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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.
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.
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.
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.
Poster Sessions, Expo North
Sunday, March 10, 2013, 3:45 p.m.–4:30 p.m.
Session Title: Preclinical and Translational Research
Abstract Category: 52. TCT@ACC–i2: Translation and Pre–clinical Research
Presentation Number: 2111–239
- 2013 American College of Cardiology Foundation