Environmental Exposures Influence Fetal Brain Growth and Risk of Neonatal Brain Injury in Congenital Heart Disease

Background: Neurodevelopmental impairments are common in congenital heart disease (CHD) and fetal brain volume is an important predictor of outcomes. Social determinants of health (SDOH) and environmental factors influence brain growth in other populations and likely play a neurodevelopmental role in CHD. This study evaluated the influence of SDOH and environmental factors on fetal and neonatal brain volume, growth, and risk of brain injury in CHD. Methods: This prospective single-center longitudinal cohort study enrolled fetuses with severe CHD to undergo third-trimester fetal and preoperative brain MRIs. Controls underwent third-trimester brain MRIs. Participants completed SDOH and environmental exposure surveys. Fetal and neonatal brain volumes, brain growth, and presence of white matter injury (WMI) were assessed. Results: 57 CHD patients and 24 controls were enrolled, resulting in 33 fetal and 44 neonatal MRIs in the CHD group and 21 fetal control MRIs. Several SDOH and environmental factors, including maternal smoking, were associated with smaller brain volume and slower brain growth in CHD but not in controls. With CHD, repeated-measures analysis showed smaller fetal brain volume (coeff: -13.3, 95%CI: -25.5,-1.1 p = 0.03) and slower growth (coeff: -2.5, 95%CI: -5.0, -0.07, p = 0.04) with exposure to any risk factor. CHD subjects from high Childhood Opportunity Index neighborhoods had lower odds of moderate to severe preoperative WMI (OR = 0.16, 95%CI: 0.03, 0.9, p = 0.04). Conclusions: SDOH and environmental exposures influence fetal brain growth and preoperative brain injury risk in CHD. These results highlight additive environmental prenatal risks which may be amenable to early intervention.