Introduction: Early epidemiologic studies reported inconsistent associations between occupational exposure to organic solvents during pregnancy and congenital heart defects (CHD). Data from the National Birth Defects Prevention Study (NBDPS), an ongoing, population-based case-control study, were used to examine the association between 31 CHD subtypes in children and maternal occupational exposure to six chlorinated solvents - carbon tetrachloride, chloroform, methylene chloride, perchloroethylene, trichloroethane, and trichloroethylene, three aromatic solvents - benzene, toluene, and xylene, and Stoddard solvent from the month before conception through the end of the first trimester (B I-P3). Methods: Mothers of cases with CHD and live-born infants without birth defects who participated in the NBDPS between 1997 and 2002 and reported working outside the home during pregnancy were eligible for this study. Industrial hygienists determined whether each mother-job was exposed to a solvent. Potential confounders included in multi-variable logistic regression models were maternal age, race-ethnicity, education, smoking during BI-P3, and folic acid supplement use during BI-P3. Results: There were 3,121 CHD case mothers and 2,951 control mothers available for analysis. Overall 8.1% of control mothers and 9.5% of case mothers were exposed to any organic solvent. Considering all heart defects combined, there were no statistically significant associations with any of the six chlorinated solvents, three aromatic solvents, or Stoddard solvent. Left ventricular outflow tract obstruction defects were associated with benzene (OR=2.54; 95% CI=1.04-6.35), an association driven by aortic stenosis (OR=5.48; 95% CI= I .52-19.75). Right ventricular outflow tract obstruction (RYOTO) defects were associated with Stoddard solvent (OR=1.74; 95% CI=1.06-2.85), an association driven by pulmonary valve stenosis (OR=1.86; 95% CI=1.07-3 .22). RYOTO defects were also associated with carbon tetrachloride (OR=3.47; 95% CI=1.02-11.76), perchloroethylene (OR=1.61; 95% CI=1.03-2.49), and trichloroethane (OR=1.63; 95% CI=1.07-2.19). Discussion: There is limited evidence of an association between exposure to organic solvents and CHD. The few significant associations, although noteworthy, should be interpreted with caution. To date, this is the largest epidemiologic study of maternal occupational exposure to organic solvents and CRD.
Epidemiology; Organic-solvents; Occupational-exposure; Case-studies; Reproductive-effects; Reproductive-hazards; Birth-defects; Molecular-biology; Teratogenesis; Congenital-effects; Heart; Cardiac-function; Children; Ethanes; Ethylenes; Chlorides; Demographic-characteristics; Racial-factors; Smoking; Pregnancy; Prenatal-exposure; Statistical-analysis; Solvents