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.

Leveraging External Validation Data: The Challenges of Transporting Measurement Error Parameters.

Approaches to address measurement error frequently rely on validation data to estimate measurement error parameters (e.g., sensitivity and specificity). Acquisition of validation data can be costly, thus secondary use of existing data for validation is attractive. To use these external validation data, however, we may need to address systematic differences between these data and the main study sample. Here, we derive estimators of the risk and the risk difference that leverage external validation data to account for outcome misclassification. If misclassification is differential with respect to covariates that themselves are differentially distributed in the validation and study samples, the misclassification parameters are not immediately transportable. We introduce two ways to account for such covariates: (1) standardize by these covariates or (2) iteratively model the outcome. If conditioning on a covariate for transporting the misclassification parameters induces bias of the causal effect (e.g., M-bias), the former but not the latter approach is biased. We provide proof of identification, describe estimation using parametric models, and assess performance in simulations. We also illustrate implementation to estimate the risk of preterm birth and the effect of maternal HIV infection on preterm birth. Measurement error should not be ignored and it can be addressed using external validation data via transportability methods.

Accounting for nonmonotone missing data using inverse probability weighting.

Inverse probability weighting can be used to correct for missing data. New estimators for the weights in the nonmonotone setting were introduced in 2018. These estimators are the unconstrained maximum likelihood estimator (UMLE) and the constrained Bayesian estimator (CBE), an alternative if UMLE fails to converge. In this work we describe and illustrate these estimators, and examine performance in simulation and in an applied example estimating the effect of anemia on spontaneous preterm birth in the Zambia Preterm Birth Prevention Study. We compare performance with multiple imputation (MI) and focus on the setting of an observational study where inverse probability of treatment weights are used to address confounding. In simulation, weighting was less statistically efficient at the smallest sample size and lowest exposure prevalence examined (n = 1500, 15% respectively) but in other scenarios statistical performance of weighting and MI was similar. Weighting had improved computational efficiency taking, on average, 0.4 and 0.05 times the time for MI in R and SAS, respectively. UMLE was easy to implement in commonly used software and convergence failure occurred just twice in >200 000 simulated cohorts making implementation of CBE unnecessary. In conclusion, weighting is an alternative to MI for nonmonotone missingness, though MI performed as well as or better in terms of bias and statistical efficiency. Weighting's superior computational efficiency may be preferred with large sample sizes or when using resampling algorithms. As validity of weighting and MI rely on correct specification of different models, both approaches could be implemented to check agreement of results.

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.

Sulfur dioxide reduction at coal-fired power plants in North Carolina and associations with preterm birth among surrounding residents.

Coal-fired power plants (CFPP) are major contributors of air pollution, including the majority of anthropogenic sulfur dioxide (SO2) emissions, which have been associated with preterm birth (PTB). To address a 2002 North Carolina (NC) policy, 14 of the largest NC CFPPs either installed desulfurization equipment (scrubbers) or retired coal units, resulting in substantial reductions of SO2 air emissions. We investigated whether SO2 air emission reduction strategies at CFPPs in NC were associated with changes in prevalence of PTB in nearby communities. Methods: We used US EPA Air Markets Program Data to track SO2 emissions and determine the implementation dates of intervention at CFPPs and geocoded 2003-2015 NC singleton live births. We conducted a difference-in-difference analysis to estimate change in PTB associated with change in SO2 reduction strategies for populations living 0-<4 and 4-<10 miles from CFPPs pre- and postintervention, with a comparison of those living 10-<15 miles from CFPPs. Results: With the spatial-temporal exposure restrictions applied, 42,231 and 41,218 births were within 15 miles of CFPP-scrubbers and CFPP-retired groups, respectively. For residents within 4-<10 miles from a CFPP, we estimated that the absolute prevalence of PTB decreased by -1.5% [95% confidence interval (CI): -2.6, -0.4] associated with scrubber installation and -0.5% (95% CI: -1.6, 0.6) associated with the retirement of coal units at CFPPs. Our findings were imprecise and generally null-to-positive among those living within 0-<4 miles regardless of the intervention type. Conclusions: Results suggest a reduction of PTB among residents 4-<10 miles of the CFPPs that installed scrubbers.

North Carolina's Changing Energy Generation Profile and Reductions in Key Air Pollutants, 2000-2019.

BACKGROUND Coal combustion releases a number of airborne toxins. The North Carolina Clean Smokestacks Act (CSA) of 2002 required North Carolina coal-fired power plants (CFPP) to reduce nitrogen oxides (NOX) emissions by 2009 and sulfur dioxide (SO2) emissions to 2 benchmarks by 2009 and 2013.METHODS We utilized publicly available databases from the Energy Information Administration and the Environmental Protection Agency to characterize North Carolina's electricity generation profile from 2000 until 2019 and evaluate corresponding NOx and SO2 emissions by sector over the same time period.RESULTS Between 2000 and 2008 in North Carolina, approximately 60% of electric power was generated by CFPPs. Since then, North Carolina's electric power generation has transformed from predominant dependence on coal to approximately equal dependence on natural gas and nuclear power (each at ~ 30%), with coal close behind (~ 25%). Renewables have increased, although marginally relative to the rapid increase in natural gas. Despite the stark drop in reliance on CFPPs for energy in North Carolina and subsequent drop in emissions, CFPPs still contribute ~ 60% of SO2 air pollution as of 2017.LIMITATIONS This analysis relies upon electricity generation and emissions data self-reported by utilities and publicly available from federal agenciesCONCLUSION North Carolina's electric utilities met the 2009 and 2013 regulatory benchmarks set by the CSA, which resulted in substantial reductions in SO2 emissions from the fuel combustion electric generation sector. Still, CFPPs remain the primary utility-related and overall anthropogenic contributor of SO2 air pollution in North Carolina.

Patterns of Children's Blood Lead Screening and Blood Lead Levels in North Carolina, 2011-2018-Who Is Tested, Who Is Missed?

BACKGROUND: No safe level of lead in blood has been identified. Blood lead testing is required for children on Medicaid, but it is at the discretion of providers and parents for others. Elevated blood lead levels (EBLLs) cannot be identified in children who are not tested. OBJECTIVES: The aims of this research were to identify determinants of lead testing and EBLLs among North Carolina children and estimate the number of additional children with EBLLs among those not tested. METHODS: We linked geocoded North Carolina birth certificates from 2011-2016 to 2010 U.S. Census data and North Carolina blood lead test results from 2011-2018. We estimated the probability of being screened for lead and created inverse probability (IP) of testing weights. We evaluated the risk of an EBLL of ≥3µg/dL at <30 months of age, conditional on characteristics at birth, using generalized linear models and then applied IP weights to account for missing blood lead results among unscreened children. We estimated the number of additional children with EBLLs of all North Carolina children using the IP-weighted population and bootstrapping to produce 95% credible intervals (CrI). RESULTS: Mothers of the 63.5% of children (402,002 of 633,159) linked to a blood lead test result were disproportionately young, Hispanic, Black, American Indian, or on Medicaid. In full models, maternal age ≤20y [risk ratio (RR)=1.10; 95% confidence interval (CI): 1.13, 1.20] or smoking (RR=1.14; 95% CI: 1.12, 1.17); proximity to a major roadway (RR=1.10; 95% CI: 1.05, 1.15); proximity to a lead-releasing Toxics Release Inventory site (RR=1.08; 95% CI: 1.03, 1.14) or a National Emissions Inventory site (RR=1.11; 95% CI: 1.07, 1.14); and living in neighborhoods with more housing built before 1950 (RR=1.10; 95% CI: 1.05, 1.14) or before 1940 (RR=1.18; 95% CI: 1.11, 1.25) or more vacant housing (RR=1.14; 95% CI: 1.11, 1.17) were associated with an increased risk of EBLL, whereas overlap with a public water service system was associated with a decreased risk of EBLL (RR=0.85; 95% CI: 0.83, 0.87). Children of Black mothers were no more likely than children of White mothers to have EBLLs (RR=0.98; 95% CI: 0.96, 1.01). Complete blood lead screening in 2011-2018 may have identified an additional 17,543 (95% CrI: 17,462, 17,650) children with EBLLs ≥3µg/dL. DISCUSSION: Our results indicate that current North Carolina lead screening strategies fail to identify over 30% (17,543 of 57,398) of children with subclinical lead poisoning and that accounting for characteristics at birth alters the conclusions about racial disparities in children's EBLLs. https://doi.org/10.1289/EHP10335.

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.

Cardiometabolic Pregnancy Complications in Association With Autism-Related Traits as Measured by the Social Responsiveness Scale in ECHO.

Prior work has examined associations between cardiometabolic pregnancy complications and autism spectrum disorder (ASD) but not how these complications may relate to social communication traits more broadly. We addressed this question within the Environmental Influences on Child Health Outcomes program, with 6,778 participants from 40 cohorts conducted from 1998-2021 with information on ASD-related traits via the Social Responsiveness Scale. Four metabolic pregnancy complications were examined individually, and combined, in association with Social Responsiveness Scale scores, using crude and adjusted linear regression as well as quantile regression analyses. We also examined associations stratified by ASD diagnosis, and potential mediation by preterm birth and low birth weight, and modification by child sex and enriched risk of ASD. Increases in ASD-related traits were associated with obesity (ß = 4.64, 95% confidence interval: 3.27, 6.01) and gestational diabetes (ß = 5.21, 95% confidence interval: 2.41, 8.02), specifically, but not with hypertension or preeclampsia. Results among children without ASD were similar to main analyses, but weaker among ASD cases. There was not strong evidence for mediation or modification. Results suggest that common cardiometabolic pregnancy complications may influence child ASD-related traits, not only above a diagnostic threshold relevant to ASD but also across the population.

Maternal tobacco smoking and offspring autism spectrum disorder or traits in ECHO cohorts.

Given inconsistent evidence on preconception or prenatal tobacco use and offspring autism spectrum disorder (ASD), this study assessed associations of maternal smoking with ASD and ASD-related traits. Among 72 cohorts in the Environmental Influences on Child Health Outcomes consortium, 11 had ASD diagnosis and prenatal tobaccosmoking (n = 8648). and 7 had Social Responsiveness Scale (SRS) scores of ASD traits (n = 2399). Cohorts had diagnoses alone (6), traits alone (2), or both (5). Diagnoses drew from parent/caregiver report, review of records, or standardized instruments. Regression models estimated smoking-related odds ratios (ORs) for diagnoses and standardized mean differences for SRS scores. Cohort-specific ORs were meta-analyzed. Overall, maternal smoking was unassociated with child ASD (adjusted OR, 1.08; 95% confidence interval [CI], 0.72-1.61). However, heterogeneity across studies was strong: preterm cohorts showed reduced ASD risk for exposed children. After excluding preterm cohorts (biased by restrictions on causal intermediate and exposure opportunity) and small cohorts (very few ASD cases in either smoking category), the adjusted OR for ASD from maternal smoking was 1.44 (95% CI, 1.02-2.03). Children of smoking (versus non-smoking) mothers had more ASD traits (SRS T-score + 2.37 points, 95% CI, 0.73-4.01 points), with results homogeneous across cohorts. Maternal preconception/prenatal smoking was consistently associated with quantitative ASD traits and modestly associated with ASD diagnosis among sufficiently powered United States cohorts of non-preterm children. Limitations resulting from self-reported smoking and unmeasured confounders preclude definitive conclusions. Nevertheless, counseling on potential and known risks to the child from maternal smoking is warranted for pregnant women and pregnancy planners. LAY SUMMARY: Evidence on the association between maternal prenatal smoking and the child's risk for autism spectrum disorder has been conflicting, with some studies reporting harmful effects, and others finding reduced risks. Our analysis of children in the ECHO consortium found that maternal prenatal tobacco smoking is consistently associated with an increase in autism-related symptoms in the general population and modestly associated with elevated risk for a diagnosis of autism spectrum disorder when looking at a combined analysis from multiple studies that each included both pre- and full-term births. However, this study is not proof of a causal connection. Future studies to clarify the role of smoking in autism-like behaviors or autism diagnoses should collect more reliable data on smoking and measure other exposures or lifestyle factors that might have confounded our results.

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.

Peri-Pregnancy Cannabis Use and Autism Spectrum Disorder in the Offspring: Findings from the Study to Explore Early Development.

The association of autism spectrum disorder (ASD) with self-reported maternal cannabis use from 3 months pre-conception to delivery ("peri-pregnancy") was assessed in children aged 30-68 months, born 2003 to 2011. Children with ASD (N = 1428) were compared to children with other developmental delays/disorders (DD, N = 1198) and population controls (POP, N = 1628). Peri-pregnancy cannabis use was reported for 5.2% of ASD, 3.2% of DD and 4.4% of POP children. Adjusted odds of peri-pregnancy cannabis use did not differ significantly between ASD cases and DD or POP controls. Results were similar for any use during pregnancy. However, given potential risks suggested by underlying neurobiology and animal models, further studies in more recent cohorts, in which cannabis use and perception may have changed, are needed.

Pregnancy exposure to organophosphate esters and the risk of attention-deficit hyperactivity disorder in the Norwegian mother, father and child cohort study.

BACKGROUND: Organophosphate esters (OPEs) are a class of flame retardants in common use. OPEs can easily leach from materials, resulting in human exposure. Increasing concentrations have been reported in human populations over the past decade. Recent studies have linked prenatal OPE exposure to hyperactivity and attention problems in children. Such behaviors are often found among children with attention-deficit hyperactivity disorder (ADHD), however, no study has investigated OPEs in relation to clinically assessed ADHD. OBJECTIVE: To evaluate prenatal exposure to OPEs as risk factors for clinically assessed ADHD using a case-cohort study nested within the Norwegian Mother, Father, and Child Cohort Study (MoBa). METHODS: We included in the case group 295 ADHD cases obtained via linkage with the Norwegian Patient Registry, and the sub-cohort group 555 children sampled at baseline, irrespective of their ADHD case status. Prenatal concentrations of OPE metabolites were measured in maternal urine collected at 17 weeks of gestation, and included diphenyl phosphate (DPHP), di-n-butyl phosphate (DNBP), bis(2-butoxyethyl) hydrogen phosphate (BBOEP), and bis(1,3-dichloro-2-propyl) phosphate (BDCIPP). We estimated risk ratios and the corresponding 95% confidence intervals [95% CI] using logistic regression, adjusting for season of urine collection, child sex, birth year, and maternal depression, education, and sum of urinary di(2-ethylhexyl) phthalate metabolites (∑DEHP) concentration during pregnancy. To assess the overall impact of simultaneously decreasing exposure to all chemical constituents of an OPE-phthalate mixture, quantile based g-computation was implemented. The mixture constituents included OPE and phthalate metabolites commonly detected in our study. In all models, we considered effect measure modification by child sex and polymorphisms in genes encoding paraoxonase 1 (PON1) and cytochrome P450 (P450) enzymes. Mediation analysis was conducted using thyroid function biomarkers estimated from maternal blood collected at 17 weeks of gestation. RESULTS: DPHP was detected in nearly all samples (97.2%), with a higher geometric mean among the case group (0.70 µg/L) as compared to the sub-cohort (0.52 µg/L). DNBP was commonly detected as well (93.8%), while BBOEP (52.9%) and BDCIPP (22.9%) were detected less frequently. A higher risk of ADHD was observed in children with greater than median exposure to DPHP during pregnancy (risk ratio: 1.38 [95% CI: 0.96, 1.99]), which was slightly higher among girls (2.04 [1.03, 4.02]) and children of mothers with PON1 Q192R genotype QR (1.69 [0.89, 3.19]) or PON1 Q192R genotype RR (4.59 [1.38, 15.29]). The relationship between DPHP and ADHD (total risk ratio: 1.34 [0.90, 2.02]) was partially mediated through total triiodothyronine to total thyroxine ratio (natural direct effect: 1.29 [0.87, 1.94]; natural indirect effect: 1.04 [1.00, 1.10]; 12.48% mediated). We also observed an elevated risk of ADHD in relation to BDCIPP detection during pregnancy (1.50 [0.98, 2.28]). We did not observe notable differences in ADHD by DNBP (0.88 [0.62, 1.26]) or BBOEP (1.03 [0.73, 1.46]) during pregnancy. Simultaneously decreasing all constituents of common-detect OPE-phthalate mixture, specifically DPHP, DNBP, and 6 phthalate metabolites, by a quartile resulted in an ADHD risk ratio of 0.68 [0.64, 0.72]. CONCLUSION: Prenatal exposure to DPHP and BDCIPP may increase the risk of ADHD. For DPHP, we observed potential modification by child sex and maternal PON1 Q192R genotype and partial mediation through maternal thyroid hormone imbalance at 17 weeks gestation.

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.

Pregnancy exposure to common-detect organophosphate esters and phthalates and maternal thyroid function.

BACKGROUND: Contemporary human populations are exposed to elevated concentrations of organophosphate esters (OPEs) and phthalates. Some metabolites have been linked with altered thyroid function, however, inconsistencies exist across thyroid function biomarkers. Research on OPEs is sparse, particularly during pregnancy, when maintaining normal thyroid function is critical to maternal and fetal health. In this paper, we aimed to characterize relationships between OPEs and phthalates exposure and maternal thyroid function during pregnancy, using a cross-sectional investigation of pregnant women nested within the Norwegian Mother, Father, and Child Cohort (MoBa). METHODS: We included 473 pregnant women, who were euthyroid and provided bio-samples at 17 weeks' gestation (2004-2008). Four OPE and six phthalate metabolites were measured from urine; six thyroid function biomarkers were estimated from blood. Relationships between thyroid function biomarkers and log-transformed concentrations of OPE and phthalate metabolites were characterized using two approaches that both accounted for confounding by co-exposures: co-pollutant adjusted general linear model (GLM) and Bayesian Kernal Machine Regression (BKMR). RESULTS: We restricted our analysis to common-detect OPE and phthalate metabolites (>94%): diphenyl phosphate (DPHP), di-n-butyl phosphate (DNBP), and all phthalate metabolites. In GLM, pregnant women with summed di-isononyl phthalate metabolites (∑DiNP) concentrations in the 75th percentile had a 0.37 ng/µg lower total triiodothyronine (TT3): total thyroxine (TT4) ratio (95% credible interval: [-0.59, -0.15]) as compared to those in the 25th percentile, possibly due to small but diverging influences on TT3 (-1.99 ng/dL [-4.52, 0.53]) and TT4 (0.13 µg/dL [-0.01, 0.26]). Similar trends were observed for DNBP and inverse associations were observed for DPHP, monoethyl phthalate, mono-isobutyl phthalate, and mono-n-butyl phthalate. Most associations observed in co-pollutants adjusted GLMs were attenuated towards the null in BKMR, except for the case of ∑DiNP and TT3:TT4 ratio (-0.48 [-0.96, 0.003]). CONCLUSIONS: Maternal thyroid function varied modestly with ∑DiNP, whereas results for DPHP varied by the type of statistical models.

Gastrointestinal Symptoms in 2- to 5-Year-Old Children in the Study to Explore Early Development.

Gastrointestinal symptoms (GIS) are commonly reported in children with autism spectrum disorder (ASD). This multi-site study evaluated the prevalence of GIS in preschool-aged children with ASD/(n = 672), with other developmental delays (DD)/(n = 938), and children in the general population (POP)/(n = 851). After adjusting for covariates, children in the ASD group were over 3 times more likely to have parent-reported GIS than the POP group, and almost 2 times more likely than the DD group. Children with GIS from all groups had more behavioral and sleep problems. Within the ASD group, children with developmental regression had more GIS than those without; however, there were no differences in autism severity scores between children with and without GIS. These findings have implications for clinical management.

Family Composition and Stability for Orphans: A Longitudinal Study of Well-Being in 5 Low- and Middle-Income Countries.

Objectives: Many orphaned children in low- and middle-income countries live with family. Yet, their household composition and its stability are not well-characterized, nor is impact of stability on longer-term outcomes. Methods: We used the longitudinal, multi-country Positive Outcomes for Orphans cohort to describe adult family living with orphans. Stability was measured by changes in presence of six familial relations over time, and related to three outcomes: 1) incident abuse, 2) cognitive functioning, 3) emotional difficulties. Associations were estimated using generalized linear models fit with generalized estimating equations. For abuse, Poisson regression estimated risk ratios. For continuous scores of cognitive functioning and emotional difficulties, linear models estimated mean differences (MDs) with 95% confidence intervals. Results: Among 1,359 orphans, 53-61% reported living with their mother each year; 7-13% with father; nearly 60% reported ≥1 change in composition over follow-up. Compared to 0 changes, difficulties increased with 1 change [MD: 0.23 (-0.33, 0.79)], 2 changes [MD: 0.57 (0.00, 1.16)] and ≥3 changes [MD: 0.73 (0.18, 1.29)]. No associations were found with abuse or cognitive functioning. Conclusion: Orphan well-being may be improved through supports stabilizing household composition or targeting emotional resilience.

Histologic chorioamnionitis and risk of neurodevelopmental impairment at age 10 years among extremely preterm infants born before 28 weeks of gestation.

BACKGROUND: Extremely preterm infants whose placenta had histologic evidence of chorioamnionitis have early brain dysfunction, but little is known about neurologic development at 10 years of age. OBJECTIVE: We investigated the association between histologic chorioamnionitis and neurodevelopmental impairment at 10 years among children born <28 weeks' gestation (extremely preterm). STUDY DESIGN: The multicenter Extremely Low Gestational Age Newborns study enrolled extremely preterm newborns from 2002 to 2004 at 14 hospitals in the United States. Chorioamnionitis was defined by histologic stage (early, moderate, and advanced) and grade (mild/moderate and severe) of chorionic plate and umbilical cord inflammation. The children were examined for cerebral palsy at 2 years and for autism spectrum disorder, cognitive impairment (intelligence quotient >2 standard deviations below the mean), and epilepsy at the age of 10 years by blinded evaluators using validated measures. Multivariable logistic regression with generalized estimating equations was used. RESULTS: Among 805 placentas, 43% (347/805) had histologic chorioamnionitis by moderate or advanced maternal stage, 36% (286/805) by severe maternal grade, 18% (132/737) by moderate or advanced fetal stage, and 1% (10/737) by severe fetal grade. The frequencies of impairments were 11% (88/767) for cerebral palsy, 7% (56/773) for autism spectrum disorder, 15% (120/788) for cognitive impairment, and 7% (52/763) for epilepsy. After adjustment for maternal age, body mass index, race, insurance status, maternal education, tobacco use, infant sex, and multiple gestations, the adjusted odds ratio for the association between histologic chorioamnionitis and cerebral palsy years was increased with advanced maternal stage (adjusted odds ratio, 2.5; 95% confidence interval, 1.6-3.9), severe maternal grade (adjusted odds ratio, 2.0; 95% confidence interval, 1.2-3.4), moderate fetal stage (adjusted odds ratio, 2.20; 95% confidence interval, 2.1-2.2), and mild or moderate fetal grade (adjusted odds ratio, 1.5; 95% confidence interval, 1.0-2.2). Similarly, the adjusted odds ratio for the association between histologic chorioamnionitis and epilepsy was increased with advanced maternal stage (adjusted odds ratio, 1.5; 95% confidence interval, 1.3-1.6) and severe fetal grade (adjusted odds ratio, 5.9; 95% confidence interval, 1.9-17.8). In addition, the adjusted odds ratio for the association between histologic chorioamnionitis and autism spectrum disorder was increased with mild or moderate fetal grade (adjusted odds ratio, 1.7; 95% confidence interval, 1.0-2.9). Histologic chorioamnionitis was not associated with cognitive impairment. These findings held after adjustment for gestational age at delivery. In contrast to histologic chorioamnionitis, a clinical diagnosis of chorioamnionitis was not associated with neurodevelopmental impairment. CONCLUSION: Histologic chorioamnionitis may be associated with some forms of neurodevelopmental impairment at 10 years of life among infants born <28 weeks' gestation.

Early Identification of Autism Spectrum Disorder Among Children Aged 4 Years - Early Autism and Developmental Disabilities Monitoring Network, Six Sites, United States, 2016.

PROBLEM/CONDITION: Autism spectrum disorder (ASD). PERIOD COVERED: 2016. DESCRIPTION OF SYSTEM: The Early Autism and Developmental Disabilities Monitoring (Early ADDM) Network, a subset of the overall ADDM Network, is an active surveillance program that estimates ASD prevalence and monitors early identification of ASD among children aged 4 years. Children included in surveillance year 2016 were born in 2012 and had a parent or guardian who lived in the surveillance area in Arizona, Colorado, Missouri, New Jersey, North Carolina, or Wisconsin, at any time during 2016. Children were identified from records of community sources including general pediatric health clinics, special education programs, and early intervention programs. Data from comprehensive evaluations performed by community professionals were abstracted and reviewed by trained clinicians using a standardized ASD surveillance case definition with criteria from the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). RESULTS: In 2016, the overall ASD prevalence was 15.6 per 1,000 (one in 64) children aged 4 years for Early ADDM Network sites. Prevalence varied from 8.8 per 1,000 in Missouri to 25.3 per 1,000 in New Jersey. At every site, prevalence was higher among boys than among girls, with an overall male-to-female prevalence ratio of 3.5 (95% confidence interval [CI] = 3.1-4.1). Prevalence of ASD between non-Hispanic white (white) and non-Hispanic black (black) children was similar at each site (overall prevalence ratio: 0.9; 95% CI = 0.8-1.1). The prevalence of ASD using DSM-5 criteria was lower than the prevalence using Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria at one of four sites that used criteria from both editions. Among sites where ≥60% of children aged 4 years had information about intellectual disability (intelligence quotient ≤70 or examiner's statement of intellectual disability documented in an evaluation), 53% of children with ASD had co-occurring intellectual disability. Of all children aged 4 years with ASD, 84% had a first evaluation at age ≤36 months and 71% of children who met the surveillance case definition had a previous ASD diagnosis from a community provider. Median age at first evaluation and diagnosis for this age group was 26 months and 33 months, respectively. Cumulative incidence of autism diagnoses received by age 48 months was higher for children aged 4 years than for those aged 8 years identified in Early ADDM Network surveillance areas in 2016. INTERPRETATION: In 2016, the overall prevalence of ASD in the Early ADDM Network using DSM-5 criteria (15.6 per 1,000 children aged 4 years) was higher than the 2014 estimate using DSM-5 criteria (14.1 per 1,000). Children born in 2012 had a higher cumulative incidence of ASD diagnoses by age 48 months compared with children born in 2008, which indicates more early identification of ASD in the younger group. The disparity in ASD prevalence has decreased between white and black children. Prevalence of co-occurring intellectual disability was higher than in 2014, suggesting children with intellectual disability continue to be identified at younger ages. More children received evaluations by age 36 months in 2016 than in 2014, which is consistent with Healthy People 2020 goals. Median age at earliest ASD diagnosis has not changed considerably since 2014. PUBLIC HEALTH ACTION: More children aged 4 years with ASD are being evaluated by age 36 months and diagnosed by age 48 months, but there is still room for improvement in early identification. Timely evaluation of children by community providers as soon as developmental concerns have been identified might result in earlier ASD diagnoses, earlier receipt of evidence-based interventions, and improved developmental outcomes.

Prevalence of Autism Spectrum Disorder Among Children Aged 8 Years - Autism and Developmental Disabilities Monitoring Network, 11 Sites, United States, 2016.

PROBLEM/CONDITION: Autism spectrum disorder (ASD). PERIOD COVERED: 2016. DESCRIPTION OF SYSTEM: The Autism and Developmental Disabilities Monitoring (ADDM) Network is an active surveillance program that provides estimates of the prevalence of ASD among children aged 8 years whose parents or guardians live in 11 ADDM Network sites in the United States (Arizona, Arkansas, Colorado, Georgia, Maryland, Minnesota, Missouri, New Jersey, North Carolina, Tennessee, and Wisconsin). Surveillance is conducted in two phases. The first phase involves review and abstraction of comprehensive evaluations that were completed by medical and educational service providers in the community. In the second phase, experienced clinicians who systematically review all abstracted information determine ASD case status. The case definition is based on ASD criteria described in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. RESULTS: For 2016, across all 11 sites, ASD prevalence was 18.5 per 1,000 (one in 54) children aged 8 years, and ASD was 4.3 times as prevalent among boys as among girls. ASD prevalence varied by site, ranging from 13.1 (Colorado) to 31.4 (New Jersey). Prevalence estimates were approximately identical for non-Hispanic white (white), non-Hispanic black (black), and Asian/Pacific Islander children (18.5, 18.3, and 17.9, respectively) but lower for Hispanic children (15.4). Among children with ASD for whom data on intellectual or cognitive functioning were available, 33% were classified as having intellectual disability (intelligence quotient [IQ] ≤70); this percentage was higher among girls than boys (39% versus 32%) and among black and Hispanic than white children (47%, 36%, and 27%, respectively) [corrected]. Black children with ASD were less likely to have a first evaluation by age 36 months than were white children with ASD (40% versus 45%). The overall median age at earliest known ASD diagnosis (51 months) was similar by sex and racial and ethnic groups; however, black children with IQ ≤70 had a later median age at ASD diagnosis than white children with IQ ≤70 (48 months versus 42 months). INTERPRETATION: The prevalence of ASD varied considerably across sites and was higher than previous estimates since 2014. Although no overall difference in ASD prevalence between black and white children aged 8 years was observed, the disparities for black children persisted in early evaluation and diagnosis of ASD. Hispanic children also continue to be identified as having ASD less frequently than white or black children. PUBLIC HEALTH ACTION: These findings highlight the variability in the evaluation and detection of ASD across communities and between sociodemographic groups. Continued efforts are needed for early and equitable identification of ASD and timely enrollment in services.