Early Life Environmental Exposures Research Articles

A maternal high-fat diet during pregnancy and lactation induced depression-like behavior in offspring and myelin-related changes in the rat prefrontal cortex.

In accordance with the developmental origins of health and disease, early-life environmental exposures, such as maternal diet, can enhance the probability and gravity of health concerns in their offspring in the future. Over the past few years, compelling evidence has emerged suggesting that prenatal exposure to a maternal high-fat diet (HFD) could trigger neuropsychiatric disorders in the offspring, such as depression. The majority of brain development takes place before birth and during lactation. Nevertheless, our understanding of the impact of HFD on myelination in the offspring's brain during both gestation and lactation remains limited. In the present study, we investigated the effects of maternal HFD (60% energy from fat) on depressive-like and myelin-related changes in adolescent and adult rat offspring. Maternal HFD increased immobility time during the forced swimming test in both adolescent and adult offspring. Correspondingly, the depressive-like phenotype in offspring correlated with dysregulation of several genes and proteins in the prefrontal cortex, especially of myelin-oligodendrocyte glycoprotein (MOG), myelin and lymphocyte protein (MAL), 2',3'-cyclic-nucleotide 3'-phosphodiesterase (CNPase), kallikrein 6, and transferrin in male offspring, as well as of MOG and kallikrein 6 in female offspring, which persist even into adulthood. Maternal HFD also induced long-lasting adaptations manifested by the reduction of immature and mature oligodendrocytes in the prefrontal cortex in adult offspring. In summary, maternal HFD-induced changes in myelin-related genes are correlated with depressive-like behavior in adolescent offspring, which persists even to adulthood.

EARLY-LIFE EXPOSURE TO THE GREAT DEPRESSION AND THE PACE OF BIOLOGICAL AGING

Abstract The Developmental Origins of Health and Disease hypothesis proposes that insults to early-life development can result in increased risk for aging-related disease later in life. There is growing interest within gerontology in the potential role such early life exposures play in shaping processes of aging. However, causal research linking early-life exposures to processes of aging in later life is rare. Moreover, there are difficulties in distinguishing the impacts of exposures occurring at different stages of early life development. In this study, we build on a quasi-natural experiment design we developed that leverages state-year variation in economic shocks during the Great Depression to examine the causal effect of environmental exposure in early life on aging outcomes in the US Health and Retirement Study (HRS) (2022 PNAS). Our design allows us to distinguish effects of exposure during different periods of early life development – in-utero, in the first year of life, and later in childhood. In the present study, we apply this framework specifically to study impacts of early-life exposure to the Great Depression on pace of aging in later life. We measure pace of aging using repeated-measures longitudinal functional test and biomarker data and, in parallel, a single-timepoint blood-DNA methylation assessment of the DunedinPACE epigenetic clock through the 2016 HRS assessment wave. We further examine whether impacts of the Great Depression on the pace of aging translate into differences in morbidity and mortality through 2020.

Congener Variation of Genetic Dependent-Developmental Toxicology in Two Emerging Classes of Dioxin-like Compounds.

Emerging classes of dioxin-like compounds (DLCs) like hydroxylated/methoxylated polybrominated diphenyl ethers (HO-/MeO-PBDEs) and polychlorinated diphenyl sulfides (PCDPSs) could lead to diverse adverse outcomes in humans and wildlife, yet knowledge gaps exist in their molecular mechanisms associated with different structures following early life environmental exposure. This study integrated a genetic knockout technique and concentration-dependent reduced zebrafish transcriptome approach (CRZT) to unravel the toxicological pathways underpinning developmental toxicity of four HO-/MeO-PBDEs and five PCDPSs at environmentally relevant doses. Generally, the dependence of aryl hydrocarbon receptor (AhR) on the embryotoxicity and transcriptomic potencies induced by the HO-PBDEs and PCDPSs varied across different congeners. The knockout of the ahr2 gene led to 1.02- to 76.48-fold decreases of DLC-induced embryotoxicities and reduced the transcriptome-based potencies ranging from 1.38 to 2124.74 folds in the CRZT test. The fold changes denoting AhR-mediated potentials significantly increased with the increasing chlorination degrees of MeO-PBDEs and PCDPSs (p < 0.05). Moreover, ahr2 knockout primarily affected the DLC-induced early molecular responses relevant to DNA damage, enzyme activation, and organ development. Our integrated approach revealed the differential role of AhR in mediating the developmental toxicity of emerging DLCs possessing varied structures at environmentally relevant doses.

From preschool wheezing to asthma: Immunological determinants.

Asthma represents a chronic respiratory disease affecting millions of children worldwide. The transition from preschool wheezing to school-age asthma involves a multifaceted interplay of various factors, including immunological aspects in early childhood. These factors include complex cellular interactions among different immune cell subsets, induction of pro-inflammatory mediators and the molecular impact of environmental factors like allergens or viral infections on the developing immune system. Furthermore, the activation of specific genes and signalling pathways during this early phase plays a pivotal role in the manifestation of symptoms and subsequent development of asthma. Early identification of the propensity or risk for asthma development, for example by allergen sensitisation and viral infections during this critical period, is crucial for understanding the transition from wheeze to asthma. Favourable immune regulation during a critical 'window of opportunity' in early childhood can induce persistent changes in immune cell behaviour. In this context, trained immunity, including memory function of innate immune cells, has significant implications for understanding immune responses, potentially shaping long-term immunological outcomes based on early-life environmental exposures. Exploration of these underlying immune mechanisms that drive disease progression will provide valuable insights to understand childhood asthma development. This will be instrumental to develop preventive strategies at different stages of disease development for (i) inhibiting progression from wheeze to asthma or (ii) reducing disease severity and (iii) uncovering novel therapeutic strategies and contributing to more tailored and effective treatments for childhood asthma. In the long term, this shall empower healthcare professionals to develop evidence-based interventions that reduce the burden of asthma for children, families and society overall.

Maternal nutritional factors and environmental exposure in early life and childhood atopic dermatitis

Atopic dermatitis(AD)is a chronic, recurrent, inflammatory skin disease in children. The disease is characterized by dryness, chronic eczema-like lesions and obvious itching, seriously affecting the quality of life of children and their families. The pathogenesis of AD is not yet to be clear, and it might be the interaction of genetic susceptibility and environmental exposure to induce skin barrier impairment and immune system dysfunction. In recent years, the role of maternal factors or intrauterine environment exposure on childhood allergic diseases has been attracted attention, and the hypothesis that allergic diseases originate from the fetal period has been postulated. Maternal exposures called "early life exposure", such as nutritional factors during pregnancy (folate, vitamin D, vitamin E and polyunsaturated fatty acid) and tobacco exposure, home environmental exposure may be related with childhood atopic dermatitis. This article would focus on the recent research about maternal nutritional factors and family environmental exposure during pregnancy on offspring's atopic dermatitis.

Early-life air pollution and green space exposures as determinants of stunting among children under age five in Sub-Saharan Africa.

Childhood malnutrition is a major public health issue in Sub-Saharan Africa (SSA) and 61.4 million children under the age of five years in the region are stunted. Although insight from existing studies suggests plausible pathways between ambient air pollution exposure and stunting, there are limited studies on the effect of different ambient air pollutants on stunting among children. Explore the effect of early-life environmental exposures on stunting among children under the age of five years. In this study, we used pooled health and population data from 33 countries in SSA between 2006 and 2019 and environmental data from the Atmospheric Composition Analysis Group and NASA's GIOVANNI platform. We estimated the association between early-life environmental exposures and stunting in three exposure periods - in-utero (during pregnancy), post-utero (after pregnancy to current age) and cumulative (from pregnancy to current age), using Bayesian hierarchical modelling. We also visualise the likelihood of stunting among children based on their region of residence using Bayesian hierarchical modelling. The findings show that 33.6% of sampled children were stunted. In-utero PM2.5 was associated with a higher likelihood of stunting (OR = 1.038, CrI = 1.002-1.075). Early-life exposures to nitrogen dioxide and sulphate were robustly associated with stunting among children. The findings also show spatial variation in a high and low likelihood of stunting based on a region of residence. This study explores the effect of early-life environmental exposures on child growth or stunting among sub-Saharan African children. The study focuses on three exposure windows - pregnancy, after birth and cumulative exposure during pregnancy and after birth. The study also employs spatial analysis to assess the spatial burden of stunted growth in relation to environmental exposures and socioeconomic factors. The findings suggest major air pollutants are associated with stunted growth among children in sub-Saharan Africa.

Opportunities for understanding the COVID-19 pandemic and child health in the United States: the Environmental influences on Child Health Outcomes (ECHO) program.

Ongoing pediatric cohort studies offer opportunities to investigate the impact of the COVID-19 pandemic on children's health. With well-characterized data from tens of thousands of US children, the Environmental influences on Child Health Outcomes (ECHO) Program offers such an opportunity. ECHO enrolled children and their caregivers from community- and clinic-based pediatric cohort studies. Extant data from each of the cohorts were pooled and harmonized. In 2019, cohorts began collecting data under a common protocol, and data collection is ongoing with a focus on early life environmental exposures and five child health domains: birth outcomes, neurodevelopment, obesity, respiratory, and positive health. In April of 2020, ECHO began collecting a questionnaire designed to assess COVID-19 infection and the pandemic's impact on families. We describe and summarize the characteristics of children who participated in the ECHO Program during the COVID-19 pandemic and novel opportunities for scientific advancement. This sample (n = 13,725) was diverse by child age (31% early childhood, 41% middle childhood, and 16% adolescence up to age 21), sex (49% female), race (64% White, 15% Black, 3% Asian, 2% American Indian or Alaska Native, <1% Native Hawaiian or Pacific Islander, 10% Multiple race and 2% Other race), Hispanic ethnicity (22% Hispanic), and were similarly distributed across the four United States Census regions and Puerto Rico. ECHO data collected during the pandemic can be used to conduct solution-oriented research to inform the development of programs and policies to support child health during the pandemic and in the post-pandemic era.

Effect of prenatal exposure to organophosphates and pyrethroid pesticides on neonatal anthropometric measures and gestational age

Several studies have examined the association between prenatal exposure to organophosphate and pyrethroid pesticides and their impact on foetal growth and newborn anthropometry; however, the available evidence is limited and inconclusive. This study examined whether prenatal organophosphate and pyrethroid pesticide exposure was associated with anthropometric measures at birth (weight, length, head circumference), ponderal index, gestational age, and prematurity in 537 mother-child pairs. These were randomly selected from the 800 pairs participating in the prospective birth cohort GENEIDA (Genetics, early life environmental exposures and infant development in Andalusia). Six non-specific organophosphate metabolites (dialkylphosphates, DAPs), one metabolite relatively specific to chlorpyrifos (3,5,6-trichloro-2-pyridinol, TCPy) and a common metabolite to several pyrethroids (3-phenoxybenzoic acid, 3-PBA) were measured in maternal urine from the 1st and 3rd pregnancy trimesters. Information on anthropometric measures at birth, gestational age and prematurity was retrieved from medical records. The sum on a molar basis of DAPs with methyl (ƩDMs) and ethyl (ƩDEs) moieties and the sum of the 6 DAPs metabolites (ƩDAPs) was calculated for both trimesters of pregnancy. High urinary levels of dimethyl phosphate (DMP) during the 3rd trimester were associated with a decrease in birth weight (β = −0.24; 95% CI: 0.41; −0.06) and birth length (β = −0.20; 95% CI: 0.41; 0.02). Likewise, ΣDMs during 3rd trimester were near-significantly associated with decreased birth weight (β = −0.18; 95% CI: 0.37; 0.01). In turn, increased urinary TCPy during 1st trimester was associated with a decreased head circumference (β = −0.31; 95% CI: 0.57; −0.06). Finally, an increase in 3-PBA in the 1st trimester was associated with a decreased gestational age (β = −0.36 95% CI: 0.65–0.08), whereas increased 3-PBA at 1st and 3rd trimester was associated with prematurity. These results indicate that prenatal exposure to organophosphate and pyrethroid insecticides could affect normal foetal growth, shorten gestational age and alter anthropometric measures at birth.

Developmental origins of diabetes mellitus: Environmental epigenomics and emerging patterns.

Mounting epidemiological evidence indicates that environmental exposures in early life have roles in diabetes susceptibility in later life. Additionally, environmentally induced diabetic susceptibility could be transmitted to subsequent generations. Epigenetic modifications provide a potential association with the environmental factors and altered gene expression that might cause disease phenotypes. Here, we bring the increasing evidence that environmental exposures early in development are linked to diabetes through epigenetic modifications. This review first summarizes the epigenetic targets, including metastable epialleles and imprinting genes, by which the environmental factors can modify the epigenome. Then we review the epigenetics changes in response to environmental challenge during critical developmental windows, gametogenesis, embryogenesis, and fetal and postnatal period, with the specific example of diabetic susceptibility. Although the mechanisms are still largely unknown, especially in humans, the new research methods are now gradually available, and the animal models can provide more in-depth study of mechanisms. These have implications for investigating the link of the phenomena to human diabetes, providing a new perspective on environmentally triggered diabetes risk.

The molecular mechanisms in prenatal drug exposure-induced fetal programmed adult cardiovascular disease.

The "developmental origins of health and disease" (DOHaD) hypothesis posits that early-life environmental exposures have a lasting impact on individual's health and permanently shape growth, structure, and metabolism. This reprogramming, which results from fetal stress, is believed to contribute to the development of adulthood cardiovascular diseases such as hypertension, coronary artery disease, heart failure, and increased susceptibility to ischemic injuries. Recent studies have shown that prenatal exposure to drugs, such as glucocorticoids, antibiotics, antidepressants, antiepileptics, and other toxins, increases the risk of adult-onset cardiovascular diseases. In addition, observational and animal experimental studies have demonstrated the association between prenatal drug exposure and the programming of cardiovascular disease in the offspring. The molecular mechanisms underlying these effects are still being explored but are thought to involve metabolism dysregulation. This review summarizes the current evidence on the relationship between prenatal drug exposure and the risk of adult cardiovascular disorders. Additionally, we present the latest insights into the molecular mechanisms that lead to programmed cardiovascular phenotypes after prenatal drug exposure.

Impact of Early-Life Factors on Risk for Schizophrenia and Bipolar Disorder.

Schizophrenia (SCZ) and bipolar disorder (BD) have shared genetic risk and clinical symptoms, yet the extent to which environmental risk factors are shared is not well known. We aimed to examine the associations of early-life environmental exposures with the risk of SCZ and BD. We conducted a Swedish register-based nested case-control study using 4184 SCZ and 18 681 BD cases diagnosed 1988-2013, individually matched to 5 population-based controls by birth year, sex and birthplace. Conditional logistic regression was used to evaluate the risk of SCZ and BD by seasonality, severe prenatal infections, and perinatal factors. Seasonality had similar patterns of risk for both disorders: Higher risk for births November-December; lower risk April-June. Experiencing any perinatal factor was associated with a significantly higher risk of SCZ (incidence rate ratio [IRR] 1.19, 95%CI 1.11-1.63) and to a lesser extent BD (IRR 1.08, 95%CI 1.05-1.12). Prenatal infections were only associated with a greater risk of SCZ (IRR 1.30, 95%CI 1.04-1.63). In the mutually adjusted model, only perinatal factors were associated with outcomes. Several perinatal factors were associated with both disorders, but estimates were significantly higher for SCZ for low birth weight, low APGAR, and high parity. Congenital malformations were only associated with risk of SCZ, and jaundice with BD. Adverse perinatal factors and winter birth were the risk factors for both disorders, while severe prenatal infections were only risk a factor for SCZ. Early-life exposures were associated with a higher risk of both disorders, but may play a larger role in the development of SCZ than BD.

Associations of maternal gestational urinary environmental phenols concentrations with bone mineral density among 12-year-old children in the HOME Study.

Early life environmental exposures may affect bone mass accrual in childhood, but only one study has assessed the role of environmental phenols on child bone health. We used data from 223 mother-child dyads enrolled in the Health Outcomes and Measures of the Environment (HOME) Study (Cincinnati, OH; 2003-2006). We quantified benzophenone-3, bisphenol A (BPA), 2,5-dichlorophenol, and triclosan in maternal urine collected at 16- and 26-weeks gestation and calculated the average of creatinine-adjusted concentrations. We performed dual x-ray absorptiometry at age 12 years and calculated Z-scores for whole body (less head), total hip, femoral neck, and 1/3rd distal radius bone mineral content (BMC) and areal bone mineral density (aBMD) as well as ultra-distal radius aBMD and spine BMC and bone mineral apparent density (BMAD). We estimated covariate-adjusted associations per doubling of maternal urinary environmental phenol concentrations in linear regression models. We also examined effect measure modification by child's sex and estimated associations of the environmental phenol mixture with BMC and aBMD using quantile g-computation. We observed generally null associations for all analytes and bone measures. Yet, in adjusted models, higher urinary 2,5-dichlorophenol concentrations were associated with higher 1/3rd distal radius BMC (β: 0.09; 95% CI: 0.02, 0.17) and aBMD (β: 0.09; 95% CI: 0.02, 0.17) Z-scores in the overall sample. In sex-stratified analyses, the magnitude of the BMC association was positive for females (β: 0.16; 95% CI: 0.06, 0.26) and null for males (β: 0.02; 95% CI: 0.08, 0.13). The environmental phenol mixture was associated with greater 1/3rd distal radius BMC and aBMD Z-scores in both sexes, which was mostly driven by benzophenone-3 in males and 2,5-dichlorophenol in females. In this prospective cohort study, we observed generally null associations for environmental phenols with BMC and aBMD at age 12 years. While there was a positive association of 2,5-dichlorophenol concentrations during fetal development with distal radius BMC and aBMD at age 12 years, future studies utilizing methods capable of differentiating cortical and trabecular bone are needed to elucidate potential mechanisms and implications for bone strength and microarchitecture.

Early-life residential green spaces and traffic exposure in association with young adult body composition: a longitudinal birth cohort study of twins

BackgroundGlobally, the rapid increase of obesity is reaching alarming proportions. A new approach to reduce obesity and its comorbidities involves tackling the built environment. Environmental influences seem to play an important role, but the environmental influences in early life on adult body composition have not been thoroughly investigated. This study seeks to fill the research gap by examining early-life exposure to residential green spaces and traffic exposure in association with body composition among a population of young adult twins.MethodsAs part of the East Flanders Prospective Twin Survey (EFPTS) cohort, this study included 332 twins. Residential addresses of the mothers at time of birth of the twins were geocoded to determine residential green spaces and traffic exposure. To capture body composition, body mass index, waist-to-hip ratio (WHR), waist circumference, skinfold thickness, leptin levels, and fat percentage were measured at adult age. Linear mixed modelling analyses were conducted to investigate early-life environmental exposures in association with body composition, while accounting for potential confounders. In addition, moderator effects of zygosity/chorionicity, sex and socio-economic status were tested.ResultsEach interquartile range (IQR) increase in distance to highway was found associated with an increase of 1.2% in WHR (95%CI 0.2–2.2%). For landcover of green spaces, each IQR increase was associated with 0.8% increase in WHR (95%CI 0.4–1.3%), 1.4% increase in waist circumference (95%CI 0.5–2.2%), and 2.3% increase in body fat (95%CI 0.2–4.4%). Stratified analyses by zygosity/chorionicity type indicated that in monozygotic monochorionic twins, each IQR increase in land cover of green spaces was associated with 1.3% increase in WHR (95%CI 0.5–2.1%). In monozygotic dichorionic twins, each IQR increase in land cover of green spaces was associated with 1.4% increase in waist-circumference (95%CI 0.6–2.2%).ConclusionsThe built environment in which mothers reside during pregnancy might play a role on body composition among young adult twins. Our study revealed that based on zygosity/chorionicity type differential effects of prenatal exposure to green spaces on body composition at adult age might exist.

The Presence of Cotinine at 3 months of Age is Associated with Decreased Microbial Diversity of the Upper Airway

Disruption to the upper airway microbiome is associated with asthma development, as evidenced by studies that show that airway colonization with Moraxella catarrhalis, Hemophilus influenzae, and Streptococcal pneumoniae increases the risk of childhood wheeze. It is suggested that smoke exposure decreases airway microbiome diversity in adults, but little has been described regarding the impact of smoke exposure on the infant microbiome. We hypothesized that early life environmental smoke exposure is associated with decreased bacterial diversity in the infant upper airway microbiome.

Early Life Environmental Exposure to Cadmium, Lead, and Arsenic and Age at Menarche: A Longitudinal Mother-Child Cohort Study in Bangladesh.

Several metals act as endocrine disruptors, but there are few large longitudinal studies about associations with puberty onset. We evaluated whether early life cadmium, lead, and arsenic exposure was associated with timing of menarche. In a mother-child cohort in rural Bangladesh (), the exposure was assessed by concentrations in maternal erythrocytes in early pregnancy and in girls' urine at 5 and 10 years of age using inductively coupled plasma mass spectrometry. The girls were interviewed twice, at average ages 13.3 [standard deviation ] and 13.8 () y, and the date of menarche, if present, was recorded. Associations were assessed using Kaplan-Meier analysis and multivariable-adjusted Cox regression. In total, 77% of the girls () had reached menarche by the second follow-up. The median age of menarche among all girls was 13.0 y (25th-75th percentiles: 12.4-13.7 y). At 10 years of age, median urinary cadmium was (5th-95th percentiles: ), lead (), and arsenic (). Given the same age, girls in the highest quartile of urinary cadmium at 5 and 10 years of age had a lower rate of menarche than girls in the lowest quartile, with an adjusted hazard ratio of (HR) 0.80 (95% CI: 0.62, 1.01) at 5 years of age, and 0.77 (95% CI: 0.60, 0.98) at 10 years of age. This implies that girls in the highest cadmium exposure quartile during childhood had a higher age at menarche. Comparing girls in the highest to the lowest quartile of urinary lead at 10 years of age, the former had a higher rate of menarche [adjusted 1.23 (95% CI: 0.97, 1.56)], implying lower age at menarche, whereas there was no association with urinary lead at 5 years of age. Girls born to mothers in the highest quartile of erythrocyte arsenic during pregnancy were less likely to have attained menarche than girls born to mothers in the lowest quartile [adjusted 0.79 (95% CI: 0.62, 0.99)]. No association was found with girls' urinary arsenic exposure. Long-term childhood cadmium exposure was associated with later menarche, whereas the associations with child lead exposure were inconclusive. Maternal exposure to arsenic, but not cadmium or lead, was associated with later menarche. https://doi.org/10.1289/EHP11121.

The external housing environment of participants in the Avon Longitudinal Study of Parents and Children (ALSPAC): a resource for studies of influences on health.

Background: Early life environmental health exposures related to housing can have a significant impact on an individual's physical and mental health and physical development. Housing exposures can fall into two main areas - a representation of social circumstances and physical conditions. Methods: During pregnancy and post-delivery, self-completion questionnaires concerning the housing environment were administered to the ALSPAC (Avon Longitudinal Study of Parents & Children) study mothers and their partners until the study offspring were aged 18. Data collected included types of housing, housing tenure, numbers of rooms in the home, whether shared or sole use of kitchen and indoor flushing toilet, household moves, Council Tax band, difficulties in affording rent/mortgage and becoming homeless. Here we also describe the historic development of housing in the Bristol and surrounding Avon areas. Results: Data collected included the tenure (e.g., owned/rented) of the home, its size (indexed by the number of rooms), the presence of over-crowding (measured by the number of residents per room), presence of amenities, and frequency of household moves. This information was collected on over 13,000 women during pregnancy >8000 at age 10 and >4000 at 18 years. Council Tax bands were asked at 10 and 18 years. Conclusions: This is the first of two Data Notes on the housing type and housing circumstances of the families enrolled in ALSPAC. The second Data Note will detail their internal housing conditions. The data provides an excellent resource for researchers when considering the influences of housing on physical and mental health and development.

Select Early-Life Environmental Exposures and DNA Methylation in the Placenta.

To summarize recent literature relating early-life environmental exposures on DNA methylation in the placenta, to identify how variation in placental methylation is regulated in an exposure-specific manner, and to encourage additional work in this area. Multiple studies have evaluated associations between prenatal environmental exposures and placental methylation in both gene-specific and epigenome-wide frameworks. Specific exposures lead to unique variability in methylation, and cross-exposure assessments have uncovered certain genes that demonstrate consistency in differential placental methylation. Exposure studies that assess methylation effects in a trimester-specific approach tend to find larger effects during the 1st trimester exposure. Earlier studies have more targeted gene-specific approaches to methylation, while later studies have shifted towards epigenome-wide, array-based approaches. Studies focusing on exposures such as air pollution, maternal smoking, environmental contaminants, and trace metals appear to be more abundant, while studies of socioeconomic adversity and circadian disruption are scarce but demonstrate remarkable effects. Understanding the impacts of early-life environmental exposures on placental methylation is critical to establishing the link between the maternal environment, epigenetic variation, and long-term health. Future studies into this field should incorporate repeated measures of exposure throughout pregnancy, in order to determine the critical windows in which placental methylation is most heavily affected. Additionally, the use of methylation-based scores and sequencing technology could provide important insights into epigenetic gestational age and uncovering more genomic regions where methylation is affected. Studies examining the impact of other exposures on methylation, including pesticides, alcohol, and other chemicals are also warranted.

Allergic disease and sensitization disparity in urban and rural China: A EuroPrevall-INCO study.

Studies in comparison with allergic diseases and sensitization between rural and urban environments in westernized countries might be biased and not adequately reflect countries undergoing rapid transition. A total of 5542 schoolchildren from urban area and 5139 from rural area were recruited for the EuroPrevall-INCO survey. A subsequent case-control sample with 196 children from urban area and 202 from rural area was recruited for a detailed face-to-face questionnaire and assessment of sensitization. Skin prick tests and serum-specific IgE measurements were used to assess sensitizations against food and aeroallergens. Logistic regression analysis was used to determine associations between risk/protective factors, food adverse reactions (FAR), allergic diseases, and sensitizations. Prevalence of self-reported allergic diseases, including asthma (6.6% vs.2.5%), rhinitis (23.2% vs.5.3%), and eczema (34.1% vs.25.9%), was higher in urban than in rural children. Urban children had a significantly higher prevalence of FAR and related allergic diseases, and lower food/inhalation allergen sensitization rate, than those of rural children. In urban children, frequent changing places of residency (odds ratio 2.85, 95% confidence interval: 1.45-5.81) and antibiotic usage (3.54, 1.77-7.32) in early life were risk factors for sensitization, while sensitization and family history of allergy were risk factors for allergic diseases. In rural children, exposure to rural environments in early life was protective against both allergen sensitizations (0.46, 0.21-0.96) and allergic diseases (0.03, 0.002-0.19). We observed a disparity in rates of allergic diseases and allergen sensitization between rural and urban children. In addition to family history, the development of allergic diseases and allergen sensitization were associated with specific urban/rural environmental exposures in early life.

Estimating Causal Effects of Interventions on Early-life Environmental Exposures Using Observational Data.

We discuss how epidemiologic studies have used observational data to estimate the effects of potential interventions on early-life environmental exposures. We summarize the value of posing questions about interventions, how a group of techniques known as "g-methods" can provide advantages for estimating intervention effects, and how investigators have grappled with the strong assumptions required for causal inference. We identified nine studies that estimated health effects of hypothetical interventions on early-life environmental exposures. Of these, six examined air pollution. Interventions evaluated by these studies included setting exposure levels at a specific value, shifting exposure distributions, and limiting exposure levels to less than a threshold value. Only one study linked exposure contrasts to a specific intervention on an exposure source, however. There is growing interest in estimating intervention effects of early-life environmental exposures, in part because intervention effects are directly related to possible public health actions. Future studies can build on existing work by linking research questions to specific hypothetical interventions that could reduce exposure levels. We discuss how framing questions around interventions can help overcome some of the barriers to causal inference and how advances related to machine learning may strengthen studies by sidestepping the overly restrictive assumptions of parametric regression models. By leveraging advancements in causal inference and exposure science, an intervention framework for environmental epidemiology can guide actionable solutions to improve children's environmental health.

074 Investigation of gene-environment interactions in atopic eczema using data from 200,000 European cohort participants

Gene-environment (GxE) interactions are thought to play a role in the pathogenesis of atopic eczema, but specific genes and environmental factors remain to be elucidated. We analysed data from 25 European studies from 7 countries to test for interaction between 24 loci identified by genome-wide association studies and 10 early-life environmental exposures, on atopic eczema as an outcome. Fourteen of the 240 pairwise interactions reached nominal significance (P<0.05) in the discovery analysis (N=25,300), one was nominally significant in replication analysis (N=198,000) and four were nominally significant in the combined meta-analysis of discovery and replication data (N>200,000).