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: In this paper, a case-control study was conducted to determine whether the risk of childhood acute lymphoblastic leukemia (ALL) associated with drinking water disinfection byproducts was modified in the presence of variants in genes involved in the metabolism of trihalomethanes (THMs).
Abstract: The purpose of the study was to determine whether the risk of childhood acute lymphoblastic leukemia (ALL) associated with drinking water disinfection by-products was modified in the presence of variants in genes involved in the metabolism of trihalomethanes (THMs). We included a subset of cases from a population-based case-control study in a case-only study to estimate the interaction odds ratios (IORs) between prenatal and postnatal exposure to THMs and polymorphisms in the GSTT1 and CYP2E1 genes. We compared cases with and without a given variant regarding their exposure to THMs using unconditional logistic regression. The IOR for a postnatal average of total THM above the 95th percentile with GSTT1 null genotype was 9.1 [95% confidence interval (95% CI), 1.4-57.8]. With CYP2E1 (variant G-1259C, known as the allele CYP2E1*5), the effect of exposure during pregnancy for an average exposure to total THM at or above the 75th percentile was 9.7 (95% CI, 1.1-86.0). These results contrast strongly with those from our case-control analysis, in which we considered the exposure to THMs only in relation with ALL, and observed no increase in risk or very moderate ones. The present preliminary study shows suggestive but imprecise results. We found no similar results in the literature, underscoring the need for other studies as well as the potential usefulness of combining exposure and relevant genetic information in such studies.
48 citations
TL;DR: Certain genetic variants involved in the metabolism of xenobiotics increase the risk of SGA, as well as modify the effects of maternal smoking by increasing or decreasing its risk.
Abstract: Background:Little is known about the role of xenobiotic-metabolizing gene variants as risk factors for small-for-gestational-age (SGA) births or as modifiers for the effects of exposures such as maternal smoking.Methods:We conducted 2 joint studies: a case–control design including 493 cases (birth w
47 citations
"Exposure to Drinking Water Trihalom..." refers background in this paper
...The metabolism of environmental toxicants includes the several allelic variants of the polymorphic GST group whose show impaired enzyme activities and increase the susceptibility to both environmental xenobiotics and adverse birth outcomes [31,32]....
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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 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
"Exposure to Drinking Water Trihalom..." refers background in this paper
...We did find a nonsignificant elevated risk for SGA for those exposed to TTHMs during the three trimesters with highest ORs during the third trimester among women carriers of the GSTM1–0 genotype (OR: 1.81, 95% CI: 0.92–3.56) and GSTT1–0 genotype (OR: 1.51, 95% CI: 0.43–5.29)....
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...Some study results provide no evidence of any increased risk of LBW, TLBW, and preterm delivery at the relatively low concentration of TTHMs [23,24]....
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TL;DR: In this article, analytical methods for the determination of major categories of DBPs, trihalomethanes (THMs), haloacetic acids (HAAs), Haloacetonitriles, haloketones, chloral hydrate and chloropicrin were optimized and evaluated in order to be applicable for the routine analysis of these compounds in drinking water.
26 citations
"Exposure to Drinking Water Trihalom..." refers methods in this paper
...Samples were analysed at the University of the Aegean (Mitilini, Greece) using gas chromatography with electron capture detection [15]....
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