothelin-1 / Q000378:metabolism*; D005260:Female; D005269:Femur / Q000033:anatomy & histology; D005317:Fetal Growth Retardation / Q000378:metabolism* / Q000503:physiopathology; D006257:Head / Q000033:anatomy & histology; D006801:Humans; D007231:Infant, Newborn; D007236:Infant, Small for Gestational Age; D009569:Nitric Oxide / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism; D011247:Pregnancy; D012044:Regression Analysis; D014599:Uterus / Q000098:blood supply* / Q000378:metabolism*
chemical_list: D019332:Endothelin-1; D009569:Nitric Oxide; D010100:Oxygen