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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.)

Study objective: To determine the association between adverse psychosocial characteristics at work and risk of first myocardial infarction in the occupational categories of Kaunas men, Lithuania. Design: The analysis was based upon a case-control study among full time working men in the general population of Kaunas. Outcome measure: First non-fatal myocardial infarction diagnosed in 2001–2002. The Swedish version of the demand-control questionnaire was used to examine the effect of job control and demands. Setting: Kaunas, the second largest city in Lithuania, a former socialist country in a transition market economy. Participants: Cases were 203 men 25–64 years of age with a first non-fatal myocardial infarction and controls were 287 men group randomly selected from the study base. Main results: Low job control had a significant effect on myocardial infarction risk in the general 25–64 year old Kaunas male population (OR = 2.68; 95% CI 1.68 to 4.28) after adjustment for age and socioeconomic status. Low job control was a risk factor in the occupational categories of the increased myocardial infarction risk (1st occupational category—legislators, senior officials and managers and the 8th—plant and machine operators and assemblers; OR = 2.78; 95% CI 1.31 to 5.93 and 2.72; 95% CI 1.56 to 4.89, respectively, after adjustment for age and socioeconomic status). Though the adjusted odds ratio estimates were significantly high for the rest of the occupational categories (2nd—professionals, 3rd—technicians and associate professionals, and 7th—craft and related trades workers). Conclusions: The association between low job control and first myocardial infarction risk was significant for all occupational categories of Kaunas men.

Chronic noise exposure is associated with adverse pathophysiological effects, which may contribute to the progression of hypertension. However, evidence supporting its effect on women is still inconsistent. The aim of the study was to examine the hypertension risk related to road traffic noise in residential settings in an urban community amongst reproductive-aged women. Cross-sectional study data including 3,121 pregnant women, 20-45 years old, and a geographic information system (GIS) to assess the average road noise (LAeq 24 hr) for every subject at the current residential address were used. Effects on physician-diagnosed hypertension were estimated by logistic regression with adjustments for age, social status, marital status, education, alcohol consumption, ethnic group, parity, body mass index, chronic disease, and exposure duration. The prevalence of hypertension amongst women aged 20-45 years in the lowest exposure category was 13.1% in comparison to 13.6% and 18.1% amongst those exposed to the medium and the highest exposure category, respectively. After making adjustments for the selected variables, no exposure effects [Odds ratio (OR) ≈ 1.0] were noted in the medium exposure category [51-60 dB(A)]. However, a slight increase was noted in the highest exposure category [≥61 dB(A)), OR 1.36; 95% CI 0.86-2.15]. The effect was more pronounced amongst women aged 30-45 years and a positive exposure-response relation was indicated for hypertension: An effect was seen at noise levels 51-60 dB(A) (OR = 1.03; 95% CI 0.72-1.49) and at >61 dB(A) (OR = 1.94, 95% CI 1.01-3.72). The present study shows some evidence for an association between the residential road traffic noise and hypertension amongst reproductive-aged women, and an exposure-response relationship.

Background: Many pregnancy and birth cohort studies investigate the health effects of early-life environmental contaminant exposure. An overview of existing studies and their data is needed to improve collaboration, harmonization, and future project planning. Objectives: OUT goal was to create a comprehensive overview of European birth cohorts with environmental exposure data. Methods: Birth cohort studies were included if they a) collected data on at least one environmental exposure, b) started enrollment during pregnancy or at birth, c) included at least one follow-up point after birth, d) included at least 200 mother-child pairs, and e) were based in a European country. A questionnaire collected information on basic protocol details and exposure and health outcome assessments, including specific contaminants, methods and samples, timing, and number of subjects. A full inventory can be searched on www.birthcohortsenrieco.net. Results: Questionnaires were completed by 37 cohort studies of > 350,000 mother—child pairs in 19 European countries. Only three cohorts did not participate. All cohorts collected biological specimens of children or parents. Many cohorts collected information on passive smoking (n = 36), maternal occupation (n = 33), outdoor air pollution (n = 27), and allergens/biological organisms (n = 27). Fewer cohorts (n = 12-19) collected information on water contamination, ionizing or nonionizing radiation exposures, noise, metals, persistent organic pollutants, or other pollutants. All cohorts have information on birth outcomes; nearly all on asthma, allergies, childhood growth and obesity; and 26 collected information on child neurodevelopment. Conclusion: Combining forces in this field will yield more efficient and conclusive studies and ultimately improve causal inference. This impressive resource of existing birth cohort data could form the basis for longer-term and worldwide coordination of research on environment and child health.

Background/objective There is limited knowledge on how diet affects the epigenome of children. Ultra-processed food (UPF) consumption is emerging as an important factor impacting health, but mechanisms need to be uncovered. We therefore aimed to assess the association between UPF consumption and DNA methylation in children. Methods We conducted a meta-analysis of epigenome-wide association studies (EWAS) from a total of 3152 children aged 5–11 years from four European studies (HELIX, Generation XXI, ALSPAC, and Generation R). UPF consumption was defined applying the Nova food classification system (group 4), and DNA methylation was measured in blood with Illumina Infinium Methylation arrays. Associations were estimated within each cohort using robust linear regression models, adjusting for relevant covariates, followed by a meta-analysis of the resulting EWAS estimates. Results Although no CpG was significant at FDR level, we found suggestive associations ( p -value < 10 –5 ) between UPF consumption and methylation at seven CpG sites. Three of them, cg00339913 (PHYHIP), cg03041696 (intergenic), and cg03999434 (intergenic), were negatively associated, whereas the other four, cg14665028 (NHEJ1), cg18968409 (intergenic), cg24730307 (intergenic), and cg09709951 (ATF7), were positively associated with UPF intake. These CpGs have been previously associated with health outcomes such as carcinomas, and the related genes are mainly involved in pathways related to thyroid hormones and liver function. Conclusion We only found suggestive changes in methylation at 7 CpGs associated with UPF intake in a large EWAS among children: although this shows a potential impact of UPF intake on DNAm, this might not be a key mechanism underlying the health effects of UPFs in children. There is a need for more detailed dietary assessment in children studies and of intervention studies to assess potential epigenetic changes linked to a reduction in UPF in the diet. Graphical abstract

A three-year study was conducted on the occurrence of disinfection by-products (DBPs)—trihalomethanes (THMs), haloacetic acids (HAAs), and haloacetonitriles—in drinking water of regions of Europe where epidemiology studies were being carried out. Thirteen systems in six countries (i.e., Italy, France, Greece, Lithuania, Spain, United Kingdom) were sampled. Typically chlorinated DBPs dominated. However, in most of Catalonia (Spain) and in Heraklion (Greece), brominated DBPs dominated. The degree of bromine incorporation into the DBP classes was in general similar among them. This is important, as brominated DBPs are a greater health concern. In parts of Catalonia, the reported levels of tribromoacetic acid were higher than in other parts of the world. In some regions, the levels of HAAs tended to be peaked in concentration in a different time period than when the levels of THMs peaked. In most epidemiology studies, THMs are used as a surrogate for other halogenated DBPs. This study provides exposure assessment information for epidemiology studies.

BackgroundWomen of reproductive age can be exposed to endocrine-disrupting chemicals (EDCs) at work and exposure to EDCs in pregnancy may affect fetal growth.ObjectivesWe assessed whether maternal occupational exposure to EDCs during pregnancy as classified by application of a job exposure matrix was associated with birth weight, term low birth weight (LBW), length of gestation, and preterm delivery.MethodsUsing individual participant data from 133,957 mother-child pairs in 13 European cohorts spanning births from 1994 to 2011, we linked maternal job titles with exposure to 10 EDC groups as assessed through a job exposure matrix. For each group, we combined the two levels of exposure categories (possible and probable) and compared birth outcomes with the unexposed group (exposure unlikely). We performed meta-analyses of cohort-specific estimates.ResultsEleven percent of pregnant women were classified as exposed to EDCs at work during pregnancy based on job title. Classification of exposure to one or more EDC group was associated with an increased risk of term LBW (OR 1.25, 95% CI: 1.04, 1.49), as were most specific EDC groups; this association was consistent across cohorts. Further, the risk increased with increasing number of EDC groups (OR 2.11 95% CI: 1.10, 4.06 for exposure to 4 or more EDC groups). There were few associations (p < 0.05) with the other outcomes; women holding job titles classified as exposed to bisphenol A or brominated flame retardants were at higher risk for longer length of gestation.ConclusionResults from our large population-based birth cohort design indicate that employment during pregnancy in occupations classified as possibly or probably exposed to EDCs was associated with an increased risk of term LBW.

Aims: To investigate the risk of a first time myocardial infarction (MI) among different occupational categories in 25–64 year old men in Kaunas, Lithuania, a country in a transition market economy. Methods: Case-control study among men aged 25–64 who were residents in Kaunas between 1997 and 2000. First time, non-fatal MI cases (n = 448) were identified from the MI hospital register (International Classification of Diseases, 10th revision, code I21). Controls (n = 1777) were selected and matched on age, gender, and city district of residence. Information was obtained on occupation, smoking, hypertension, psychosocial, and behavioural factors. The International Standard Classification of Occupations (ISCO) was used to code for occupational categories. The relation between MI and occupational categories was evaluated by logistic regression analysis, adjusting for a number of selected risk factors. Results: Legislators, senior officials, and managers (1st ISCO category) had a twofold increased risk for MI compared to craft and related trades workers (7th ISCO category) after adjustment for age, district, smoking, hypertension, obesity, stress, education, and employment duration. An increased risk for professionals (2nd ISCO category) and plant and machine operators and assemblers (8th ISCO category) was also observed. Employment duration in the last occupation for 20 years and more almost doubled the risk of MI in the whole population. We also found an increased risk for other traditional IHD risk factors such as smoking and arterial hypertension. Conclusions: Differences in first time MI risk among occupational categories were found. Legislators, senior officials, and managers (1st ISCO category), professionals (2nd ISCO category), and plant and machine operators and assemblers (8th ISCO category) were at an increased risk. Differences in psychosocial factors in transition market economy countries may contribute to observed results.

BackgroundWomen of reproductive age can be exposed to endocrine-disrupting chemicals (EDCs) at work and exposure to EDCs in pregnancy may affect fetal growth.ObjectivesWe assessed whether maternal occupational exposure to EDCs during pregnancy as classified by application of a job exposure matrix was associated with birth weight, term low birth weight (LBW), length of gestation, and preterm delivery.MethodsUsing individual participant data from 133,957 mother-child pairs in 13 European cohorts spanning births from 1994 to 2011, we linked maternal job titles with exposure to 10 EDC groups as assessed through a job exposure matrix. For each group, we combined the two levels of exposure categories (possible and probable) and compared birth outcomes with the unexposed group (exposure unlikely). We performed meta-analyses of cohort-specific estimates.ResultsEleven percent of pregnant women were classified as exposed to EDCs at work during pregnancy based on job title. Classification of exposure to one or more EDC group was associated with an increased risk of term LBW (OR 1.25, 95% CI: 1.04, 1.49), as were most specific EDC groups; this association was consistent across cohorts. Further, the risk increased with increasing number of EDC groups (OR 2.11 95% CI: 1.10, 4.06 for exposure to 4 or more EDC groups). There were few associations (p < 0.05) with the other outcomes; women holding job titles classified as exposed to bisphenol A or brominated flame retardants were at higher risk for longer length of gestation.ConclusionResults from our large population-based birth cohort design indicate that employment during pregnancy in occupations classified as possibly or probably exposed to EDCs was associated with an increased risk of term LBW.

Introduction Genetic susceptibility to tobacco smoke might modify the effect of smoking on pregnancy outcomes. 1 2 Although separate GSTM1 and GSTT1 gene deletions are well-studied functional variants, the synergistic effects of these two genes on the infant birth weight in smoking women is not known.