The effect of disinfection by-products and mutagenic activity on birth weight and gestational duration.

Abstract

Epidemiologic studies of disinfection by-products have traditionally focused on total trihalomethane (TTHM) concentration as a surrogate for maternal exposure during pregnancy. We used birth certificate data on 196,000 infants to examine the effect of third-trimester exposures on various indices of fetal development. We examined the effect of town-average concentrations of TTHM and additional exposure metrics in relation to mean birth weight, mean gestational age, small for gestational age (SGA) infancy, and preterm delivery. Trihalomethane data (TTHM, chloroform, and bromodichloromethane) from 1995-1998 were available for 109 towns in Massachusetts. Data from 1997-1998 on haloacetic acid (total haloacetic acids, dichloroacetic acid, and trichloroacetic acid), 3-chloro-4-(dichloromethyl)-5- hydroxy-2(5H)-furanone (MX), and mutagenicity were available for a limited number of towns. We observed reductions in mean birth weight (12-18 g) for maternal trihalomethane exposures > the 90th percentile compared with those < the 50th percentile. Birth weight reductions were detected for chloroform exposures > 20 microg/L and TTHM exposures > 40 microg/L. Elevated trihalomethanes were associated with increases in gestational duration and a reduced risk of preterm delivery. We found evidence of an exposure-response effect of trihalomethanes on risk of SGA, with odds ratios (ORs) ranging from 1.09 to 1.23 for bromodichloromethane exposures > 5 microg/L. Elevated mutagenic activity was associated with SGA [OR = 1.25; 95% confidence interval (CI), 1.04 to 1.51] and mean birth weight (-27 g; 95% CI, -54 to -1). Although smaller in magnitude, our findings are consistent with previous studies reporting associations between trihalomethanes and SGA. These data also suggest a relationship between fetal development indices and mutagenic activity independent of exposure to trihalomethanes, haloacetic acids, and MX.

The epidemiology and possible mechanisms of disinfection by-products in drinking water

“…Wright et al (2004) and Jaakkola et al (2001) found a statistically significant decreased risk of pre-term delivery.…”

“…Hinckley et al (2005) found no association with THMs, but did for some specific HAAs. Studies on small for gestational age (SGA) and/or intrauterine growth retardation (IUGR) showed some more consistent results, and a good proportion of them have found statistically significant associations (Kramer et al 1992;Bove et al 1995;Wright et al 2003Wright et al , 2004, while some did not (Dodds et al 1999;Porter et al 2005;Yang et al 2007;Hoffman et al 2008b) (table 3). Aggazzotti et al (2004) found some effects with by-products of chlorine dioxide.…”

“…Halogenated acetic acids have been found to cause testicular damage in rats through disruption of spermatogenesis and motility, with the brominated analogues being the strongest toxicants (Smith et al 1989;Toth et al 1992;Linder et al 1994a,b, et al (2001) chlorinated (average TTHM = 9.4 μg l −1 ) versus non-chlorinated 1.00 (0.91-1.10) * * Kramer et al (1992) 0 versus ≥10 μg l −1 CHCl 3 1.8 (1.1-2.9) * Bove et al (1995) ≤20 versus >100 μg l −1 TTHM 1.5 (1.2-1.9) * Dodds et al (1999) 0-49 versus >100 μg l −1 TTHM 1.08 (0.99-1.18) * * * Wright et al (2003) 0-60 versus >80 μg l −1 TTHM 1.14 (1.02-1.26) Wright et al (2004) >74-163 versus 0-33 μg l −1 TTHM 1.13 (1.07-1.20) Aggazzotti et al (2004) THMs ≥30 ≥53 versus <40 μg l −1 TTHM 1.09 (1.00-1.18) Yang et al (2007) THM4 >13.1 versus ≤4.9 μg l −1 0.96 (0.91-1.02) Hoffman et al (2008) 74.9-108.8 versus 2.2-4.6 1.3 (0.7-2.3) * ≤5th percentile; * * ≤10th percentile; * * * ≤2 s.d. Table 4.…”

A sensitivity analysis of bias in relative risk estimates due to disinfection by-product exposure misclassification

“…The sampling distribution from a previous study was used to assign the number of sampling locations per town (Wright et al, 2004). In all, 26 of the towns had two sampling sites, 47 of the towns had four sites, five towns had five sites, 16 towns had eight sites, and two towns each had six, eight and 10 sites, respectively.…”

“…Several reproductive epidemiologic studies of DBPs have used town average concentrations to estimate maternal exposure (Kramer et al, 1992;Bove et al, 1995;Savitz et al, 1995;Gallagher et al, 1998;Waller et al, 1998;Dodds et al, 1999;Klotz and Pyrch, 1999;Wright et al, 2003Wright et al, , 2004. Gallagher et al (1998) used geographic information system mapping and water hydraulic models to limit the impact of spatial variability on exposure misclassification.…”