Early Environmental Risk Research Articles

Adolescent understanding of concepts related to the developmental origins of health and disease: a Pacific perspective

ABSTRACT The Developmental Origins of Health and Disease (DOHaD) framework has highlighted the link between an adverse early life environment and later disease risk. There is an increasing focus on adolescents as the next generation of parents as DOHaD agents of change to break the disease cycle. However, DOHaD awareness in adolescents is key to enabling knowledge uptake and behavioural change, particularly in Pacific adolescents who have a higher non-communicable disease (NCD) burden. The present study investigated understanding of DOHaD-related concepts among Pacific, Māori and other ethnic groups in New Zealand (ages 16–19 years, n = 209). Awareness of the term NCDs was low across all groups with awareness of the term DOHaD or the First 1000 Days lower in the Pacific group compared to others. Similarly, awareness of some key DOHaD concepts was low overall with some gender differences in response within ethnicity. Interestingly, adolescents' understanding that the early life nutritional environment can impact health across the life-course diminishes significantly with each advancing life-course stage. These results indicate that both education and healthcare DOHaD-related health promotion are lacking with a need for increased engagement with adolescents, particularly Pacific adolescents, to develop and communicate DOHaD content and messaging relevant to this demographic.

A194 EARLY LIFE WESTERN-TYPE DIET ACCELERATES THE ONSET OF MURINE IL-10 KO COLITIS

Abstract Background Early life is a critical time for gut microbiome and immune development, including the establishment of proper host-microbe interactions. While exposures to western world environmental factors are associated with inflammatory bowel disease (IBD) susceptibility, the link between environment in early life and later disease onset is unclear. One of the most important western world environmental factors is diet, which can distinctly alter the gut microbiome. We believe an early life western-type diet (WD) can affect disease progression in a murine IL-10 KO colitis model through dysregulated T-cell responses against the microbiome. Aims We aimed to characterize how an early life WD given to IL-10 KO mice would affect colitis development and the gut microbiome. Methods IL-10 KO mice were housed in specific pathogen free conditions and fed normal chow (NC) or WD ad libitum, either between days 10 to 35 (early WD, eWD) or days 35 to 60 (adolescent WD, aWD). Stool was collected from mice at days 35, 56, and 84 for lipocalin-2 (LCN-2) and 16S rDNA sequencing. Mice were sacrificed at day 84, assessing mesenteric lymph node weight, gene expression, colon damage by histopathology, and colon lamina propria leukocyte (LPL) phenotype and cytokine expression by flow cytometry. Results Compared to NC and aWD, the eWD fed IL-10 KO mice displayed increased fecal LCN-2 at days 56 and 84, indicating greater inflammation. At sacrifice, eWD fed mice had larger mesenteric lymph nodes and more significant colon damage by histopathological scoring. Colon LPL preparations showed that eWD fed IL-10 KO mice had higher proportions and absolute numbers of effector and regulatory T-cells. Additionally, higher proportions and absolute numbers of those T-cells were IFNγ+, IL-17A+, and IL-22+. qPCR of distal colon tissue revealed increased gene expression of innate and type 3 proinflammatory cytokines such as Il1b, Tnfα, and Il23, while showing no change in Il6 and Il4. Taxa positively associated with WD were able to establish a persistent niche in eWD fed mice but not in aWD fed mice. An increase in only one specific taxon was associated with eWD at all timepoints while also most strongly correlating with inflammatory markers. Conclusions This data suggests that eWD feeding during gut microbiome and immune development is uniquely capable of increasing long-term susceptibility to intestinal inflammation in IL-10 KO mice. This appears to be associated with persistent colonization of potentially more inflammatory taxa. This work provides insight into the potential role of early life environmental risk factors, i.e. WD, in the later development of IBD. Funding Agencies CAG, CIHRUniversity of Toronto, Taconic Biosciences

Is reproductive development adaptively calibrated to early experience? Evidence from a national sample of females.

Many developmental theories have not been sufficiently evaluated using designs that control for unobserved familial confounds. Our long-term goal is to determine the causal structure underlying associations between early environmental conditions and later psychosocial and health outcomes. Our overall objective in this study was to further evaluate predictions derived from applications of life history theory to female reproductive development, key among them that reproductive milestones translate early environmental risk into fertility, health, and behavioral outcomes. To this end, we used female data from the National Longitudinal Survey of Youth 1979 and structural equation modeling to conduct increasingly severe tests, beginning with covariate control and then progressing to sibling control and behavioral genetic designs. After adjusting for confounds varying between sets of siblings, we did not find evidence that age at menarche reflected components of early environment or that any focal outcomes reflected early fragmented family structure (birth to age nine). Although we detected no links between measured environment and individual differences in age at sexual debut, we did find that it reflected both shared and nonshared influences in our behavior genetic models. Interestingly, delayed sexual debut (into young adulthood) reflected identification of parents as the greatest influences and forecasted an array of fertility-related outcomes. Taken together, these findings challenge theories suggesting menarche timing is adaptively calibrated to early environment. They also highlight the need for more research using sibling control and related designs to examine the roles of environments in development. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Childhood unpredictability and sleep quality in adulthood: the mediating roles of life history strategy and perceived stress.

Early environmental risk have been found to be related to lifelong health. However, the impact of childhood unpredictability, a type of early environmental risk, on health, especially on sleep quality in adulthood, has not been adequately studied. The present study aimed to examine the relationship between childhood unpredictability and sleep quality in adulthood and to explore the possible mediating roles of life history strategy and perceived stress. A cross-sectional study was conducted on 472 participants from a university in Zhejiang Province, China. The questionnaire inquired about demography, childhood unpredictability, life history strategy (Mini-K), perceived stress (14-item Perceived Stress Scale), and Sleep Quality (Pittsburgh Global Sleep Quality Index). Higher childhood unpredictability was significantly associated with worse sleep quality in adulthood. Moreover, the link between higher childhood unpredictability and worse sleep quality in adulthood was explained by the chain mediation of life history strategy and perceived stress. In line with the life history theory, individuals who have experienced higher unpredictability in childhood tend to develop a faster life history strategy and become more sensitive to stress in adulthood, and subsequently suffer a decrease in sleep quality.

Eosinophilic esophagitis is associated with increased risk of later inflammatory bowel disease in a nationwide Swedish population cohort.

Earlier studies on the possible association between eosinophilic esophagitis (EoE) and inflammatory bowel disease (IBD) have been contradictory. Patients with biopsy-verified EoE diagnosed between 1990 and 2017 in Sweden (n=1587) were age- and sex-matched with up to five general population reference individuals (n=7808). EoE was defined using pathology reports from all 28 pathology centers in Sweden (the ESPRESSO study). Multivariate Cox regression then estimated hazard ratios for future IBD. IBD was defined based on the international classification of disease codes and histopathology codes. In secondary analyses, sibling comparators were used to further reduce potential familial confounding. Additionally, we performed logistic regression examining earlier IBD in EoE. During follow-up until 2020, 16 (0.01%) EoE patients and 21 (0.003%) general population reference individuals diagnosed with IBD, corresponding to a 3.5-fold increased risk of future IBD (aHR=3.56; 95% CI 1.79-7.11). EoE was linked to Crohn's disease (aHR=3.39 [95% CI 1.02-9.60]) but not to ulcerative colitis (aHR=1.37; 95% CI 0.38-4.86). Compared to their siblings, patients with EoE were at a 2.48-fold increased risk of IBD (aHR=2.48; 95% CI 0.92-6.70). Earlier IBD was 15 times more likely in EoE patients than in matched reference individuals (odds ratio, 15.39; 95% CI 7.68-33.59). In this nationwide cohort study, EoE was associated with a 3.5-fold increased risk of later IBD diagnosis. This risk increase may be due to shared genetic or early environmental risk factors, but also surveillance bias could play a role.

Early environmental risk factors and coeliac disease in adolescents: a population-based cohort study in Denmark

ObjectivesOur aim was to investigate the association between early environmental factors and the development of coeliac disease (CeD) in adolescents, recruited from a cohort nested in the Danish National Birth...

S476 Early Childhood Environmental Risks for Eosinophilic Esophagitis: A Systemic Review and Meta-analysis

S476 Early Childhood Environmental Risks for Eosinophilic Esophagitis: A Systemic Review and Meta-analysis

Early biomarkers of neurodevelopmental disorders in preterm infants: protocol for a longitudinal cohort study

IntroductionPreterm (PT) infants are at high likelihood for poor neurodevelopmental outcomes, including autism spectrum disorder (ASD), attention-deficit hyperactivity disorder (ADHD) and other neurodevelopmental disorders (NDDs), which could considerably impair the...

Cohort study of early life environmental factors and risk of decreased lung function at age 6 years in children with a history of severe bronchiolitis

Bronchiolitis is the leading cause of infant hospitalization. Identifying modifiable risk factors for decreased lung function in these children who are already at high-risk for recurrent wheezing and asthma will help guide efforts to prevent additional respiratory morbidity.

Nonshared environmental factors in the aetiology of autism and other neurodevelopmental conditions: a monozygotic co-twin control study

BackgroundA significant proportion of variation in likelihood of neurodevelopmental conditions (NDCs) has been attributed to nonshared environmental (NSE) factors, although it remains unclear which NSE factors pose specific risks for certain NDCs.MethodsA monozygotic co-twin design was applied in a sample of 224 twins (mean age = 17.70 years, SD = 6.28) controlling for confounders such as genes and shared environment. Generalized estimating equation models were fitted, using perinatal and postnatal indications of NSEs as exposure, operationalized both as separate risk factors and as cumulative risk loads. Categorical and dimensional operationalizations of autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), intellectual disability and other NDCs were used as outcomes.ResultsBirth weight discordance was associated with dimensional autism and ADHD for the smaller twin, and medication during infancy was associated with dimensional autism. Among postnatal factors scarlet fever during early childhood was associated with lower IQ. Especially autism was associated with a greater cumulative perinatal or postnatal risk load.LimitationsWhen exploring the associations between each condition and specific NSEs the risk of being statistically underpowered increases. Hence, we limit the reported findings on specific indicators of NSEs to trait levels and present descriptive data for categorical NDCs.ConclusionsThe findings support previous research by indicating an association between exposure to perinatal and postnatal risks and subsequent NDCs within twin pairs and suggest that autism may be especially linked to accumulative early environmental risks. The findings are potentially important for developmental outcomes prognoses and may inform targeted prevention and early interventions.

Effects of Ca(OH)2 on the early hydration, macro-performance and environmental risks of the calcined phosphogypsum

The effects of Ca(OH)2 (CH) content (0–2.0 wt%) on the early hydration, macro-performance, and environmental risks of calcined phosphogypsum (CPG) were studied. Particularly, the reasons for “lime sensitivity” were revealed from the perspective of dissolution and precipitation of CPG. Results show that OH− rather than Ca2+ from CH influences the early reaction of CPG. The dissolved OH− makes Al3+, Fe3+, PO43- and F- precipitate, and then a wrapping layer forms around CPG. Besides, excessive CH acts as seeds for crystallization sites and provides sufficient Ca2+ for reaction. Among all the samples, the CPG containing 0.4 wt% CH shows the longest setting time and the lowest 2-h compressive strength, while the CPG containing 2 wt% CH shows reduced setting time and increased compressive strength. The compressive strengths of specimens are consistent with their corresponding pore structure that tested by a mercury intrusion porosimetry (MIP). With the addition of CH, the volume stability of the CPG-CH systems can be significantly improved. In addition, CH can efficiently stabilize the heavy metal ions and impurity ions. The concentrations of Zn, Ni, Mn, Cr, Cu, and Pb are below the detection limit (approximately 0.02 mg/L), and the concentrations of P and F are reduced to the range of 0.18–0.31 mg/L and 0.085–0.114 mg/L, respectively, which meets the requirements of the Chinese standard GB 8978.

Age-related differences in the error-related negativity and error positivity in children and adolescents are moderated by sample and methodological characteristics: A meta-analysis.

The error‐related negativity (ERN) and the error positivity (Pe) are electrophysiological components associated with error processing that are thought to exhibit distinctive developmental trajectories from childhood to adulthood. To investigate the age and age moderation effects on the ERN and the Pe strength during development, we conducted a preregistered three‐level meta‐analysis synthesizing 120 and 41 effect sizes across 18 group comparison studies and 19 correlational studies, respectively. The meta‐analysis included studies with mean age between 3.6 and 28.7 (min‐max age range: 3.5 and 49.8) years for age‐group comparisons and 6.1 to 18.7 (min‐max age range: 4.0–35.7) years for age correlations. Results showed that age was associated with a more negative ERN (SMD = −.433, r = −.230). No statistically significant association between age and the Pe was found (SMD = .059, r = −.091), except for in a group comparison between younger and older adolescents. The age effects were not significantly moderated by whether a Flanker or a Go/No‐Go task was used, whereas a probabilistic learning task moderated the age effect on the Pe. Moreover, the Fz and Cz electrode sites yielded stronger negative associations between age and the ERN and the Pe, respectively. The results confirm that the ERN and the Pe show differential development courses and suggest that sample and methodological characteristics influence the age effects, and lay the foundation for investigations of developmental patterns of the ERN and the Pe in relation to psychopathology and early genetic and environmental risk factors.

Molding influences of prematurity: Interviews with adults born preterm

BackgroundTremendous medical advancements over the last several decades have supported the survival of younger and sicker newborns. Substantial quantitative research exists about health and developmental outcomes following preterm birth, however, limited published literature has explored what this experience means to the survivors. AimThe purpose was to describe, interpret and understand how adults born preterm perceive prematurity to have affected their lives. Study designQualitative thematic analysis. MethodsSemi-structured interviews were conducted with 33 adults born preterm from the RHODĒ Study, a longitudinal preterm birth cohort. A cross-section of participants with high and low early life medical and environmental risk was interviewed. Data were analyzed using a constructionist method of latent theme analysis. ResultsFrom the data, 3 themes were identified: 1) My parents call me their miracle, 2) It's not a big deal, I'm the same as everyone else, 3) I've overcome a lot. Themes represent a continuum of experience, from positive to neutral to negative. Common life experiences of family, education, friends, and health are subthemes that help to illuminate how participants assign meaning to their prematurity. Meaning was linked to how typical or not participants perceive their health, learning and friends compared to peers. ConclusionPerceptions about prematurity and adversity are influenced by the ways parents and families represent prematurity in shared stories and actions. These findings should inform future research with adult survivors of prematurity. Participants identified ongoing need for support and advocacy, particularly from healthcare and education communities.

Testing the specificity of environmental risk factors for developmental outcomes.

Developmental theories often assume that specific environmental risks affect specific outcomes. Canonical Correlation Analysis was used to test whether 28 developmental outcomes (measured at 11-15years) share the same early environmental risk factors (measured at 0-3years), or whether specific outcomes are associated with specific risks. We used data from the UK Millennium Cohort Study (N=10,376, 51% Female, 84% White) collected between 2001 and 2016. A single environment component was mostly sufficient for explaining cognition and parent-rated behavior outcomes. In contrast, adolescents' alcohol and tobacco use were specifically associated with their parents', and child-rated mental health was weakly associated with all risks. These findings suggest that with some exceptions, many different developmental outcomes share the same early environmental risk factors.

Genome-Wide Association Study of Motor Coordination.

The ability to finely control our movement is key to achieving many of the educational milestones and life-skills we develop throughout our lives. Despite the centrality of coordination to early development, there is a vast gap in our understanding of the underlying biology. Like most complex traits, both genetics and environment influence motor coordination, however, the specific genes, early environmental risk factors and molecular pathways are unknown. Previous studies have shown that about 5% of school-age children experience unexplained difficulties with motor coordination. These children are said to have Developmental Coordination Disorder (DCD). For children with DCD, these motor coordination difficulties significantly impact their everyday life and learning. DCD is associated with poorer academic achievement, reduced quality of life, it can constrain career opportunities and increase the risk of mental health issues in adulthood. Despite the high prevalence of coordination difficulties, many children remain undiagnosed by healthcare professionals. Compounding under-diagnosis in the clinic, research into the etiology of DCD is severely underrepresented in the literature. Here we present the first genome-wide association study to examine the genetic basis of early motor coordination in the context of motor difficulties. Using data from the Avon Longitudinal Study of Parents and Children we generate a derived measure of motor coordination from four components of the Movement Assessment Battery for Children, providing an overall measure of coordination across the full range of ability. We perform the first genome-wide association analysis focused on motor coordination (N = 4542). No single nucleotide polymorphisms (SNPs) met the threshold for genome-wide significance, however, 59 SNPs showed suggestive associations. Three regions contained multiple suggestively associated SNPs, within five preliminary candidate genes: IQSEC1, LRCC1, SYNJ2B2, ADAM20, and ADAM21. Association to the gene IQSEC1 suggests a potential link to axon guidance and dendritic projection processes as a potential underlying mechanism of motor coordination difficulties. This represents an interesting potential mechanism, and whilst further validation is essential, it generates a direct window into the biology of motor coordination difficulties. This research has identified potential biological drivers of DCD, a first step towards understanding this common, yet neglected neurodevelopmental disorder.

Sex-specific associations of basal steroid hormones and neuropeptides with Conduct Disorder and neuroendocrine mediation of environmental risk

Conduct Disorder (CD) is characterized by severe aggressive and antisocial behavior. The stress hormone system has frequently been investigated as a neurobiological correlate of CD, while other interacting neuroendocrine biomarkers of sex hormone or neuropeptide systems have rarely been studied, especially in females. We examined multiple basal neuroendocrine biomarkers in female and male adolescents with CD compared to healthy controls (HCs), and explored whether they mediate effects of environmental risk factors on CD. Within the FemNAT-CD study, salivary cortisol, alpha-amylase, testosterone, dehydroepiandrosterone-sulfate (DHEA-S), estradiol, progesterone, oxytocin, and arginine-vasopressin were measured under basal conditions in 166 pubertal adolescents with CD, and 194 sex-, age-, and puberty-matched HCs (60% females, 9–18 years). Further, environmental risk factors were assessed. Single hormone analyses showed higher DHEA-S, and lower estradiol and progesterone levels in both females and males with CD relative to HCs. When accounting for interactions between neuroendocrine systems, a male-specific sex hormone factor (testosterone/DHEA-S) predicted male CD, while estradiol and a stress-system factor (cortisol/alpha-amylase) interacting with oxytocin predicted female CD. Estradiol, progesterone, and oxytocin partly explained associations between early environmental risk and CD. Findings provide evidence for sex-specific associations between basal neuroendocrine measures and CD. Especially altered sex hormones (androgen increases in males, estrogen reductions in females) robustly related to CD, while basal stress-system measures did not. Early environmental risk factors for CD may act partly through their effects on the neuroendocrine system, especially in females. Limitations (e.g., basal neuroendocrine assessment, different sample sizes per sex, pubertal participants, exploratory mediation analyses) are discussed.

Associations between genes methylation, postnatal risk factors and psychiatric symptoms in a clinical sample of children and adolescents: Preliminar results from the remind longitudinal study

IntroductionEpigenetics hypothesizes a crucial link between postnatal risk factors, individual response to stress, DNA methylation and psychiatric symptomatology changes during life.ObjectivesWe analyzed methylation within two gene exons: NR3C1 and SLC6A4, which are involved in responses to environmental stressors. We investigated the relationship between methylation, postnatal risk factors and psychopathology assessed by Child Behavior Checklist (CBCL) in our help-seeking sample evaluated in infancy (W1), preadolescence (W2) and adult life (W3).MethodsPostnatal risk factors data were collected at W1 in 205 clinical subjects (156 M, 49 F; age=9,13±1,95). The CBCL scores were collected at W1 and W2 (W2 age=14,52±2,12). Data regarding methylation were collected at W2. At W3 we are also collecting clinical scores. A Spearman correlation coefficient was calculated between methylation percentage and clinical data at W2. The externalizing and internalizing trajectories were evaluated through repeated measure ANOVA with postnatal risk factors (presence/absence) as between-groups factor.ResultsSignificant associations were found between methylation and internalizing and total clinical scores (Table 1). The rm-ANOVA results showed a significant interaction between the CBCL internalizing score and presence/absence of postnatal risk, with higher internalizing problems in subjects that were exposed to postnatal risk factors. This effect was significant at W2 but not at W1 (Figure 1).ConclusionsPsychopathological symptoms trajectories could depend on epigenetics and early environmental risk factors. Further analyses will address a Linear Discriminant Analysis to proceed to a machine learning oriented approach.DisclosureNo significant relationships.

Cohort profile of the longitudinal Netherlands Study of Depression and Anxiety (NESDA) on etiology, course and consequences of depressive and anxiety disorders

IntroductionThe Netherlands Study of Depression and Anxiety (NESDA, www.nesda.nl) is a longitudinal, multi-site, naturalistic, case-control cohort study set up to examine the etiology, course and consequences of depressive and anxiety disorders. This paper presents a cohort profile of NESDA. Methods and ResultsThe NESDA sample recruited initially 2329 persons with a remitted or current DSM-IV based depressive (major depressive disorder, dysthymia) and/or anxiety disorder (panic disorder, social phobia, agoraphobia, generalized anxiety disorder), 367 of their siblings and 652 healthy controls, yielding a total of 3348 participants. Half-day face-to-face assessments of participants started in 2004 and since then have been repeated six times over a period of 9 years. A 13-year follow-up assessment is ongoing, at what time we also recruit offspring of participants. Retention rates are generally high, ranging from 87.1% (after 2 years) to 69.4% (after 9 years). Psychiatric diagnostic interviews have been administered at all face-to-face assessments, as was monitoring of clinical characteristics, psychosocial functioning and somatic health. Assessed etiological factors include e.g. early and current environmental risk factors, psychological vulnerability and resilience factors as well as (neuro)biology through hypothesis-driven biomarker assessments, genome-wide and large-scale ‘-omics’ assessments, and neuroimaging assessments. LimitationsThe naturalistic design allows research into course and consequences of affective disorders but is limited in treatment response interpretation. ConclusionsNESDA provides a strong research infrastructure for research into depressive and/or anxiety disorders. Its data have been used for many scientific papers describing either NESDA-based analyses or joint collaborative consortia-projects, and are in principle available to researchers outside the NESDA consortium.

Interaction of developmental factors and ordinary stressful life events on brain structure in adults

An interplay of early environmental and genetic risk factors with recent stressful life events (SLEs) in adulthood increases the risk for adverse mental health outcomes. The interaction of early risk and current SLEs on brain structure has hardly been investigated.Whole brain voxel-based morphometry analysis was performed in N = 786 (64.6% female, mean age = 33.39) healthy subjects to identify correlations of brain clusters with commonplace recent SLEs. Genetic and early environmental risk factors, operationalized as those for severe psychopathology (i.e., polygenic scores for neuroticism, childhood maltreatment, urban upbringing and paternal age) were assessed as modulators of the impact of SLEs on the brain.SLEs were negatively correlated with grey matter volume in the left medial orbitofrontal cortex (mOFC, FWE p = 0.003). This association was present for both, positive and negative, life events. Cognitive-emotional variables, i.e., neuroticism, perceived stress, trait anxiety, intelligence, and current depressive symptoms did not account for the SLE-mOFC association. Further, genetic and environmental risk factors were not correlated with grey matter volume in the left mOFC cluster and did not affect the association between SLEs and left mOFC grey matter volume.The orbitofrontal cortex has been implicated in stress-related psychopathology, particularly major depression in previous studies. We find that SLEs are associated with this area. Important early life risk factors do not interact with current SLEs on brain morphology in healthy subjects.

Evidence for familial clustering in breast cancer age of onset.

Familial clustering of age at onset would have implications for both personalized screening and aetiology, but has not been studied for breast cancer. We prospectively studied a cohort of 23145 sisters to explore whether their breast cancer risk changed near the age at diagnosis of a previously affected older sister. Using an age-time-dependent variable in a Cox regression model, we estimated hazard ratios for breast cancer when participants were near their sister's diagnosis age, relative to similarly aged women whose sister was diagnosed at a very different age. To rule out a correlation driven by young-onset familial cancer, we separately investigated women who had enrolled at age 50 or older. Of the 23145 women, 1412 developed breast cancer during follow-up (median 9.5 years). The estimated hazard ratio was 1.80 (95% confidence interval: 1.18, 2.74) at their sister's age at diagnosis, suggesting a substantial increase in risk compared with women of the same age but whose sister was diagnosed at a very different age. Restriction to women who enrolled at or after age 50 produced similar results. This familial clustering suggests that there may be important genetic and/or early environmental risk factors that influence the timing of breast cancer, even when onset is late in life. Personalized screening might need to account for the age at which a sister was earlier diagnosed with breast cancer.