Maternal BMI modulates cord plasma NT-proBNP in gestational diabetes linking cardiac stress to insulin-cortisol crosstalk

Abstract

Abstract Gestational diabetes mellitus (GDM) is an increasingly prevalent pregnancy disorder associated with adverse maternal and neonatal outcomes, including an increased risk of early-onset cardiovascular disease in infants. GDM is associated with cardiac structural and functional changes as early as in utero. However, pathways linking maternal metabolic status to fetal cardiac stress remain poorly defined. We investigated N-teminal pro-B-type natriuretic peptide (NT-proBNP) in umbilical cord plasma (UCP) as a candidate biomarker of fetal cardiac stress, together with additional cardiac, endocrine and endothelial biomarkers to identify novel links between fetal cardiac health and maternal and fetal metabolic, inflammatory and hormonal characteristics. UCP from 82 term pregnancies (57 controls, 25 GDM) was analyzed for NT-proBNP and complementary cardiac, endocrine, and endothelial markers. Associations with maternal metabolic parameters, neonatal outcomes, and other UCP parameters were assessed using correlation, regression, and mediation analyses, adjusted for gestational age and neonatal sex. NT-proBNP levels were elevated in the cord plasma of GDM pregnancies, specifically in the presence of increased maternal pre-pregnancy BMI. Across the cohort, NT-proBNP was further associated with maternal BMI at delivery, fasting glucose levels, placental weight, and neonatal C-peptide, while inversely associated with cord plasma cortisol. Mediation analyses identified a significant indirect association involving neonatal C-peptide and suggested a potential mediating role of NT-proBNP in the association between maternal pre-pregnancy BMI and cord plasma cortisol. These findings suggest that NT-proBNP may reflect fetal cardiac load in GDM and is associated with maternal metabolic status and fetal insulin secretion. The inverse association between NT-proBNP and cortisol raises the possibility of an interplay between natriuretic peptide signaling and glucocorticoid regulation, pointing towards a potential cardiac-endocrine adaptation to intrauterine metabolic stress. While these observations deserve further investigation, they provide new insights into cardiovascular programming.