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: To better understand the science linking environmental contaminants exposures with adverse pregnancy outcomes, the relevant epidemiologic literature was reviewed and PubMed was searched using the key word combinations for select environmental exposures and pregnancy outcomes.
Abstract: To better understand the science linking environmental contaminants exposures with adverse pregnancy outcomes, we reviewed the relevant epidemiologic literature. We searched PubMed (primarily 1995-2006) using the key word combinations for select environmental exposures and pregnancy outcomes. Environmental tobacco smoke is a risk factor for reduced birth weight and preterm delivery. Outdoor air pollution is associated with reduced term birth weight and preterm delivery. Suggestive evidence associates pesticides and polychlorinated biphenyls with decreased fetal growth and length of gestation. Stronger evidence, primarily occupational, links certain birth defects with exposure to organic solvents and chlorophenoxy herbicides. Evidence suggests dichlorodiphenyltrichloroethane and bisphenol-A could be associated with pregnancy loss. Exposures in utero can also increase the risk of developmental delays (ie, impaired neurological function), adult chronic illnesses (ie, heart disease, diabetes, cancer), and next generation effects (ie, reduced reproductive capacity). Further research, education, and improved public health policy are needed to reduce potentially adverse exposures.
335 citations
334 citations
"Exposure to Drinking Water Trihalom..." refers background in this paper
...[14] to determine the presence (at least one allele present: AA or Aa) or absence (complete deletion of both alleles: aa) of GSTM1 and GSTT1 genes....
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TL;DR: The hypothesis has been put forward that genetic polymorphism of GSTM1 might be linked with the occurrence of human bladder cancer, and this supports the hypothesis that exposure to PAH might causally be involved in urothelial cancers.
172 citations
"Exposure to Drinking Water Trihalom..." refers background in this paper
...“Conjugator” and “non-conjugator” phenotypes are coincident with the presence (GSTT1–1) and absence (GSTT1–0) of the gene activity that may lead to altered individual susceptibility to environmental exposures [9,10]....
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TL;DR: Interventions with pregnant women, especially those assessing perceived stress and attitudes toward the pregnancy, have the potential to improve pregnancy outcomes.
Abstract: While low birth weight is the leading cause of infant mortality and morbidity the factors influencing low birth weight are not well understood. In particular the relationship between stressful life events and birth outcomes is unclear. It is important for health care providers to better understand the impact of stress on health outcomes. Data from a statewide case-control study of 2378 Missouri mothers are used to examine the relationship of perceived stress pregnancy attitudes and major life events as psychosocial risk factors on very low birth weight (i.e. birth weight <1500 g). Such births are contrasted with moderately low-birth-weight infants (those weighing 1500-2499 g) and normal-birth-weight infants (those weighing 2500 g or more). A stepwise logistic regression model is used to control for all study and control variables. The risk of very low birth weight is one and one-half times greater if the mother perceived that she "almost always" felt stress during her pregnancy. The regression model confirms that besides perceived stress several other factors are independently associated with an increased risk of very low or moderately low birth weight. For example getting back with a husband or partner or experiencing a major injury accident or illness were associated with an elevated risk of low birth weight (odds ratio (OR) 1.7) as was pregnancy denial (1.4-1.6) and unhappiness about the pregnancy (1.3). On the other hand a few factors (taking out a mortgage or loan having a close relative die and having a mistimed pregnancy) appear to have reduced the odds of low birth weight (OR 0.5-0.8). Interventions with pregnant women especially those assessing perceived stress and attitudes toward the pregnancy have the potential to improve pregnancy outcomes. Additional prospective research with pregnant women on the origins and effects of stress including the biological effects of stress is needed. (authors)
167 citations
TL;DR: Pregnancy loss was not associated with high personal trihalomethane exposure, and results provide some assurance that drinking water DBPs in the range commonly encountered in the United States do not affect fetal survival.
Abstract: Previous research has suggested that exposure to elevated levels of drinking water disinfection by-products (DBPs) may cause pregnancy loss. In 2000-2004, the authors conducted a study in three US locations of varying DBP levels and evaluated 2,409 women in early pregnancy to assess their tap water DBP concentrations, water use, other risk factors, and pregnancy outcome. Tap water concentrations were measured in the distribution system weekly or biweekly. The authors considered DBP concentration and ingested amount and, for trihalomethanes only, bathing/showering and integrated exposure that included ingestion. On the basis of 258 pregnancy losses, they did not find an increased risk of pregnancy loss in relation to trihalomethane, haloacetic acid, or total organic halide concentrations; ingested amounts; or total exposure. In contrast to a previous study, pregnancy loss was not associated with high personal trihalomethane exposure (> or =75 micro g/liter and > or =5 glasses of water/day) (odds ratio = 1.1, 95% confidence interval: 0.7, 1.7). Sporadic elevations in risk were found across DBPs, most notably for ingested total organic halide (odds ratio = 1.5, 95% confidence interval: 1.0, 2.2 for the highest exposure quintile). These results provide some assurance that drinking water DBPs in the range commonly encountered in the United States do not affect fetal survival.
167 citations