• Hidestrand P
  • Pelech A
  • Divakaran K
  • et al.
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Background: Maternal volatile organic compound (VOC) exposure during pregnancy has been thought to increase offspring HLHS risk; however, prior study methodology has been limited by use of maternal exposure recall. Solvent metabolites have been implicated in congenital heart disease (CHD); common, functional genetic polymorphisms are known in human ADH & CYP2E1, two enzymes metabolizing many VOCs. Our objective was to determine whether verified fetal specific VOC exposure is associated with HLHS risk & whether VOC-related enzyme genetic differences alter risk. Methods: VOCs (N=17) were measured in meconium (fetal stool) samples from term infants with & without HLHS. Demographic data, CHD family history, maternal tobacco, alcohol & vitamin use prior to conception & during pregnancy were analyzed. Maternal & infant ADH1B, ADH1C & CYP2E1*1D genotypes were determined. Results: Compared to controls (N=432), infants with HLHS (N=31), were more likely to be Caucasian males. Fetal exposure to benzene, ethylbenzene, meta/para (m/p)-xylene & ortho-xylene were independently associated with HLHS (ORs; 2.5-5.8; 95% CI > 1.0; each). In an adjusted linear regression model, fetal m/p-xylene exposure was associated with a 7-fold increased HLHS risk (OR; 95% CI: 3-18; p < 0.001); whereas the sum of two acetic acid trichloroethylene metabolites was associated with > 3-fold increased HLHS risk (OR; 95% CI: 1.3-8.4; p < 0.01). Maternal ADH1C*2 homozygosity increased offspring HLHS risk by ~6-fold (OR; 95% CI 2.5-16.3; p < 0.001). With these variables included, no other factors were significant. Conclusions: This is the first report of a link between HLHS & verified fetal xylene and trichloroethylene exposure. Xylene exposure sources include gasoline, cleaners, rubber, glue, paint, & tobacco. Trichloroethylene is a degreaser commonly found in cleaners & paint removers. ADH metabolizes multiple solvents, including many studied herein; thus, the mechanism of the ADH1C variant effect may be complex. Because exposure to both HLHS risk-related solvents is widespread, these findings offer the possibility for exposure prevention measures to improve cardiac developmental outcome




Hidestrand, P., Pelech, A., Divakaran, K., Simpson, P., & McCarver, D. G. (2013). HYPOPLASTIC LEFT HEART SYNDROME (HLHS) RISK INCREASED WITH MEASURED FETAL SOLVENT EXPOSURE. Journal of the American College of Cardiology, 61(10), E1827. https://doi.org/10.1016/s0735-1097(13)61827-6

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