Examining the association between prenatal cannabis exposure and child autism traits: A multi-cohort investigation in the environmental influences on child health outcome program.

This study examined the association between prenatal cannabis exposure and autism spectrum disorder (ASD) diagnoses and traits. A total sample of 11,570 children (ages 1-18; 53% male; 25% Hispanic; 60% White) from 34 cohorts of the National Institutes of Health-funded environmental influences on child health outcomes consortium were included in analyses. Results from generalized linear mixed models replicated previous studies showing that associations between prenatal cannabis exposure and ASD traits in children are not significant when controlling for relevant covariates, particularly tobacco exposure. Child biological sex did not moderate the association between prenatal cannabis exposure and ASD. In a large sample and measuring ASD traits continuously, there was no evidence that prenatal cannabis exposure increases the risk for ASD. This work helps to clarify previous mixed findings by addressing concerns about statistical power and ASD measurement.

Early childhood exposure to environmental phenols and parabens, phthalates, organophosphate pesticides, and trace elements in association with attention deficit hyperactivity disorder (ADHD) symptoms in the CHARGE study.

BACKGROUND: A growing body of literature investigated childhood exposure to environmental chemicals in association with attention-deficit/hyperactivity disorder (ADHD) symptoms, but limited studies considered urinary mixtures of multiple chemical classes. This study examined associations of concurrent exposure to non-persistent chemicals with ADHD symptoms in children diagnosed with autism spectrum disorder (ASD), developmental delay (DD), and typical development (TD). METHODS: A total of 549 children aged 2-5 years from the Childhood Autism Risks from Genetics and Environment (CHARGE) case-control study were administered the Aberrant Behavior Checklist (ABC). This study focused on the ADHD/noncompliance subscale and its two subdomains (hyperactivity/impulsivity, inattention). Sixty-two chemicals from four classes (phenols/parabens, phthalates, organophosphate pesticides, trace elements) were quantified in child urine samples, and 43 chemicals detected in > 70% samples were used to investigate their associations with ADHD symptoms. Negative binomial regression was used for single-chemical analysis, and weighted quantile sum regression with repeated holdout validation was applied for mixture analysis for each chemical class and all chemicals. The mixture analyses were further stratified by diagnostic group. RESULTS: A phthalate metabolite mixture was associated with higher ADHD/noncompliance scores (median count ratio [CR] = 1.10; 2.5th, 97.5th percentile: 1.00, 1.21), especially hyperactivity/impulsivity (median CR = 1.09; 2.5th, 97.5th percentile: 1.00, 1.25). The possible contributors to these mixture effects were di-2-ethylhexyl phthalate (DEHP) metabolites and mono-2-heptyl phthalate (MHPP). These associations were likely driven by children with ASD as these were observed among children with ASD, but not among TD or those with DD. Additionally, among children with ASD, a mixture of all chemicals was associated with ADHD/noncompliance and hyperactivity/impulsivity, and possible contributors were 3,4-dihydroxy benzoic acid, DEHP metabolites, MHPP, mono-n-butyl phthalate, and cadmium. CONCLUSIONS: Early childhood exposure to a phthalate mixture was associated with ADHD symptoms, particularly among children with ASD. While the diverse diagnostic profiles limited generalizability, our findings suggest a potential link between phthalate exposure and the comorbidity of ASD and ADHD.

Strategies for recruitment and retention of adolescent and young adult cancer patients in research studies.

We conducted a literature review to identify commonly used recruitment and retention strategies in research among adolescent and young adult (AYA) cancer survivors 15-39 years of age and examine the effectiveness of these strategies based on the reported recruitment and retention rates. We identified 18 publications published after 2010, including 14 articles describing recruitment strategies and four articles discussing retention strategies and addressing reasons for AYA cancer patients dropping out of the studies. In terms of recruitment, Internet and social networking strategies were used most frequently and resulted in higher participation rates of AYA cancer survivors compared to other conventional methods, such as hospital-based outreach, mailings, and phone calls. In terms of retention, investigators used monetary incentives in all four studies and regular emails in two studies. There was no association between the number of strategies employed and the overall recruitment (p = 0.09) and retention rates (p = 0.33). Future research and planned studies testing recruitment and retention strategies are needed to identify optimal, modern communication procedures to increase AYA participation and adherence. More education should be provided to AYAs to increase their knowledge of research studies and strengthen the connection between AYA cancer survivors and their health providers.

Perinatal Factors and Emotional, Cognitive, and Behavioral Dysregulation in Childhood and Adolescence.

OBJECTIVE: This cohort study assessed perinatal factors known to be related to maternal and neonatal inflammation and hypothesized that several would be associated with emotional, cognitive, and behavioral dysregulation in youth. METHOD: The Environmental influences on Child Health Outcomes (ECHO) is a research consortium of 69 pediatric longitudinal cohorts. A subset of 18 cohorts that had both Child Behavior Checklist (CBCL) data on children (6-18 years) and information on perinatal exposures including maternal prenatal infections was used. Children were classified as having the CBCL-Dysregulation Profile (CBCL-DP) if the sum of their T scores for 3 CBCL subscales (attention, anxious/depressed, and aggression) was ≥180. Primary exposures were perinatal factors associated with maternal and/or neonatal inflammation, and associations between these and outcome were assessed. RESULTS: Approximately 13.4% of 4,595 youth met criteria for CBCL-DP. Boys were affected more than girls (15.1% vs 11.5%). More youth with CBCL-DP (35%) were born to mothers with prenatal infections compared with 28% of youth without CBCL-DP. Adjusted odds ratios indicated the following were significantly associated with dysregulation: having a first-degree relative with a psychiatric disorder; being born to a mother with lower educational attainment, who was obese, had any prenatal infection, and/or who smoked tobacco during pregnancy. CONCLUSION: In this large study, a few modifiable maternal risk factors with established roles in inflammation (maternal lower education, obesity, prenatal infections, and smoking) were strongly associated with CBCL-DP and could be targets for interventions to improve behavioral outcomes of offspring. DIVERSITY & INCLUSION STATEMENT: We worked to ensure race, ethnic, and/or other types of diversity in the recruitment of human participants. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented sexual and/or gender groups in science. We actively worked to promote sex and gender balance in our author group. The author list of this paper includes contributors from the location and/or community where the research was conducted who participated in the data collection, design, analysis, and/or interpretation of the work.

Early childhood exposure to environmental phenols and parabens, phthalates, organophosphate pesticides, and trace elements in association with attention deficit hyperactivity disorder (ADHD) symptoms in the CHARGE study.

Background: Agrowing body of literature investigated childhood exposure to environmental chemicals in association with attention deficit hyperactivity disorder (ADHD) symptoms, but limited studies considered urinary mixtures of multiple chemical classes. This study examined associations of concurrent exposure to non-persistent chemicals with ADHD symptoms in children diagnosed with autism spectrum disorder (ASD), developmental delay, and typical development. Methods: A total of 574 children aged 2-5 years from the Childhood Autism Risks from Genetics and Environment (CHARGE) case-control study was administered the Aberrant Behavior Checklist (ABC). This study focused on the Hyperactivity subscale and its two subdomains (hyperactivity/impulsivity, inattention). Sixty-two chemicals from four classes (phenols/parabens, phthalates, organophosphate pesticides, trace elements) were quantified in child urine samples, and 43 chemicals detected in >70% samples were used in statistical analyses. Weighted quantile sum regression for negative binomial outcomes with repeated holdout validation was performed to investigate covariate-adjusted associations between mixtures and ABC scores in 574 children. The mixture analyses were further restricted to 232 children with ASD. Results: Phthalate metabolite mixtures, weighted for mono-n-butylphthalate (MNBP), mono-2-heptyl phthalate, and mono-carboxy isononyl phthalate, were associated with the Hyperactivity subscale (mean incidence rate ratio [mIRR] = 1.11; 2.5th, 97.5th percentile: 1.00, 1.23), especially the hyperactivity/impulsivity subdomain (mIRR = 1.14; 2.5th, 97.5th percentile: 1.06, 1.26). These associations remained similar after restricting to children with ASD. The inattention subdomain was associated with a phenols/parabens mixture, weighted for several parabens and bisphenols (mIRR = 1.13; 2.5th, 97.5th percentile: 1.00, 1.28) and a total mixture, weighted for 3,4-dihydroxy benzoic acid, MNBR and mono-(2-ethyl-5-carboxypentyl) phthalate (mIRR = 1.11; 2.5th, 97.5th percentile: 1.01,1.25) only among children with ASD. Conclusions: Concurrent exposure to phthalate mixtures was associated with hyperactivity in early childhood. Though causal inference cannot be made based on our cross-sectional findings, this study warrants further research on mixtures of larger number of chemicals from multiple classes in association with ADHD-related behaviors in young children.

Environmental exposures to pesticides, phthalates, phenols and trace elements are associated with neurodevelopment in the CHARGE study.

OBJECTIVE: To determine if higher exposures measured in early childhood to environmental phenols, phthalates, pesticides, and/or trace elements, are associated with increased odds of having a diagnosis of Autism Spectrum Disorder (ASD), Developmental Delay (DD), or Other Early Concerns (OEC) compared to typically developing children (TD). METHODS: This study included 627 children between the ages of 2-5 who participated in the Childhood Autism Risks from Genetics and Environment (CHARGE) study. Urine samples were collected at the same study visit where diagnostic assessments to confirm diagnosis indicated during the recruitment process were performed. Adjusted multinomial regression models of each chemical with diagnosis as the outcome were conducted. Additionally, two methods were used to analyze mixtures: repeated holdout multinomial weighted quantile sum (WQS) regression for each chemical class; and a total urinary mixture effect was assessed with repeated holdout random subset WQS. RESULTS: Many urinary chemicals were associated with increased odds of ASD, DD or OEC compared to TD; however, most did not remain significant after false discovery rate adjustment. Repeated holdout WQS indices provided evidence for associations of both a phenol/paraben mixture effect and a trace element mixture effect on DD independently. In analyses adjusted for confounders and other exposures, results suggested an association of a pesticide mixture effect with increased risk for ASD. Results also suggested associations of a total urinary mixture with greater odds of both ASD and DD separately. CONCLUSION: Higher concentrations of urinary biomarkers were associated with ASD, DD, and OEC compared to TD, with consistency of the results comparing single chemical analyses and mixture analyses. Given that the biospecimens used for chemical analysis were generally collected many months after diagnoses were made, the direction of any causal association is unknown. Hence findings may reflect higher exposures among children with non-typical development than TD children due to differences in behaviors, metabolism, or toxicokinetics.

Childhood and adolescent onset psychiatric disorders, substance use, and failure to graduate high school on time.

We examined the joint predictive effects of childhood and adolescent onset psychiatric and substance use disorders on failure to graduate high school (HS) on time. Structured diagnostic interviews were conducted with a US national sample of adults (18 and over). The analysis sample included respondents with at least 8 years of education who were born in the US or arrived in the US prior to age 13 (N = 29,662). Psychiatric disorders, substance use and substance use disorders were examined as predictors of termination or interruption of educational progress prior to HS graduation, with statistical adjustment for demographic characteristics and childhood adversities. Failure to graduate HS on time was more common among respondents with any of the psychiatric and substance use disorders examined, ranging from 18.1% (specific phobia) to 33.2% (ADHD-combined type), compared with respondents with no disorder (15.2%). After adjustment for co-occurring disorders, significant associations with failure to graduate on time remained only for conduct disorder (OR = 1.89, 95% CI 1.57-2.26) and the three ADHD subtypes (Inattentive OR = 1.78, 95% CI 1.44-2.20, Hyperactive-Impulsive OR = 1.38, 95% CI 1.14-1.67, and Combined OR = 2.06, 95% CI 1.66-2.56). Adjusting for prior disorders, tobacco use was associated with failure to graduate on time (OR = 1.97, 95% CI 1.80-2.16). Among substance users, substance use disorders were not associated with on-time graduation. The findings suggest that the adverse impact of childhood and adolescent onset psychiatric disorders on HS graduation is largely accounted for by problems of conduct and inattention. Adjusting for these disorders, smoking remains strongly associated with failure to graduate HS on time.