Drinking Water Disinfection by-Products and Congenital Malformations: A Nationwide Register-Based Prospective Study

BACKGROUND: Drinking water chlorination by-products have been associated with adverse reproductive outcomes, although the findings for congenital malformations are still inconclusive. OBJECTIVE: We conducted a nationwide register-based prospective study to assess whether first trimester maternal exposure to the four most common trihalomethanes [total trihalomethanes (TTHM)] via municipal drinking water was associated with risk of congenital malformation among newborns. METHODS: We included all births during 2005–2015 (live and stillbirths) of mothers residing in Swedish localities having [Formula: see text] inhabitants, two or fewer operating water works, and sufficient municipal TTHM monitoring data. Individual maternal first trimester exposure was obtained by linking TTHM measurements to residential information, categorized into no chlorination and [Formula: see text] , 5–15, and [Formula: see text] TTHM/L. We also made chlorination treatment-specific analyses (exclusive use of chloramine or hypochlorite). Outcomes and covariates were obtained via linkage to health care and administrative registers. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by logistic regression. RESULTS: Based on 623,468 births and a prevalence of congenital malformation of [Formula: see text] cases/100 births, we observed associations between TTHM exposure in areas using chloramine and malformations of the nervous system ([Formula: see text]; 95% CI: 1.07, 3.12), urinary system ([Formula: see text]; 95% CI: 1.53, 2.78), genitals ([Formula: see text]; 95% CI: 1.38, 2.26), and limbs ([Formula: see text]; 95% CI: 1.10, 1.64), comparing the highest exposed category with the unexposed. No associations were observed in areas using exclusively hypochlorite as the primary water treatment method. By contrast, for malformations of the heart, a significant inverse association was observed only in areas using hypochlorite. DISCUSSION: TTHM exposure was associated with the increased risk of malformations of the nervous system, urinary system, genitals, and limbs in areas exclusively using chloramine. An association between chloramine-related chlorination by-products and congenital malformations has not previously been highlighted and needs further attention. https://doi.org/10.1289/EHP9122