Afforded by Andean Ancestry? Do Anti-angiogenic or Angiogenic Factors Contribute to the Protection of Birth Weight at High Altitude

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. Study design: Plasma sFlt-1 and PlGF levels, uterine artery (UA) blood flow, and fetal biometry were determined in low-altitude (400 m; Andean n 1⁄4 27, European n 1⁄4 28) and highaltitude (3600 m; Andean n 1⁄4 51, European n 1⁄4 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.