Birth defects research · 2025
Risks of Birth Defects Following In Utero Exposures to Unregulated Brominated Haloacetic Acids.
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Kaufman John A, Wright J Michael
Аннотация
INTRODUCTION: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSION: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSION: 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.