Exposure to Drinking Water Trihalomethanes and Their Association with Low Birth Weight and Small for Gestational Age in Genetically Susceptible Women
06 Dec 2012-International Journal of Environmental Research and Public Health (Multidisciplinary Digital Publishing Institute (MDPI))-Vol. 9, Iss: 12, pp 4470-4485
TL;DR: It is suggested that THM internal dose may affect foetal growth and that maternal GSTM1 genotype modifies the THM exposure effects on LBW.
Abstract: Little is known about genetic susceptibility to individual trihalomethanes (THM) in relation to adverse pregnancy outcomes. We conducted a nested case-control study of 682 pregnant women in Kaunas (Lithuania) and, using individual information on drinking water, ingestion, showering and bathing, and uptake factors of THMs in blood, estimated an internal THM dose. We used logistic regression to evaluate the relationship between internal THM dose, birth outcomes and individual and joint (modifying) effects of metabolic gene polymorphisms. THM exposure during entire pregnancy and specific trimesters slightly increased low birth weight (LBW) risk. When considering both THM exposure and maternal genotypes, the largest associations were found for third trimester among total THM (TTHM) and chloroform-exposed women with the GSTM1–0 genotype (OR: 4.37; 95% CI: 1.36–14.08 and OR: 5.06; 95% CI: 1.50–17.05, respectively). A test of interaction between internal THM dose and GSTM1–0 genotype suggested a modifying effect of exposure to chloroform and bromodichloromethane on LBW risk. However, the effect on small for gestational age (SGA) was not statistically significant. These data suggest that THM internal dose may affect foetal growth and that maternal GSTM1 genotype modifies the THM exposure effects on LBW.
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TL;DR: Maternal genotypes for enzymes participating in metabolism of polycyclic aromatic hydrocarbons alter the association between cigarette smoking and birth weight, and this finding raises the question of whether metabolic genes interact with smoking.
Abstract: This study sought to clarify the relation, if any, between genetic susceptibility to cigarette smoke and adverse pregnancy outcomes. The working hypothesis was that the risk of reduced birth weight (or increased risk of low birth weight [LBW], <2500 g) is modified by maternal genetic susceptibility as defined by polymorphisms for two genes regulating the metabolism of polycyclic aromatic hydrocarbons, the most important carcinogens in tobacco smoke. A case-control study enlisted 741 women delivering live singleton infants, 567 had never smoked, whereas 174 had smoked at some time. The series included 207 preterm or LBW infants. All three possible genotypes for the CYP1A1 Mspl polymorphism (AA, homozygous wild type; Aa, heterozygous variant type; aa, homozygous variant type) were analyzed, as was the presence or absence of the GSTT1 deletion polymorphism. The mean birth weight in women who had smoked at some time in their lives was 280 g lower than for those who had never smoked, and the mean gestational age was 0.8 week shorter. The odds ratio (OR) for preterm birth was 1.8 in the smokers. Continuous smoking during pregnancy carried an OR for LBW of 2.1; the mean birth weight was reduced by 377 g compared with nonsmokers. When analyzing CYP1A1, the reduction in birth weight was 252 g for the AA genotype (OR, 1.3) and 520 g for the Aalaa genotype group (OR, 3.2). Birth weight was reduced by 285 g (OR, 1.7) when the GSTT1 was present and 642 g (OR, 3.5) when it was absent. Birth weights were most reduced, by a mean of 1285 g, in smoking mothers bearing the CYP1A1 Aalaa and GSTT1 absent genotypes. Similar effects were noted for gestational age. Genotype had no independent adverse effect on women who had never smoked. Comparable results emerged when allowing for maternal ethnicity. Maternal genotypes for enzymes participating in metabolism of polycyclic aromatic hydrocarbons alter the association between cigarette smoking and birth weight. This finding raises the question of whether metabolic genes interact with smoking, and it may in time help to identify high-risk women who might be persuaded not to smoke.
39 citations
TL;DR: The findings demonstrate associations between THM, but not HAA, exposure during pregnancy and reduced birth weight, but suggest this differs by ethnicity, and suggest that THMs are not acting as a proxy for HAAs, or vice-versa.
Abstract: This research was funded by HiWATE (Health Impacts of Long-Term Exposure to Disinfection By-products in Drinking Water in Europe) (EU 6th Framework Programme contract no Food-CT-2006-036224), the Joint Environment & Human Health Programme (NERC grant NE/ E008844/1), an Economic and Social Research Council studentship (PTA-031-2006-00544 to RBS), an MRC Capacity Building Studentship 2010-2013 to SCE, and a Research Training support stipend (SCE) The MRC-PHE Centre for Environment and Health is funded by the UK Medical Research Council and Public Health England
38 citations
TL;DR: A new comprehensive bioanalytical method has been developed that can quantify mixtures of organic halogenated compounds, including DBPs, in human urine as total organic chlorine (TOCl), total organic bromine (TOBr), and total organic iodine (TOI).
Abstract: Disinfection by-products (DBPs) are a complex mixture of compounds unintentionally formed as a result of disinfection processes used to treat drinking water. Effects of long-term exposure to DBPs are mostly unknown and were the subject of recent epidemiological studies. However, most bioanalytical methods focus on a select few DBPs. In this study, a new comprehensive bioanalytical method has been developed that can quantify mixtures of organic halogenated compounds, including DBPs, in human urine as total organic chlorine (TOCl), total organic bromine (TOBr), and total organic iodine (TOI). The optimized method consists of urine dilution, adsorption to activated carbon, pyrolysis of activated carbon, absorption of gases in an aqueous solution, and halide analysis with ion chromatography and inductively coupled plasma-mass spectrometry. Spike recoveries for TOCl, TOBr, and TOI measurements ranged between 78% and 99%. Average TOCl, TOBr, and TOI concentrations in five urine samples from volunteers who consumed tap water were 1850, 82, and 21.0μg/L as X-, respectively. Volunteers who consumed spring water (control) had TOCl, TOBr, and TOI average concentrations in urine of 1090, 88, and 10.3μg/L as X-, respectively. TOCl and TOI in the urine samples from tap water consumers were higher than the control. However, TOBr was slightly lower in tap water urine samples compared to mineral water urine samples, indicating other sources of environmental exposure other than drinking water. A larger sample population that consumes tap water from different cities and mineral water is needed to determine TOCl, TOBr, and TOI exposure from drinking water.
34 citations
Additional excerpts
...…birth outcomes (Swan et al., 1998; Waller et al., 1998; Nieuwenhuijsen et al., 2000, 2013; Villanueva et al., 2004, 2007; IARC, 2004; Bove et al., 2007; Costet et al., 2011; Grazuleviciene et al., 2011, 2013; Danileviciute et al., 2012; Jeong et al., 2012; Righi et al., 2012; Smith et al., 2016)....
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TL;DR: 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.
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.
29 citations
Pompeu Fabra University1, University of Valencia2, French Institute of Health and Medical Research3, University of Rennes4, University of the Aegean5, Metropolitan Water District of Southern California6, King's College London7, University of Crete8, University of Oviedo9, Imperial College London10, Bradford Royal Infirmary11
TL;DR: There was no association between birth outcomes and trihalomethane exposures during pregnancy in the total population or in potentially genetically susceptible subgroups in this large European study.
Abstract: Background: We examined the association between exposure during pregnancy to trihalomethanes, the most common water disinfection by-products, and birth outcomes in a European cohort study (Health Impacts of Long-Term Exposure to Disinfection By-Products in Drinking Water). We took into account exposure through different water uses, measures of water toxicity, and genetic susceptibility. Methods: We enrolled 14,005 mothers (2002–2010) and their children from France, Greece, Lithuania, Spain, and the UK. Information on lifestyle- and water-related activities was recorded. We ascertained residential concentrations of trihalomethanes through regulatory records and ad hoc sampling campaigns and estimated route-specific trihalomethane uptake by trimester and for whole pregnancy. We examined single nucleotide polymorphisms and copy number variants in disinfection by-product metabolizing genes in nested case–control studies. Results: Average levels of trihalomethanes ranged from around 10 μg/L to above the regulatory limits in the EU of 100 μg/L between centers. There was no association between birth weight and total trihalomethane exposure during pregnancy (β = 2.2 g in birth weight per 10 μg/L of trihalomethane, 95% confidence interval = 3.3, 7.6). Birth weight was not associated with exposure through different routes or with specific trihalomethane species. Exposure to trihalomethanes was not associated with low birth weight (odds ratio [OR] per 10 μg/L = 1.02, 95% confidence interval = 0.95, 1.10), small-for-gestational age (OR = 0.99, 0.94, 1.03) and preterm births (OR = 0.98, 0.9, 1.05). We found no gene–environment interactions for mother or child polymorphisms in relation to preterm birth or small-for-gestational age. Conclusions: In this large European study, we found no association between birth outcomes and trihalomethane exposures during pregnancy in the total population or in potentially genetically susceptible subgroups. (See video abstract at http://links.lww.com/EDE/B104.)
27 citations
References
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TL;DR: The HIWATE project was a systematic analysis that combined the epidemiology on adverse pregnancy outcomes and other health effects with long-term exposure to low levels of drinking water disinfection byproducts in the European Union, and this study is the first to integrate quantitative in vitro toxicological data with analytical chemistry and human epidemiologic outcomes for drinking water DBPs.
Abstract: The HIWATE (Health Impacts of long-term exposure to disinfection byproducts in drinking WATEr) project was a systematic analysis that combined the epidemiology on adverse pregnancy outcomes and other health effects with long-term exposure to low levels of drinking water disinfection byproducts (DBPs) in the European Union. The present study focused on the relationship of the occurrence and concentration of DBPs with in vitro mammalian cell toxicity. Eleven drinking water samples were collected from five European countries. Each sampling location corresponded with an epidemiological study for the HIWATE program. Over 90 DBPs were identified; the range in the number of DBPs and their levels reflected the diverse collection sites, different disinfection processes, and the different characteristics of the source waters. For each sampling site, chronic mammalian cell cytotoxicity correlated highly with the numbers of DBPs identified and the levels of DBP chemical classes. Although there was a clear difference in the genotoxic responses among the drinking waters, these data did not correlate as well with the chemical analyses. Thus, the agents responsible for the genomic DNA damage observed in the HIWATE samples may be due to unresolved associations of combinations of identified DBPs, unknown emerging DBPs that were not identified, or other toxic water contaminants. This study represents the first to integrate quantitative in vitro toxicological data with analytical chemistry and human epidemiologic outcomes for drinking water DBPs.
147 citations
"Exposure to Drinking Water Trihalom..." refers background in this paper
...Recently reported DBP toxicity of HIWATE program site water samples revealed that chronic mammalian cell cytotoxicity correlated highly with the numbers of DBPs identified and the levels of DBP chemical classes [38]....
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TL;DR: There was a significant interaction between the two pollutants such that the combined exposure to high ETS and high adducts had a significant multiplier effect on birth weight and head circumference.
Abstract: Inner-city, minority populations are high-risk groups for adverse birth outcomes and also are more likely to be exposed to environmental contaminants, including environmental tobacco smoke (ETS), benzo[a]pyrene (BaP), and other polycyclic aromatic hydrocarbons (PAHs) found in urban air. In a sample of nonsmoking African-American and Dominican women, we evaluated the effects on birth outcomes of prenatal exposure to ETS, using questionnaire data and plasma cotinine as a biomarker of exposure, and environmental PAHs using BaP-DNA adducts as a molecular dosimeter. We previously reported that among African Americans, high prenatal exposure to PAHs estimated by prenatal personal air monitoring was associated with lower birth weight (p = 0.003) and smaller head circumference (p = 0.01) after adjusting for potential confounders. In the present analysis, self-reported ETS was associated with decreased head circumference (p = 0.04). BaP-DNA adducts were not correlated with ETS or dietary PAHs. There was no main effect of BaP-DNA adducts on birth outcomes. However, there was a significant interaction between the two pollutants such that the combined exposure to high ETS and high adducts had a significant multiplicative effect on birth weight (p = 0.04) and head circumference (p = 0.01) after adjusting for ethnicity, sex of newborns, maternal body mass index, dietary PAHs, and gestational age. This study provides evidence that combined exposure to environmental pollutants at levels currently encountered in New York City adversely affects fetal development.
138 citations
TL;DR: Increased pregnancy average and second trimester TTHM exposure were associated with small for gestational age and reductions in birth weight after adjusting for potential confounding variables, and maternal exposure to THMs may be associated with fetal growth retardation.
Abstract: average (odds ratio (OR) 1.14; 95% CI 1.02 to 1.26) and second trimester (OR 1.13, 95% CI 1.03 to 1.24) TTHM levels greater than 80 µg/l. There was no evidence of an association between preterm delivery and increased TTHM levels, but there were slight increases in gestational duration associated with TTHM concentrations. Conclusions: Maternal exposure to THMs may be associated with fetal growth retardation. Our find- ings are consistent with most previous work, although we generally found smaller effects of TTHMs on low birth weight and intrauterine growth retardation.
111 citations
"Exposure to Drinking Water Trihalom..." refers background in this paper
...[22] found increased risk of SGA for second trimester (OR: 1....
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TL;DR: The results suggest that in embryonic and early fetal development cysteine, GSH and GSTs are present in high amounts, and that GSTP1 is the most important GST isoform at these developmental stages.
Abstract: BACKGROUND: Glutathione S-transferases (GSTs) are important in intracellular binding and transport of numerous compounds, and play a central role in human detoxification processes. Human GSTs mainly consist of class Pi (GSTP), Mu (GSTM), Alpha (GSTA) and Theta (GSTT) enzymes, each subdivided into one or more isoenzymes. They catalyse the conjugation of glutathione (GSH) to toxic compounds, resulting in more water-soluble and less biologically active products that may be easily excreted. The reactive -SH group in GSH is provided by cysteine, an important amino acid in GSH synthesis. METHODS: GST expression, enzyme activity and concentrations of cysteine and GSH in cytosolic fractions of organs from an embryo and a fetus at 8 and 13 weeks gestational age respectively were investigated. RESULTS: GSTP 1 was predominantly present in all tissues of both the embryo and fetus. GSTA (GSTA 1 + GSTA 2 ) concentrations were moderate as compared with GSTP 1 , whereas GSTM 1 was present in only low amounts. GSTT 1 was not detected in any tissue. GST activity was highest in organs exposed directly to amniotic fluid. In all embryonic and fetal organs, considerable amounts of GSH and cysteine were detected, with higher GSH concentrations in organs where lower cysteine concentrations were demonstrated. CONCLUSIONS: These results suggest that in embryonic and early fetal development cysteine, GSH and GSTs are present in high amounts, and that GSTP 1 is the most important GST isoform at these developmental stages.
110 citations
TL;DR: The overall aim of the HIWATE study is to investigate potential human health risks associated with long-term exposure to low levels of disinfectants and DBPs occurring in water for human consumption and use in the food industry.
Abstract: There appears to be very good epidemiological evidence for a relationship between chlorination by-products, as measured by trihalomethanes (THMs), in drinking water and bladder cancer, but the evidence for other cancers, including colorectal cancer appears to be inconclusive and inconsistent. There appears to be some evidence for a relationship between chlorination by-products, as measured by THMs, and small for gestational age (SGA)/intrauterine growth retardation (IUGR) and preterm delivery, but evidence for other outcomes such as low birth weight (LBW), stillbirth, congenital anomalies and semen quality appears to be inconclusive and inconsistent.The overall aim of the HIWATE study is to investigate potential human health risks (e.g. bladder and colorectal cancer, premature births, SGA, semen quality, stillbirth, congenital anomalies) associated with long-term exposure to low levels of disinfectants (such as chlorine) and DBPs occurring in water for human consumption and use in the food industry. The study will comprise risk-benefit analyses including quantitative assessments of risk associated with microbial contamination of drinking water versus chemical risk and will compare alternative treatment options. The outcome will be improved risk assessment and better information for risk management. The work is divided into different topics (exposure assessment, epidemiology, risk assessment and management) and studies.
101 citations
"Exposure to Drinking Water Trihalom..." refers background in this paper
...This Kaunas (Lithuania) cohort study is as a part of European Commission FP6 Health Impacts of Long-term Exposure to Disinfection By-products in Drinking Water in Europe (HiWATE) project [11]....
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