Disinfection Byproducts and Pregnancy

Disinfection Byproducts and Pregnancy - Journal Abstracts

TITLE: Exposure to Trihalomethanes through Different Water Uses and Birth Weight, Small for Gestational Age and Preterm Delivery in Spain.
http://www.ncbi.nlm.nih.gov/pubmed/21810554
AUTHORS: Villanueva CM, Gracia-Lavedan E, Ibarluzea J, Santa Marina L, Ballester F, Llop S, Tardón A, Fernandez MF, Freire C, Goñi F, Basagaña X, Kogevinas M, Grimalt JO,
SOURCE: Environ Health Perspect. 2011 Aug 2
CONCLUSIONS. Despite the high THM levels in some areas and the extensive exposure assessment, results suggest that residential trihalomethane exposure during pregnancy driven by inhalation and dermal contact routes is not associated with birth weight, small for gestational age, low birth weight or preterm delivery in Spain.

TITLE: The effect of water disinfection by-products on pregnancy outcomes in two southeastern US communities.
http://www.ncbi.nlm.nih.gov/pubmed/21915074
AUTHORS: Horton BJ, Luben TJ, Herring AH, Savitz DA, Singer PC, Weinberg HS, Hartmann KE.
SOURCE: J Occup Environ Med. 2011 Oct;53(10):1172-8.
CONCLUSIONS: Our results do not support an association between TTHMs or HAA5 and the birth outcomes investigated, but an association was found between increased total organic halides and preterm birth.

TITLE: Individual exposures to drinking water trihalomethanes, low birth weight and small for gestational age risk: a prospective Kaunas cohort study.
http://www.ncbi.nlm.nih.gov/pubmed/21501533
AUTHORS: Grazuleviciene R, Nieuwenhuijsen MJ, Vencloviene J, Kostopoulou-Karadanelli M, Krasner SW, Danileviciute A, Balcius G, Kapustinskiene V.
SOURCE: Environ Health. 2011 Apr 19;10:32.
BACKGROUND: Evidence for an association between exposure during pregnancy to trihalomethanes (THMs) in drinking water and impaired fetal growth is still inconsistent and inconclusive, in particular, for various exposure routes. We examined the relationship of individual exposures to THMs in drinking water on low birth weight (LBW), small for gestational age (SGA), and birth weight (BW) in singleton births.
CONCLUSIONS: THM internal dose in pregnancy varies substantially across individuals, and depends on both water THM levels and water use habits. Increased internal dose may affect fetal growth.

TITLE: Identification of developmentally toxic drinking water disinfection byproducts and evaluation of data relevant to mode of action.
http://www.ncbi.nlm.nih.gov/pubmed/21296098
AUTHORS: Colman J, Rice GE, Wright JM, Hunter ES 3rd, Teuschler LK, Lipscomb JC, Hertzberg RC, Simmons JE, Fransen M, Osier M, Narotsky MG.
SOURCE: Toxicol Appl Pharmacol. 2011 Jul 15;254(2):100-26.
ABSTRACT: Reactions between chemicals used to disinfect drinking water and compounds present in source waters produce chemical mixtures containing hundreds of disinfection byproducts (DBPs). Although the results have been somewhat inconsistent, some epidemiological studies suggest associations may exist between DBP exposures and adverse developmental outcomes. The potencies of individual DBPs in rodent and rabbit developmental bioassays suggest that no individual DBP can account for the relative risk estimates reported in the positive epidemiologic studies, leading to the hypothesis that these outcomes could result from the toxicity of DBP mixtures. As a first step in a mixtures risk assessment for DBP developmental effects, this paper identifies developmentally toxic DBPs and examines data relevant to the mode of action (MOA) for DBP developmental toxicity. We identified 24 developmentally toxic DBPs and four adverse developmental outcomes associated with human DBP exposures: spontaneous abortion, cardiovascular defects, neural tube defects, and low birth weight infancy. A plausible MOA, involving hormonal disruption of pregnancy, is delineated for spontaneous abortion, which some epidemiologic studies associate with total trihalomethane and bromodichloromethane exposures. The DBP data for the other three outcomes were inadequate to define key MOA steps.

TITLE: Exposure to disinfection by-products, fetal growth, and prematurity: a systematic review and meta-analysis.
http://www.ncbi.nlm.nih.gov/pubmed/20375841
AUTHORS: Grellier J, Bennett J, Patelarou E, Smith RB, Toledano MB, Rushton L, Briggs DJ, Nieuwenhuijsen MJ.
SOURCE: Epidemiology. 2010 May;21(3):300-13.
CONCLUSIONS: There was little or no evidence for associations between total trihalomethane concentration and adverse birth outcomes relating to fetal growth and prematurity, with the possible exception of SGA (small for gestational age). We discuss these findings and the uncertainties-relating particularly to exposure-that may have affected them. {basically the same as the 2009 paper}

TITLE: Chlorination disinfection by-products in drinking water and congenital anomalies: review and meta-analyses.
http://www.ncbi.nlm.nih.gov/pubmed/20019896
AUTHORS: Nieuwenhuijsen MJ, Martinez D, Grellier J, Bennett J, Best N, Iszatt N, Vrijheid M, Toledano MB.
SOURCE: Environ Health Perspect. 2009 Oct;117(10):1486-93.
CONCLUSION: Although some individual studies have suggested an association between chlorination disinfection by-products and congenital anomalies, meta-analyses of all currently available studies demonstrate little evidence of such an association.

TITLE: Water disinfection by-products and the risk of specific birth defects: a population-based cross-sectional study in Taiwan.
http://www.ncbi.nlm.nih.gov/pubmed/18518952
AUTHORS: Hwang BF, Jaakkola JJ, Guo HR.
SOURCE: Environ Health. 2008 Jun 2;7:23.
BACKGROUND: Recent findings suggest that exposure to disinfection by-products may increase the risk of birth defects. Previous studies have focused mainly on birth defects in general or groups of defects. The objective of the present study was to assess the effect of water disinfection by-products on the risk of most common specific birth defects.
CONCLUSION: The present study suggests that prenatal exposure to disinfection by-products increases the risk of ventricular septal defects, cleft palate, and anencephalus. The evidence on ventricular septal defects is consistent in the three available studies.

TITLE: Drinking water disinfection by-product exposure and duration of gestation.
http://www.ncbi.nlm.nih.gov/pubmed/18633329
AUTHORS: Hoffman CS, Mendola P, Savitz DA, Herring AH, Loomis D, Hartmann KE, Singer PC, Weinberg HS, Olshan AF.
SOURCE: Epidemiology. 2008 Sep;19(5):738-46.
CONCLUSIONS: The probability of preterm birth was not increased with high DBP exposure.

TITLE: Association between trihalomethane concentrations in drinking water and adverse pregnancy outcome in Taiwan.
http://www.ncbi.nlm.nih.gov/pubmed/17324396
AUTHORS: Yang CY, Xiao ZP, Ho SC, Wu TN, Tsai SS.
SOURCE: Environ Res. 2007 Jul;104(3):390-5.
ABSTRACT: Chlorination has been the major strategy for disinfection of drinking water in Taiwan. Recently there has been interest in the relationship between by-products of disinfection of drinking water and pregnancy outcomes including low birth weight and preterm delivery. We performed a study to examine the effects of exposure to total trihalomethanes (TTHMs) on the risk of term low birth weight (TLBW), small for gestational age (SGA), and preterm delivery in Taiwan. TTHMs data were available for 65 municipalities in Taiwan. The study population comprised 90,848 women residing in the 65 municipalities who had a first parity singleton birth between January 1, 2000 and December 31, 2002, and for which complete information on maternal age, education, gestational age, birth weight, and sex of the baby were available. Maternal TTHMs exposure was estimated from the TTHMs concentration for the municipality of residence at birth. The study results provide no evidence of an increased risk of TLBW, SGA, and preterm delivery at the relatively low concentrations of TTHMs in Taiwan's drinking water.

TITLE: Relation of trihalomethane concentrations in public water supplies to stillbirth and birth weight in three water regions in England.
http://www.ncbi.nlm.nih.gov/pubmed/15687062
AUTHORS: Toledano MB, Nieuwenhuijsen MJ, Best N, Whitaker H, Hambly P, de Hoogh C, Fawell J, Jarup L, Elliott P.
SOURCE: Environ Health Perspect. 2005 Feb;113(2):225-32.
ABSTRACT: We investigated the association between total trihalomethanes (TTHMs) and risk of stillbirth and low and very low birth weight in three water regions in England, 1992-1998; associations with individual trihalomethanes (THMs) were also examined. Modeled estimates of quarterly TTHM concentrations in water zones, categorized as low (< 30 microg/L), medium (30-59 microg/L), or high (> or = 60 microg/L), were linked to approximately 1 million routine birth and stillbirth records using maternal residence at time of birth. In one region, where there was a positive socioeconomic deprivation gradient across exposure categories, there was also a positive, significant association of TTHM with risk of stillbirth and low and very low birth weight. Overall summary estimates across the three regions using a random-effects model to allow for between-region heterogeneity in exposure effects showed small excess risks in areas with high TTHM concentrations for stillbirths [odds ratio (OR) = 1.11; 95% confidence interval (CI), 1.00-1.23), low birth weight (OR = 1.09; 95% CI, 0.93-1.27), and very low birth weight (OR = 1.05; 95% CI, 0.82-1.34). Among the individual THMs, chloroform showed a similar pattern of risk as TTHM, but no association was found with concentrations of bromodichloromethane or total brominated THMs. Our findings overall suggest a significant association of stillbirths with maternal residence in areas with high TTHM exposure. Further work is needed looking at cause-specific stillbirths and effects of other disinfection by-products and to help differentiate between alternative (noncausal) explanations and those that may derive from the water supply.

TITLE: Chlorination byproducts and nitrate in drinking water and risk for congenital cardiac defects.
http://www.ncbi.nlm.nih.gov/pubmed/12123645
AUTHORS: Cedergren MI, Selbing AJ, Löfman O, Källen BA.
SOURCE: Environ Res. 2002 Jun;89(2):124-30.
ABSTRACT: Drinking water disinfection byproducts have been associated with an increased risk for congenital defects including cardiac defects. Using Swedish health registers linked to information on municipal drinking water composition, individual data on drinking water characteristics were obtained for 58,669 women. Among the infants born, 753 had a cardiac defect. The risk for a cardiac defect was determined for ground water versus surface water, for different chlorination procedures, and for trihalomethane and nitrate concentrations. Ground water was associated with an increased risk for cardiac defect when crude rates were analyzed but after suitable adjustments this excess rate was found to be determined by chlorination procedures including chlorine dioxide. Chlorine dioxide appears itself as an independent risk factor for cardiac defects (adjusted odds ratio 1.61 (95%CI 1.00-2.59)). The risk for cardiac defects increased with increasing trihalomethane concentrations (P=0.0005). There was an indicated but statistically nonsignificant excess risk associated with nitrate concentration. The individual risk for congenital cardiac defect caused by chlorine dioxide and trihalomethanes is small but as a large population is exposed to public drinking water, the attributable risk for cardiac defects may not be negligible.

TITLE: Relation between trihalomethane compounds and birth defects.
AUTHORS: Dodds L, King WD.
SOURCE: Occup Environ Med 2001 Jul;58(7):443-6
OBJECTIVES: To evaluate the risk of birth defects relative to exposure to specific trihalomethanes in public water supplies. METHODS: A retrospective cohort study was conducted based on data from a population based perinatal database in Nova Scotia, Canada and from the results of routine water monitoring tests. The cohort consisted of women who had a singleton birth in Nova Scotia between 1988 and 1995 and who lived in an area with a municipal water supply. The birth defects analyzed included neural tube defects, cardiovascular defects, cleft defects, and chromosomal abnormalities. Two of the four trihalomethane compounds occur in large enough concentrations to be analyzed (chloroform and bromodichloromethane (BDCM)). RESULTS: Exposure to BDCM at concentrations of 20 microg/l or over was associated with an increased risk of neural tube defects (adjusted relative risk (RR) 2.5, 95% confidence interval (95% CI) 1.2 to 5.1) whereas exposure to chloroform was not. Exposure to BDCM of 20 microg/l and over was associated with decreased risks of cardiovascular anomalies (RR 0.3, 95% CI 0.2 to 0.7). There was a suggestion of an increased risk of chromosomal abnormalities associated with exposure to chloroform, and no evidence of any association between either trihalomethane compound and cleft defects. CONCLUSIONS: In this cohort, differences were found in the RR associated with exposure to chloroform and BDCM for each of the congenital anomalies under study. These findings point to the importance of examining specific byproduct compounds relative to risk for these birth outcomes and in particular implicate BDCM and other correlated disinfection byproducts in the aetiology of neural tube defects.

TITLE: Chlorination disinfection byproducts in water and their association with adverse reproductive outcomes: a review.
AUTHORS: Nieuwenhuijsen MJ, Toledano MB, Eaton NE, Fawell J, Elliott P.
SOURCE: Occup Environ Med. 2000 Feb;57(2):73-85.
OBJECTIVES AND METHODS: Chlorination has been the major disinfectant process for domestic drinking water for many years. Concern about the potential health effects of the byproducts of chlorination has prompted the investigation of the possible association between exposure to these byproducts and incidence of human cancer, and more recently, with adverse reproductive outcomes. This paper evaluates both the toxicological and epidemiological data involving chlorination disinfection byproducts (DBPs) and adverse reproductive outcomes, and makes recommendations for future research. RESULTS AND CONCLUSIONS: Relatively few toxicological and epidemiological studies have been carried out examining the effects of DBPs on reproductive health outcomes. The main outcomes of interest so far have been low birth weight, preterm delivery, spontaneous abortions, stillbirth, and birth defects--in particular central nervous system, major cardiac defects, oral cleft, and respiratory, and neural tube defects. Various toxicological and epidemiological studies point towards an association between trihalomethanes (THMs), one of the main DBPs and marker for total DBP load, and (low) birth weight, although the evidence is not conclusive. Administered doses in toxicological studies have been high and even though epidemiological studies have mostly shown excess risks, these were often not significant and the assessment of exposure was often limited. Some studies have shown associations for DBPs and other outcomes such as spontaneous abortions, stillbirth and birth defects, and although the evidence for these associations is weaker it is gaining weight. There is no evidence for an association between THMs and preterm delivery. The main limitation of most studies so far has been the relatively crude methodology, in particular for assessment of exposure. RECOMMENDATIONS: Large, well designed epidemiological studies focusing on well defined end points taking into account relevant confounders and with particular emphasis on exposure characterisation are ideally needed to confirm or refute these preliminary findings. In practice, these studies may be impracticable, partly due to the cost involved, but this is an issue that can be put right--for example, by use of subsets of the population in the design of exposure models. The studies should also reflect differences of culture and water treatment in different parts of the world. To identify the specific components that may be of aetiological concern and hence to fit the most appropriate exposure model with which to investigate human exposure to chlorinated DBPs, further detailed toxicological assessments of the mixture of byproducts commonly found in drinking water are also needed.

TITLE: Deteriorating trends in male reproduction: idiopathic or environmental?
AUTHORS: Veeramachaneni DN.
SOURCE: Anim Reprod Sci 2000 Jul 2;60-61:121-30
Animal Reproduction and Biotechnology Laboratory, Department of Physiology, College of
Recent reports portend deterioration in male reproductive health in several human populations. Similar trends might exist in domestic animals, but data are not available because of the inherent nature of animal husbandry practices - culling of the reproductively inefficient food- and fiber-producing animals at an early age. Although the causes for this deterioration are unknown, a variety of endocrine-mimicking environmental pollutants have been implicated. Data for relevant laboratory animal models exposed to several classes of suspect chemicals indicate that a variety of chemicals ubiquitously present in the environment can disrupt normal reproductive phenomena in the male at exposure rates encountered in nature. Data are presented for occurrence of cryptorchidism, carcinoma in situ of the testis, acrosomal malformations, and impaired sexual function following in utero and/or postnatal exposures to pesticides (e.g., DDT and vinclozolin), high-volume industrial chemicals (e.g., alkylphenols and phthalates), and commonly occurring organic and inorganic chemical contaminants in drinking water (e.g., chemical mixtures and water disinfection byproducts). These observations are discussed in the context of similar, so-called idiopathic conditions

TITLE: Drinking water chlorination and delivery outcome-a registry-based study in Sweden.
AUTHORS: Kallen BA, Robert E.
SOURCE: Reprod Toxicol 2000 Jul-Aug;14(4):303-9
By using the Swedish Medical Birth Registry and official data on drinking water chlorination, three cohorts were identified and compared: women who lived in areas where drinking water was disinfected with chlorine dioxide, women who lived in areas that used sodium hypochlorite disinfection, and women who lived in areas where there was no chlorination of the drinking water. There was a statistically significant increase in short gestational duration and low birth weight and especially in short body length and very small head circumference in areas using sodium hypochlorite, but no significant effects on these variables were found in areas using chlorine dioxide. No effects on congenital malformations, childhood cancer, infant mortality, low Apgar score, neonatal jaundice, or neonatal hypothyroidism were associated with either of the two drinking water chlorination methods. Because the exposure information in this study was based on the chlorination method and not the amount of byproducts in the water, the general lack of significant effects could be due to a low concentration of such byproducts.

TITLE: Chlorination disinfection byproducts in water and their association with adverse reproductive outcomes: a review.
AUTHORS: Nieuwenhuijsen MJ; Toledano MB; Eaton NE; Fawell J; Elliott P
SOURCE: Occup Environ Med 2000 Feb;57(2):73-85 CITATION IDS: PMID: 10711274 UI: 20176614
ABSTRACT: OBJECTIVES AND METHODS: Chlorination has been the major disinfectant process for domestic drinking water for many years. Concern about the potential health effects of the byproducts of chlorination has prompted the investigation of the possible association between exposure to these byproducts and incidence of human cancer, and more recently, with adverse reproductive outcomes. This paper evaluates both the toxicological and epidemiological data involving chlorination disinfection byproducts (DBPs) and adverse reproductive outcomes, and makes recommendations for future research. RESULTS AND CONCLUSIONS: Relatively few toxicological and epidemiological studies have been carried out examining the effects of DBPs on reproductive health outcomes. The main outcomes of interest so far have been low birth weight, preterm delivery, spontaneous abortions, stillbirth, and birth defects--in particular central nervous system, major cardiac defects, oral cleft, and respiratory, and neural tube defects. Various toxicological and epidemiological studies point towards an association between trihalomethanes (THMs), one of the main DBPs and marker for total DBP load, and (low) birth weight, although the evidence is not conclusive. Administered doses in toxicological studies have been high and even though epidemiological studies have mostly shown excess risks, these were often not significant and the assessment of exposure was often limited. Some studies have shown associations for DBPs and other outcomes such as spontaneous abortions, stillbirth and birth defects, and although the evidence for these associations is weaker it is gaining weight. There is no evidence for an association between THMs and preterm delivery. The main limitation of most studies so far has been the relatively crude methodology, in particular for assessment of exposure. RECOMMENDATIONS: Large, well designed epidemiological studies focusing on well defined end points taking into account relevant confounders and with particular emphasis on exposure characterisation are ideally needed to confirm or refute these preliminary findings. In practice, these studies may be impracticable, partly due to the cost involved, but this is an issue that can be put right--for example, by use of subsets of the population in the design of exposure models. The studies should also reflect differences of culture and water treatment in different parts of the world. To identify the specific components that may be of aetiological concern and hence to fit the most appropriate exposure model with which to investigate human exposure to chlorinated DBPs, further detailed toxicological assessments of the mixture of byproducts commonly found in drinking water are also needed.

TITLE: Water chlorination and birth defects.
AUTHORS: Magnus P; Jaakkola JJ; Skrondal A; Alexander J; Becher G; Krogh T; Dybing E
SOURCE: Epidemiology 1999 Sep;10(5):513-7
ABSTRACT: Chlorination of drinking water that contains organic compounds leads to the formation of by-products, some of which have been shown to have mutagenic or carcinogenic effects. As yet, too little is known about the possible teratogenic effects on the human fetus. We linked the Norwegian waterwork registry, containing 1994 data on chlorination practice and color (an indicator for natural organic matter), with the Medical Birth Registry for 1993-1995. The proportion of the population exposed to chlorination and a weighted mean color number in drinking water was computed for each municipality. Among 141,077 births, 2,608 (1.8%) had birth defects. In a comparison between exposed (high color; chlorination) and reference groups (low color; no chlorination), the adjusted odds ratio was 1.14 (0.99-1.31) for any malformation, 1.26 (0.61-2.62) for neural tube defects, and 1.99 (1.10-3.57) for urinary tract defects. This study provides further evidence of the role of chlorination of humic water as a potential cause of birth defects, in a country with relatively low levels of chlorination byproducts. TITLE: Water chlorination: essential process or cancer hazard?

TITLE: Neural tube defects and drinking water disinfection by-products.
AUTHORS: Klotz JB; Pyrch LA
SOURCE: Epidemiology 1999 Jul;10(4):383-90
ABSTRACT: We conducted a population-based case control study of neural tube defects and drinking water contaminants, specifically, disinfection by- products. We used public monitoring records concurrent with the first month of gestation to assess exposure. The prevalence odds ratios (PORs) for the highest tertile of total trihalomethanes compared with the lowest was 1.6 (95% confidence interval [CI] = 0.9-2.70). Surface water source was also associated with neural tube defects (POR = 1.5; 95% CI = 0.9-2.5). Sensitivity analyses restricted to isolated neural tube defect cases and mothers with known residence at conception yielded stronger associations [total trihalomethanes, POR = 2.1 (95% CI = 1.1-4.0); surface water, POR = 1.7 (95% CI = 0.9-3.2)]. Other major groups of disinfection by-products (haloacetic acids and haloacetonitriles) showed little relation to these defects.

TITLE: Trihalomethanes in public water supplies and adverse birth outcomes.
AUTHORS: Dodds L; King W; Woolcott C; Pole J
SOURCE: Epidemiology 1999 May;10(3):233-7
ABSTRACT: We conducted a retrospective cohort study to evaluate the relation between the level of total trihalomethanes in drinking water and adverse birth outcomes. The study population comprised women residing in an area with municipal surface water who had a singleton birth in Nova Scotia between January 1, 1988, and December 31, 1995, or a pregnancy termination for a major fetal anomaly. We found little association between trihalomethane level and the outcomes related to fetal weight or gestational age, but we found an elevated relative risk for stillbirths for average trihalomethane levels during pregnancy of 100 microg/liter or greater (adjusted relative risk = 1.66; 95% confidence interval = 1.09-2.52) relative to women exposed to trihalomethane levels of 0-49 microg/liter. We saw little evidence of an elevated prevalence or dose-response pattern for congenital anomalies, with the possible exception of chromosomal abnormalities (adjusted prevalence ratio = 1.38 and 95% confidence interval = 0.73-2.59 for women exposed to trihalomethane levels of 100 microg/liter or greater).

TITLE: Exposure to trihalomethanes and adverse pregnancy outcomes [see comments]
AUTHORS: Gallagher MD; Nuckols JR; Stallones L; Savitz DA
SOURCE: Epidemiology 1998 Sep;9(5):484-9 Comment in: Epidemiology 1998 Sep;9(5):479-81
ABSTRACT: Exposure during pregnancy to disinfection by-products in drinking water has been hypothesized to lead to several adverse reproductive outcomes. We performed a retrospective cohort study to examine the relation of trihalomethane exposure during the third trimester of pregnancy to low birthweight, term low birthweight, and preterm delivery. We matched Colorado birth certificates from January 1, 1990, through December 31, 1993, to historical water sample data with respect to time and location of maternal residence based on census block groups. After excluding births from all census block groups with no trihalomethane sample data and restricting to singleton white births with 28-42 weeks of completed gestation (>400 gm), we studied 1,893 livebirths within 28 census block groups. We found a weak association of trihalomethane exposure during the third trimester with low birthweight (odds ratio = 2.1 for the highest exposure level; 95% confidence interval = 1.0-4.8); a large increase in risk for term low birthweight at the highest level of exposure (odds ratio = 5.9; 95% confidence interval = 2.0-17.0); and no association between exposure and preterm delivery (odds ratio = 1.0 for the highest exposure level; 95% confidence interval = 0.3-2.8). The small number of adverse outcomes reduced the precision of risk estimates, but these data indicate a potentially important relation between third trimester exposure to trihalomethanes and retarded fetal growth.

TITLE: Trihalomethanes in drinking water and spontaneous abortion [see comments]
AUTHORS: Waller K; Swan SH; DeLorenze G; Hopkins B
SOURCE: Epidemiology 1998 Mar;9(2):134-40 Comment in: Epidemiology 1999 Mar;10(2):203-4
ABSTRACT: Trihalomethanes (chloroform, bromoform, bromodichloromethane, and chlorodibromomethane) are common contaminants of chlorinated drinking water. Although animal data indicate that these compounds may be reproductive toxicants, little information exists on their relation to spontaneous abortion in humans. We examined exposure to trihalomethanes and spontaneous abortion in a prospective study of 5,144 pregnant women in a prepaid health plan. Seventy-eight drinking water utilities provided concurrent trihalomethane sampling data. We calculated total trihalomethane levels by averaging all measurements taken by the subject's utility during her first trimester. We calculated exposures to individual trihalomethanes in an analogous manner. Women who drank > or = 5 glasses per day of cold tapwater containing > or = 75 micrograms per liter total trihalomethanes had an adjusted odds ratio (OR) of 1.8 for spontaneous abortion [95% confidence interval (CI) = 1.1-3.0]. Of the four individual trihalomethanes, only high bromodichloromethane exposure (consumption of > or = 5 glasses per day of cold tapwater containing > or = 18 micrograms per liter bromodichloromethane) was associated with spontaneous abortion both alone (adjusted OR = 2.0; 95% CI = 1.2-3.5) and after adjustment for the other trihalomethanes (adjusted OR = 3.0; 95% CI = 1.4-6.6).

TITLE: A prospective study of spontaneous abortion: relation to amount and source of drinking water consumed in early pregnancy [see comments]
AUTHORS: Swan SH; Waller K; Hopkins B; Windham G; Fenster L; Schaefer C; Neutra RR SOURCE: Epidemiology 1998 Mar;9(2):126-33 COMMENT: Comment in: Epidemiology 1999 Mar;10(2):203-4
ABSTRACT: In 1992, we published four retrospective studies, conducted primarily within a single California county, which found higher spontaneous abortion rates among women who drank more tapwater than bottled water in early pregnancy. The current prospective study extends that investigation to other water systems. Pregnant women from three regions in California were interviewed during their first trimester. Multivariate analyses modeled the amount and type of water consumed at 8 weeks' gestation in each region in relation to spontaneous abortion rate. In Region I, which was within the previous study area, the adjusted odds ratio (OR) comparing high (> or = 6 glasses per day) consumption of cold tapwater with none was 2.17 [95% confidence interval (CI) = 1.22-3.87]. Furthermore, when women with high cold tapwater and no bottled water consumption were compared with those with high bottled water and no cold tapwater consumption, the adjusted odds ratio was 4.58 (95% CI = 1.97-10.64). Conversely, women with high bottled water consumption and no tapwater had a reduced rate of spontaneous abortion compared with those drinking tapwater and no bottled water (adjusted OR = 0.22; 95% CI = 0.09-0.51). Neither tap nor bottled water consumption altered the risk of spontaneous abortion in Regions II and III. Although controlling for age, prior spontaneous abortion, race, gestational age at interview, and weight somewhat strengthened the association in Region I, the distribution of these confounders did not vary appreciably across regions. This study confirms the association between cold tapwater and spontaneous abortion first seen in this county in 1980. If causal, the agent(s) is not ubiquitous but is likely to have been present in Region I for some time.

TITLE: Reproductive and developmental effects of disinfection by-products in drinking water.
AUTHORS: Reif JS; Hatch MC; Bracken M; Holmes LB; Schwetz BA; Singer PC
SOURCE: Environ Health Perspect 1996 Oct;104(10):1056-61
ABSTRACT: Recent epidemiologic studies have reported associations between the consumption of chlorinated drinking water and reproductive and developmental effects. Here we review the available epidemiologic data, assess the hazard potential posed by exposure to disinfection by- products, identify critical data gaps, and offer recommendations for further research. The epidemiologic evidence supporting associations between exposure to water disinfection by-products (DBPs) and adverse pregnancy outcomes is sparse, and positive findings should be interpreted cautiously. The methods used during the early stages of research in this area have been diverse. Variability in exposure assessment and endpoints makes it difficult to synthesize or combine the available data. Exposure misclassification and unmeasured confounding may have lead to bias in risk estimation. Future studies of reproductive outcome and exposure to chlorinated water should use improved methods for exposure assessment to 1) assure selection of appropriate exposure markers, 2) assess seasonal and annual fluctuations in DBPs, 3) assess variability within the distribution system, and 4) assess exposure through multiple routes such as bathing and showering, as well as consumption. Population-based studies should be conducted to evaluate male and female fertility, conception delay, growth retardation, and specific birth defects. The reproductive and developmental effects of exposure to DBPs could be efficiently explored in ongoing investigations by incorporating valid exposure markers and relevant questionnaire information. Future studies should make use of naturally occurring variability in the concentrations of DBPs and may incorporate biomarkers of exposure and effect in their design. Epidemiologic investigations should be conducted in parallel with laboratory-based and animal studies in a coordinated, multidisciplinary approach.

TITLE: Drinking water and pregnancy outcome in central North Carolina: source, amount, and trihalomethane levels.
AUTHORS: Savitz DA; Andrews KW; Pastore LM
SOURCE: Environ Health Perspect 1995 Jun;103(6):592-6
ABSTRACT: In spite of the recognition of potentially toxic chemicals in chlorinated drinking water, few studies have evaluated reproductive health consequences of such exposure. Using data from a case-control study of miscarriage, preterm delivery, and low birth weight in central North Carolina, we evaluated risk associated with water source, amount, and trihalomethane (THM) concentration. Water source was not related to any of those pregnancy outcomes, but an increasing amount of ingested water was associated with decreased risks of all three outcomes (odds ratios around 1.5 for 0 glasses per day relative to 1-3 glasses per day, falling to 0.8 for 4+ glasses per day). THM concentration and dose (concentration x amount) were not related to pregnancy outcome, with the possible exception of an increased risk of miscarriage in the highest sextile of THM concentration (adjusted odds ratio = 2.8, 95% confidence interval = 1.1-2.7), which was not part of an overall dose-response gradient. These data do not indicate a strong association between chlorination by-products and adverse pregnancy outcome, but given the limited quality of our exposure assessment and the increased miscarriage risk in the highest exposure group, more refined evaluation is warranted.

TITLE: Public drinking water contamination and birth outcomes [see comments]
AUTHORS: Bove FJ; Fulcomer MC; Klotz JB; Esmart J; Dufficy EM; Savrin JE
SOURCE: Am J Epidemiol 1995 May 1;141(9):850-62
ABSTRACT: The effects of public drinking water contamination on birth outcomes were evaluated in an area of northern New Jersey. After excluding plural births and chromosomal defects, 80,938 live births and 594 fetal deaths that occurred during the period 1985-1988 were studied. Information on birth outcome status and maternal risk factors was obtained from vital records and the New Jersey Birth Defects Registry. Monthly exposures during pregnancy were estimated for all births using tap water sample data. Odds ratios of > or = 1.50 were found for the following: total trihalomethanes with small for gestational age, central nervous system defects, oral cleft defects, and major cardiac defects; carbon tetrachloride with term low birth weight, small for gestational age, very low birth weight, total surveillance birth defects, central nervous system defects, neural tube defects, and oral cleft defects; trichloroethylene with central nervous system defects, neural tube defects, and oral cleft defects; tetrachloroethylene with oral cleft defects; total dichloroethylenes with central nervous system defects and oral cleft defects; benzene with neural tube defects and major cardiac defects; and 1,2-dichloroethane with major cardiac defects. Total trihalomethane levels > 100 ppb reduced birth weight among term births by 70.4 g. By itself, this study cannot resolve whether the drinking water contaminants caused the adverse birth outcomes; therefore, these findings should be followed up utilizing available drinking water contamination databases.

TITLE: Quality of community drinking water and the occurrence of late adverse pregnancy outcomes.
AUTHORS: Aschengrau A; Zierler S; Cohen A
SOURCE: Arch Environ Health 1993 Mar-Apr;48(2):105-13
ABSTRACT: The relationship between community drinking water quality and the occurrence of late adverse pregnancy outcomes was investigated by conducting a case-control study among women who delivered infants during August 1977 through March 1980 at Brigham and Women's Hospital in Massachusetts. The water quality indices were compared among 1,039 congenital anomaly cases, 77 stillbirth cases, 55 neonatal death cases, and 1,177 controls. Trace element levels were gathered from routine analyses of public water supplies from the communities in which the women resided during pregnancy. It was observed that, after adjustment for confounding, the frequency of stillbirths was increased for women exposed to chlorinated surface water (OR 2.6 95% CI 0.9-7.5) and for women exposed to detectable lead levels (OR 2.1; 95% CI 0.6-7.2); the frequency of cardiovascular defects was increased relative to detectable lead levels (OR 2.2, 95% CI 0.9-5.7); and the frequency of central nervous system defects was increased relative to the highest tertile of potassium (OR 6.3, 95% CI 1.1-37.3). The frequency of ear, face, and neck anomalies was increased in relation to detectable silver levels (OR 3.3, 95% CI 0.9-12.2), but the frequency decreased relative to high potassium levels (OR 0.2, 95% CI 0.1-0.7). The frequency of neonatal deaths was decreased relative to detectable fluoride levels (OR 0.4, 95% CI 0.2-1.0), and the frequency of musculoskeletal defects was decreased relative to detectable chromium levels (OR 0.4, 95% CI 0.2-1.0). The majority of these associations were not stable statistically. Further research is needed to corroborate these findings.

Title The association of waterborne chloroform with intrauterine growth retardation.
Author Kramer MD; Lynch CF; Isacson P; Hanson JW
Source Epidemiology, 1992 Sep, 3:5, 407-13
The paper discusses the association of waterborne chloroform with low birthweight (less than 2,500 gm), prematurity (less than 37 weeks gestation), and intrauterine growth retardation (less than 5th percentile of weight for gestational age). After adjustment for maternal age, parity, adequacy of prenatal care, marital status, education, and maternal smoking by multiple logistic regression, residence in municipalities where chloroform concentrations were greater than or equal to 10 micrograms/liter was associated with an increased risk for intrauterine growth retardation (odds ratio = 1.8, 95% confidence interval = 1.1-2.9). The limitatio ns of the study were discussed.

Title Problems in assessing the risks of mixtures of contaminants in drinking water.
Author Vanderslice RR; Orme J; Ohanian EV; Sonich-Mullin C
Source Toxicol Ind Health, 1989 Oct, 5:5, 747-55
Partial abstract - In conducting risk assessments on drinking water contaminants, the U.S. Environmental Protection Agency (EPA) attempts to evaluate all available toxicity data to develop Health Advisory (HA) and Maximum Contaminant Level Goal (MCLG) values. Potential toxic interactions between drinking water contaminants are difficult to predict because experimental studies are generally performed only at high doses relative to environmental levels. Although the contamination of drinking water involves mixtures of contaminants, drinking water regulations are generally based on an assessment of the risks of individual contaminants. This paper discusses three issues of major concern to the EPA: the synergistic effects of solvent mixtures, vehicle effects in laboratory studies, and setting standards for essential trace nutrients where the absorption and/or toxicity are affected by an individual's nutritional status or other dietary components.

TITLE: Spontaneous abortions in relation to consumption of tap water: an application of methods from survival analysis to a pregnancy follow-up study.
AUTHORS: Hertz-Picciotto I; Swan SH; Neutra RR; Samuels SJ
SOURCE: Am J Epidemiol 1989 Jul;130(1):79-93
ABSTRACT: A previous study of pregnant women whose water supply was potentially contaminated revealed a significant increase in spontaneous abortions among those drinking tap as opposed to bottled water, regardless of exposure to the contamination. The relation between reported prenatal water consumption and risk of spontaneous abortion was therefore analyzed in an independent cohort of pregnancies seen in 1981-1982 at a health maintenance organization in three counties in northern California. The study used a nested case-control design. Since early miscarriages are left-truncated, gestational age at which a pregnancy comes to medical attention may confound results of pregnancy outcome studies. Risk set analyses were therefore conducted in two stages: 1) the life of table-adjusted risk for those drinking mainly bottled water was 8.4%; the risk for those drinking mainly tap water was 12.5%, and 2) the Cox proportional hazards model was used to control for multiple confounders, yielding a hazard ratio for spontaneous abortion of 1.5 (95% confidence interval 1.1-2.0) for consumers of tap water compared with bottled water. Tap water drinkers whose home source of water included ground water had the greatest risk (13.8) and, after controlling for confounders, their hazard ratio was 1.7. Based on external data from comparable studies, bottled water drinkers appeared to have had unusually low risks, and tap water drinkers who received ground water may have had slightly high risks. Inconsistencies in the reporting of tap water consumption suggest recall bias. Causal factors could not be ruled out, however, although no reproductive toxins, either biological or chemical, have yet been identified in the tap water in this area.