Maternal exposure to arsenic in drinking water and risk of congenital heart disease in the offspring.

Prenatal exposure to arsenic is suspected to impair fetal health, including congenital malformations. Few studies investigated an association between maternal exposure to arsenic and congenital heart disease. To examine the association between maternal exposure to arsenic through drinking water and congenital heart disease among offspring. This nationwide cohort study included all liveborn children in Denmark, 1997-2014. Maternal addresses at fetal age 4 weeks were linked to drinking water supply areas. Exposure was arsenic concentration in drinking water in first trimester in four categories (<0.5 μg/L, 0.5-0.9 μg/L, 1.0-4.9 μg/L, ≥5.0 μg/L). Outcomes were defined as congenital heart disease diagnosed within the first year of life, with sub-categorization of severe, septal defects and valvular heart defect. Associations between arsenic levels and congenital heart disease were analysed using logistic regression, presented as odds ratios (OR) with 95% confidence interval (CI), and adjusted for year of birth, mother's educational level and ethnicity. A total of 1,042,413 liveborn children were included of whom 1.0% had a congenital heart disease. The OR of congenital heart disease was higher among children exposed to all levels of arsenic above 0.5 μg/L; the OR was 1.13 (95% CI: 1.08-1.19) for exposure of 0.5-0.9 μg/L, 1.33 (95% CI: 1.27-1.39) for 1.0-4.9 μg/L and 1.42 (95% CI: 1.24-1.63) for ≥5.0 μg/L. Similar associations were observed for congenital septal defects. The OR was also higher for severe congenital heart disease but at the same level among all exposure levels ≥0.5 μg/L. The OR of congenital valvular heart defects was only higher among children with maternal exposure to arsenic in drinking water ≥5.0 μg/L. The associations were similar for boys and girls. The findings indicate that maternal exposure to arsenic in drinking water even at low concentrations (i.e., 0.5-0.9 μg/L) increased the risk of congenital heart disease in the offspring.

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