Cardiovascular health in early pregnancy and circulating biomarkers of placental health and function

Abstract

AbstractBackgroundMaternal cardiovascular health (CVH) and placental health are related to pregnancy outcomes, yet how early pregnancy CVH affects placentation is not well characterized. The objective of this study was to determine associations between CVH and concentrations of placental proteins.MethodsParticipants from the nuMoM2b prospective cohort were included (n=2188). Maternal CVH was defined three ways: (1) composite scores using 6 components measured in the 1sttrimester (four behavioral components of physical activity, diet, sleep duration, and smoking, and the health factors of blood pressure and body mass index); (2) latent classes of the four behavioral components; and (3) individual health behaviors. Linear regression associated composite CVH, latent classes, and individual health behaviors with 1stand 2ndtrimester circulating markers of placental growth and development (pregnancy-associated plasma protein A, PAPP-A), pro-angiogenic (vascular endothelial growth factor, VEGF; placental growth factor, PlGF), and anti-angiogenic factors (soluble FMS-like tyrosine kinase 1, sFlt-1; soluble endoglin, sEng).Results and ConclusionsMore favorable composite CVH was associated with higher PAPP-A (representing better 1sttrimester placental growth and development) and lower VEGF and higher sEng (representing an anti-angiogenic 1sttrimester profile). Higher levels of physical activity were associated with lower 2ndtrimester PAPP-A and higher 1sttrimester VEGF and lower sFlt-1 (pro-angiogenic). In the four groups identified with latent class analysis (Healthy Behaviors, Active with Poor Diet, Inactive with Poor Diet, and Less Healthy Behaviors), first trimester sFlt- 1 was lower in the Healthy Behaviors group compared to Inactive with Poor Diet group. Modifiable aspects of CVH in early pregnancy are related to placental health and function and may be useful targets for intervention.Clinical PerspectiveWhat is New?Combinations of modifiable health behaviors in early pregnancy are related to circulating markers of placental development and function.These associations varied according to trimester of placental biomarker assessment, suggesting that patterns across gestation may be informative.More physical activity in the 1sttrimester was associated with lower PAPP-A concentrations in the 2ndtrimester without a concurrent increase in the rate of adverse outcomes.What are the Clinical Implications?This study suggests that more favorable cardiovascular health in early pregnancy may be related to differences in placental health and function as reflected by higher concentrations of PAPP-A.One mechanism of the benefits of physical activity in early pregnancy may be through improved angiogenic/anti-angiogenic balance as measured by VEGF and sFlt-1 in the 1sttrimester.