Maternal Smoking Status and Residual Risk: Current and Former Smoking Amplify Congenital Heart Disease Incidence and Severity in Offspring

Background: Congenital heart disease (CHD) remains a leading cause of infant morbidity and mortality globally, and maternal smoking during pregnancy is recognized as a significant, modifiable risk factor. Despite public health efforts, a substantial proportion of women continue smoking into pregnancy, potentially exacerbating CHD risk and severity in offspring. The specific effects of smoking cessation timing on CHD outcomes remain unclear, and the residual risk associated with former smoking status requires further characterization. Objective(s): This study aimed to determine how maternal smoking status (current, former, never) influences the incidence and severity of congenital heart disease in infants, as well as associated neonatal health outcomes. The hypothesis tested was that both current and former maternal smoking increase CHD risk and severity compared to never smokers. Study Design: A cross-sectional analysis was conducted using data from 746 mother-child dyads enrolled in the University of Iowa Perinatal Family Tissue Bank from July 2010 to June 2020. Subjects included 270 CHD cases (infants diagnosed with CHD) and 476 controls without CHD. Maternal smoking status was categorized as current, former, or never, based on self-reported data at prenatal visits. CHD severity was classified as simple, moderate, or severe based on standardized clinical criteria. Statistical analyses included multivariable logistic regression to evaluate CHD incidence and severity, negative binomial regression for neonatal hospital outcomes, and Fisher’s exact tests for categorical comparisons, with significance defined as p < 0.05. Results: Current smokers exhibited significantly higher odds of fetal CHD (OR: 3.58, 95% CI: 1.95–6.68; p<0.001) compared to never smokers. Former smokers demonstrated intermediate but nonsignificant elevated risk (OR: 1.29, 95% CI: 0.82–2.00; p=0.27). The severity of CHD was greatest among current smokers (OR: 2.82; 95% CI: 1.69–4.68; p<0.001) and showed a nonsignificant upward trend among former smokers (OR: 1.45, 95% CI: 0.95–2.19; p=0.08). Infants born to current smokers required significantly longer hospitalizations (median: 13 days vs. 4 days; p=0.012) and experienced higher mortality rates at 1 year (8.2% [5/61] vs. 1.9% [10/532]; p=0.021). Conclusion(s): Maternal smoking during pregnancy significantly increases the incidence and severity of congenital heart disease in offspring. Although cessation before pregnancy reduces CHD risk, former smokers still retain residual elevated risk compared to never smokers. These findings emphasize the importance of robust public health strategies aimed at smoking prevention, cessation, and preconception counseling to mitigate the adverse impacts of maternal smoking on neonatal cardiac health.