MATERNAL SOCIO-ENVIRONMENTAL EXPOSURES DURING EARLY PREGNANCY AND MORTALITY AMONG CHILDREN BORN WITH CRITICAL CONGENITAL HEART DEFECTS

Background: Children with critical congenital heart defects (CCHDs) experience high infant mortality (~25%). While various factors like severity and prenatal diagnosis impact survival, the role of environmental exposures remain understudied. We evaluated the associations between maternal neighborhood-level socioeconomic position (nSEP) and air pollution exposure during early pregnancy and survival in children with CCHDs. Methods: Children with CCHDs in the National Birth Defects Prevention Study (1999–2011) classified as univentricular (UVHDs; more severe) or biventricular (BVHDs) were linked to vital records for 1-year and 5-year mortality. To characterize nSEP, we applied principal component analysis to construct the Neighborhood Deprivation Index (NDI) [low (reference), moderate, or high deprivation] based on maternal addresses reported via interview. To evaluate per-IQR increases in ambient air pollutants, we assigned weekly averages (gestational weeks 2-8) using the nearest air monitor ≤50 kilometers. We estimated survival probabilities and hazard ratios (HRs) with 95% confidence intervals (CIs), adjusting for maternal and infant characteristics. Results: One-year survival was high (87-92%), though lower among children with UVHDs (60-75%) than BVHDs (93-95%). Among all CCHDs, survival differed significantly by deprivation (p<0.001), with the lowest survival among those living in highdeprivation areas. Compared to living in areas characterized as having low deprivation, living in areas characterized as having high deprivation was associated with an increased risk of 1-year mortality for all CCHDs (1.18 [0.83, 1.68]) and UVHDs (1.19 [0.73, 1.95]), though non-significant. Estimates for BVHDs were null (1.01 [0.58, 1.77]). For pollutant exposures, per-IQR increases in carbon monoxide (CO) were associated with increased mortality risk (1.25-1.36) across weeks 2-8. No associations were observed among children with UVHDs, but increased mortality risk was observed among children with BVHDs for CO (1.30-1.72) and sulfur dioxide (1.37-1.38). Associations with 5-year mortality were stronger in magnitude for both exposures, with greater deprivation-related disparities among BVHDs and higher CO-related mortality in UVHDs. Conclusion: These observations suggest that the socio-environmental context during pregnancy is associated with childhood mortality risk, with differences observed across severity of CCHDs. Further research could inform underlying structural, environmental, and/or physiological factors that contribute to increased early childhood mortality.