Air Pollution Exposures and Child Executive Function: A U.S. Multi-Cohort Study.

BACKGROUND: Executive function, which develops rapidly in childhood, enables problem solving, focused attention, and planning. Animal models describe executive function decrements associated with ambient air pollution exposure, but epidemiologic studies are limited. METHODS: We examined associations between early childhood air pollution exposure and school-aged executive function in 1,235 children from three U.S. pregnancy cohorts in the ECHO-PATHWAYS Consortium. We derived point-based residential exposures to ambient particulate matter ≤2.5µm in aerodynamic diameter (PM2.5) and nitrogen dioxide (NO2), and ozone (O3) at ages 0-4 years from spatiotemporal models with a 2-week resolution. We assessed executive function across three domains -- cognitive flexibility, working memory, and inhibitory control -- using performance-based measures and calculated a composite score quantifying overall performance. We fitted linear regressions to assess air pollution - child executive function associations, adjusting for sociodemographic characteristics, maternal mental health, and health behaviors, and examined modification by child sex, maternal education, and neighborhood educational opportunity. RESULTS: In the overall sample, we found hypothesized inverse associations in crude but not adjusted models. Modified associations between NO2 exposure and working memory by neighborhood education opportunity were present (P interaction = 0.05), with inverse associations more pronounced in the "High" and "Very high" categories. Associations of interest did not differ by child sex or maternal education. CONCLUSIONS: This work contributes to the evolving science regarding early-life environmental exposures and child development. There remains a need for continued exploration in future research endeavors, to elucidate the complex interplay between natural environment and social determinants influencing child neurodevelopment.

Prenatal exposure to polycyclic aromatic hydrocarbons and executive functions at school age: Results from a combined cohort study.

BACKGROUND: Executive functions develop rapidly in childhood, enabling problem-solving, focused attention, and planning. Exposures to environmental toxicants in pregnancy may impair healthy executive function development in children. There is increasing concern regarding polycyclic aromatic hydrocarbons (PAHs) given their ability to transfer across the placenta and the fetal blood-brain barrier, yet evidence from epidemiological studies is limited. METHODS: We examined associations between prenatal PAH exposure and executive functions in 814 children of non-smoking mothers from two U.S. cohorts in the ECHO-PATHWAYS Consortium. Seven mono-hydroxylated PAH metabolites were measured in mid-pregnancy urine and analyzed individually and as mixtures. Three executive function domains were measured at age 8-9: cognitive flexibility, working memory, and inhibitory control. A composite score quantifying overall performance was further calculated. We fitted linear regressions adjusted for socio-demographics, maternal health behaviors, and psychological measures, and examined modification by child sex and stressful life events in pregnancy. Bayesian kernel machine regression was performed to estimate the interactive and overall effects of the PAH mixture. RESULTS: The results from primary analysis of linear regressions were generally null, and no modification by child sex or maternal stress was indicated. Mixture analyses suggested several pairwise interactions between individual PAH metabolites in varied directions on working memory, particularly interactions between 2/3/9-FLUO and other PAH metabolites, but no overall or individual effects were evident. CONCLUSION: We conducted a novel exploration of PAH-executive functions association in a large, combined sample from two cohorts. Although findings were predominantly null, the study carries important implications for future research and contributes to evolving science regarding developmental origins of diseases.

Developmental characteristics and accuracy of autism screening among two-year-old toddlers in the ECHO program.

BACKGROUND: The Modified Checklist for Autism in Toddlers (M-CHAT) is a common pediatric screening tool with mixed accuracy findings. Prior evidence supports M-CHAT screening for developmental concerns, especially in toddlers born preterm. This study examined M-CHAT accuracy in a large, nationwide sample. METHODS: 3393 participants from the Environmental influences on Child Health Outcomes (ECHO) program were included. Harmonized M-CHAT (M-CHAT-H) results were compared with parent-reported autism diagnosis and autism-related characteristics to assess accuracy for term and preterm children, together and separately. Generalized estimating equations, clustering for ECHO cohort and controlling for demographic covariates, were used to examine associations between developmental and behavioral characteristics with M-CHAT-H accuracy. RESULTS: Sensitivity of the M-CHAT-H ranged from 36 to 60%; specificity ranged from 88 to 99%. Positive M-CHAT-H was associated with more developmental delays and behavior problems. Children with severe motor delays and more autism-related problems were more likely to have a false-negative M-CHAT-H. Children with fewer behavior problems and fewer autism-related concerns were more likely to have a false-positive screen. CONCLUSION: The M-CHAT-H accurately detects children at low risk for autism and children at increased risk with moderate accuracy. These findings support use of the M-CHAT-H in assessing autism risk and developmental and behavioral concerns in children. IMPACT: Previous literature regarding accuracy of the Modified Checklist for Autism in Toddlers (M-CHAT) is mixed but this study provides evidence that the M-CHAT performs well in detecting children at low risk for autism and consistently detects children with developmental delays and behavioral problems. The M-CHAT moderately detects children at increased risk for autism and remains a useful screening tool. This study examines M-CHAT accuracy in a large-scale, nationwide sample, examining associations between screening accuracy and developmental outcomes. These findings impact pediatric screening for autism, supporting continued use of the M-CHAT while further elucidating the factors associated with inaccurate screens.

Associations of Pre- and Postnatal Air Pollution Exposures with Child Behavioral Problems and Cognitive Performance: A U.S. Multi-Cohort Study.

BACKGROUND: Population studies support the adverse associations of air pollution exposures with child behavioral functioning and cognitive performance, but few studies have used spatiotemporally resolved pollutant assessments. OBJECTIVES: We investigated these associations using more refined exposure assessments in 1,967 mother-child dyads from three U.S. pregnancy cohorts in six cities in the ECHO-PATHWAYS Consortium. METHODS: Pre- and postnatal nitrogen dioxide (NO2) and particulate matter (PM) ≤2.5µm in aerodynamic diameter (PM2.5) exposures were derived from an advanced spatiotemporal model. Child behavior was reported as Total Problems raw score using the Child Behavior Checklist at age 4-6 y. Child cognition was assessed using cohort-specific cognitive performance scales and quantified as the Full-Scale Intelligence Quotient (IQ). We fitted multivariate linear regression models that were adjusted for sociodemographic, behavioral, and psychological factors to estimate associations per 2-unit increase in pollutant in each exposure window and examined modification by child sex. Identified critical windows were further verified by distributed lag models (DLMs). RESULTS: Mean NO2 and PM2.5 ranged from 8.4 to 9.0 ppb and 8.4 to 9.1 µg/m3, respectively, across pre- and postnatal windows. Average child Total Problems score and IQ were 22.7 [standard deviation (SD): 18.5] and 102.6 (SD: 15.3), respectively. Children with higher prenatal NO2 exposures were likely to have more behavioral problems [ß: 1.24; 95% confidence interval (CI): 0.39, 2.08; per 2 ppb NO2], particularly NO2 in the first and second trimester. Each 2-µg/m3 increase in PM2.5 at age 2-4 y was associated with a 3.59 unit (95% CI: 0.35, 6.84) higher Total Problems score and a 2.63 point (95% CI: -5.08, -0.17) lower IQ. The associations between PM2.5 and Total Problems score were generally stronger in girls. Most predefined windows identified were not confirmed by DLMs. DISCUSSION: Our study extends earlier findings that have raised concerns about impaired behavioral functioning and cognitive performance in children exposed to NO2 and PM2.5 in utero and in early life. https://doi.org/10.1289/EHP10248.

Executive functioning skills in early childhood children with autism, intellectual disability, and co-occurring autism and intellectual disability.

BACKGROUND: Many children with autism and intellectual disability (ID) experience executive functioning (EF) difficulties. However, there is minimal research on EF skills in children with autism, ID, and co-occurring autism/ID in early childhood. AIMS: To address this gap in the research, we evaluated EF profiles using the BRIEF-P among early childhood children (2-5 years of age) with autism, ID, and co-occurring autism/ID. METHOD AND PROCEDURES: Participants in the current study were 87 children between the ages of 24 and 71 months (M = 46.8, SD = 12.7) diagnosed with autism (n = 24, 27.6 %), ID (n = 23, 26.4 %), or co-occurring autism/ID (n = 40, 46.0 %) that completed a comprehensive psychological evaluation at a university development center. We used a mixed Analysis of Variance (ANOVA) and between- and within-subjects ANOVAs as follow-up analyses. OUTCOMES AND RESULTS: Results suggested that early childhood children with autism, ID, and autism/ID may have unique EF skill profiles. Children with ID exhibited the most significant EF impairments and children with autism had the least. Working memory was the most impaired EF domain across all diagnostic groups. CONCLUSIONS AND IMPLICATIONS: Overall, our findings show that early childhood children with autism, ID, and autism/ID exhibit difficulties in EF skills. Children with ID exhibit the most significant EF impairments whereas children with autism show the least. However, regardless of diagnosis, working memory is the most impaired EF skill.

Maternal Plasma 25-Hydroxyvitamin D during Gestation Is Positively Associated with Neurocognitive Development in Offspring at Age 4-6 Years.

BACKGROUND: Vitamin D is critical to embryonic neuronal differentiation and other developmental processes that may affect future neurocognitive function. However, observational studies have found inconsistent associations between gestational vitamin D and neurocognitive outcomes. OBJECTIVES: We examined the association of gestational 25-hydroxyvitamin D [25(OH)D] with children's IQ at 4-6 y, and explored whether associations differed by race. METHODS: This study used data from the CANDLE (Conditions Affecting Neurocognitive Development and Learning in Early Childhood) cohort. Between 2006 and 2011, CANDLE recruited 1503 women in their second trimester of healthy singleton pregnancies. Inclusion criteria for this analysis were gestation of ≥34 wk and availability of 25(OH)D and IQ data. Associations between second-trimester 25(OH)D plasma concentration and Stanford-Binet IQ scores in offspring at 4-6 y were examined using multivariable linear regression; interaction terms were used to explore possible effect modification by race. RESULTS: Mean ± SD 25(OH)D concentration among 1019 eligible dyads was 21.6 ± 8.4 ng/mL, measured at a mean ± SD gestational age of 23.0 ± 3.0 wk. Vitamin D deficiency [25(OH)D < 20 ng/mL] was observed in 45.6%. Maternal 25(OH)D differed by race with a mean ± SD of 19.8 ± 7.2 ng/mL in Blacks sand 25.9 ± 9.3 ng/mL in Whites ( P  < 0.001). In adjusted models a 10-ng/mL increase in 25(OH)D was associated with a 1.17-point higher Full Scale IQ (95% CI: 0.27, 2.06 points), a 1.17-point higher Verbal IQ (95% CI: 0.19, 2.15 points), and a 1.03-point higher Nonverbal IQ (95% CI: 0.10, 1.95 points). We observed no evidence of effect modification by race. CONCLUSIONS: Second-trimester maternal 25(OH)D was positively associated with IQ at 4-6 y, suggesting that gestational vitamin D status may be an important predictor of neurocognitive development. These findings may help inform prenatal nutrition recommendations and may be especially relevant for Black and other dark-skinned women at high risk of vitamin D deficiency.

Demographic and psychosocial factors associated with hair cortisol concentrations in preschool children.

BACKGROUND: Early life stress has enduring effects on physical and mental health. Hair cortisol concentrations (HCCs) reflect exposures to contextual stressors in early life, but are understudied in preschool children. METHODS: Hair samples from children (N = 693) during clinic visits (CVs) scheduled at 1-4 years (CV1-CV4) were measured using validated assay methods for HCC. RESULTS: HCCs were highest at CV1 and decreased at CV2-CV4, with no sex differences. Black children had higher HCC than White/other children; these differences persisted even after adjusting for socioeconomic factors. Bivariable analyses showed significant effects on HCC for Black race, with specific demographic and psychosocial factors at different ages. Multivariable analyses showed that higher HCC at CV1 were associated with Black race and male sex; at CV2 with Black race, lower maternal self-esteem, socioeconomic adversity, and the child's risk for developmental delay; at CV3 with Black race; at CV4 with maternal depression and the child's prior HCC values. CONCLUSIONS: HCCs were higher in Black children than White/other races; differences were related to maternal factors, socioeconomic adversity, and the child's risk for developmental delay. Public health measures to reduce disparities between Blacks and other races must also consider the long-term effects of chronic stress in early life.

Socio-demographic, maternal, and child indicators of socioemotional problems in 2-year-old children: A cohort study.

Throughout infancy and early childhood, stable and secure relationships with caregivers are needed to promote optimal socioemotional (SE) and cognitive development.The objective is to examine socio-demographic, maternal, and child indicators of SE problems in 2-year-olds living in an urban-suburban community in the southern United States.Mother-infant pairs enrolled in a prospective pregnancy cohort study.Shelby County (Memphis), Tennessee.One thousand five hundred three women were recruited during their second trimester and followed with their children through the child's age of 2 years.Child SE development was measured by the Brief Infant-Toddler Social Emotional Assessment at 2 years of age. Mothers reported their own behavioral and mental health, temperament, parenting stress, and potential for child abuse during gestation and/or when their child was 1 year of age. Examiners measured maternal IQ during data collection at the child's age of 1 year. Child communication, cognitive development, and risk for autism spectrum disorder were assessed at 1 and 2 years of age. Multivariable regression models were developed to predict mother-reported SE problems.In bivariate analyses, multiple maternal behavioral and mental health indicators and child cognitive skills were associated with reported child SE problems at 2 years of age. Regression analyses, controlling for socio-demographic, maternal, and child variables, showed the following factors were independently associated with mother-reported child SE problems: maternal education of high school or less, lower maternal IQ, higher maternal cyclothymic temperament score, greater parenting stress, greater maternal psychological distress, lower child expressive communication score, and child risk for autism spectrum disorder. Socio-demographic variables accounted for the variance often attributed to race.Since mothers in the study were medically low-risk, generalizing these findings to medically high-risk mothers is unwarranted. In addition, these SE outcomes in 2-year-old children do not reflect the trajectory of SE development throughout early childhood.Attention to independent indicators of future SE problems in children may help identify individual children and families needing intervention and target public prevention/treatment programs in communities.

Prospective Associations Between Infant Sleep at 12 Months and Autism Spectrum Disorder Screening Scores at 24 Months in a Community-Based Birth Cohort.

BACKGROUND: Sleep problems have been associated with autism spectrum disorder (ASD) symptoms and diagnosis. However, past research has studied the simultaneous association of sleep problems with precursor ASD symptoms. Using data from a birth cohort, we estimate prospective associations between infant sleep characteristics at 12 months and later ASD screening scores at 24 months. METHODS: We obtained data from children (N = 1,096) and their mothers as participants in the Conditions Affecting Neurocognitive Development and Learning in Early Childhood longitudinal birth cohort study. Mothers were enrolled between 2006 and 2011, when they were 16-26 weeks pregnant. Using linear regression, we examined the influence of infant sleep characteristics (nighttime and daytime sleep, night wakings, and sleep onset latency) at 12 months on ASD screening scores at 24 months while controlling for other psychosocial characteristics. RESULTS: The number of night wakings was the only sleep characteristic at 12 months to be significantly associated with the development of early ASD symptoms at 24 months (B = 0.097, P = .021; 95% CI, 0.014 to 0.180). However, other competing risks, especially child socioemotional competence at 12 months (B = 0.573, P < .001; 95% CI, 0.361 to 0.785), showed stronger relative contributions in predicting ASD risk. CONCLUSIONS: Infants with more sleep problems by 12 months, especially those waking more often during the night, showed an increased number of early ASD symptoms a year later. This study suggests that infant sleep characteristics could constitute one clinical sign of ASD risk, together with key psychosocial characteristics.

Inattention and hyperactivity/impulsivity among children with attention-deficit/hyperactivity-disorder, autism spectrum disorder, and intellectual disability.

BACKGROUND: Attention-Deficit/Hyperactivity Disorder (ADHD), Autism Spectrum Disorder (ASD), and Intellectual Disability (ID) are common co-occurring neurodevelopmental disorders; however, limited research exists regarding the presentation and severity of overlapping symptomology, particularly inattention and hyperactivity/impulsivity, when a child is diagnosed with one of more of these neurodevelopmental disorders. AIMS: As difficulties with inattention and hyperactivity/impulsivity are symptoms frequently associated with these disorders, the current study aims to determine the differences in the severity of inattention and hyperactivity/impulsivity in children diagnosed with ADHD, ASD, ID, and co-occurring diagnosis of ADHD/ID, ASD/ADHD, and ASD/ID. METHODS AND PROCEDURES: Participants in the current study included 113 children between the ages of 6 and 11 who were diagnosed with ADHD, ASD, ID, ADHD/ID, ASD/ADHD, or ASD/ID. Two MANOVA analyses were used to compare these groups witih respsect to symptom (i.e., inattention, hyperactivity/impulsivity) severity. OUTCOMES AND RESULTS: Results indicated that the majority of diagnostic groups experienced elevated levels of both inattention and hyperactivity/impulsivity. However, results yielded differences in inattention and hyperactivity/impulsivity severity. In addition, differences in measure sensitivity across behavioral instruments was found. CONCLUSIONS AND IMPLICATIONS: Children with neurodevelopmental disorders often exhibit inattention and hyperactivity/impulsivity, particularly those with ADHD, ASD, ASD/ADHD, and ADHD/ID; therefore, differential diagnosis may be complicated due to similarities in ADHD symptom severity. However, intellectual abilities may be an important consideration for practitioners in the differential diagnosis process as children with ID and ASD/ID exhibited significantly less inattention and hyperactive/impulsive behaviors. Additionally, the use of multiple behavior rating measures in conjunction with other assessment procedures may help practitioners determine the most appropriate diagnosis.

Maternal and Child Characteristics Associated With Mother-Child Interaction in One-Year-Olds.

Mothers' interactions with their young children have predicted later child development, behavior, and health, but evidence has been developed mainly in at-risk clinical samples. An economically and racially diverse sample of pregnant women who were not experiencing a high-risk pregnancy were recruited to participate in a community-based, longitudinal study of factors associated with child cognitive and social-emotional development during the first 3 years. The purpose of the present analysis was to identify associations between the characteristics of 1125 mothers and their 1-year-olds and the mothers' and children's scores on the Nursing Child Assessment Teaching Scale (NCATS). A multivariable approach was used to identify maternal and child characteristics associated with NCATS scores and to develop prediction models for NCATS total and subscale scores of mothers and children. Child expressive and receptive communication and maternal IQ, marital status, age, and insurance predicted NCATS Mother total score, accounting for 28% of the score variance. Child expressive communication and birth weight predicted the NCATS Child total score, accounting for 4% of variance. Child's expressive communication and mother's IQ and marital status predicted NCATS mother-child total scores. While these findings were similar to reports of NCATS scores in at-risk populations, no previous teams examined all of the mother and child characteristics included in this analysis. These findings support the utility of the NCATS for assessing mother-child interaction and predicting child outcomes in community-based, non-clinical populations. © 2017 Wiley Periodicals, Inc.

Gestational Vitamin 25(OH)D Status as a Risk Factor for Receptive Language Development: A 24-Month, Longitudinal, Observational Study.

Emerging data suggest that vitamin D status during childhood and adolescence can affect neurocognitive development. The purpose of this study was to investigate whether gestational 25(OH)D status is associated with early childhood cognitive and receptive language development. The Conditions Affecting Neurocognitive Development and Learning in Early Childhood Study (CANDLE) study enrolled 1503 mother-child dyads during the second trimester of healthy singleton pregnancies from Shelby County TN. Among 1020 participants of the total CANDLE cohort for whom 25(OH)D levels were available, mean gestational 25(OH)D level during the second trimester was 22.3 ng/mL (range 5.9-68.4), with 41.7% of values <20 ng/dL. Cognitive and language scaled scores increased in a stair-step manner as gestational 25(OH)D levels in the second trimester rose from <20 ng/dL, through 20-29.99 ng/dL, to ≥30 ng/dL. When controlling for socioeconomic status, race, use of tobacco products, gestational age of the child at birth, and age at the 2-year assessment, the gestational 25(OH)D was positively related to receptive language development (p < 0.017), but not cognitive or expressive language.

Epigenetic analysis of neurocognitive development at 1 year of age in a community-based pregnancy cohort.

Multiple studies show that molecular genetic changes and epigenetic modifications affect the risk of cognitive disability or impairment. However, the role of epigenetic variation in cognitive development of neurotypical young children remains largely unknown. Using data from a prospective, community-based study of mother-infant pairs, we investigated the association of DNA methylation patterns in neonatal umbilical cord blood with cognitive and language development at 1 year of age. No CpG loci achieved genome-wide significance, although a small number of weakly suggestive associations with Bayley-III Receptive Communication scales were noted. While umbilical cord blood is a convenient resource for genetic analyses of birth outcomes, our results do not provide conclusive evidence that its use for DNA methylation profiling yields epigenetic markers that are directly related to postnatal neurocognitive outcomes at 1 year of age.

Early adversity, socioemotional development, and stress in urban 1-year-old children.

OBJECTIVE: To determine demographic, maternal, and child factors associated with socioemotional (SE) problems and chronic stress in 1-year-old children. STUDY DESIGN: This was a prospective, longitudinal, community-based study, which followed mother-infant dyads (n = 1070; representative of race, education, and income status of Memphis/Shelby County, Tennessee) from midgestation into early childhood. Child SE development was measured using the Brief Infant-Toddler Social and Emotional Assessment in all 1097 1-year-olds. Chronic stress was assessed by hair cortisol in a subsample of 1-year-olds (n = 297). Multivariate regression models were developed to predict SE problems and hair cortisol levels. RESULTS: More black mothers than white mothers reported SE problems in their 1-year-olds (32.9% vs 10.2%; P < .001). In multivariate regression, SE problems in blacks were predicted by lower maternal education, greater parenting stress and maternal psychological distress, and higher cyclothymic personality score. In whites, predictors of SE problems were Medicaid insurance, higher maternal depression score at 1 year, greater parenting stress and maternal psychological distress, higher dysthymic personality score, and male sex. SE problem scores were associated with higher hair cortisol levels (P = .01). Blacks had higher hair cortisol levels than whites (P < .001). In the entire subsample, increased hair cortisol levels were associated with higher parenting stress (P = .001), lower maternal depression score (P = .01), lower birth length (P < .001), and greater length at 1 year of age (P = .003). CONCLUSION: Differences in maternal education, insurance, mental health, and early stress may disrupt SE development in children. Complex relationships between hair cortisol level in 1-year-olds and maternal parenting stress and depression symptoms suggest dysregulation of the child's hypothalamic-pituitary-adrenal axis.

[Influence of premenstrual syndrome and oral contraceptive effects on food choice during the follicular and luteal phase of the menstrual cycle]. / Influencia del síndrome premenstrual y el uso de anticonceptivos orales en la selección de alimentos durante las fases folicular y lútea del ciclo menstrual.

BACKGROUND AND OBJECTIVE: Food intake and motivation for food varies according to the phase of the menstrual cycle. These changes seem to be more marked in women with premenstrual syndrome (PMS) and may be modified by the use of oral contraceptives (OC). This study examined the effect of menstrual cycle, PMS and OC use on the intake and hedonic rating of sweet and savory snack foods. MATERIAL AND METHODS: Fifty-five women were recruited and assigned to either a PMS group or a control group. In addition, based on OC use, the women were assigned to an OC-user or non-user group. During the luteal and follicular phases, the participants were asked to consume and rate sweet and savory snacks. RESULTS: The luteal phase induced greater caloric intake from sweet foods. PMS sufferers did not consume significantly more calories in either phase. There was a significant interaction between phase, flavor, PMS status and OC use. OC users consumed more calories from sweet foods in the follicular phase. CONCLUSIONS: Food intake is increased in the luteal phase. This effect was modulated by both PMS and OC use. OC use seems to eliminate cyclic fluctuations in caloric intake.