Impaired maternal central hemodynamics precede the onset of vascular disorders of pregnancy at high altitude

Hypertensive disorders of pregnancy represent an escalating global health concern with increasing incidence in low- to middle-income countries and high-income countries alike. The current lack of methods to detect the subclinical stages of preeclampsia (PE) and fetal growth restriction (FGR), two common vascular disorders of pregnancy, limits treatment options to minimize acute- and long-term adverse outcomes for both mother and child. To determine whether impaired maternal cardiovascular or uteroplacental vascular function precedes the onset of PE and/or FGR (PE-FGR), we used non-invasive techniques to obtain serial measurements of maternal cardiac output (CO), stroke volume (SV), systemic vascular resistance (SVR), as well as uterine and fetal arterial resistance at gestational weeks 10-16, 20-24 and 30-34 for 79 maternal-infant pairs in La Paz-El Alto, Bolivia (3850 m), where the chronic hypoxia of high altitude increases the incidence of PE and FGR. Compared to controls (n=55), PE-FGR cases (n=24) had lower SV, higher SVR, and greater uterine artery resistance at 10-16 weeks. In addition, fetuses of women with lower SV and higher SVR at 10-16 weeks showed evidence of brain sparing at 30-34 weeks and had lower birth weights, respectively. While the trajectory of SV and SVR across pregnancy was similar between groups, PE-FGR cases had a comparatively blunted rise in CO from the first to the third visit. Impaired maternal central hemodynamics and increased uteroplacental resistance precede PE-FGR onset, highlighting the potential use of such measures for identifying high-risk pregnancies at high altitudes.