Potential Risk Factors for Total Anomalous Pulmonary Venous Return: National Birth Defects Prevention Study, 1997-2011 and the Birth Defects Study to Evaluate Pregnancy Exposures, 2014-2021.

BACKGROUND

Total anomalous pulmonary venous return (TAPVR) is a rare heart defect in which the pulmonary veins do not connect to the left atrium, instead draining into the right atrium or directly into other venous systems. We explored factors associated with TAPVR using the National Birth Defects Prevention Study (NBDPS; 1997-2011) and Birth Defects Study To Evaluate Pregnancy exposureS (BD-STEPS; 2014-2021) data.

METHODS

We identified potential risk or protective factors from the literature and used logistic regression to calculate crude and adjusted odds ratios (OR) and 95% confidence intervals (CI) for the association between 22 factors encompassing maternal demographics, health history, and medication use and TAPVR. In an exploratory analysis among the subset of NBDPS cases and controls, we examined 163 potential factors using random forest.

RESULTS

In the primary analysis including 393 cases with TAPVR and 13,914 non-malformed controls, we observed positive associations between TAPVR and maternal age at delivery < 20 (OR 2.00; 95% CI 1.30-3.06) and 20-24 (1.62; 1.19-2.22) vs. 25-29 years, having one (1.40; 1.07-1.82) and two or more previous live births (1.69; 1.25-2.27) vs. none, and multiple gestation (1.85; 1.11-2.92). Non-Hispanic Black mothers had the lowest risk (0.55; 0.35-0.85) while mothers of other races/ethnicities had the highest risk (1.72; 1.19-2.44) compared to non-Hispanic White mothers. The random forest identified an inverse effect of maternal fish consumption.

CONCLUSIONS

Our findings confirmed previously observed associations of younger maternal age and having previous live births with TAPVR. Maternal fish consumption may confer a protective effect and deserves further investigation.