Childhood Environmental Factors Research Articles

The Importance of Childhood for Adult Health and Development-Study Protocol of the Zurich Longitudinal Studies.

Evidence is accumulating that individual and environmental factors in childhood and adolescence should be considered when investigating adult health and aging-related processes. The data required for this is gathered by comprehensive long-term longitudinal studies. This article describes the protocol of the Zurich Longitudinal Studies (ZLS), a set of three comprehensive cohort studies on child growth, health, and development that are currently expanding into adulthood. Between 1954 and 1961, 445 healthy infants were enrolled in the first ZLS cohort. Their physical, motor, cognitive, and social development and their environment were assessed comprehensively across childhood, adolescence, and into young adulthood. In the 1970s, two further cohorts were added to the ZLS and assessed with largely matched study protocols: Between 1974 and 1979, the second ZLS cohort included 265 infants (103 term-born and 162 preterm infants), and between 1970 and 2002, the third ZLS cohort included 327 children of participants of the first ZLS cohort. Since 2019, the participants of the three ZLS cohorts have been traced and invited to participate in a first wave of assessments in adulthood to investigate their current health and development. This article describes the ZLS study protocol and discusses opportunities, methodological and conceptual challenges, and limitations arising from a long-term longitudinal cohort recruited from a study about development in early life. In the future, the ZLS will provide data to investigate childhood antecedents of adult health outcomes and, ultimately, will help respond to the frequent call of scientists to shift the focus of aging research into the first decades of life and, thus, to take a lifespan perspective on aging.

The Association between Childhood Myopia Prevalence and Environmental Factors in China: A Metaregression Analysis

Background. Myopia prevalence varies across the country among schoolchildren in China. Recently, environmental factors have been shown to be important in myopia development and progression. Given China’s geographical diversity with variable environmental factors, we investigated whether environmental factors could explain the regional variations in myopia in mainland China. Methods. We searched PubMed, Web of Science, and Chinese Science Periodical Databases for studies with reports of myopia prevalence in schoolchildren in mainland China from the years 1979 to 2019. Data on environmental factors (annual sunshine hours, temperature, and population density) were obtained from past records. A random-effect univariate metaregression analysis was used to investigate the association between the environmental factors and myopia prevalence and to determine the proportion of variation in regional myopia prevalence that can be attributed to each factor. Results. Forty-nine eligible studies were identified that included 666,864 schoolchildren aged 6 to 20 years. The pooled estimate of myopia prevalence was 32.88% (95% confidence interval: 26.69–39.08%). Univariate metaregression analysis indicated that annual sunshine hours (27.97% of variance), annual temperature (24.66%), and population density (7.06%) significantly contributed to regional myopia prevalence variation (eachp<0.05), while seasonal variation in sunshine hours (1.54%,p=0.604) was not a significant predictor of myopia prevalence. However, only annual sunshine hours was significantly associated with myopia prevalence in the multivariate metaregression model. Conclusion. Myopia prevalence in children was higher in regions with low sunshine hours, and annual sunshine hours was significantly associated with regional variation in myopia prevalence in mainland China.

Thumb sucking or nail biting in childhood and adolescence is associated with an increased risk of Crohn’s disease: results from a large case–control study

Background The hygiene hypothesis suggests that a reduction in microbial exposure contributes to an impaired immune response later in life and increases the incidence of immune-mediated diseases such as inflammatory bowel diseases (IBD). Thumb sucking and nail biting are two early habits that modulate the oral microbiota composition and antigen load. Objective We hypothesized a lower risk of Crohn’s disease (CD) and ulcerative colitis (UC) in adults with prior thumb sucking and nail biting. Methods 918 IBD cases and their 918 siblings without IBD were asked to fill out a survey containing 32 questions on environmental factors in childhood and early adulthood. Prevalence of thumb sucking and/or nail biting at the usually well-remembered time of (1) school enrollment and (2) coming-of-age ceremonies was the predefined combined risk factor of this study. Results 65% of the patients were female and 57% suffered from CD. About 49% of IBD patients but only 44% of their siblings reported thumb sucking/nail biting at the time of school enrollment or coming-of-age (p = .007). Sensitivity analysis revealed that this difference was observed in patients with CD (50% versus 41%; RR= 1.22; 95% CI 1.09–1.37, p = .001) but not in patients with UC (49% versus 48%; RR= 1.02; 95% CI 0.90–1.17; p = .83). Conclusion Contrary to our expectation and challenging the hygiene hypothesis, we found that common oral habits are not protective against IBD. Instead, nail biting at the time of school enrollment and coming-of-age was a statistically significant risk factor for CD in our cohort. Key summary Evidence available before this study: The hygiene hypothesis suggests that a reduction in microbial exposure due to improved health activities has contributed to an immunological imbalance in the intestine and an increased incidence of allergic and autoimmune diseases. A population-based birth cohort study has demonstrated that thumb-sucking and nail biting in children lead to a reduction of the risk of atopic sensitization, asthma, and hay fever. Added value of this study: Contrary to the hypothesis, thumb sucking and nail biting were not associated with a reduced risk of IBD. Instead, thumb sucking and/or nail biting at the usually well-remembered points in time of school enrollment and of religious or secular coming-of-age ceremonies was associated with a higher risk of Crohn’s disease but not of ulcerative colitis. Our data did not support the hygiene hypothesis, one pathogenic concept in the context of IBD.

Interaction between early environment and genetic predisposition instigates the metabolically obese, normal weight phenotype in children: findings from the BCAMS study.

A subset of normal-weight individuals appears predisposed to obesity-related cardiometabolic abnormalities. Studies of this metabolically obese, normal weight (MONW) phenotype in youth are scarce. We aimed to identify early environmental and genetic factors associated with MONW in children. Overall, 1475 normal-weight Chinese children aged 6-18 were recruited from the Beijing Children and Adolescents Metabolic Syndrome study cohort. Birthweight, childhood lifestyle, socio-economic factors, and 20 genetic variants previously shown to be associated with BMI or glucose metabolism in East Asian adults were examined for their association with the MONW phenotype. MONW was defined by exhibiting any metabolic syndrome component. After adjusting for covariates including BMI, low birthweight and low levels of physical activity, fruit consumption, parental education and household income, as well as CDKAL1 rs2206734 genotype were independent predictors of the MONW phenotype (all P < 0.05). Moreover, rs2206734 interacted with birthweight to predict the MONW phenotype (Pinteraction = 0.0008). Among high (>75th percentile) birthweight individuals, each C allele at this locus was associated with a 62% reduced risk of MONW (OR = 0.38; 95% CI = 0.26-0.58; P = 5.71 × 10-6), while no such genetic associations were found in intermediate or low birthweight individuals (P > 0.1). This CDKAL1-MONW relationship in high birthweight individuals was especially strong in the presence of favorable childhood environmental factors (high levels of physical activity, fruit consumption, parental education and household income) (Pinteraction = 0.013). Our findings provided the novel evidence that early environment (especially birthweight) and genetics, along with their interaction with one another, play important roles in predicting the MONW phenotype among children.

Can perturbations in microbial maturation cause asthma?

Microbial colonisation in children is believed to initiate at birth, and from this point onwards, complex microbial populations evolve in niche-specific patterns throughout the body. In all niches, both transient and more persistent colonisers emerge in a temporal fashion. Such temporal changes are especially observed in the first year of life, when the composition of the microbiota is unstable, all environmental exposures are novel, and dietary patterns change considerably. 1 Subramanian S Blanton LV Frese SA Charbonneau M Mills DA Gordon JI Cultivating healthy growth and nutrition through the gut microbiota. Cell. 2015; 161: 36-48 Summary Full Text Full Text PDF PubMed Scopus (91) Google Scholar Although environmental factors in childhood act as microbial reservoirs and seeding sources for the developing microbiome, the gut microbiome in early life is further shaped by the nutritional components of the diet, 2 Bokulich NA Chung J Battaglia T et al. Antibiotics, birth mode, and diet shape microbiome maturation during early life. Sci Transl Med. 2016; 8343ra82 Crossref PubMed Scopus (529) Google Scholar with different species thriving on specific dietary compounds and thereby being selected for. The microbiome in early life is dominated by bacterial species that can digest oligosaccharides and lipids from breast milk; the subsequent introduction of solid foods allows for new microbes to emerge and colonise. As such, the microbial composition of the gut is dynamic and develops rapidly during the first year of life, and this process of development characterises the normal maturation of the microbiome. 1 Subramanian S Blanton LV Frese SA Charbonneau M Mills DA Gordon JI Cultivating healthy growth and nutrition through the gut microbiota. Cell. 2015; 161: 36-48 Summary Full Text Full Text PDF PubMed Scopus (91) Google Scholar , 3 Stokholm J Blaser MJ Thorsen J et al. Maturation of the gut microbiome and risk of asthma in childhood. Nat Commun. 2018; 9: 141 Crossref PubMed Scopus (171) Google Scholar Decreasing antibiotic use, the gut microbiota, and asthma incidence in children: evidence from population-based and prospective cohort studiesOur findings suggest that the reduction in the incidence of paediatric asthma observed in recent years might be an unexpected benefit of prudent antibiotic use during infancy, acting via preservation of the gut microbial community. Full-Text PDF

Childhood Family Environment and Depression in Early Adulthood in Botswana

The childhood family environment is a determinant of mental health outcomes later in life. Yet, few studies have examined its role in outcomes such as depression in early adulthood, especially in low- and middle-income countries such as Botswana. This study explores the relationship between childhood family environmental factors and depression among young adults in Botswana. A sample of 351 students at the University of Botswana was surveyed through a self-administered questionnaire, which included various childhood environmental factors, the Beck Depression Inventory-II and socio-demographic items. Descriptive statistics, t-tests and regression models were used in the data analyses. About one in four young adults reported moderate to severe symptoms of depression with about one in ten in the severe category. Childhood alcohol use, parental drug and alcohol use, physical assault, and psychological aggression towards parents or guardians during childhood, all significantly predicted symptoms of depression in early adulthood. Altogether, the childhood family environmental factors and gender explained significant variance in depressive symptoms. Multiple adverse childhood environments constitute significant risk factors for depression in early adulthood and the next generation. Preventive and early intervention services for vulnerable children, evaluation of mental health, childhood family experiences, and creating awareness of the need for treatment are critical. Cognitive behavioural therapy and mindfulness training are possible strategies to reduce the life-course effects of adverse childhood family environmental factors on depression in young adults.

A genome-wide association study of cocaine use disorder accounting for phenotypic heterogeneity and gene–environment interaction

Phenotypic heterogeneity and complicated gene–environment interplay in etiology are among the primary factors that hinder the identification of genetic variants associated with cocaine use disorder. To detect novel genetic variants associated with cocaine use disorder, we derived disease traits with reduced phenotypic heterogeneity using cluster analysis of a study sample (n = 9965). We then used these traits in genome-wide association tests, performed separately for 2070 African Americans and 1570 European Americans, using a new mixed model that accounted for the moderating effects of 5 childhood environmental factors. We used an independent sample (918 African Americans, 1382 European Americans) for replication. The cluster analysis yielded 5 cocaine use disorder subtypes, of which subtypes 4 (n = 3258) and 5 (n = 1916) comprised heavy cocaine users, had high heritability estimates (h2 = 0.66 and 0.64, respectively) and were used in association tests. Seven of the 13 identified genetic loci in the discovery phase were available in the replication sample. In African Americans, rs114492924 (discovery p = 1.23 × E−8), a single nucleotide polymorphism in LINC01411, was replicated in the replication sample (p = 3.63 × E−3). In a meta-analysis that combined the discovery and replication results, 3 loci in African Americans were significant genome-wide: rs10188036 in TRAK2 (p = 2.95 × E−8), del-1:15511771 in TMEM51 (p = 9.11 × E−10) and rs149843442 near LPHN2 (p = 3.50 × E−8). Lack of data prevented us from replicating 6 of the 13 identified loci. Our results demonstrate the importance of considering phenotypic heterogeneity and gene–environment interplay in detecting genetic variations that contribute to cocaine use disorder, because new genetic loci have been identified using our novel analytic method.

Early Life Multiple Exposures and Child Cognitive Function: A Multi-Centric Birth Cohort Study in Six European Countries

Background: Epidemiological studies on environmental risk factors for cognitive outcomes mostly focus on single environmental exposures or exposure families. The present study aims to systematically assess associations between a wide range of prenatal and childhood environmental exposures and cognitive functioning. Methods:The study sample included 1,298 children, aged 6-11 years, from six European birth cohorts. We measured 87 exposures during pregnancy and 122 cross-sectionally during childhood, including air pollution, built environment, meteorology, natural spaces, traffic, noise, chemicals and life styles. The measured cognitive domains were fluid intelligence (Raven's Coloured Progressive Matrices test, CPM), attention function (Attention Network Test, ANT) and working memory (N-Back task). We used two statistical approaches to assess associations between exposure and child cognition: the exposome-wide association study (ExWAS) considering each exposure independently, and the deletion-substitution-addition algorithm (DSA) considering all exposures simultaneously to build a final multiexposure model. Findings: Based on multiexposure model, child organic food intake was associated with higher fluid intelligence (CPM) scores (beta=1.18; 95% CI=0.50, 1.87) and higher working memory (N-Back) scores (0.23; 0.05, 0.41), and child fast food intake (-1.25; -2.10, -0.40), house crowding (-0.39; -0.62, -0.16), and child environmental tobacco smoke (ETS) (-0.89; -1.42, -0.35), were all associated with lower CPM scores. Indoor PM 2.5 exposure was associated with lower N-Back scores (-0.09; -0.16, -0.02). Additional associations in the unexpected direction were also found. Namely, higher prenatal mercury levels, maternal alcohol consumption and child higher perfluorooctane sulfonic acid (PFOS) levels were associated with better cognitive performance and higher green exposure during pregnancy with lower cognitive performance. Interpretation:This first comprehensive and systematic study of many prenatal and childhood environmental risk factors suggests that unfavourable child nutrition, family crowdedness and child indoor air pollution and ETS exposures adversely affect cognitive function. Unexpected associations were also observed and maybe due to confounding and reverse causality. Funding:European Community’s Seventh Framework Programme (FP7/2007-206) under grant agreement no 308333 – the HELIX project. Declaration of Interests: The authors have no conflicts of interest to declare. Ethics Approval Statement: The ethics committee for each cohort approved the consent form. We obtained written informed consent for all participants, signed by the parent.

1322-P: Early Environment and Genetic Predisposition to Metabolically Obese Normal-Weight Phenotype in Children: Findings from a Cohort Study

Some normal-weight individuals are predisposed to obesity-related cardiometabolic abnormalities, namely, metabolically obese normal weight (MONW). Studies of the MONW phenotype in youths are scarce. We aimed to identify early environmental and genetic factors associated with MONW in children. Overall, 1,484 normal-weight Chinese children aged 6-18, including 588 subjects with MONW phenotype, were recruited from the Beijing Children and Adolescents Metabolic Syndrome cohort. Birth weight (BW) childhood lifestyle and socio-economic factors, and 20 genetic variants which had been previously shown to be associated with BMI or T2D in East Asian adults were examined for the associations with pediatric MONW phenotype. Metabolically unhealthy was defined as having any metabolic syndrome component or HOMA-IR≥3.0. Independent risk factors for MONW phenotype were low BW, increased BMI, and lower levels of physical activity, maternal education and family income (all P&amp;lt;0.05), while amongst genetic variants, CDKAL1 rs2206734 shown the strongest association with MONW (OR per C allele=0.81, 95% CI=0.70-0.95; P=0.008). Moreover, rs2206734 interacted with BW on MONW phenotype (P interaction=0.005). Every C allele was associated with a 50% reduced risk of MONW in high (&amp;gt;75th percentile) BW (95% CI=0.34-0.72; P=0.0002), while the genetic associations were nonsignificant in intermediate and low (≤75th percentile) BW (P&amp;gt;0.1). The effect of high BW on the CDKAL1-MONW relationship could be further augmented by the combined impact of beneficial childhood environmental factors (physically active, high maternal education and family income) (Pinteraction=0.017). In conclusion, both early environments, particularly BW, and genetic predisposition plus their interaction were associated with MONW in children. Our study provides new insights into MONW and suggests a long-term prevention strategy, especially in genetically susceptible individuals. Disclosure M. Li: None. G. Li: None. S. Gao: None. S.M. Willi: Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Roche Diagnostic USA. Research Support; Self; Jaeb Center for Health Research, National Institute of Allergy and Infectious Diseases, Sanofi-Aventis. Other Relationship; Self; National Institute of Diabetes and Digestive and Kidney Diseases. Funding National Key Research Program of China (2016YFC1304801); Beijing Municipal Science &amp; Technology Commission (D111100000611001, D111100000611002); Beijing Natural Science Foundation (7172169); Beijing Science &amp; Technology Star Program (2004A027), Novo Nordisk (2011A002); National Key Program of Clinical Science (WBYZ 2011-873); Central Research Institute Fund of Chinese Academy of Medical Sciences (2017PT32020, 2018PT32001)

Genetic and Environmental Factors in Childhood Affecting High Brain Function

The brain and mind are not only determined genetically but are also nurtured by environmental stimuli in early life. However, the relationship between early life environment and phenotypes in adulthood remains elusive. Using the IntelliCage-based competition task for group-housed mice, we previously found that maternal exposure to a low dose of an environmental pollutant, dioxin, resulted in abnormal social behavior, that is, low competitive dominance, which is defined by decreased occupancy of limited resource sites under highly competitive circumstances. Although we were unable to identify which behavioral phenotype applies to abnormalities such as "human social nature", we found signs of hypoactivation of the medial prefrontal cortex, as seen in patients with autism spectrum disorder. In addition, another model of environmental factors, repeated isolation during development, and that of genetic factors including mice with neuronal heterotopia, which refers to brain malformations resulting from deficits of neuronal migration, showed low competitive dominance. These results indicate that a constitutive approach to capture the neural network of the whole brain is necessary especially in cases where the temporal gap of causal relationships is large such as DOHaD.

How much atopy is attributable to common childhood environmental exposures? A population-based birth cohort study followed to adulthood.

The rising prevalence of atopic diseases implies a strong influence of environmental determinants. Epidemiological studies have identified several early life exposures that appear to influence the risk of developing atopic sensitization, but the combined influence of these exposures is unknown. We sought to estimate the proportion of atopy that could be attributed to common childhood exposures associated with atopic sensitization in adolescence and young adulthood. Atopic sensitization was measured by skin-prick tests for common aeroallergens in a population-based New Zealand birth cohort at ages 13 and 32 years. The independent effects of previously identified risk and protective factors for atopic sensitization were assessed using multiple logistic regression. Population attributable fractions were calculated for atopic sensitization in childhood and adulthood. Tobacco smoke exposure, dog and cat ownership, nail-biting and thumb-sucking, attending pre-school day care, and household crowding were associated with a lower risk of atopic sensitization whereas breastfeeding was associated with a higher risk. Population attributable fractions for combined effects of these environmental factors suggest that they may account for 58% of atopic sensitization at age 13 and 49% at age 32 years. A substantial proportion of atopic sensitization appears to be attributable to common childhood environmental and lifestyle factors, and the influence of these exposures persists into adulthood. The absolute risks attributable to these exposures will be different in other cohorts and we cannot assume that these associations are necessarily causal. Nevertheless, the findings suggest that identifiable childhood environmental factors contribute substantially to atopic sensitization.

Helicobacter, Hygiene, Atopy, and Asthma.

The hygiene hypothesis links environmental and microbial exposures in early life to the prevalence of atopy, allergy, and asthma. Helicobacter pylori infection is typically acquired in childhood and acquisition of the infection is associated with poor household hygiene. Some population surveys have shown an inverse association between H. pylori infection and atopy, allergy, and asthma leading to the suggestion that H. pylori infection may be protective against disease; others consider it simply a biomarker for poor household hygiene. We review the relevant surveys, cohort studies, meta-analyses, and studies testing the protective hypothesis. Overall, the results of surveys and cohort studies are inconsistent, whereas meta-analyses show a significant but weak inverse correlation. In contrast, studies directly testing the protection hypothesis in relation to asthma in populations with poor hygiene and low H. pylori prevalence failed to confirm a protective effect. H. pylori is a major cause of human disease including chronic gastritis, peptic ulcer, and gastric malignancies. H. pylori infections most likely serve as a biomarker for poor hygienic conditions in childhood. We conclude that while synergistic interactions between environmental factors in childhood are important determinants of the pathogenesis of atopy, allergy, and asthma; H. pylori is inversely related to good hygiene and thus it's presence serves as a biomarker rather than for a specific prevention role for H. pylori or H. pylori antigens.

Symptoms of major depression: Their stability, familiality, and prediction by genetic, temperamental, and childhood environmental risk factors.

Psychiatry has long sought to develop biological diagnostic subtypes based on symptomatic differences. This effort assumes that symptoms reflect, with good fidelity, underlying etiological processes. We address this question for major depression (MD). We examine, in twins from a population-based registry, similarity in symptom endorsement in individuals meeting criteria for last-year MD at separate interview waves and in concordant twin pairs. Among individuals with MD, we explore the impact of genetic-temperamental and child adversity risk factors on individual reported symptoms. Aggregated criteria do not separate insomnia from hypersomnia, weight gain from loss, etc. while disaggregated criteria do. In twins with MD at two different waves, the mean tetrachoric correlations (±SEM) for aggregated and disaggregated DSM-IV A criteria were, respectively, +0.31 ± 0.06 and +0.34 ± 0.03. In monozygotic (MZ) and dizygotic (DZ) twin pairs concordant for last-year MD, the mean tetrachoric correlations for aggregated and disaggregated criteria were, respectively, +0.33 ± 0.07 and +0.43 ± 0.04, and +0.05 ± 0.08 and +0.07 ± 0.04. In individuals meeting MD criteria, neuroticism predicted the most MD symptoms (10), followed by childhood sexual abuse (8), low parental warmth (6), and genetic risk (4). The correlations for individual depressive symptoms over multiple episodes and within MZ twins concordant for MD are modest suggesting the important role of transient influences. The multidetermination of individual symptoms was further evidenced by their prediction by personality and exposure to early life adversities. The multiple factors influencing symptomatic presentation in MD may contribute to our difficulties in isolating clinical depressive subtypes with distinct pathophysiologies.

Bridging the Gap between Aetiological and Maintaining Factors in Social Anxiety Disorder: The Impact of Socially Traumatic Experiences on Beliefs, Imagery and Symptomatology.

A number of key environmental factors during childhood have been implicated in the aetiology of social anxiety disorder (SAD), including aversive social experiences, traumatic life events and parent-child interaction. However, understanding the nature, interactions and relative contributions of these factors remains unclear. Furthermore, the relation of aversive social experiences to the development of key maintaining factors in SAD requires elucidation. The current study aimed to extend previous research regarding the aetiology of SAD by investigating the relationship between key environmental factors in childhood, negative beliefs and self-imagery, and the development of SAD. Social anxiety disorder individuals (n = 40, 87.5% female, Mage = 20.25 years) completed self-report measures of social anxiety symptomatology, traumatic experiences and parenting style. In addition, participants were administered interviews assessing various domains of childhood trauma, as well as negative self-imagery and associated socially traumatic memories. Participants reported a high frequency of early traumatic experiences across all domains (physical, emotional, sexual, social and non-relational), as well as a high degree of parental overcontrol. However, social anxiety symptomatology was most strongly correlated with socially traumatic experiences, and mediation analyses suggest that appraisal of aversive social/peer experiences accounts for the relationship of SAD symptomatology with negative self-beliefs and imagery. These outcomes suggest that social trauma may be a key proximal cause of SAD development, leading to the development of negative beliefs and imagery that subsequently maintain the disorder. These findings have implications for understanding SAD aetiology, and improving treatment outcomes for the disorder. Copyright © 2016 John Wiley & Sons, Ltd. Negative social experiences have been implicated in the development of social anxiety disorder (SAD), but the role of this predisposing factor remains unclear. Compared with other risk factors for SAD, social anxiety symptomatology was most strongly correlated with socially traumatic experiences. Mediation analyses suggested that appraisal of aversive social experiences accounted for the relationship of SAD symptomatology with negative self-beliefs and imagery. These outcomes suggest that SAD individuals would benefit from interventions targeted at processing socially traumatic memories (e.g., imagery rescripting).

Maternal and child cytokine relationship in early life is not altered by cytokine gene polymorphisms.

The development of immune responses is influenced by the interaction between environmental and genetic factors. Our previous study showed a close association between maternal and young infant's cytokine responses. The question is how this association evolves over time and the contribution of genetic polymorphisms to this association. Five cytokines in mitogen-stimulated whole blood culture were measured from pregnant mothers and their children aged 2, 5, 12, 24 and 48 months. Cytokine gene polymorphisms were determined in both mothers and children. High production of maternal interleukin (IL)-10, tumour necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) was significantly associated with higher levels of the corresponding cytokines in their children at 2 months (T2), but the association decreased over time. Maternal single-nucleotide polymorphism (SNP) in IFN-γ gene, rs3181032, was found to be associated with child's IFN-γ levels at T2 only, whereas maternal IL-10 rs4579758 and child's TNF-α rs13215091 were associated with child's corresponding cytokines at later ages but not at T2. In the final models including the gene polymorphisms, maternal cytokines were still the strongest determinant of child cytokines. Maternal cytokine during pregnancy, which could be a proxy for child's environmental factors, showed its highest impact at early age, with no or little influence from genetic factors.

Early marijuana initiation: The link between prenatal marijuana exposure, early childhood behavior, and negative adult roles

We investigated the associations among gestational factors including prenatal marijuana exposure (PME), child behavior at age 3, early age of onset of marijuana use (EAOM, <15years), and adult roles at 22years. Participants were drawn from the Maternal Health Practices and Child Development (MHPCD) Project, a longitudinal study of prenatal substance exposure in offspring who have been studied for over 22years since the prenatal phase. Data from the prenatal, birth, 3-, and 22-year phases (N=608) were used in the present study. Age of onset of offspring substance use was determined based on data from the 14-, 16-, and 22-year phases. The subjects were of lower socioeconomic status, 43% were Caucasian and the remaining were African-American, and 48% were males. Early childhood behavior was significantly (p<0.05) related to EAOM after controlling for PME, birth and childhood environmental risk factors, and Conduct Disorder. EAOM was significantly associated with negative adult roles including increased risk of being arrested (p<0.001), lower educational attainment (p<0.001), having a child without being married (p<0.05), and unemployment at 22years (p<0.001). The correlations between PME and negative adult roles and between early childhood behavior and negative adult roles were also statistically significant. Pathway analysis demonstrated that EAOM significantly mediated the associations between PME and fulfillment of adult roles and between early childhood behavior and adult roles. There are a number of intervention points that could be targeted that would have a long-term impact on lowering the probability of EAOM and less success in adult roles.

PTH-089 Childhood Environmental Factors and Trends in Inflammatory Bowel Disease

Introduction Genetic predisposition, does not account solely for disease aetiology. Other environmental and childhood factors might explain the rise of inflammatory bowel disease (IBD) in recent years. Methods All patients diagnosed with IBD between 2012 and 2014 at Mater Dei Hospital in Malta were included in this study. Each patient was then asked to fill in a questionnaire related to childhood factors. Results 152 patients (mean age 42.4 years sd±17.7; mean age at diagnosis 39.8 years sd±17.7) were included in this study. 55.9% were male. 65.8% patients suffered from UC. Association between Montreal classification and childhood factors: If patients were brought up with siblings, they were more likely to have an older Montreal age at diagnosis (p Association of type of IBD with childhood factors: When factors were assessed individually, more patients with UC than CD shared a bedroom with their siblings (p Association of childhood factors with age at diagnosis: Factors leading to an older age at diagnosis of IBD: whether patients were brought up with siblings (p Conclusion Certain factors such as vaccination and swimming at a young age might predispose to a younger age at diagnosis of IBD. Other factors such as being brought up with siblings were protective and lead to an older age at diagnosis. Studying such factors on a bigger scale might further confirm these trends and may influence lifestyle changes. Disclosure of Interest None Declared

Traffic-related air pollution and childhood acute leukemia in Oklahoma

BackgroundWhile many studies have evaluated the association between acute childhood leukemia and environmental factors, knowledge is limited. Ambient air pollution has been classified as a Group 1 carcinogen, but studies have not established whether traffic-related air pollution is associated with leukemia. The goal of our study was to determine if children with acute leukemia had higher odds of exposure to traffic-related air pollution at birth compared to controls. MethodsWe conducted a case-control study using the Oklahoma Central Cancer Registry to identify cases of acute leukemia in children diagnosed before 20 years of age between 1997 and 2012 (n=307). Controls were selected from birth certificates and matched to cases on week of birth (n=1013). Using a novel satellite-based land-use regression model of nitrogen dioxide (NO2) and estimating road density based on the 2010 US Census, we evaluated the association between traffic-related air pollution and childhood leukemia using conditional logistic regression. ResultsThe odds of exposure to the fourth quartile of NO2 (11.19–19.89ppb) were similar in cases compared to controls after adjustment for maternal education (OR: 1.08, 95% CI: 0.75, 1.55). These estimates were stronger among children with acute myeloid leukemia (AML) than acute lymphoid leukemia, with a positive association observed among urban children with AML (4th quartile odds ratio: 5.25, 95% confidence interval: 1.09, 25.26). While we observed no significant association with road density, male cases had an elevated odds of exposure to roads at 500m from the birth residence compared to controls (OR: 1.39, 95% CI: 0.93, 2.10), which was slightly attenuated at 750m. ConclusionsAlthough we observed no association overall between NO2 or road density, this was the first study to observe an elevated odds of exposure to NO2 among children with AML compared to controls suggesting further exploration of traffic-related air pollution and AML is warranted.

Birth Weight and Adulthood Risk of Impaired Glucose Tolerance: A Related Research Between Childhood Environmental Factors of Growth and Lifestyle-Related Diseases in the Examinee of Special Health Checkup

Birth Weight and Adulthood Risk of Impaired Glucose Tolerance: A Related Research Between Childhood Environmental Factors of Growth and Lifestyle-Related Diseases in the Examinee of Special Health Checkup

Reprint of: Perinatal and early childhood environmental factors influencing allergic asthma immunopathogenesis.

The prevalence of asthma has increased dramatically over the past several decades. While hereditary factors are highly important, the rapid rise outstrips the pace of genomic variation. Great emphasis has been placed on potential modifiable early life exposures leading to childhood asthma. We reviewed the recent medical literature for important studies discussing the role of the perinatal and early childhood exposures and the inception of childhood asthma. Early life exposure to allergens (house dust mite (HDM), furred pets, cockroach, rodent and mold), air pollution (nitrogen dioxide (NO2), ozone (O3), volatile organic compounds (VOCs), and particulate matter (PM)) and viral respiratory tract infections (Respiratory syncytial virus (RSV) and human rhinovirus (hRV)) has been implicated in the development of asthma in high risk children. Conversely, exposure to microbial diversity in the perinatal period may diminish the development of atopy and asthma symptoms.