Disinfection By-Product Exposures and the Risk of Specific Cardiac Birth Defects

Abstract

Background:Epidemiological studies suggest that women exposed to disinfection by-products (DBPs) have an increased risk of delivering babies with cardiovascular defects (CVDs).Objective:We examined 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).Methods:We calculated adjusted odds ratios (aORs) in a case–control study of birth defects in Massachusetts with complete quarterly 1999–2004 trihalomethane (THM) and haloacetic acid (HAA) data. We randomly matched 10 controls each to 904 CVD cases based on week of conception. Weight-averaged aggregate first-trimester DBP exposures were assigned to individuals based on residence at birth.Results:We detected 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 between 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). Ventricular septal defects (VSDs) were associated with the highest 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) exposure categories.Conclusions:To our knowledge, this is the first birth defect study to develop multi-DBP adjusted regression models as well as the first CVD study to evaluate HAA exposures and the second to evaluate bromoform exposures. Our findings, therefore, inform exposure specificity for the consistent associations previously reported between THM4 and CVDs including VSDs.Citation:Wright JM, Evans A, Kaufman JA, Rivera-Núñez Z, Narotsky MG. 2017. Disinfection by-product exposures and the risk of specific cardiac birth defects. Environ Health Perspect 125:269–277; http://dx.doi.org/10.1289/EHP103

Impact of chloroform exposures on reproductive and developmental outcomes: A systematic review of the scientific literature

“…Twenty‐five had been reviewed previously by OEHHA (). There were five studies not included in the OEHHA review (Brender et al, ; Cao et al, ; Kogevinas et al, ; Levallois et al, ; Wright et al, ). Eleven studies were prospective cohort studies, 11 studies were retrospective cohort studies, and 8 were case–control studies (7 population‐based and 1 hospital‐based case–control study).…”

“…Because exposure assessment is so fundamental to the validity of epidemiologic research, we classified study quality based largely on whether exposure assessment was integrated using individualized data. That is, we classified the studies with integrated exposure estimates as being relatively strong methodologically (Botton et al, ; Cao et al, ; Costet et al, ; Danileviciute et al, ; Grazuleviciene et al, ; Grazuleviciene et al, ; Iszatt et al, ; Kogevinas et al, ; Levallois et al, ; Levallois et al, ; Savitz et al, ; Smith et al, ; Villanueva et al, ) compared with studies that lacked integrated exposure estimates (Brender et al, ; Dodds & King, ; Hinckley et al, ; Hoffman et al, ; Infante‐Rivard, ; Iszatt et al, ; Kramer et al, ; Lewis et al, ; Lewis et al, ; Porter, PutnaD, Hunting, & Riddle, ; Rivera‐Núñez & Wright, ; Summerhayes et al, ; Toledano et al, ; Wennborg et al, ; Wright et al, ; Wright et al, ; Zhou et al, ). While exposure assessment is one of many aspects that influence the quality of any study, given the critical importance of exposure assessment in this subject matter, we determined that the use of an integrated (i.e., individualized) exposure assessment method should be required of any study to be considered informative on the potential causal relationship between chloroform exposure and developmental outcomes (Koepsell & Weiss, ; Morgenstern, ).…”

“…Five epidemiologic studies investigated the risk of birth defects in association with chloroform exposure (Brender et al, ; Dodds & King, ; Grazuleviciene et al, ; Iszatt et al, ; Wright et al, ) (Table ). Of the 30 associations evaluated in these studies, 25 associations were statistically null, and only 5 statistically significant associations were detected.…”

“…When parsing risk values into intensity levels (four categories of the risk value), Brender et al () found a significant positive association of mild intensity ambient chloroform exposure with spina bifida occurrence (OR = 1.74; 95% CI = 1.02, 2.99); however, moderate and high levels of exposure were not significantly associated with spina bifida occurrence, indicating the absence of a positive exposure‐response trend. Wright et al () examined seven different congenital heart defects, none of which were associated with chloroform concentrations in water. In contrast, two relatively high‐quality studies of birth defects used integrated exposure measures of chloroform (Grazuleviciene et al, ; Iszatt et al, ); both showed no significant association between chloroform exposure and cardiovascular, musculoskeletal, or urogenital birth defects (Table ).…”

Exposure to disinfectant by-products and the risk of stillbirth in Massachusetts

“…The trimester-specific DBP exposure scores were based on weighted averages for multiple quarters overlapping the second or third trimesters derived from the date of birth and the timing of quarterly DBP samples previously reported 23. For example, a stillbirth of 37 gestational weeks delivered in January 2000 would have nine second-trimester weeks that occurred in quarter 4 of 1999 and four second-trimester weeks that occurred in quarter 3 of 1999.…”