Health Stream Literature Summary - Issue 58 - June 2010

Exposure to disinfection by-products, fetal growth, and prematurity: A systematic review and meta-analysis
Grellier, J., Bennett, J., Patelarou, E., Smith, R.B., Toledano, M.B., Rushton, L., Briggs, D.J. and Nieuwenhuijsen, M.J. (2010) Epidemiology, 21 (3), 300-313.

Human studies over the past two decades have investigated associations between exposure to disinfection by-products (DBPs) and various outcomes related to foetal growth and prematurity. The outcomes studied include low birth weight (LBW), term LBW (TLBW), very LBW, small for gestational age (SGA), intrauterine growth retardation (IUGR), preterm delivery (PTD) and very PTD, and foetal death (miscarriage, spontaneous abortion, and stillbirth). The findings of these studies have been the subject of a number of reviews. The weight of evidence on foetal growth and prematurity suggests a small, positive association between trihalomethane concentrations (the most abundant of the DBPs) in drinking water and some adverse birth outcomes related to foetal growth restriction (TLBW, SGA, IUGR), however the evidence is not conclusive. This study was a systematic review of the existing epidemiological evidence and a meta-analysis of this data, to produce best-estimate exposure-response slopes of total trihalomethane exposure and adverse birth outcomes relating to foetal growth and prematurity.

A systematic review of the existing literature on trihalomethanes and adverse birth outcomes related to foetal growth and prematurity was undertaken and only those studies that were reported in peer-reviewed journals or published by a reputable independent body were included. Other inclusion criteria included use of maternal residence to estimate exposure, use of an appropriate measure of effect (eg odds ratio, relative risk) and at least three categories of exposure. The literature search yielded 60 studies, of which 23 underwent detailed review and 15 of these were deemed suitable to be included in the meta-analysis. The studies were defined for the purposes of the review as population case-control studies, retrospective pregnancy cohort studies or prospective pregnancy cohort studies. The studies were found to differ in their geographical location, their quoted measure of effect, adjustment for confounders, exposure characterisation and categorisation, and the definitions of health outcomes. Articles were divided by health outcomes and those outcomes which had at least four separate studies available were included in the random-effects meta-analyses. There was sufficient data available for 4 adverse birth outcomes to be included in the meta-analysis: LBW (n=6) TLBW (n=6), PTD (n=8) and SGA (n=8). A 2-stage subset analyses was also conducted to investigate differences in exposure agent and the effects of exposure timing. The analysis was first divided on the basis of including a study using chloroform as the exposure agent. The analysis was further divided according to exposure timing for each of these 2 subsets. The first subset included studies that reported measures of effect only with exposure in the third trimester and the second included only those reporting on the entire pregnancy. A third subset was used that included all studies regardless of exposure, for completeness.

This analysis found little or no evidence for associations between third trimester trihalomethane exposure and LBW (odds ratio (OR) per 10 micro g total trihalomethane/L = 1.00 [95% confidence interval = 0.97-1.03]), TLBW (1.03 [0.93-1.15]), or PTD (0.99 [0.98-1.00]) however there was some evidence for SGA (1.01 [1.00-1.02]). The subset analyses found a small positive effect for SGA, only for analyses that included total trihalomethane as the exposure agent and third-trimester exposure or any exposure timing. The Cochran test for homogeneity indicated a lack of heterogeneity among studies. The least heterogeneity between studies was found for SGA. Summary estimates of effect were applied to United States and European guidelines (80 micro g/L and 100 micro g/L, respectively) and the risks for SGA for third trimester exposure to total trihalomethanes at these levels were OR= 1.08 (95% CI = 1.01-1.17) and 1.10 (1.01-1.21), respectively.

Overall there was little or no evidence for associations between total trihalomethane concentration and adverse birth outcomes with the exception of SGA. The results are generally in line with previous reviews. This meta-analysis did not find a positive association with term LBW and this is in contrast to previous qualitative results of these reviews. Meta-analysis provides the best possible estimate measure for use in risk assessment and public health policy in the absence of large, well-designed epidemiological studies which take into account relevant confounders and characterise disinfection by-product exposure, with carefully defined health outcomes.

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