Environmental Exposures, Genetic Susceptibility and Preterm Birth

Preterm births cause a large public-health burden because of its high prevalence, leading cause of neonatal morbidity and mortality, and environmental hazards is considered to be a potential risk factors (Adams et al., 2000; Bloom et al., 2001; Tucker & McGuire, 2004; Colvin et al. 2004; Fraser et al. 2004; Murphy et al. 2004). The frequency of preterm births is about 12–13% in the USA and 5–9% in many other developed countries; however, the rate of preterm birth has increased in many locations (Goldenberg et al., 2008). Thus, to elicit of risk factors that could predict high risk of preterm birth represents a challenge to practitioners and researchers. The increasing rate of preterm birth in recent decades, despite improvements in health care, creates an impetus to better understand and prevent this disorder. The identification of women at increased risk of preterm delivery is an important challenge. Preterm birth likely depends on a number of interacting factors, including genetic, epigenetic, and environmental risk factors (Windham et al., 2000; Plunkett & Muglia, 2008). The epidemiological data suggested that both genetic factors and socioenvironmental factors may influence preterm birth (Wang et al., 2000; Nukui et al., 2004; Lewis et al., 2006; Suh et al., 2008)Aplinkotyros katedraVytauto Didžiojo universiteta

Maternal Smoking, GSTM1 and GSTT1 Polymorphism and Susceptibility to Adverse Pregnancy Outcomes

The objective of the study was to investigate the association between maternal smoking, GSTM1, GSTT1 polymorphism, low birth weight (LBW, < 2,500 g) and intra-uterine growth restriction (IUGR, < 2,500 g and gestation ≥ 37 weeks) risk. Within a prospective cohort study in Kaunas (Lithuania), a nested case-control study on LBW and IUGR occurrence among 646 women with genotyping of GSTT1 and GSTM1 polymorphisms who delivered live singletons was conducted. Multivariate logistic regression analysis was used to study the association of maternal smoking and polymorphism in two genes metabolizing xenobiotics. Without consideration of genotype, light-smoking (mean 4.8 cigarettes/day) during pregnancy was associated with a small increase in LBW risk, adjusted OR 1.21; 95% CI 0.44 – 3.31. The corresponding odds for IUGR risk was 1.57; 95% CI 0.45 – 5.55. The findings suggested the greater LBW risk among light-smoking mothers with the GSTM1-null genotype (OR 1.91; 95% CI 0.43 – 8.47) compared to those with GSTM1-present genotype (OR 1.11; 95% CI 0.26 – 4.47). When both GSTM1 and GSTT1 genotypes were considered, the synergistic effect was found among smoking mothers: GSTT1-present and GSTM1-null genotype OR for LBW was 3.31; 95% CI 0.60–18.4 and that for IUGR was 2.47; 95% CI 0.31 – 13.1. However there was no statistically significant interaction between maternal smoking, GSTT1- present and GSTM1-null genotypes for LBW (OR 1.45; 95% CI 0.22 – 10.1, p = 0.66) and for IUGR (OR 1.10; 95% CI 0.10 – 12.6, p = 0.93). The results of this study suggested that smoking, even at a low-level, ought to be considered a potential risk factor for adverse birth outcomes and that genetic polymorphism may contribute to individual variation in tobacco smoke response

Positive health effects of the natural outdoor environment in typical populations in different regions in Europe (PHENOTYPE): a study programme protocol

Introduction Growing evidence suggests that close contact with nature brings benefits to human health and well-being, but the proposed mechanisms are still not well understood and the associations with health remain uncertain. The Positive Health Effects of the Natural Outdoor environment in Typical Populations in different regions in Europe (PHENOTYPE) project investigates the interconnections between natural outdoor environments and better human health and well-being. Aims and methods The PHENOTYPE project explores the proposed underlying mechanisms at work (stress reduction/restorative function, physical activity, social interaction, exposure to environmental hazards) and examines the associations with health outcomes for different population groups. It implements conventional and new innovative high-tech methods to characterise the natural environment in terms of quality and quantity. Preventive as well as therapeutic effects of contact with the natural environment are being covered. PHENOTYPE further addresses implications for land-use planning and green space management. The main innovative part of the study is the evaluation of possible short-term and long-term associations of green space and health and the possible underlying mechanisms in four different countries (each with quite a different type of green space and a different use), using the same methodology, in one research programme. This type of holistic approach has not been undertaken before. Furthermore there are technological innovations such as the use of remote sensing and smartphones in the assessment of green space. Conclusions The project will produce a more robust evidence base on links between exposure to natural outdoor environment and human health and well-being, in addition to a better integration of human health needs into land-use planning and green space management in rural as well as urban areas

Occupational Exposure to Endocrine-Disrupting Chemicals and Birth Weight and Length of Gestation: A European Meta-Analysis

BACKGROUND: Women of reproductive age can be exposed to endocrine-disrupting chemicals (EDCs) at work and exposure to EDCs in pregnancy may affect fetal growth. OBJECTIVES: We 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. METHODS: Using 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. RESULTS: Eleven 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. CONCLUSION: Results 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

Individual exposures to drinking water trihalomethanes, low birth weight and small for gestational age risk: a prospective Kaunas cohort study

<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Methods</p> <p>We conducted a cohort study of 4,161 pregnant women in Kaunas (Lithuania), using individual information on drinking water, ingestion, showering and bathing, and uptake factors of THMs in blood, to estimate an internal dose of THM. We used regression analysis to evaluate the relationship between internal THM dose and birth outcomes, adjusting for family status, education, smoking, alcohol consumption, body mass index, blood pressure, ethnic group, previous preterm, infant gender, and birth year.</p> <p>Results</p> <p>The estimated internal dose of THMs ranged from 0.0025 to 2.40 mg/d. We found dose-response relationships for the entire pregnancy and trimester-specific THM and chloroform internal dose and risk for LBW and a reduction in BW. The adjusted odds ratio for third tertile vs. first tertile chloroform internal dose of entire pregnancy was 2.17, 95% CI 1.19-3.98 for LBW; the OR per every 0.1 μg/d increase in chloroform internal dose was 1.10, 95% CI 1.01-1.19. Chloroform internal dose was associated with a slightly increased risk of SGA (OR 1.19, 95% CI 0.87-1.63 and OR 1.22, 95% CI 0.89-1.68, respectively, for second and third tertile of third trimester); the risk increased by 4% per every 0.1 μg/d increase in chloroform internal dose (OR 1.04, 95% CI 1.00-1.09).</p> <p>Conclusions</p> <p>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.</p

Maternal occupation during pregnancy, birth weight, and length of gestation: Combined analysis of 13 European birth cohorts

Objectives We assessed whether maternal employment during pregnancy – overall and in selected occupational sectors – is associated with birth weight, small for gestational age (SGA), term low birth weight (LBW), length of gestation, and preterm delivery in a population-based birth cohort design. Methods We used data from >200 000 mother-child pairs enrolled in 13 European birth cohorts and compared employed versus non-employed women. Among employees, we defined groups of occupations representing the main sectors of employment for women where potential reproductive hazards are considered to be present. The comparison group comprised all other employed women not included in the occupational sector being assessed. We performed meta-analyses of cohort-specific estimates and explored heterogeneity. Results Employees had a lower risk of preterm delivery than non-employees [adjusted odds ratio (ORadj) 0.86, 95% confidence interval (95% CI) 0.81–0.91]. Working in most of the occupational sectors studied was not associated with adverse birth outcomes. Being employed as a nurse was associated with lower risk SGA infants (ORadj 0.91, 95% CI 0.84–0.99) whereas food industry workers had an increased risk of preterm delivery (ORadj 1.50, 95% CI 1.12–2.02). There was little evidence for heterogeneity between cohorts. Conclusions This study suggests that, overall, employment during pregnancy is associated with a reduction in the risk of preterm birth and that work in certain occupations may affect pregnancy outcomes. This exploratory study provides an important platform on which to base further prospective studies focused on the potential consequences of maternal occupational exposures during pregnancy on child development

Exposure to drinking water trihalomethanes and their association with low birth weight and small for gestational age in genetically susceptible women

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

Low level maternal smoking and infant birthweight reduction: genetic contributions of <it>GSTT1</it> and <it>GSTM1</it> polymorphisms

<p>Abstract</p> <p>Background</p> <p>Genetic susceptibility to tobacco smoke might modify the effect of smoking on pregnancy outcomes.</p> <p>Methods</p> <p>We conducted a case–control study of 543 women who delivered singleton live births in Kaunas (Lithuania), examining the association between low-level tobacco smoke exposure (mean: 4.8 cigarettes/day) during pregnancy, <it>GSTT1</it> and <it>GSTM1</it> polymorphisms and birthweight of the infant. Multiple linear-regression analysis was performed adjusting for gestational age, maternal education, family status, body mass index, blood pressure, and parity. Subsequently, we tested for the interaction effect of maternal smoking, <it>GSTT1</it> and <it>GSTM1</it> genes polymorphisms with birthweight by adding all the product terms in the regression models.</p> <p>Results</p> <p>The findings suggested a birthweight reduction among light-smoking with the <it>GSTT1–null</it> genotype (−162.9 g, <it>P</it> = 0.041) and those with the <it>GSTM1–null</it> genotype (−118.7 g, <it>P</it> = 0.069). When a combination of these genotypes was considered, birthweight was significantly lower for infants of smoking women the carriers of the double-null genotypes (−311.2 g, <it>P</it> = 0.008). The interaction effect of maternal smoking, <it>GSTM1</it> and <it>GSTT1</it> genotypes was marginally significant on birthweight (−234.5 g, <it>P</it> = 0.078). Among non-smokers, genotype did not independently confer an adverse effect on infant birthweight.</p> <p>Conclusions</p> <p>The study shows the <it>GSTT1–null</it> genotype, either presents only one or both with <it>GSTM1–null</it> genotype in a single subject, have a modifying effect on birthweight among smoking women even though their smoking is low level. Our data also indicate that identification of the group of susceptible subjects should be based on both environmental exposure and gene polymorphism. Findings of this study add additional evidence on the interplay among two key GST genes and maternal smoking on birth weight of newborns.</p