Do anti-angiogenic or angiogenic factors contribute to the protection of birth weight at high altitude afforded by Andean ancestry?
OBJECTIVE
This prospective study was designed to determine whether variation in angiogenic (placental growth factor [PlGF]) and/or anti-angiogenic (soluble fms-like tyrosine kinase [sFlt-1]) factors contribute to the protective effect of highland ancestry (Andean) from altitude-associated reductions in fetal growth.


METHODS
Plasma sFlt-1 and PlGF levels, uterine artery (UA) blood flow, and fetal biometry were determined in low-altitude (400 m; Andean n = 27, European n = 28) and high-altitude (3600 m; Andean n = 51, European n = 44) residents during pregnancy (20 and 36 weeks) and 4 months postpartum.


RESULTS
High-altitude decreased sFlt-1 levels in both groups, Andeans had lower sFlt-1, comparable PlGF, lower sFlt-1/PlGF ratios, and higher UA blood flow throughout pregnancy relative to Europeans. Altitude decreased birth weight in Europeans but not Andeans. In high-altitude Europeans sFlt-1/PlGF and sFlt-1 levels were negatively associated with UA diameter and birth weight, respectively.


CONCLUSIONS
Lower sFlt-1 and sFlt-1/PLGF ratio may contribute to or result from variations in maternal vascular adaptation to pregnancy between Andean and Europeans at high altitude. Subsequently, these effects could potentially influence ancestry-associated differences in birth weight.
Dávila
R Daniela
RD
Altitude Research Center, University of Colorado-Denver, Aurora, CO 80045, USA. daniela.davila@ucdenver.edu
Julian
Colleen G
CG
Wilson
Megan J
MJ
Browne
Vaughn A
VA
Rodriguez
Carmelo
C
Bigham
Abigail W
AW
Shriver
Mark D
MD
Vargas
Enrique
E
Moore
Lorna G
LG
D000064:Acclimatization / Q000235:genetics*; D000328:Adult; D000531:Altitude; D044467:American Indian or Alaska Native / Q000235:genetics*; D042501:Angiogenic Proteins / Q000097:blood*; D043165:Angiostatic Proteins / Q000097:blood*; D001724:Birth Weight / Q000235:genetics*; D001838:Bolivia; D016009:Chi-Square Distribution; D005260:Female; D047109:Fetal Development / Q000235:genetics; D005317:Fetal Growth Retardation / Q000097:blood / Q000235:genetics / Q000503:physiopathology / Q000517:prevention & control*; D020022:Genetic Predisposition to Disease; D005865:Gestational Age; D006801:Humans; D010375:Pedigree; D000072483:Placenta Growth Factor; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000097:blood; D011446:Prospective Studies; D012039:Regional Blood Flow; D018570:Risk Assessment; D012307:Risk Factors; D055988:Uterine Artery / Q000503:physiopathology; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood; D044465:White People / Q000235:genetics*; D055815:Young Adult
D042501:Angiogenic Proteins; D043165:Angiostatic Proteins; C000608036:PGF protein, human; D011257:Pregnancy Proteins; D000072483:Placenta Growth Factor; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1