Neurodevelopmental assessment of normocephalic children born to Zika virus exposed and unexposed pregnant people.

BACKGROUND: Studies examining the association between in utero Zika virus (ZIKV) exposure and child neurodevelopmental outcomes have produced varied results. METHODS: We aimed to assess neurodevelopmental outcomes among normocephalic children born from pregnant people enrolled in the Zika in Pregnancy in Honduras (ZIPH) cohort study, July-December 2016. Enrollment occurred during the first prenatal visit. Exposure was defined as prenatal ZIKV IgM and/or ZIKV RNA result at enrollment. Normocephalic children, >6 months old, were selected for longitudinal follow-up using the Bayley Scales of Infant and Toddler Development (BSID-III) and the Ages & Stages Questionnaires: Social-Emotional (ASQ:SE-2). RESULTS: One hundred fifty-two children were assessed; after exclusion, 60 were exposed and 72 were unexposed to ZIKV during pregnancy. Twenty children in the exposed group and 21 children in the unexposed group had a composite score <85 in any of the BSID-III domains. Although exposed children had lower cognitive and language scores, differences were not statistically significant. For ASQ:SE-2 assessment, there were not statistically significant differences between groups. CONCLUSIONS: This study found no statistically significant differences in the neurodevelopment of normocephalic children between in utero ZIKV exposed and unexposed. Nevertheless, long-term monitoring of children with in utero ZIKV exposure is warranted. IMPACT: This study found no statistically significant differences in the neurodevelopment in normocephalic children with in utero Zika virus exposure compared to unexposed children, although the exposed group showed lower cognitive and language scores that persisted after adjustment by maternal age and education and after excluding children born preterm and low birth weight from the analysis. Children with prenatal Zika virus exposure, including those normocephalic and have no evidence of abnormalities at birth, should be monitored for neurodevelopmental delays. Follow-up is important to be able to detect developmental abnormalities that might not be detected earlier in life.

Reasons for participation in a child development study: Are cases with developmental diagnoses different from controls?

BACKGROUND: Current knowledge about parental reasons for allowing child participation in research comes mainly from clinical trials. Fewer data exist on parents' motivations to enrol children in observational studies. OBJECTIVES: Describe reasons parents of preschoolers gave for participating in the Study to Explore Early Development (SEED), a US multi-site study of autism spectrum disorder (ASD) and other developmental delays or disorders (DD), and explore reasons given by child diagnostic and behavioural characteristics at enrolment. METHODS: We included families of children, age 2-5 years, participating in SEED (n = 5696) during 2007-2016. We assigned children to groups based on characteristics at enrolment: previously diagnosed ASD; suspected ASD; non-ASD DD; and population controls (POP). During a study interview, we asked parents their reasons for participating. Two coders independently coded responses and resolved discrepancies via consensus. We fit binary mixed-effects models to evaluate associations of each reason with group and demographics, using POP as reference. RESULTS: Participants gave 1-5 reasons for participation (mean = 1.7, SD = 0.7). Altruism (48.3%), ASD research interest (47.4%) and perceived personal benefit (26.9%) were most common. Two novel reasons were knowing someone outside the household with the study conditions (peripheral relationship; 14.1%) and desire to contribute to a specified result (1.4%). Odds of reporting interest in ASD research were higher among diagnosed ASD participants (odds ratio [OR] 2.89, 95% confidence interval [CI] 2.49-3.35). Perceived personal benefit had higher odds among diagnosed (OR 1.92, 95% CI 1.61-2.29) or suspected ASD (OR 3.67, 95% CI 2.99-4.50) and non-ASD DD (OR 1.80, 95% CI 1.50-2.16) participants. Peripheral relationship with ASD/DD had lower odds among all case groups. CONCLUSIONS: We identified meaningful differences between groups in parent-reported reasons for participation. Differences demonstrate an opportunity for future studies to tailor recruitment materials and increase the perceived benefit for specific prospective participants.

Many Young Children with Autism Who Use Psychotropic Medication Do Not Receive Behavior Therapy: A Multisite Case-Control Study.

OBJECTIVES: To explore how many pre-school aged children with autism spectrum disorder (ASD) used psychotropic medication, child and geographic factors associated with psychotropic medication use, and how many children who used psychotropic medication did or did not ever receive behavior therapy. STUDY DESIGN: Children 2-5 years of age were enrolled from 2012 to 2016 in a multisite case-control study designed to investigate the development and risk factors of ASD. Children with a positive ASD screen or ASD diagnosis upon enrollment were asked to complete a comprehensive evaluation to determine ASD status and developmental level. Caregivers completed a Services and Treatments Questionnaire and multiple self-administered questionnaires to determine child use of psychotropic medication, ever receipt of behavior therapy, and presence of co-occurring symptoms. RESULTS: There were 763 children who were classified as ASD and had data collected on the Services and Treatments Questionnaire. Of those, 62 (8.1%) used psychotropic medication to treat behavioral symptoms and 28 (3.7%) were ≤3 years of age when medication was first started. Attention problems (aOR, 7.65; 95% CI, 3.41-16.1; P < .001) and study site (aOR, 2.62; 95% CI, 1.04-6.56; P = .04) were significantly associated with psychotropic medication use after controlling for maternal race/ethnicity. More than one-half (59.7%) of those who used psychotropic medication did not ever receive behavior therapy. CONCLUSIONS: Many preschool-aged children with ASD who use psychotropic medication do not receive behavior therapy. Pediatricians are an important resource for children and families and can help facilitate behavioral treatment for children with ASD and other disorders.

Health Status and Health Care Use Among Adolescents Identified With and Without Autism in Early Childhood - Four U.S. Sites, 2018-2020.

Persons identified in early childhood as having autism spectrum disorder (autism) often have co-occurring health problems that extend into adolescence (1-3). Although only limited data exist on their health and use of health care services as they transition to adolescence, emerging data suggest that a minority of these persons receive recommended guidance* from their primary care providers (PCPs) starting at age 12 years to ensure a planned transition from pediatric to adult health care (4,5). To address this gap in data, researchers analyzed preliminary data from a follow-up survey of parents and guardians of adolescents aged 12-16 years who previously participated in the Study to Explore Early Development (https://www.cdc.gov/ncbddd/autism/seed.html). The adolescents were originally studied at ages 2-5 years and identified at that age as having autism (autism group) or as general population controls (control group). Adjusted prevalence ratios (aPRs) that accounted for differences in demographic characteristics were used to compare outcomes between groups. Adolescents in the autism group were more likely than were those in the control group to have physical difficulties (21.2% versus 1.6%; aPR = 11.6; 95% confidence interval [CI] = 4.2-31.9), and to have additional mental health or other conditions† (one or more condition: 63.0% versus 28.9%; aPR = 1.9; 95% CI = 1.5-2.5). Adolescents in the autism group were more likely to receive mental health services (41.8% versus 22.1%; aPR = 1.8, 95% CI = 1.3-2.6) but were also more likely to have an unmet medical or mental health service need§ (11.0% versus 3.2%; aPR = 3.1; 95% CI = 1.1-8.8). In both groups, a small percentage of adolescents (autism, 7.5%; control, 14.1%) received recommended health care transition (transition) guidance. These findings are consistent with previous research (4,5) indicating that few adolescents receive the recommended transition guidance and suggest that adolescents identified with autism in early childhood are more likely than adolescents in the general population to have unmet health care service needs. Improved provider training on the heath care needs of adolescents with autism and coordination of comprehensive programs¶ to meet their needs can improve delivery of services and adherence to recommended guidance for transitioning from pediatric to adult health care.

DSM-5 criteria for autism spectrum disorder maximizes diagnostic sensitivity and specificity in preschool children.

PURPOSE: The criteria for autism spectrum disorder (ASD) were revised in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM). The objective of this study was to compare the sensitivity and specificity of DSM-IV-Text Revision (DSM-IV-TR) and DSM-5 definitions of ASD in a community-based sample of preschool children. METHODS: Children between 2 and 5 years of age were enrolled in the Study to Explore Early Development-Phase 2 (SEED2) and received a comprehensive developmental evaluation. The clinician(s) who evaluated the child completed two diagnostic checklists that indicated the presence and severity of DSM-IV-TR and DSM-5 criteria. Definitions for DSM-5 ASD, DSM-IV-TR autistic disorder, and DSM-IV-TR Pervasive Developmental Disorder Not Otherwise Specified (PDD-NOS) were created from the diagnostic checklists. RESULTS: 773 children met SEED2 criteria for ASD and 288 met criteria for another developmental disorder (DD). Agreement between DSM-5 and DSM-IV-TR definitions of ASD were good for autistic disorder (0.78) and moderate for PDD-NOS (0.57 and 0.59). Children who met DSM-IV-TR autistic disorder but not DSM-5 ASD (n = 71) were more likely to have mild ASD symptoms, or symptoms accounted for by another disorder. Children who met PDD-NOS but not DSM-5 ASD (n = 66), or vice versa (n = 120) were less likely to have intellectual disability and more likely to be female. Sensitivity and specificity were best balanced with DSM-5 ASD criteria (0.95 and 0.78, respectively). CONCLUSIONS: The DSM-5 definition of ASD maximizes diagnostic sensitivity and specificity in the SEED2 sample. These findings support the DSM-5 conceptualization of ASD in preschool children.

Cognitive outcomes and age of detection of severe mucopolysaccharidosis type 1.

The US Secretary of Health and Human Services recommended in February 2016 that mucopolysaccharidosis type 1 (MPS I) be added to the recommended uniform screening panel for state newborn screening programs. One of the key factors in this decision was the evidence suggesting that earlier treatment with hematopoietic cell transplantation (HCT) for the most severe form, Hurler syndrome (MPS IH), would lead to improved cognitive outcomes. Consistent evidence from peer-reviewed studies suggests that transplantation in the first year of life is associated with improved developmental quotient or intelligence quotient and continued cognitive growth, with earlier age of treatment associated with improved outcomes. However, available evidence suggests that cognitive functioning and attention can still lag behind unaffected age-matched children, leading to the need for special education services. Verbal and nonverbal cognitive abilities outcomes may be affected differently by HCT. With the recent addition of MPS I to the recommended uniform screening panel, future work is needed to evaluate the impact of earlier, presymptomatic detection and treatment initiation and other supportive therapies on cognitive outcomes.Genet Med advance online publication 26 January 2017.

Risk factors and clinical correlates of sensory dysfunction in preschool children with and without autism spectrum disorder.

Sensory dysfunction is a common feature of autism spectrum disorder (ASD). The objectives of this analysis were to examine risk factors and clinical correlates of sensory dysfunction in preschool children with and without ASD. Children aged 2-5 years were enrolled in a multi-site case-control study. Data were collected in eight areas across the United States in three phases. Caregivers completed an interview with questions on assisted delivery, maternal alcohol use, maternal anxiety during pregnancy, pregnancy weight gain, neonatal jaundice, preterm birth, and child sensory diagnosis given by a healthcare provider. Caregivers also completed an interview and questionnaires on sensory symptoms and clinical correlates of sensory dysfunction in their child. There were 2059 children classified as ASD, 3139 as other developmental delay or disability (DD), and 3249 as population comparison (POP). Caregivers reported significantly more sensory diagnoses and sensory symptoms in children classified as ASD than DD or POP (23.7%, 8.6%, and 0.8%, respectively, for a sensory diagnosis and up to 78.7% [ASD] vs. 49.6% [DD] for sensory symptoms). Maternal anxiety during pregnancy and neonatal jaundice were significantly associated with a sensory diagnosis and certain sensory symptoms in children with ASD and DD. Children's anxiety, attention deficits/hyperactivity, and sleep problems were significantly albeit subtly correlated with both a sensory diagnosis and sensory symptoms in children with ASD and DD. These findings support sensory dysfunction as a distinguishing symptom of ASD in preschool children and identify risk factors and clinical correlates to inform screening and treatment efforts in those with atypical development.

Depressive symptoms and activity engagement in autistic adolescents and those with other developmental disabilities.

BACKGROUND: Autistic adults and those with other developmental disabilities (DD) have increased depressive symptoms and decreased activity engagement when compared to those with no DD. Few studies explore activities related to depressive symptoms in autistic people and those with other DD during adolescence. OBJECTIVE: The objectives of this analysis were to describe depressive symptoms and activity engagement among autistic adolescents and those with other DD and no DD and explore types of activities associated with depressive symptoms, stratified by study group. METHODS: Parents of adolescents completed a multi-site case-control study of autism and other DD when their child was 2-5 years of age and a follow-up survey when their child was 12-16 years of age. Questions asked about the adolescent's current diagnoses, depressive symptoms (i.e., diagnosis, medication use, or symptoms), and engagement in club, social, sport, vocational, volunteer, and other organized activities. RESULTS: Autistic adolescents (N = 238) and those with other DD (N = 222) were significantly more likely to have depressive symptoms than adolescents with no DD (N = 406), (31.9 %, 30.6 %, and 15.0 % respectively). Lower percentages of autistic adolescents participated in activities than peers with other DD, who had lower percentages than peers with no DD. Participation in sports was associated with lower likelihood of depressive symptoms in all groups. CONCLUSIONS: Autistic adolescents and those with other DD are at increased risk for depressive symptoms and reduced activity engagement. Participation in sports may be especially important for adolescent mental health regardless of disability status. Implications for public health education and intervention are discussed.

Economic impacts of the COVID-19 pandemic on families of children with autism and other developmental disabilities.

Background: To control the spread of the coronavirus disease (COVID-19), many jurisdictions throughout the world enacted public health measures that had vast socio-economic implications. In emergency situations, families of children with developmental disabilities (DDs), including autism, may experience increased difficulty accessing therapies, economic hardship, and caregiver stress, with the potential to exacerbate autism symptoms. Yet, limited research exists on the economic impacts of the COVID-19 pandemic on families of children with autism or another DD compared to families of children from the general population. Objectives: To assess impact of the COVID-19 pandemic related to parental employment and economic difficulties in families of children with autism, another DD, and in the general population, considering potential modification by socioeconomic disadvantage before the pandemic and levels of child behavioral and emotional problems. Methods: The Study to Explore Early Development (SEED) is a multi-site, multi-phase, case-control study of young children with autism or another DD as compared to a population comparison group (POP). During January-July 2021, a COVID-19 Impact Assessment Questionnaire was sent to eligible participants (n=1,789) who had enrolled in SEED Phase 3 from September 2017-March 2020. Parents completed a questionnaire on impacts of the pandemic in 2020 and completed the Child Behavior Checklist (CBCL) to measure behavioral and emotional health of their child during this time. Multiple logistic regression models were built for employment reduction, increased remote work, difficulty paying bills, or fear of losing their home. Covariates include group status (autism, DD, POP), household income at enrollment, child's race and ethnicity, and binary CBCL Total Problems T-score (<60 vs. ≥60). Unadjusted and adjusted odds ratios (aOR) and 95% confidence intervals (CI) were calculated. Results: The study included 274 children with autism, 368 children with another DD, and 385 POP children. The mean age of 6.1 years (standard deviation, 0.8) at the COVID-19 Impact Assessment did not differ between study groups. Parents of children with autism were less likely to transition to remote work (aOR [95% CI] = 0.6 [0.4, 1.0]) and more likely to report difficulty paying bills during the pandemic (1.8 [1.2, 2.9]) relative to parents of POP children. Lower income was associated with greater employment reduction, difficulty paying bills, and fear of losing their home, but inversely associated with transitioning to remote work. Parents of non-Hispanic (NH) Black children experienced greater employment reduction compared to parents of NH White children (1.9 [1.1, 3.0]). Parents from racial and ethnic minority groups were more likely to experience difficulty paying bills and fear losing their home, relative to NH White parents. Caregivers of children with CBCL scores in the clinical range were more likely to fear losing their home (2.1 [1.3, 3.4]). Conclusion: These findings suggest that families of children with autism, families of lower socio-economic status, and families of racial and ethnic minority groups experienced fewer work flexibilities and greater financial distress during the pandemic. Future research can be used to assess if these impacts are sustained over time.

Racial and ethnic disparities in the co-occurrence of intellectual disability and autism: Impact of incorporating measures of adaptive functioning.

Intellectual disability (ID) commonly co-occurs in children with autism. Although diagnostic criteria for ID require impairments in both cognitive and adaptive functioning, most population-based estimates of the frequency of co-occurring ID in children with autism-including studies of racial and ethnic disparities in co-occurring autism and ID-base the definition of ID solely on cognitive scores. The goal of this analysis was to examine the effect of including both cognitive and adaptive behavior criteria on estimates of co-occurring ID in a well-characterized sample of 2- to 5-year-old children with autism. Participants included 3264 children with research or community diagnoses of autism enrolled in the population-based Study to Explore Early Development (SEED) phases 1-3. Based only on Mullen Scales of Early Learning (MSEL) composite cognitive scores, 62.9% (95% confidence interval [CI]: 61.1, 64.7%) of children with autism were estimated to have co-occurring ID. After incorporating Vineland Adaptive Behavior Scales, Second Edition (VABS-II) composite or domains criteria, co-occurring ID estimates were reduced to 38.0% (95% CI: 36.2, 39.8%) and 45.0% (95% CI: 43.1, 46.9%), respectively. The increased odds of meeting ID criteria observed for non-Hispanic (NH) Black and Hispanic children relative to NH White children when only MSEL criteria were used were substantially reduced, though not eliminated, after incorporating VABS-II criteria and adjusting for selected socioeconomic variables. This study provides evidence for the importance of considering adaptive behavior as well as socioeconomic disadvantage when describing racial and ethnic disparities in co-occurring ID in epidemiologic studies of autism.

Remote Delivery of Allied and Behavioral Healthcare During COVID-19 for Children With Developmental Disabilities.

Objective: Many children with autism spectrum disorder (ASD) and other developmental disabilities (DD) transitioned to telehealth services due to the COVID-19 pandemic. Our objectives were to describe reductions in allied and behavioral healthcare services and receipt of caregiver training to deliver services at home because of COVID-19 for children with ASD and other DD, and factors associated with worse response to remote delivery of services for children with ASD. Method: Prior to the pandemic, children 2 to 5 years of age were enrolled in a multi-site case-control study and completed a developmental assessment. Caregivers completed questionnaires on child behavior problems and ASD symptoms. Children were classified as having ASD vs another DD based on standardized diagnostic measures. Subsequently, caregivers completed a survey during January to June 2021 to assess how COVID-19 affected children and families. Results: Caregivers reported that most children with ASD and other DD had a decrease in service hours (50.0%-76.9% by service type) during the COVID-19 pandemic. Children with ASD were significantly more likely to experience reduced speech/language therapy than children with other DD. Receipt of caregiver training to deliver services at home ranged from 38.1% to 57.4% by service type. Among children with ASD, pre-pandemic problems with internalizing behaviors and social communication/interaction were associated with worse response to behavioral telehealth but no other common therapies. Conclusion: Our study demonstrates the caregiver-reported impacts of COVID-19 on remote delivery of allied and behavioral healthcare services for children with ASD and other DD. Considerations for caregiver support and remote delivery of services are provided.

Health and Education Services During the COVID-19 Pandemic Among Young Children with Autism Spectrum Disorder and Other Developmental Disabilities.

OBJECTIVE: Understanding how the COVID-19 pandemic affected children with disabilities is essential for future public health emergencies. We compared children with autism spectrum disorder (ASD) with those with another developmental disability (DD) and from the general population (POP) regarding (1) missed or delayed appointments for regular health/dental services, immunizations, and specialty services; (2) reasons for difficulty accessing care; and (3) use of remote learning and school supports. METHOD: Caregivers of children previously enrolled in the Study to Explore Early Development, a case-control study of children with ASD implemented during 2017 to 2020, were recontacted during January-June 2021 to learn about services during March-December 2020. Children were classified as ASD, DD, or POP during the initial study and were aged 3.4 to 7.5 years when their caregivers were recontacted during the pandemic. RESULTS: Over half of all children missed or delayed regular health/dental appointments (58.4%-65.2%). More children in the ASD versus DD and POP groups missed or delayed specialty services (75.7%, 58.3%, and 22.8%, respectively) and reported difficulties obtaining care of any type because of issues using telehealth and difficulty wearing a mask. During school closures, a smaller proportion of children with ASD versus another DD were offered live online classes (84.3% vs 91.1%), while a larger proportion had disrupted individualized education programs (50.0% vs 36.2%). CONCLUSION: Minimizing service disruptions for all children and ensuring continuity of specialty care for children with ASD is essential for future public health emergencies. Children may need additional services to compensate for disruptions during the pandemic.

Using adaptive behavior scores to convey level of functioning in children with autism spectrum disorder: Evidence from the Study to Explore Early Development.

LAY ABSTRACT: Autistic people are often described as "low-" or "high-functioning" based on their scores on cognitive tests. These terms are common in publications and in everyday communication. However, recent research and feedback from the autistic community suggests that relying on cognitive ability alone to describe functioning may miss meaningful differences in the abilities of autistic children and adults and in the kinds of support they may need. Additional methods are needed to describe "functioning" in autistic children. We examined whether scores from a test measuring adaptive behaviors would provide information on the functional abilities of children with autism that is different from cognitive ability and autism symptom severity. Adaptive behaviors include age-appropriate skills that allow people to function in their everyday lives and social interactions. We found that a large amount of the variation in adaptive behavior scores was not explained by cognitive development, autism symptom severity, and behavioral and emotional problems. In addition, there was a wide range of adaptive ability levels in children with autism in our study, including in those with low, average, or high cognitive scores. Our results suggest that adaptive behavior scores could provide useful information about the strengths and support needs of autistic children above and beyond measures of cognitive ability and autism symptom severity. Adaptive behavior scores provide important information on the needs of autistic people.

Toileting Resistance Among Preschool-Age Children with and Without Autism Spectrum Disorder.

OBJECTIVE: Children with autism spectrum disorder (ASD) may achieve continence later than other children. Little is known about factors associated with toileting resistance in children with ASD and other developmental delays/disabilities (DD). We sought to describe toileting resistance in children with ASD and DD and those from the general population (POP) and identify factors associated with toileting resistance in children with ASD and DD. METHOD: Families and children aged 24 to 68 months were enrolled in the Study to Explore Early Development, a multisite case-control study on ASD. Children with ASD (N = 743) and DD (N = 766) and those from the POP (N = 693) who were 48 months or older were included in this study. Parents reported toileting resistance, gastrointestinal issues, behavior problems, and ASD symptoms in their children. Children completed an in-person evaluation to determine ASD status and developmental level. RESULTS: Toileting resistance was more common among children with ASD (49.1%) than children with DD (23.6%) and those from the POP (8.0%). Diarrhea and deficits in social awareness were significantly associated with toileting resistance in children with ASD and DD. Constipation, expressive language delays, and low social motivation were significantly associated with toileting resistance only in children with ASD; very low visual reception skills and oppositional behaviors were significantly associated with toileting resistance in only children with DD (all p ≤ 0.05). CONCLUSION: Evaluating gastrointestinal issues, developmental delays, and social deficits before toileting training may help identify children with atypical development who are likely to present with toileting resistance. These evaluations can be incorporated into health supervision visits.

Sensory features in autism: Findings from a large population-based surveillance system.

Sensory features (i.e., atypical responses to sensory stimuli) are included in the current diagnostic criteria for autism spectrum disorder. Yet, large population-based studies have not examined these features. This study aimed to determine the prevalence of sensory features among autistic children, and examine associations between sensory features, demographics, and co-occurring problems in other areas. Analysis for this study included a sample comprised of 25,627 four- or eight-year-old autistic children identified through the multistate Autism and Developmental Disabilities Monitoring Network (2006-2014). We calculated the prevalence of sensory features and applied multilevel logistic regression modeling. The majority (74%; 95% confidence interval: 73.5%-74.5%) of the children studied had documented sensory features. In a multivariable model, children who were male and those whose mothers had more years of education had higher odds of documented sensory features. Children from several racial and ethnic minority groups had lower odds of documented sensory features than White, non-Hispanic children. Cognitive problems were not significantly related to sensory features. Problems related to adaptive behavior, emotional states, aggression, attention, fear, motor development, eating, and sleeping were associated with higher odds of having documented sensory features. Results from a large, population-based sample indicate a high prevalence of sensory features in autistic children, as well as relationships between sensory features and co-occurring problems. This study also pointed to potential disparities in the identification of sensory features, which should be examined in future research. Disparities should also be considered clinically to avoid reduced access to supports for sensory features and related functional problems. LAY SUMMARY: In a large, population-based sample of 25,627 autistic children, 74% had documented differences in how they respond to sensation. We also identified significant associations of sensory features with adaptive behavior and problems in other domains. Sensory features were less common among girls, children of color, and children of mothers with fewer years of education, suggesting potential disparities in identification.

Pre- and Postnatal Fine Particulate Matter Exposure and Childhood Cognitive and Adaptive Function.

Increasing evidence exists for an association between early life fine particulate matter (PM2.5) exposure and several neurodevelopmental outcomes, including autism spectrum disorder (ASD); however, the association between PM2.5 and adaptive and cognitive function remains poorly understood. Participants included 658 children with ASD, 771 with a non-ASD developmental disorder, and 849 population controls from the Study to Explore Early Development. Adaptive functioning was assessed in ASD cases using the Vineland Adaptive Behavior Scales (VABS); cognitive functioning was assessed in all groups using the Mullen Scales of Early Learning (MSEL). A satellite-based model was used to assign PM2.5 exposure averages during pregnancy, each trimester, and the first year of life. Linear regression was used to estimate beta coefficients and 95% confidence intervals, adjusting for maternal age, education, prenatal tobacco use, race-ethnicity, study site, and season of birth. PM2.5 exposure was associated with poorer VABS scores for several domains, including daily living skills and socialization. Associations were present between prenatal PM2.5 and lower MSEL scores for all groups combined; results were most prominent for population controls in stratified analyses. These data suggest that early life PM2.5 exposure is associated with specific aspects of cognitive and adaptive functioning in children with and without ASD.

Evidence-Informed Milestones for Developmental Surveillance Tools.

The Centers for Disease Control and Prevention's (CDC) Learn the Signs. Act Early. program, funded the American Academy of Pediatrics (AAP) to convene an expert working group to revise its developmental surveillance checklists. The goals of the group were to identify evidence-informed milestones to include in CDC checklists, clarify when most children can be expected to reach a milestone (to discourage a wait-and-see approach), and support clinical judgment regarding screening between recommended ages. Subject matter experts identified by the AAP established 11 criteria for CDC milestone checklists, including using milestones most children (≥75%) would be expected to achieve by specific health supervision visit ages and those that are easily observed in natural settings. A database of normative data for individual milestones, common screening and evaluation tools, and published clinical opinion was created to inform revisions. Application of the criteria established by the AAP working group and adding milestones for the 15- and 30-month health supervision visits resulted in a 26.4% reduction and 40.9% replacement of previous CDC milestones. One third of the retained milestones were transferred to different ages; 67.7% of those transferred were moved to older ages. Approximately 80% of the final milestones had normative data from ≥1 sources. Social-emotional and cognitive milestones had the least normative data. These criteria and revised checklists can be used to support developmental surveillance, clinical judgment regarding additional developmental screening, and research in developmental surveillance processes. Gaps in developmental data were identified particularly for social-emotional and cognitive milestones.

Features that best define the heterogeneity and homogeneity of autism in preschool-age children: A multisite case-control analysis replicated across two independent samples.

The heterogeneous nature of children with symptoms of autism spectrum disorder (ASD) makes it difficult to identify risk factors and effective treatment options. We sought to identify behavioral and developmental features that best define the heterogeneity and homogeneity in 2-5-year-old children classified with ASD and subthreshold ASD characteristics. Children were enrolled in a multisite case-control study of ASD. Detailed behavioral and developmental data were gathered by maternal telephone interview, parent-administered questionnaires, child cognitive evaluation, and ASD diagnostic measures. Participants with a positive ASD screen score or prior ASD diagnosis were referred for comprehensive evaluation. Children in the ASD group met study criteria based on this evaluation; children who did not meet study criteria were categorized as having subthreshold ASD characteristics. There were 1480 children classified as ASD (81.6% boys) and 594 children classified as having subthreshold ASD characteristics (70.2% boys) in the sample. Factors associated with dysregulation (e.g., aggression, anxiety/depression, sleep problems) followed by developmental abilities (e.g., expressive and receptive language skills) most contributed to heterogeneity in both groups of children. Atypical sensory response contributed to homogeneity in children classified as ASD but not those with subthreshold characteristics. These findings suggest that dysregulation and developmental abilities are clinical features that can impact functioning in children with ASD and other DD, and that documenting these features in pediatric records may help meet the needs of the individual child. Sensory dysfunction could be considered a core feature of ASD and thus used to inform more targeted screening, evaluation, treatment, and research efforts. LAY SUMMARY: The diverse nature of autism spectrum disorder (ASD) makes it difficult to find risk factors and treatment options. We identified the most dissimilar and most similar symptom(s) in children classified as ASD and as having subthreshold ASD characteristics. Factors associated with dysregulation and developmental abilities contributed to diversity in both groups of children. Sensory dysfunction was the most common symptom in children with ASD but not those with subthreshold characteristics. Findings can inform clinical practice and research.

Evaluation of sex differences in preschool children with and without autism spectrum disorder enrolled in the study to explore early development.

BACKGROUND AND AIMS: Research in school-aged children, adolescents, and adults with autism spectrum disorder (ASD) has found sex-based differences in behavioral, developmental, and diagnostic outcomes. These findings have not been consistently replicated in preschool-aged children. We examined sex-based differences in a large sample of 2-5-year-old children with ASD symptoms in a multi-site community-based study. METHODS AND PROCEDURES: Based on a comprehensive evaluation, children were classified as having ASD (n = 1480, 81.55 % male) or subthreshold ASD characteristics (n = 593, 70.15 % male). Outcomes were behavior problems, developmental abilities, performance on ASD screening and diagnostic tests, and parent-reported developmental conditions diagnosed before study enrollment. OUTCOMES AND RESULTS: We found no statistically significant sex differences in behavioral functioning, developmental functioning, performance on an ASD screening test, and developmental conditions diagnosed before study enrollment among children with ASD or subthreshold ASD characteristics. Males in both study groups had more parent reported restricted interests and repetitive behaviors than females, but these differences were small in magnitude and not clinically meaningful. CONCLUSIONS AND IMPLICATIONS: Preschool males and females who showed risk for ASD were more similar than different in the outcomes assessed in our study. Future research could examine sex-based differences in ASD phenotypes as children age.