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

Abstract

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 TTHM-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 lg 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 lg to the unexposed. Similar results were obtained when, instead of unexposed, the lowest exposure category (<5 lg=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.

Prenatal Exposure to Disinfection Byproducts and Intrauterine Growth in a Chinese Cohort

“…Animal studies have shown that some DBPs can pass through the placenta, which can lead to intrauterine growth retardation, decreased birth length and weight, − and increased birth defects in rodent species. , Previous epidemiological studies also reported associations between gestational exposure to DBPs and fetal anthropometric measures at delivery, such as birth weight − and birth length, as well as adverse birth outcomes [e.g., small for gestational age (SGA) and preterm birth]. − However, evidence linking DBP exposure to intrauterine growth is sparse. Repeated ultrasound measures reflect the changing rate of growth in utero and capture specific fetal growth measures such as abdominal circumference (AC), biparietal diameter (BPD), and femur length (FL), which facilitates an investigation of the effects of DBP exposure on specific anthropometric parameters during different gestational periods.…”

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

“…In total, 83 localities remained as our study area ( Figure 1 ). We used a similar study design as in a study assessing TTHM exposure in relation to small for gestational age and preterm delivery ( Säve-Söderbergh et al. 2020 ).…”

“…We estimated a trimester-specific 3-month average TTHM exposure for each individual pregnancy by using a locality-specific and multiannual monthly average of TTHM [as outlined by Säve-Söderbergh et al. ( 2020 )]. Briefly, by using a multiannual average for each month and locality for assigning the exposure, we a ) accounted for seasonal variations ( Andersson et al.…”

Chloroacetonitrile reduces rat prenatal bone length and induces oxidative stress, apoptosis, and DNA damage in rat fetal liver

“…Dibromoacetic acid and bromodichloromethane can pass through amniotic fluid, placentas, fetuses (rats and rabbits), or milk (rats) (Christian et al, 2001). Thus, these compounds have induced pregnancy loss (Narotsky et al, 2011), adverse pregnancy outcomes (APO) like short gestational age and stillbirth (Bonou, Levallois, Giguère, Rodriguez, & Bureau, 2017; Cao et al, 2016; Mashau, Ncube, & Voyi, 2018; Save‐Soderbergh, Toljander, Donat‐Vargas, Berglund, & Åkesson, 2020; Summerhayes et al, 2021), congenital central nervous system anomalies (Hwang & Jaakkola, 2003), skeletal defects (Stankevič et al, 2020), pre‐term delivery (King, Dodds, & Allen, 2000). Pregnant women who drank more than five glasses of water with DBP concentrations of about 75 μg/L each day displayed a significant relationship between APO and DBP and most exhibited intrauterine growth retardation (Wright, Schwartz, & Dockery, 2004).…”