Higher Maternal Serum Ferritin in the Third Trimester is Associated with Reduced Endothelial Function in the Preadolescent Child

Introduction: Elevated iron status in pregnancy has been implicated in gestational diabetes (GDM) development and in cardiovascular (CV) disease progression in adults. Animal models, however, have suggested maternal iron deficiency anemia may increase the offspring’s risk of CV disease. Whether maternal iron levels impact the CV health of the child in humans is unknown. This study investigated the relationship between maternal iron markers and the child’s CV health. Methods: This is a nested observational study tied to the Alberta Pregnancy Outcomes and Nutrition (APrON) Study. Children of mothers with and without GDM but otherwise uncomplicated pregnancies were prospectively recruited. Maternal serum ferritin, total iron binding capacity, and hemoglobin in the 2 nd and 3 rd trimesters were obtained. CV outcomes included: left ventricular mass Z-score, reactive hyperemia index score (lnRHI, EndoPAT), Doppler-based aortic and peripheral arterial pulse wave velocity, and carotid intima-media thickness. Univariate and multiple linear regression models, including maternal GDM as a covariate, were built to explore relationships between maternal iron markers and the child’s CV health. Results: Fifty-two children, 40 (77%) female, were assessed at a mean age of 10.9±0.7 years. Maternal serum ferritin in the 2 nd (median (IQR): 38.8 (39.2) ng/mL; B=-0.0039, p=0.01) and 3 rd trimesters (13.7 (9.0); B=-0.011, p=0.008) inversely related to the child’s lnRHI in univariate analyses, whereas no other relationships were observed between maternal iron markers and the child’s CV health. While the effect of 2 nd trimester serum ferritin was attenuated in a multiple linear model adjusting for maternal GDM, another model demonstrated a persistent relationship of 3 rd trimester serum ferritin with lnRHI (B=-0.028, p=0.007), not impacted by maternal GDM (B=-0.37, p=0.11) or their interaction term (B=0.020, p=0.07). Conclusions: High maternal serum ferritin in the 3 rd trimester may be associated with reduced endothelial function of the child. If validated, further work is needed to understand pathogenic mechanisms, and the impact of supplementation guidelines in pregnancy.