Invited commentary: disinfection by-products and pregnancy loss--lessons.

Chlorine was first used to purify water in the United States almost 100 years ago (1). Since that time, the technique has been improved upon and its use expanded so that most water systems today are disinfected (1). In 1995, approximately 64 percent of community water systems (systems that provide water to the same people year-round) specifically added chlorine as a disinfectant, and the remaining systems commonly added chloramine, according to an Environmental Protection Agency survey (1). Disinfection protects against waterborne pathogens, but chlorine reacts with organic matter in the water to form both halogenated and nonhalogenated disinfection by-products (DBPs), including trihalomethanes (THMs) (2). The Environmental Protection Agency set standards for total THM levels in community water systems after the Safe Drinking Water Act of 1974 was implemented (1). As a result, exposure to THMs is generally at levels currently deemed safe. Nevertheless, given that such exposure is pervasive throughout the United States, if DBPs at levels below the current standards were found to be associated with spontaneous abortion, it would be of public health concern. For the past few decades, DBPs have been studied extensively for potential associations with different cancers, and, more recently, the literature has expanded to include reproductive outcomes (2–4). Only a few previous studies quantified THM exposures and examined spontaneous abortion, specifically those by Savitz et al. (5) and Waller et al. (6). The more comprehensive of these two earlier studies (6) suggested a possible association between spontaneous abortion and high consumption of total THMs (determined by a combination of high total THM exposure and high consumption of cold tap water). Of the individual THMs measured, bromodichloromethane (BDCM) had the strongest association. However, exposure assessment was limited to the quarterly average THM levels reported by water utilities serving the women’s residences (6) and, in a follow-up paper, THM levels at the utility sampling site closest to a participant’s home (6, 7). Although these approaches were reasonable for a preliminary investigation, even the closest site might not represent actual maternal exposure because of variability in THM levels within the system and across time. Furthermore, quarterly averages could only approximately match potential critical windows during gestation. The study by Waller et al. (6) did, however, justify a more in-depth study of THMs and spontaneous abortion. The new study by Savitz et al. reported in this issue of the Journal (8) represents the state-of-the-art for a study of environmental factors and spontaneous abortion. Their attention to the exposure assessment was impressively thorough and addressed numerous deficiencies outlined in previous critical reviews (3, 9). Strengths included selecting three sites with different chlorination by-product profiles; confirming uniform distribution of DBP levels throughout the distribution system; taking weekly measurements; assessing DBP levels at multiple locations when the distribution systems were flushed with free chlorine; and developing pregnancy-specific exposure indexes, including examining exposure during specific critical windows during gestation.