Birth Cohort Consortium Research Articles

The Legacy of Redlining: Increasing Childhood Asthma Disparities through Neighborhood Poverty.

Rationale: Identifying the root causes of racial disparities in childhood asthma is critical for health equity. Objectives: To determine whether the racist policy of redlining in the 1930s led to present-day disparities in childhood asthma by increasing community-level poverty and decreasing neighborhood socioeconomic position (SEP). Methods: We categorized census tracts at the birth address of participants from the Children's Respiratory and Environmental Workgroup birth cohort consortium into categories A, B, C, and D as defined by the Home Owners Loan Corporation, with D being the highest perceived risk. Surrogates of present-day neighborhood-level SEP were determined for each tract, including the percentage of low-income households, the CDC's Social Vulnerability Index, and other tract-level variables. We performed causal mediation analysis, which, under the assumption of no unmeasured confounding, estimates the direct and mediated pathways by which redlining may cause asthma disparities through tract-level mediators adjusting for individual-level covariates. Measurements and Main Results: Of 4,849 children, the cumulative incidence of asthma through age 11 was 26.6%, and 13.2% resided in census tracts with a Home Owners Loan Corporation grade of D. In mediation analyses, residing in Grade-D tracts (adjusted odds ratio = 1.03 [95% confidence interval = 1.01, 1.05]) was significantly associated with childhood asthma, with 79% of this increased risk mediated by percentage of low-income households; results were similar for the Social Vulnerability Index and other tract-level variables. Conclusions: The historical structural racist policy of redlining led to present-day asthma disparities in part through decreased neighborhood SEP. Policies aimed at reversing the effects of structural racism should be considered to create more just, equitable, and healthy communities.

Association between infertility treatment and hypertensive disorders of pregnancy in the Japan Birth Cohort Consortium: a meta-analysis.

Association between infertility treatment and hypertensive disorders of pregnancy in the Japan Birth Cohort Consortium: a meta-analysis.

The Population-Attributable Fractions of Small-for-Gestational-Age Births: Results from the Japan Birth Cohort Consortium.

A fetal growth restriction is related to adverse child outcomes. We investigated risk ratios and population-attributable fractions (PAF) of small-for-gestational-age (SGA) infants in the Japanese population. Among 28,838 infants from five ongoing prospective birth cohort studies under the Japan Birth Cohort Consortium, two-stage individual-participant data meta-analyses were conducted to calculate risk ratios and PAFs for SGA in advanced maternal age, pre-pregnancy underweight, and smoking and alcohol consumption during pregnancy. Risk ratio was calculated using modified Poisson analyses with robust variance and PAF was calculated in each cohort, following common analyses protocols. Then, results from each cohort study were combined by meta-analyses using random-effects models to obtain the overall estimate for the Japanese population. In this meta-analysis, an increased risk (risk ratio, [95% confidence interval of SGA]) was significantly associated with pre-pregnancy underweight (1.72 [1.42-2.09]), gestational weight gain (1.95 [1.61-2.38]), and continued smoking during pregnancy (1.59 [1.01-2.50]). PAF of underweight, inadequate gestational weight gain, and continued smoking during pregnancy was 10.0% [4.6-15.1%], 31.4% [22.1-39.6%], and 3.2% [-4.8-10.5%], respectively. In conclusion, maternal weight status was a major contributor to SGA births in Japan. Improving maternal weight status should be prioritized to prevent fetal growth restriction.

Dietary Patterns, Nutritional Status and Inflammatory Biomarkers in Adolescents from the RPS Birth Cohort Consortium.

This study aimed to identify the dietary patterns (DPs) of adolescents and assess indicators of subclinical inflammation. It was a cross-sectional study aligned with the RPS cohort with data from São Luís, Maranhão, Brazil. We evaluated 511 adolescents between 18-19 years old. DPs were identified with a factor analysis of the principal components. Nutritional status was assessed with body mass index and body fat percentages. Hierarchical modeling was performed using a linear regression to estimate the beta coefficient (β) of the independent variables with the dependent variables interleukin-6 and high-sensitivity C-reactive protein (hs-CRP). Five DPs were identified: energy-dense, sugar-sweetened beverages and breakfast cereals, prudent, traditional Brazilian and alcoholic and energy beverages. Greater adherence to the prudent DP was associated with a lower concentration of interleukin-6 (β = -0.11; p value = 0.040). Greater adherence to the DP "traditional Brazilian" and "alcoholic and energy beverages" were associated with increased IL-6, mediated by the nutritional status. A higher BMI (β = 0.36; p value = <0.001) and %BF (β = 0.02; p value = 0.014) were associated with higher hs-CRP concentrations. The nutritional status and "prudent" pattern were associated with inflammatory biomarkers. These findings show that a higher consumption of fresh and minimally processed foods and the adequacy of the nutritional status are protective factors for the inflammatory process.

Association Between Smoking and Hypertension in Pregnancy Among Japanese Women: A Meta-analysis of Birth Cohort Studies in the Japan Birth Cohort Consortium (JBiCC) and JECS

Recent literature suggest the effect of maternal smoking on risk of hypertensive disorders in pregnancy (HDP) and preeclampsia may differ by ethnicity; however, studies on Asians are limited. We investigated the association of maternal smoking with HDP and preeclampsia using a common analysis protocol to analyze the association in six birth cohorts participating in a Japanese consortium of birth cohorts (JBiCC). Results were compared with-published results from cohorts not included in this consortium, and, where possible, we produced a meta-analysis including these studies. Meta-analysis of four cohort studies including 28,219 participants produced an odds ratio (OR) of 1.24 (95% confidence interval [CI], 0.88-1.87) for the effect of smoking beyond early pregnancy compared to women who did not smoke during pregnancy. These results combined with those from the Japan Environment and Children's Study (JECS) yielded an OR of 1.19 (95% CI, 1.00-1.43, P = 0.056). Meta-analysis results for categories of smoking volume were insignificant, but when combined with JECS yielded an OR of 0.86 (95% CI, 0.65-1.12) for smoking 1-4 cigarettes, 1.25 (95% CI, 0.98-1.60) for smoking 5-9 cigarettes, and 1.27 (95% CI, 1.04-1.54) for smoking 10 or more cigarettes per day. All effects were insignificant for preeclampsia. Our results suggest that the protective effects of smoking longer and smoking more on HDP and preeclampsia repeatedly observed among Europeans and North Americans likely do not hold for the Japanese.

Longitudinal Characterization of Atopic Dermatitis Phenotypes in The Children's Respiratory and Environmental Workgroup (CREW) Birth Cohort Consortium

Previously identified longitudinal patterns of atopic dermatitis (AD) may lack generalizability and precision due to small sample size and limited time points. We identify and describe longitudinal AD phenotypes in a large consortium study.

Longitudinal assessment of Allergic Outcomes and Atopic Dermatitis Phenotypes in The Children's Respiratory and Environmental Workgroup (CREW) Birth Cohort Consortium

Atopic dermatitis (AD) is a heterogenous inflammatory skin disease often associated with other allergic diseases. We characterized AD phenotypes and associated allergic outcomes longitudinally across a multi-site consortium.

High Consumption of Sugar-Sweetened Beverages Is Associated with Low Bone Mineral Density in Young People: The Brazilian Birth Cohort Consortium.

Sugar-sweetened beverages (SSB) consumption may be associated with a reduction in bone mineral density (BMD). The aim of this study was to evaluate the association between the consumption of SSB and BMD among young people. We performed a cross-sectional study that evaluated 6620 young people (18-23 years of age) from three Brazilian birth cohorts (Ribeirão Preto, Pelotas, and São Luís). We analyzed the daily frequency and the amount and energy contribution of the SSB, which were obtained through a food frequency questionnaire. Total body and lumbar spine BMD (g/cm2), measured by dual-energy X-ray absorptiometry, were the outcomes. Unadjusted linear regression models, adjusted for sex, socioeconomic class, physical activity, smoking, alcohol consumption, and body mass index were used. The highest tertile of SSB consumption frequency (2.1-16.7 times/day) was associated with a lower lumbar spine BMD (β = -0.009; 95% CI: -0.017; -0.001; standardized β = -0.03). This association persisted after adjustment for confounders (β = -0.008; 95% CI: -0.016; -0.001; standardized β = -0.03). No association was observed between SSB consumption frequency and total body BMD or between the amount and energy contribution of SSB and total body or lumbar spine BMD. A high frequency of SSB consumption was associated with a low lumbar spine BMD.

Relative validity of a food frequency questionnaire for adolescents from a capital in the Northeastern region of Brazil

The present study was conducted to evaluate the validity of the Food Frequency Questionnaire (FFQ) used in the RPS Birth Cohort Consortium (Ribeirão Preto, Pelotas, and São Luís) to assess dietary intake of adolescents from São Luís, Maranhão. The research was developed with 152 adolescents aged 18 and 19 years. For the validation of the FFQ, the average of three 24-hour recalls (24HRs) was used as the reference method. The mean and standard deviation of energy and nutrient intake extracted from the surveys were estimated. The paired Student's t-test was used to verify the differences between the instruments. Pearson correlation coefficient, intraclass correlation coefficient (ICC), weighted Kappa, and the Bland-Altman plot were calculated in order to measure the agreement. The study adopted a level of significance <5%. Compared with the three 24HRs, the FFQ overestimated the consumption of most nutrients. Energy-adjusted and de-attenuated concordance Pearson correlation coefficients ranged from 0.06 to 0.43, and correlations were significant for iron, calcium, riboflavin, sodium, saturated fat, niacin, and vitamin C. The energy-adjusted and de-attenuated ICCs ranged from 0.01 to 0.31, and the weighted Kappa ranged from 0.01 to 0.46. The analyses of agreement were significant for vitamin C, fiber, calcium, riboflavin, niacin, sodium, lipids, and iron. In conclusion, the FFQ presented acceptable relative validity for lipids, saturated fatty acids, fiber, calcium, iron, riboflavin, niacin, vitamin C, and sodium. This instrument will be useful in studies about food consumption of adolescents in São Luís, Maranhão.

Excess weight and obesity prevalence in the RPS Brazilian Birth Cohort Consortium (Ribeirão Preto, Pelotas and São Luís).

Our objective was to estimate the prevalence of excess weight and obesity, according to sex and income in the RPS Brazilian Birth Cohort Consortium (Ribeirão Preto, Pelotas, and São Luís). Participants in the Ribeirão Preto (1978/1979 and 1994), Pelotas (1982, 1993 and 2004) and São Luís (1997/1998) birth cohorts were included in different follow-ups from 7 years old onwards. Excess weight (overweight and obesity) were assessed by body mass index. The highest prevalences were observed in Ribeirão Preto (excess weight: 27.7% at 9-11 and 47.1% at 22-23 years; obesity: 8.6% at 9-11 and 19.8% at 22-23 years) while the smallest was in São Luís (excess weight: 5.4 to 7-9 and 17.2% at 18-19 years; obesity: 1.8% at 7-9 and 3.6% at 18-19 years). The younger the cohort, the greater the prevalence of excess weight and obesity when comparing similar age groups. Increases in obesity prevalence were greater than in excess weight prevalence. Women had lower excess weight prevalence in older cohorts and higher obesity prevalence in younger cohorts. Higher excess weight and obesity prevalence were observed in higher income children and adolescents, and in poorer adults. Differences in the prevalence of excess weight and obesity evidenced that individuals from younger cohorts are more exposed to this morbidity, as well as those who were born in the most developed city, low-income adults as well as children and adolescents belonging to families of the highest income tertile. Therefore, the results of this study indicate the need to prioritize actions aimed at younger individuals.

In-utero and childhood chemical exposome in Birth Cohort Consortium of Asia

The concept of exposome, which refers to measures that reflect all exposure events of an individual during a lifetime and how those exposures relate to disease, has opened a new approach toward children’ environmental health. This study aims to characterize concentrations of numbers of environmental pollutants in pregnant women from Asia and their children, based on chemical analysis of biological samples. We use the information from Birth Cohort Consortium of Asia (BiCCA) and focus on China, Japan, Korea and Taiwan. Biomarkers or metabolites of exposure to 28 environmental pollutants include heavy metals (as arsenic, cadmium, lead, manganese and mercury), perfluoroalkyl substances (PFASs) and Phthalates were measured in biological samples from mothers during pregnancy, children at birth or postnatal followup. The detection rates of exposure biomarkers were high for phthalate metabolites, but ranged widely for PFASs. The concentrations were different between cohorts for all compounds, except for cadmium. However, the biological samples used for heavy metal measurements vary depending on blood, serum or urine, and some difficulties will be encountered when directly comparing. For PFASs, Perfluorooctanoic acid (PFOA) and Perfluorooctane sulfonate (PFOS) were the most common detectable chemicals, while the concentrations gradually decreased from maternal blood during pregnancy, cord blood to childhood blood. In addition, the composition of PFASs shows a region-specific pattern, and new alternative chemicals, such as Perfluorobutane sulfonic acid (PFBS), have been found in recently collected biological samples. Mono-n-butyl phthalat (MnBP), Mono-benzyl phthalate (MBzP) and Mono-2-ethylhexyl phthalate (MEHP) were commonly detectable phthalates, their concentrations were highest around preschool age. Here we provide the unique description of environmental pollutants including composition pattern, concentration distribution, regional differences and time trend among pregnant women and their children in Asia. It is crucial for further investigation on childrens’ health impact in consideration with exposome and international comparison. Keywords: Exposome, Birth cohort consortium of Asia, Metals, Perfluoroalkyl Substances, Phthalates

Expression quantitative trait locus fine mapping of the 17q12–21 asthma locus in African American children: a genetic association and gene expression study

African ancestry is associated with a higher prevalence and greater severity of asthma than European ancestries, yet genetic studies of the most common locus associated with childhood-onset asthma, 17q12-21, in African Americans have been inconclusive. The aim of this study was to leverage both the phenotyping of the Children's Respiratory and Environmental Workgroup (CREW) birth cohort consortium, and the reduced linkage disequilibrium in African Americans, to fine map the 17q12-21 locus. We first did a genetic association study and meta-analysis using 17q12-21 tag single-nucleotide polymorphisms (SNPs) for childhood-onset asthma in 1613 European American and 870 African American children from the CREW consortium. Nine tag SNPs were selected based on linkage disequilibrium patterns at 17q12-21 and their association with asthma, considering the effect allele under an additive model (0, 1, or 2 effect alleles). Results were meta-analysed with publicly available summary data from the EVE consortium (on 4303 European American and 3034 African American individuals) for seven of the nine SNPs of interest. Subsequently, we tested for expression quantitative trait loci (eQTLs) among the SNPs associated with childhood-onset asthma and the expression of 17q12-21 genes in resting peripheral blood mononuclear cells (PBMCs) from 85 African American CREW children and in upper airway epithelial cells from 246 African American CREW children; and in lower airway epithelial cells from 44 European American and 72 African American adults from a case-control study of asthma genetic risk in Chicago (IL, USA). 17q12-21 SNPs were broadly associated with asthma in European Americans. Only two SNPs (rs2305480 in gasdermin-B [GSDMB] and rs8076131 in ORMDL sphingolipid biosynthesis regulator 3 [ORMDL3]) were associated with asthma in African Americans, at a Bonferroni-corrected threshold of p<0·0055 (for rs2305480_G, odds ratio [OR] 1·36 [95% CI 1·12-1·65], p=0·0014; and for rs8076131_A, OR 1·37 [1·13-1·67], p=0·0010). In upper airway epithelial cells from African American children, genotype at rs2305480 was the most significant eQTL for GSDMB (eQTL effect size [β] 1·35 [95% CI 1·25-1·46], p<0·0001), and to a lesser extent showed an eQTL effect for post-GPI attachment to proteins phospholipase 3 (β 1·15 [1·08-1·22], p<0·0001). No SNPs were eQTLs for ORMDL3. By contrast, in PBMCs, the five core SNPs were associated only with expression of GSDMB and ORMDL3. Genotype at rs12936231 (in zona pellucida binding protein 2) showed the strongest associations across both genes (for GSDMB, eQTLβ 1·24 [1·15-1·32], p<0·0001; and for ORMDL3 (β 1·19 [1·12-1·24], p<0·0001). The eQTL effects of rs2305480 on GSDMB expression were replicated in lower airway cells from African American adults (β 1·29 [1·15-1·44], p<0·0001). Our study suggests that SNPs regulating GSDMB expression in airway epithelial cells have a major role in childhood-onset asthma, whereas SNPs regulating the expression levels of 17q12-21 genes in resting blood cells are not central to asthma risk. Our genetic and gene expression data in African Americans and European Americans indicated GSDMB to be the leading candidate gene at this important asthma locus. National Institutes of Health, Office of the Director.

Children's environmental health based on birth cohort studies of Asia (2) – air pollution, pesticides, and heavy metals

The life style and child raising environment in Asia are quite different compared with Western countries. Besides, the children's environmental threats and difficulties in conducting studies could be different. To address children's environmental health in Asia area, the Birth Cohort Consortium of Asia (BiCCA) was co-established in 2011. We reviewed the mercury, polychlorinated biphenyls, perfluoroalkyl substances, phthalates, and environmental tobacco smoke in pervious based on birth cohort studies in Asia. The aim of this study was to summarize the traditional environmental pollution and the target subjects were also based on the birth cohort in Asia area. Environmental pollutants included air pollutants, pesticides focusing on organochlorine pesticides, diakylphosphates, and pyrethroid, and heavy metals including lead, arsenic, cadmium, manganese, vanadium, and thallium. Fetal growth and pregnancy outcomes, childhood growth and obesity, neurodevelopment and behavioral problems, and allergic disease and immune function were classified to elucidate the children's health effects. In total, 106 studies were selected in this study. The evidences showed air pollution or pesticides may affect growth during infancy or childhood, and associated with neurodevelopmental or behavioral problems. Prenatal exposure to lead or manganese was associated with neurodevelopmental or behavioral problems, while exposure to arsenic or cadmium may influence fetal growth. In addition to the harmonization and international collaboration of birth cohorts in Asia; however, understand the whole picture of exposure scenario and consider more discipline in the research are necessary.

The Finnish psychiatric birth cohort consortium (PSYCOHORTS) – content, plans and perspectives

Background: Psychiatric disorders tend to be developmental, and longitudinal settings are required to examine predictors of psychiatric phenomena. Replicating and combining data and results from different birth cohorts, which are a source of reliable data, can make research even more valuable. The Finnish Psychiatric Birth Cohort Consortium (PSYCOHORTS) project combines birth cohorts in Finland.Aim: The aim of this paper is to introduce content, plans and perspectives of the PSYCOHORTS project that brings together researchers from Finland. In addition, we illustrate an example of data harmonization using available data on causes of death.Content: PSYCOHORTS includes eight Finnish birth cohorts. The project has several plans: to harmonize different data from birth cohorts, to incorporate biobanks into psychiatric birth cohort research, to apply multigenerational perspectives, to integrate longitudinal patterns of marginalization and inequality in mental health, and to utilize data in health economics research. Data on causes of death, originally obtained from Finnish Cause of Death register, were harmonized across the six birth cohorts using SAS macro facility.Results: Harmonization of the cause of death data resulted in a total of 21,993 observations from 1965 to 2015. For example, the percentage of deaths due to suicide and the sequelae of intentional self-harm was 14% and alcohol-related diseases, including accidental poisoning by alcohol, was 13%.Conclusions: PSYCOHORTS lays the foundation for complex examinations of psychiatric disorders that is based on compatible datasets, use of biobanks and multigenerational approach to risk factors, and extensive data on marginalization and inequality.

The Children\u2019s Respiratory and Environmental Workgroup (CREW) birth cohort consortium: design, methods, and study population

BackgroundSingle birth cohort studies have been the basis for many discoveries about early life risk factors for childhood asthma but are limited in scope by sample size and characteristics of the local environment and population. The Children’s Respiratory and Environmental Workgroup (CREW) was established to integrate multiple established asthma birth cohorts and to investigate asthma phenotypes and associated causal pathways (endotypes), focusing on how they are influenced by interactions between genetics, lifestyle, and environmental exposures during the prenatal period and early childhood.Methods and resultsCREW is funded by the NIH Environmental influences on Child Health Outcomes (ECHO) program, and consists of 12 individual cohorts and three additional scientific centers. The CREW study population is diverse in terms of race, ethnicity, geographical distribution, and year of recruitment. We hypothesize that there are phenotypes in childhood asthma that differ based on clinical characteristics and underlying molecular mechanisms. Furthermore, we propose that asthma endotypes and their defining biomarkers can be identified based on personal and early life environmental risk factors. CREW has three phases: 1) to pool and harmonize existing data from each cohort, 2) to collect new data using standardized procedures, and 3) to enroll new families during the prenatal period to supplement and enrich extant data and enable unified systems approaches for identifying asthma phenotypes and endotypes.ConclusionsThe overall goal of CREW program is to develop a better understanding of how early life environmental exposures and host factors interact to promote the development of specific asthma endotypes.

Asthma as an outcome: Exploring multiple definitions of asthma across birth cohorts in the Environmental influences on Child Health Outcomes Children's Respiratory and Environmental Workgroup

Asthma definitions vary widely across research studies and feature a trade-off between inclusivity and precision. Harmonizing definitions across multiple asthma birth cohort studies highlights these challenges.

Multi-omic signature of birthweight: metabolites and methylation driven approaches

Introduction Birthweight is a known risk factor for diseases in adult life however; the biomolecular mechanisms leading to disease processes remain poorly understood. DNA modifications, transcripts, proteins and metabolites have the potential to imprint biological responses during early life and drive adult risk profiles to chronic conditions. The aim of this study is to enhance the understanding of the complex pathways related to birthweight through integration of multiple OMIC techniques. Methods This study combines methylation (n = 468,408 CpGs), transcriptomics (n = 29,164 transcripts), inflammatory proteins (n = 16) and metabolomics (n = 4712 metabolic features) profiles from cord blood of participants in the EXPOsOMICS birth cohort consortium including ENVIRONAGE (n = 200), INMA (n = 85), Rhea (n = 99) and Piccolipiu (n = 99). We computed Pearson correlation coefficients between pairs of OMICs. Specifically, using a metabolites and methylation driven approaches, we respectively correlated metabolic (n = 68) and epigenetic (n = 8696) signatures of birthweight identified in previous EXPOsOMICS birth cohort study with the other omics platforms. The OMIC platforms have been denoised using technical variables, pairs were considered significant after Bonferroni correction for multiple testing. Significant correlations were visualized in a globe plot with the Circos visualization toolkit version 0.69–6. Transcripts that were significantly correlated to metabolites and to CpGs sites were studied in an overrepresentation analysis (ORA) using DAVID software ( https://www.david.ncifcrf.gov ). Results In the metabolites driven approach, of 33,835,984 correlations between metabolomics and the other levels, 20,097 (0.06%) were significant, mainly inverse (94%) and with a mean absolute correlation coefficient of 0.30 (range = 0.19–0.57). Over the 68 metabolites under study, 13 were significantly correlated with inflammatory proteins, 9 with the transcriptome and 20 with the methylome for a total of 28 unique metabolites. A globe plot of significant correlations showed that all the 9 metabolites were positively correlated with the transcriptome and had an inverse correlation with methylome. Few overlaps (n = 5) were detected in metabolites correlated with both methylome and proteins; the correlations in both pairs went in the same direction (mainly positive). ORA of the 38 genes associated to the significant 41 transcripts resulted in 8 significant pathways, including immune response (such as NK mediated cell cytotoxicity), signaling (MAPK signaling pathway) and also diseases-related (diabetes mellitus and thyroid autoimmunity) pathways. In the methylation driven approach, 0.02% (n = 66,719) of a total 293,606,396 correlations were identified as significant with correlation coefficients having absolute mean of 0.42 (range 0.23–0.69), and mostly negative (67%). Over the 8,663 CpG sites under study, 57 were significantly correlated with proteins, 1,467 with the transcriptome and 2174with the methylome. The globe plot of the significant correlations showed that 13 CpGs appeared in both transcripts and proteins correlation sets, 27 CpGs were common to metabolites and proteins correlation sets, and 791 CpGs were common to metabolites and transcripts correlation sets. Significant correlations in the metabolites and methylation driven approaches shared 34 transcripts, 14 metabolites, 529 CpG sites and 3 proteins. ORA among the 333 genes associated to the 391 unique transcripts significantly correlated to the methylome identified 61 pathways including 4 over the 9 pathways detected in the metabolites driven analysis (including NK mediated cell cytotoxicity and antigen processing and presentation), and also hormone (progesterone-mediated oocyte maturation) and nitrogen metabolism pathways. Conclusion This study provides initial insights into the molecular mechanisms related to birthweight and the biological pathways potentially leading to adverse health effects.

DNA Methylome Marks of Exposure to Particulate Matter at Three Time Points in Early Life.

Maternal exposure to airborne particulate matter (PM) has been associated with restricted fetal growth and reduced birthweight. Here, we performed methylome-wide analyses of cord and children's blood DNA in relation to residential exposure to PM smaller than 10 μm (PM10). This study included participants of the Avon Longitudinal Study of Pregnancy and Childhood (ALSPAC, cord blood, n = 780; blood at age 7, n = 757 and age 15-17, n = 850) and the EXPOsOMICS birth cohort consortium including cord blood from ENVIR ONAGE ( n = 197), INMA ( n = 84), Piccolipiù ( n = 99) and Rhea ( n = 75). We could not identify significant CpG sites, by meta-analyzing associations between maternal PM10 exposure during pregnancy and DNA methylation in cord blood, nor by studying DNA methylation and concordant annual exposure at 7 and 15-17 years. The CpG cg21785536 was inversely associated with PM10 exposure using a longitudinal model integrating the three studied age groups (-1.2% per 10 μg/m3; raw p-value = 3.82 × 10-8). Pathway analyses on the corresponding genes of the 100 strongest associated CpG sites of the longitudinal model revealed enriched pathways relating to the GABAergic synapse, p53 signaling and NOTCH1. We provided evidence that residential PM10 exposure in early life affects methylation of the CpG cg21785536 located on the EGF Domain Specific O-Linked N-Acetylglucosamine Transferase gene.

Birth cohorts in Asia: The importance, advantages, and disadvantages of different-sized cohorts

Asia contains half of the world's children, and the countries of Asia are the most rapidly industrializing nations on the globe. Environmental threats to the health of children in Asia are myriad. Several birth cohorts were started in Asia in early 2000, and currently more than 30 cohorts in 13 countries have been established for study. Cohorts can contain from approximately 100–200 to 20,000–30,000 participants. Furthermore, national cohorts targeting over 100,000 participants have been launched in Japan and Korea. The aim of this manuscript is to discuss the importance of Asian cohorts, and the advantages and disadvantages of different-sized cohorts. As for case, one small-sized (n=514) cohort indicate that even relatively low level exposure to dioxin in utero could alter birth size, neurodevelopment, and immune and hormonal functions. Several Asian cohorts focus prenatal exposure to perfluoroalkyo substances and reported associations with birth size, thyroid hormone levels, allergies and neurodevelopment. Inconsistent findings may possibly be explained by the differences in exposure levels and target chemicals, and by possible statistical errors. In a smaller cohort, novel hypotheses or preliminary examinations are more easily verifiable. In larger cohorts, the etiology of rare diseases, such as birth defects, can be analyzed; however, they require a large cost and significant human resources. Therefore, conducting studies in only one large cohort may not always be the best strategy. International collaborations, such as the Birth Cohort Consortium of Asia, would cover the inherent limitation of sample size in addition to heterogeneity of exposure, ethnicity, and socioeconomic conditions.

The Fourth Conference of the International Society for Environmental Epidemiology in the Asia Chapter Region

The Fourth Conference of the International Society for Environmental Epidemiology in the Asia Chapter Region