Risks of Birth Defects Following In Utero Exposures to Unregulated Brominated Haloacetic Acids

Haloacetic acids (HAAs) are water disinfection byproducts (DBPs) regulated as a mixture of five species (HAA5) in the United States and Canada. To date, two brominated HAAs (BrHAAs) in HAA5 (monobromoacetic acid [MBAA], dibromoacetic acid [DBAA]) have been associated with birth defects in some epidemiologic studies, but the other four unregulated BrHAAs remain understudied.

We analyzed registry-based case-control data on 16 birth defect phenotypes in relation to temporally weighted first-trimester exposures to the four unregulated BrHAAs (tribromoacetic acid [TBAA], bromochloroacetic acid [BCAA], bromodichloroacetic acid [BDCAA], chlorodibromoacetic acid [CDBAA]) and the sum of all six BrHAAs (HAA6 = TBAA + BCAA + BDCAA + CDBAA + MBAA + DBAA). We matched cases to controls 1:10 on the week of conception and estimated adjusted odds ratios (aORs) via conditional logistic regression.

We observed some elevated aORs for dichotomized BrHAA exposures with certain outcomes, such as cleft palate alone (BDCAA aOR = 1.75 [95% confidence interval: 1.15, 2.66]), ventricular septal defects (BDCAA aOR = 1.28 [0.97, 1.68]), tetralogy of Fallot (BDCAA OR = 1.57 [0.93, 2.64]), and obstructive genitourinary defects (CDBAA aOR = 1.65 [1.07, 2.53]), and reduced aORs for hypospadias (e.g., BCAA aOR = 0.58 [0.40, 0.84]). Most other associations were closer to the null, and many lacked precision.

Our observations warrant further investigation given their novelty and the paucity of data on health impacts of prenatal BrHAA exposures overall; ours is the first epidemiological study to investigate most of these exposure-outcome relationships. Future work would benefit from a longer study period to ascertain additional birth defect cases and more direct exposure assessment in areas served by water systems with higher bromide levels.