Malaria Vaccine Yields Parasite-Killing Antibodies in Human Volunteers

Disinfection of drinking water may result in hundreds of disinfection by-products (DBPs) (Richardson et al. 2002). Experimental, animal, and epidemiologic studies provide evidence that a number of these DBPs, including trihalomethanes, may be associated with adverse pregnancy outcomes (Balchak et al. 2000; Bove et al. 2002; Gemma et al. 2003; Goldman and Murr 2002; Plewa et al. 2004; Ward et al. 2000). However, epidemiologic studies exploring the effect of drinking water chlorination and total trihalomethane (TTHM) exposures on preterm birth in human populations have reported equivocal results. When simply comparing treatment type (i.e., chlorination vs. no chlorination) as a surrogate for DBP levels, several studies found increased risks of preterm birth (Kallen and Robert 2000; Kanitz et al. 1996; Tuthill et al. 1982; Yang 2004; Yang et al. 2000), but one reported negative associations, suggesting prolonged rather than shortened gestation in exposed subjects (Jaakkola et al. 2001). Studies that relied on quarterly TTHM measurements in water systems for exposure assessment also reported mixed results. A Massachusetts study found a small decrease in risk of preterm birth among women who experienced high secondtrimester or total pregnancy exposure to TTHM, but no association was observed for third-trimester exposures (Wright et al. 2003). However, in a second study, the same authors found that third-trimester exposures apparently decreased the risk of delivering a preterm infant (Wright et al. 2004). A New Jersey study reported a slightly increased risk for preterm births with high average exposures to TTHM throughout pregnancy, but the effects were nonlinear (Bove et al. 1992). This group also estimated stronger effects on preterm births in women whose drinking water originated from surface rather than groundwater. Finally, studies conducted in Arizona, North Carolina, Iowa, Colorado, and Canada have not found associations between preterm births and elevated levels of TTHM ( Dodds et al. 1999; Gallagher et al. 1998; Hinckley et al. 2005b; Kramer et al. 1992; Savitz et al. 1995). For water systems serving > 10,000 people in the United States, regulatory monitoring data consist of samples taken at four sites and typically collected quarterly; thus, these data may not accurately capture spatiotemporal variability in DBPs [U.S. Environmental Protection Agency (EPA) 1998]. Previous epidemiologic studies of preterm birth relying on such data for exposure assessment thus necessarily operated at a relatively crude time scale. In this study, we were able to improve the time scale by employing weekly monitoring data for TTHMs. In addition, we decreased heterogeneity in TTHM across water distribution systems by relying on only a single public utility serving multiple communities in Massachusetts. Specifically, the water treatment regimens employed by this utility minimized the geographic variability of TTHMs. The importance of such a feature for valid exposure assessment in epidemiologic studies is underscored by recent research to develop methods to identify utilities that have low spatial variability of DBP (Hinckley et al. 2005a). Linking 2 years of birth data to weekly monitoring data for TTHMs enabled us to model the associations between shorter-term peak exposures and preterm births. Unlike most previous research, in our study we matched cases and controls closely on gestational age at exposure to address the influence of exposure timing—the existence of vulnerable windows late in pregnancy. Finally, our study population is diverse and large enough to allow us to examine the relation between preterm births and TTHM in the water supplied to homes for different racial/ethnic and socioeconomic groups.