Background: Epidemiological studies suggest that women exposed to disinfection byproducts (DBPs) in treated water have an increased risk of delivering babies with cardiovascular defects (CVDs), though evidence for specific DBP-birth defect associations is limited. It also remains unclear which DBP metrics of the complex mixtures found in drinking water are the best surrogates for assessing potential risk related to reproductive toxicants. Methods: We conducted a case-control study of all birth defects in Massachusetts from 2000-2004 with complete trihalomethane (THM) and haloacetic acid (HAA) data. We randomly matched 904 CVD cases to 10 controls (n=9040) based on week of conception. We used weight-averaged aggregate first trimester DBP exposures across all quarterly monitoring sample locations linked to individuals based on residence at birth. Adjusted odds ratios (aORs) were calculated for nine CVDs in relation to categorical DBP exposures including bromoform, chloroform, dibromochloromethane (DBCM), bromodichloromethane (BDCM), monobromoacetic acid (MBAA), dichloroacetic acid (DCAA), trichloroacetic acid (TCAA), and summary DBP measures (HAA5, THMBr, THM4 and DBP9). Results: We detected strong associations for Tetralogy of Fallot and the upper exposure categories for TCAA, DCAA, and HAA5 (aOR Range: 3.34-6.51) including positive exposure-response relationships for DCAA and HAA5. aORs consistent in magnitude were detected for atrial septal defects and bromoform (aOR=1.56; 95%CI: 1.01, 2.43), as well as DBCM, chloroform, and THM4 (aOR Range: 1.26-1.67). With the exception of chloroform, TCAA, and HAA5, consistently elevated aORs were detected for ventricular septal defects (VSDs) and every DBP metric including bromoform (aOR=1.85; 95%CI: 1.20, 2.83), MBAA (aOR=1.81; 95%CI: 0.85, 3.84), and DBCM (aOR=1.54; 95%CI: 1.00, 2.37). Conclusions: Overall, we saw limited evidence of risk of CVDs based on DBP surrogate mixture measures such as THM4 and DBP9; however, several associations were detected between individual DBP species and specific types of CVDs. For example, bromoform was consistently associated with elevated aORs for all the individual and group CVDs that were examined. To our knowledge, this is the first epidemiological study of birth defects to develop multi-DBP adjusted regression models and is only the second study to evaluate brominated THMs or HAAs. Our findings, therefore, inform exposure specificity for the consistent associations previously reported between THM4 and CVDs including the VSDs. The views expressed in this abstract are those of the authors and do not necessarily reflect the views or policies of the US Environmental Protection Agency.
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