Exposure to Drinking Water Chlorination by-Products and Fetal Growth and Prematurity: A Nationwide Register-Based Prospective Study

BACKGROUND: Chlorination is globally used to produce of safe drinking water. Chlorination by-products are easily formed. and there are indications that these are associated with adverse reproductive outcomes. OBJECTIVES: We conducted a nationwide register-based prospective study to assess whether gestational exposure to the four most common chlorination by-products [total trihalomethanes (TTHMs)] via tap water was associated with risk of small for gestational age (SGA), preterm delivery, and very preterm delivery. To date, this is one of the largest studies assessing drinking water TIHM-associated adverse reproductive outcomes. METHODS: We included all singleton births 2005-2015 (live and stillbirths) of mothers residing in Swedish localities having >10,000 inhabitants, <= 2 operating waterworks, adequate information on chlorination treatment, and a sufficient number of routine TTHM measurements in tap water. Individual maternal second and third trimester exposure was obtained by linking TTHM measurements to residential history, categorized into no chlorination, <5, 5-15, and >15 mu g TTHM/L. Outcomes and covariates were obtained via the linkage to Swedish health and administrative registers. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by logistic regression using inverse probability weighting. We stratified the analyses by chlorination treatment (chloramine, hypochlorite). RESULTS: Based on approximately 500,000 births, we observed a TTHM dose-dependent association with increased risk of SGA, confined to treatment with hypochlorite, corresponding to a multivariable-adjusted OR = 1.20 (95% CI: 1.08, 1.33) comparing drinking water TTHM >15 mu g to the unexposed. Similar results were obtained when, instead of unexposed, the lowest exposure category (<5 mu g/L TTHM) was used as reference. No clear associations were observed for preterm delivery and very preterm delivery. DISCUSSION: Chlorination by-products exposure via drinking water was associated with increased risk of SGA in areas with hypochlorite treatment.