A quantitative analysis of fidgeting in ADHD and its relation to performance and sustained attention on a cognitive task.

Introduction: Attention-Deficit/Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder where hyperactivity often manifests as fidgeting, a non-goal-directed motoric action. Many studies demonstrate fidgeting varies under different conditions as a self-regulating mechanism for attention and alertness during cognitively demanding tasks. Fidgeting has also been associated with reaction time variability. However, a lack of standard variables to define and quantify fidgeting can lead to discrepancies in data and interpretability issues across studies. Furthermore, little is known about fidgeting in adults with ADHD compared to youth. This study aims to design a framework to quantify meaningful fidgeting variables and to apply them to test the relation between fidgeting and performance on a cognitive task, the Flanker, in adults with ADHD. Method: Our study included 70 adult participants diagnosed with ADHD, aged 18-50 years (30.5 ± 7.2 years). Screening included a structured clinical interview, childhood, current self and current observer ratings of ADHD symptoms. Actigraphy devices were attached to the left wrist and right ankle during completion of a cognitive control, attention task (the Flanker). Laboratory testing was subsequently completed on a single day. The relation between task performance, reaction time variability and fidgeting was examined. Results and Discussion: Our analysis revealed increased fidgeting during correct trials as defined by our new variables, consistent with previous observations. Furthermore, differences in fidgeting were observed between early and later trials while the percentage of correct trials were not significantly different. This suggests a relation between the role of fidgeting and sustaining attention. Participants with low reaction time variability, that is, those with more consistent reaction times, fidgeted more during later trials. This observation supports the theory that fidgeting aids arousal and improves sustained attention. Finally, a correlation analysis using ADHD-symptom rating scales validated the relevance of the fidget variables in relation to ADHD symptom severity. These findings suggest fidgeting may be a compensatory mechanism that aids in sustained attention for those with ADHD, although alternative explanations exist. Conclusion: Our study suggests that fidgeting may aid in sustained attention during the attention-demanding, cognitive control processes for adults with ADHD, with more fidgeting observed during correct trials and among participants with lower reaction time variability. Furthermore, the newly defined fidget variables were validated through a significant correlation with ADHD rating scales. By sharing our implementation of fidget variables, we hope to standardize and encourage further quantitative research into the role of fidgeting in ADHD.

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 exposures to phthalates in association with attention-deficit/hyperactivity disorder behaviors in middle childhood and adolescence in the ReCHARGE study.

BACKGROUND: Early-life exposure to phthalates alters behaviors in animals. However, epidemiological evidence on childhood phthalate exposure and attention-deficit/hyperactivity disorder (ADHD) behaviors is limited. METHODS: This study included 243 children from the ReCHARGE (Revisiting Childhood Autism Risks from Genetics and Environment) study, who were previously classified as having autism spectrum disorder (ASD), developmental delay, other early concerns, and typical development in the CHARGE case-control study. Twenty phthalate metabolites were measured in spot urine samples collected from children aged 2-5 years. Parents reported on children's ADHD symptoms at ages 8-18 years using Conners-3 Parent Rating Scale. Covariate-adjusted negative binomial generalized linear models were used to investigate associations between individual phthalate metabolite concentrations and raw scores. Weighted quantile sum (WQS) regression with repeated holdout validation was used to examine mixture effects of phthalate metabolites on behavioral scores. Effect modification by child sex was evaluated. RESULTS: Among 12 phthalate metabolites detected in >75% of the samples, higher mono-2-heptyl phthalate (MHPP) was associated with higher scores on Inattentive (ß per doubling = 0.05, 95% confidence interval [CI]: 0.02, 0.08) and Hyperactive/Impulsive scales (ß = 0.04, 95% CI: 0.00, 0.07), especially among children with ASD. Higher mono-carboxy isooctyl phthalate (MCiOP) was associated with higher Hyperactivity/Impulsivity scores (ß = 0.07, 95% CI: -0.01, 0.15), especially among typically developing children. The associations of the molar sum of high molecular weight (HMW) phthalate metabolites and a phthalate metabolite mixture with Hyperactivity/Impulsivity scores were modified by sex, showing more pronounced adverse associations among females. CONCLUSION: Exposure to phthalates during early childhood may impact ADHD behaviors in middle childhood and adolescence, particularly among females. Although our findings may not be broadly generalizable due to the diverse diagnostic profiles within our study population, our robust findings on sex-specific associations warrant further investigations.

Green Space and Internalizing or Externalizing Symptoms Among Children.

Importance: Evidence suggests that living near green space supports mental health, but studies examining the association of green space with early mental health symptoms among children are rare. Objective: To evaluate the association between residential green space and early internalizing (eg, anxiety and depression) and externalizing (eg, aggression and rule-breaking) symptoms. Design, Setting, and Participants: Data for this cohort study were drawn from the Environmental Influences on Child Health Outcomes cohort; analysis was conducted from July to October 2023. Children born between 2007 and 2013 with outcome data in early (aged 2-5 years) and/or middle (aged 6-11 years) childhood who resided in 41 states across the US, drawing from clinic, hospital, and community-based cohorts, were included. Cohort sites were eligible if they recruited general population participants and if at least 30 children had outcome and residential address data to measure green space exposure. Nine cohorts with 13 sites met these criteria. Children diagnosed with autism or developmental delay were excluded, and 1 child per family was included. Exposures: Green space exposure was measured using a biannual (ie, summer and winter) Normalized Difference Vegetation Index, a satellite image-based indicator of vegetation density assigned to monthly residential history from birth to outcome assessment. Main Outcome and Measures: Child internalizing and externalizing symptoms were assessed using the Child Behavior Checklist for Ages 1½ to 5 or 6 to 18. The association between green space and internalizing and externalizing symptoms was modeled with multivariable linear regression using generalized estimating equations, adjusting for birthing parent educational level, age at delivery, child sex, prematurity, and neighborhood socioeconomic vulnerability. Models were estimated separately for early and middle childhood samples. Results: Among 2103 children included, 1061 (50.5%) were male; 606 (29.1%) identified as Black, 1094 (52.5%) as White, 248 (11.9%) as multiple races, and 137 (6.6%) as other races. Outcomes were assessed at mean (SD) ages of 4.2 (0.6) years in 1469 children aged 2 to 5 years and 7.8 (1.6) years in 1173 children aged 6 to 11 years. Greater green space exposure was associated with fewer early childhood internalizing symptoms in fully adjusted models (b = -1.29; 95% CI, -1.62 to -0.97). No associations were observed between residential green space and internalizing or externalizing symptoms in middle childhood. Conclusions and Relevance: In this study of residential green space and children's mental health, the association of green space with fewer internalizing symptoms was observed only in early childhood, suggesting a sensitive period for nature exposure. Policies protecting and promoting access to green space may help alleviate early mental health risk.

Neurophysiological Patterns of Attention and Distraction during Realistic Virtual-Reality Classroom Learning in Adults with and without ADHD.

Many people, and particularly those diagnosed with ADHD, report difficulties maintaining attention and proneness to distraction during classroom learning. However, the behavioral, neural and physiological basis of attention in realistic learning contexts is not well understood, since current clinical and scientific tools used for evaluating and quantifying the constructs of "distractibility" and "inattention", are removed from the real-life experience in organic classrooms. Here we introduce a novel Virtual Reality (VR) platform for studying students' brain activity and physiological responses as they immerse in realistic frontal classroom learning. Using this approach, we studied whether adults with and without ADHD (N=49) exhibit differences in neurophysiological metrics associated with sustained attention, such as speech-tracking of the teacher's voice, power of alpha-oscillations and levels of arousal, as well as responses to potential disturbances by background sound-events in the classroom. Under these ecological conditions, we find that adults with ADHD exhibit higher auditory neural response to background sounds relative to their control-peers, which also contributed to explaining variance in the severity of ADHD symptoms, together with higher power of alpha-oscillations and more frequent gaze-shifts around the classroom. These results are in-line with higher sensitivity to irrelevant stimuli in the environment and increased mind-wandering/boredom. At the same time, both groups exhibited similar learning outcomes and showed similar neural tracking of the teacher's speech. This suggests that in this context, attention may not operate as a zero-sum game and that allocating some resources to irrelevant stimuli does not always detract from performing the task at hand. Given the dire need for more objective, dimensional and ecologically-valid measures of attention and its real-life deficits, this work provides new insights into the neurophysiological manifestations of attention and distraction experienced in real-life contexts, while challenging some prevalent notions regarding the nature of attentional challenges experienced by those with ADHD.

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.

Prediction of internalizing and externalizing symptoms in late childhood from attention-deficit/hyperactivity disorder symptoms in early childhood.

Limited analyses based on national samples have assessed whether early attention-deficit/hyperactivity disorder (ADHD) symptoms predict later internalizing and externalizing symptoms in youth and the influence of sex and pubertal timing on subsequent psychiatric symptoms. This study analyzed data (n = 2818) from the Environmental influences on Child Health Outcomes Program national cohort. Analyses used data from early childhood (mean age = 5.3 years) utilizing parent-reported ADHD symptoms to predict rates of internalizing and externalizing symptoms from late childhood/adolescence (mean age = 11.9 years). Within a subsample age at peak height velocity (APHV) acted as a proxy to assess pubertal timing from early childhood (mean age = 5.4 years) to adolescence (mean age = 12.3 years). Early-childhood ADHD symptoms predicted later psychiatric symptoms, including anxiety, depression, aggressive behavior, conduct problems, oppositional defiant disorder, and rule-breaking behavior. Earlier APHV was associated with increased Conduct Disorder symptoms from late childhood to adolescence for females only. A stronger relation between ADHD symptoms and later aggression was observed in females with earlier APHV, whereas this same pattern with aggression, conduct problems and depression was observed in males with later APHV. Clinicians should consider that both young girls and boys with elevated ADHD symptoms, particularly with off-set pubertal timing, may be at risk for later psychiatric symptoms.

Maternal education prospectively predicts child neurocognitive function: An environmental influences on child health outcomes study.

A large body of research has established a relation between maternal education and children's neurocognitive functions, such as executive function and language. However, most studies have focused on early childhood and relatively few studies have examined associations with changes in maternal education over time. Consequently, it remains unclear if early maternal education is longitudinally related to neurocognitive functions in children, adolescents, and young adults. In addition, the associations between changes in maternal education across development and more broadly defined neurocognitive outcomes remain relatively untested. The current study leveraged a large multicohort sample to examine the longitudinal relations between perinatal maternal education and changes in maternal education during development with children's, adolescents', and young adults' neurocognitive functions (N = 2,688; Mage = 10.32 years; SDage = 4.26; range = 3-20 years). Moreover, we examined the differential effects of perinatal maternal education and changes in maternal education across development on executive function and language performance. Perinatal maternal education was positively associated with children's later overall neurocognitive function. This longitudinal relation was stronger for language than executive function. In addition, increases in maternal education were related to improved language performance but were not associated with executive functioning performance. Our findings support perinatal maternal education as an important predictor of neurocognitive outcomes later in development. Moreover, our results suggest that examining how maternal education changes across development can provide important insights that can help inform policies and interventions designed to foster neurocognitive development. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Using Hot and Cool Measures to Phenotype and Predict Functional Outcomes Across Dimensions of ADHD and Typical Development in Adolescents.

Multiple pathway models propose that attention deficit hyperactivity disorder (ADHD) arises from dysfunction in separate systems comprised of a "cool" or cognitive pathway versus a "hot" or emotional/reward pathway. Interactions between these pathways and the degree of maturation may further determine functional outcomes for adolescents ranging from those diagnosed with ADHD to typical development (TD). We used a latent profile analysis on rating scales and behavioral task performance assessing emotion, irritability, impulsivity, risk-taking, future orientation, and processing speed (PS) to identify subgroups of TD adolescents and adolescents with ADHD (N = 152) based on the hot and cool pathway model. We identified four classes: 1) High-Complex Challenges; 2) Moderate-Mixed Challenges; 3) Non-Emotive Impulsivity; and 4) High Regulation and Control. A multiple pathway model of ADHD is supported with classes differing in degree of emotional lability and irritability, types of impulsivity, and ability to use future consequences to modulate impulsivity and PS. The classes differed regarding functional behavior, with the High-Complex class demonstrating the most severe functional challenges in academic-related functioning. The Moderate-Mixed class also displayed significant functional challenges but with moderate emotional lability and irritability ratings. The Non-Emotive Impulsivity class exhibited low emotionality and low irritability, yet high impulsivity with limited negative functional consequences, and was composed of a mix of ADHD and TD adolescents. Differences between classes suggest ADHD symptomatology may represent both categorical and dimensional differences. Precision health interventions may be more effective in addressing the specific challenges associated with the classes rather than a one-size-fits-all approach to treating ADHD.

Editorial: The Use of Continuous Performance Tasks in Attention-Deficit/Hyperactivity Disorder Diagnosis: A Cautionary Note.

Computer-based cognitive tasks aimed at assessing attention and executive function are used regularly-for both clinical and research purposes-with the belief that they provide an objective assessment of symptoms associated with attention-deficit/hyperactivity disorder (ADHD). As rates of the diagnosis of ADHD appear to be exploding, particularly since the onset of COVID-19,1 there is no doubt as to the need for reliable and valid diagnostic tools for ADHD. One of the most common types of such cognitive tests is continuous performance tasks (CPTs), which putatively not only help in diagnosing ADHD but can differentiate between ADHD subtypes. We urge diagnosticians to take a more cautious approach toward this practice and reconsider how CPTs are used given new evidence.

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.

Experimental Therapeutics: Opportunities and Challenges Stemming From the National Institute of Mental Health Workshop on Novel Target Discovery and Psychosocial Intervention Development.

There has been slow progress in the development of interventions that prevent and/or reduce mental-health morbidity and mortality. The National Institute of Mental Health (NIMH) launched an experimental-therapeutics initiative with the goal of accelerating the development of effective interventions. The emphasis is on interventions designed to engage a target mechanism. A target mechanism is a process (e.g., behavioral, neurobiological) proposed to underlie change in a defined clinical endpoint and through change in which an intervention exerts its effect. This article is based on discussions from an NIMH workshop conducted in February 2020 and subsequent conversations among researchers using this approach. We discuss the components of an experimental-therapeutics approach such as clinical-outcome selection, target definition and measurement, intervention design and selection, and implementation of a team-science strategy. We emphasize the important contributions of different constituencies (e.g., patients, caregivers, providers) in deriving hypotheses about novel target mechanisms. We highlight strategies for target-mechanism identification using published and hypothetical examples. We consider the decision-making dilemmas that arise with different patterns of results in purported mechanisms and clinical outcomes. We end with considerations of the practical challenges of this approach and the implications for future directions of this initiative.

Identifying the Information Needs and Format Preferences for Web-Based Content Among Adults With or Parents of Children With Attention-Deficit/Hyperactivity Disorder: Three-Stage Qualitative Analysis.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is a highly prevalent childhood and adult behavioral disorder. Internet searches for ADHD information are rising, particularly for diagnosis and treatment. Despite effective ADHD treatments, research suggests that there are delays in seeking help for ADHD. Identifying ways to shorten delays is important for minimizing morbidity associated with ADHD. One way to shorten these delays is to improve internet health information resources. Research shows that parents of children with ADHD feel that much of the information available is technical and not tailored for their child's needs and verbal instructions given by health care providers were too pharmacologically focused with limited information about how to manage and support ADHD symptoms in daily living. A majority of parents search the internet for general and pharmacological information for ADHD and prefer web-based resources for learning about ADHD, but web-based resources may be inaccurate and of low quality. Ensuring accurate information through the internet is an important step in assisting parents and adults in making informed decisions about the diagnosis and treatment of ADHD. OBJECTIVE: Although a great deal of information regarding ADHD is available on the internet, some information is not based on scientific evidence or is difficult for stakeholders to understand. Determining gaps in access to accurate ADHD information and stakeholder interest in the type of information desired is important in improving patient engagement with the health care system, but minimal research addresses these needs. This study aims to determine the information needs and formatting needs of web-based content for adults with ADHD and parents of children with ADHD in order to improve user experience and engagement. METHODS: This was a 3-phase study consisting of in-depth phone interviews about experiences with ADHD and barriers searching for ADHD-related information, focus groups where participants were instructed to consider the pathways by which they made decisions using web-based resources, and observing participants interacting with a newly developed website tailored for adults with potential ADHD and caregivers of children who had or might have ADHD. Phase 1 individual interviews and phase 2 focus groups identified the needs of the ADHD stakeholders related to website content and format. Interview and focus group findings were used to develop a website. Phase 3 used think-aloud interviews to evaluate website usability to inform the tailoring of the website based on user feedback. RESULTS: Interviews and focus group findings revealed preferences for ADHD website information and content, website layout, and information sources. Themes included a preference for destigmatizing information about ADHD, information specific to patient demographics, and evidence-based information tailored to lay audiences. CONCLUSIONS: ADHD stakeholders are specifically seeking positive information about ADHD presented in a user-friendly format.

Sociodemographic Differences in COVID-19 Pandemic Experiences Among Families in the United States.

Importance: Few population-based studies in the US collected individual-level data from families during the COVID-19 pandemic. Objective: To examine differences in COVID-19 pandemic-related experiences in a large sociodemographically diverse sample of children and caregivers. Design, Setting, and Participants: The Environmental influences on Child Health Outcomes (ECHO) multi-cohort consortium is an ongoing study that brings together 64 individual cohorts with participants (24 757 children and 31 700 caregivers in this study) in all 50 US states and Puerto Rico. Participants who completed the ECHO COVID-19 survey between April 2020 and March 2022 were included in this cross-sectional analysis. Data were analyzed from July 2021 to September 2022. Main Outcomes and Measures: Exposures of interest were caregiver education level, child life stage (infant, preschool, middle childhood, and adolescent), and urban or rural (population <50 000) residence. Dependent variables included COVID-19 infection status and testing; disruptions to school, child care, and health care; financial hardships; and remote work. Outcomes were examined separately in logistic regression models mutually adjusted for exposures of interest and race, ethnicity, US Census division, sex, and survey administration date. Results: Analyses included 14 646 children (mean [SD] age, 7.1 [4.4] years; 7120 [49%] female) and 13 644 caregivers (mean [SD] age, 37.6 [7.2] years; 13 381 [98%] female). Caregivers were racially (3% Asian; 16% Black; 12% multiple race; 63% White) and ethnically (19% Hispanic) diverse and comparable with the US population. Less than high school education (vs master's degree or more) was associated with more challenges accessing COVID-19 tests (adjusted odds ratio [aOR], 1.88; 95% CI, 1.06-1.58), lower odds of working remotely (aOR, 0.04; 95% CI, 0.03-0.07), and more food access concerns (aOR, 4.14; 95% CI, 3.20-5.36). Compared with other age groups, young children (age 1 to 5 years) were least likely to receive support from schools during school closures, and their caregivers were most likely to have challenges arranging childcare and concerns about work impacts. Rural caregivers were less likely to rank health concerns (aOR, 0.77; 95% CI, 0.69-0.86) and social distancing (aOR, 0.82; 95% CI, 0.73-0.91) as top stressors compared with urban caregivers. Conclusions: Findings in this cohort study of US families highlighted pandemic-related burdens faced by families with lower socioeconomic status and young children. Populations more vulnerable to public health crises should be prioritized in recovery efforts and future planning.

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

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

Latent Class Analysis of Prenatal Substance Exposure and Child Behavioral Outcomes.

OBJECTIVES: To predict behavioral disruptions in middle childhood, we identified latent classes of prenatal substance use. STUDY DESIGN: As part of the Environmental influences on Child Health Outcomes Program, we harmonized prenatal substance use data and child behavior outcomes from 2195 women and their 6- to 11-year-old children across 10 cohorts in the US and used latent class-adjusted regression models to predict parent-rated child behavior. RESULTS: Three latent classes fit the data: low use (90.5%; n = 1986), primarily using no substances; licit use (6.6%; n = 145), mainly using nicotine with a moderate likelihood of using alcohol and marijuana; and illicit use (2.9%; n = 64), predominantly using illicit substances along with a moderate likelihood of using licit substances. Children exposed to primarily licit substances in utero had greater levels of externalizing behavior than children exposed to low or no substances (P = .001, d = .64). Children exposed to illicit substances in utero showed small but significant elevations in internalizing behavior than children exposed to low or no substances (P < .001, d = .16). CONCLUSIONS: The differences in prenatal polysubstance use may increase risk for specific childhood problem behaviors; however, child outcomes appeared comparably adverse for both licit and illicit polysubstance exposure. We highlight the need for similar multicohort, large-scale studies to examine childhood outcomes based on prenatal substance use profiles.

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.

Childhood exposure to per- and polyfluoroalkyl substances and neurodevelopment in the CHARGE case-control study.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are shown to have neurotoxic effects on animals, but epidemiological evidence for associations between childhood PFAS exposure and neurodevelopment is inconclusive. We examined if childhood PFAS concentrations are associated with a diagnosis of autism spectrum disorder (ASD), developmental delay (DD), and other early concerns (OEC) in development. METHODS: We included 551 children 2-5 years old from the CHildhood Autism Risks from Genetics and Environment (CHARGE) case-control study. Children were clinically diagnosed and classified as having ASD, DD, OEC, and typical development (TD). Fourteen PFAS were quantified in child serum samples collected when diagnostic assessments were performed. We used multinomial logistic regression models to investigate the cross-sectional associations of individual PFAS concentrations with neurodevelopmental outcomes and weighted quantile sum (WQS) regression models with repeated holdout validation to investigate the associations with PFAS mixtures. RESULTS: Childhood perfluorooctanoic acid (PFOA) was associated with increased odds of ASD (odds ratio [OR] per ln ng/mL increase: 1.99, 95% confidence interval [CI]: 1.20, 3.29) and DD (OR: 2.16, 95% CI: 1.21, 3.84) versus TD. Perfluoroheptanoic acid (PFHpA) was associated with increased odds of ASD (OR: 1.61, 95% CI: 1.21, 2.13). However, perfluroundecanoic acid (PFUnDA) was associated with decreased odds of ASD (OR: 0.43, 95% CI: 0.26, 0.69). From mixture analyses, the WQS index was associated with increased odds of ASD (average OR: 1.57, 5th and 95th percentile: 1.16, 2.13). Child's sex and homeownership modified associations of perfluorodecanoic acid (PFDA) with DD and ASD, respectively. CONCLUSIONS: In this case-control study, childhood PFOA, PFHpA, and a PFAS mixture was associated with increased odds of ASD, while PFUnDA was associated with decreased odds of ASD. Because we used concurrent measurements of PFAS, our results do not imply causal relationships and thus need to be interpreted with caution.

Working Memory Training in Youth With Autism, Fragile X, and Intellectual Disability: A Pilot Study.

This pilot study sought to identify potential markers of improvement from pre-post treatment in response to computerized working memory (WM) training for youth (ages 8-18) with autism spectrum disorder (ASD) and comorbid intellectual disability (ID) in a single arm, pre-post design. Participants included 26 children with ASD and 18 with comorbid ASD and fragile X syndrome (ASD+FXS). Analyses were adjusted for age and IQ. The ASD group demonstrated greater improvement on WM training relative to the ASD+FXS group. Participants improved on WM and far transfer outcomes, however, there were no significant group differences in improvement except for repetitive behavior. Higher hyperactivity/impulsivity ratings predicted lower performance on visuospatial WM. Findings suggest cognitive training may be beneficial for youth with ASD and ID, warranting further exploration.