Associations between middle childhood executive control aspects and adolescent substance use and externalizing and internalizing problems.

This study examines the degree to which two middle childhood executive control aspects, working memory and combined inhibitory control/flexible shifting, predict adolescent substance use and externalizing and internalizing problems. Participants were 301 children (ages 3-6 years; 48.2% male) recruited from a Midwestern city in the United States and followed into adolescence (ages 14-18 years). Working memory had a statistically significant unadjusted association with externalizing problems (r = -.30, p = .003) in a confirmatory factor analysis. Neither factor significantly predicted any of the adolescent outcomes in a structural equation model that adjusted for each EC aspect, sociodemographic covariates, and middle childhood externalizing and internalizing problems. Stronger prediction of EC aspects might not emerge until they become more fully differentiated later in development.

Exploring the Interaction Between Preschool Executive Control and Caregiver Emotion Socialization in Predicting Adolescent Weight Trajectories.

There is a critical need for research examining how neural vulnerabilities associated with obesity, including lower executive control, interact with family factors to impact weight trajectories across adolescence. Utilizing a longitudinal design, the present study investigated caregivers' emotion socialization practices as a moderator of the association between preschool executive control and adolescent body mass index (BMI) trajectories. Participants were 229 youth (Mage = 5.24, SD = 0.03; 47.2% assigned female at birth; 73.8% White, 3.9% Black, 0.4% Asian American, 21.8% multiracial; 12.7% Hispanic) enrolled in a longitudinal study. At preschool-age, participants completed performance-based executive control tasks, and their caregivers reported on their typical emotion-related socialization behaviors (i.e., supportive and nonsupportive responses to children's negative emotions). Participants returned for annual laboratory visits at ages 14 through 17, during which their height and weight were measured to calculate BMI. Although neither preschool executive control nor caregiver emotion-related socialization behaviors were directly associated with BMI growth in adolescence, supportive responses moderated the association between executive control and BMI trajectories. The expected negative association between lower preschool executive control and greater BMI growth was present at below average levels of supportive responses, suggesting that external regulation afforded by supportive responses might reduce risk for adolescent overweight and obesity among children with lower internal self-regulatory resources during preschool. Findings highlight the importance of efforts to bolster executive control early in development and targeted interventions to promote effective caregiver emotion socialization (i.e., more supportive responses) for youth with lower internal self-regulatory abilities to mitigate risk for overweight and obesity and promote health across childhood and adolescence.

Development and psychometric validation of the Pandemic-Related Traumatic Stress Scale for children and adults.

To assess the public health impact of the COVID-19 pandemic on mental health, investigators from the National Institutes of Health Environmental influences on Child Health Outcomes (ECHO) research program developed the Pandemic-Related Traumatic Stress Scale (PTSS). Based on the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) acute stress disorder symptom criteria, the PTSS is designed for adolescent (13-21 years) and adult self-report and caregiver-report on 3-12-year-olds. To evaluate psychometric properties, we used PTSS data collected between April 2020 and August 2021 from non-pregnant adult caregivers (n = 11,483), pregnant/postpartum individuals (n = 1,656), adolescents (n = 1,795), and caregivers reporting on 3-12-year-olds (n = 2,896). We used Mokken scale analysis to examine unidimensionality and reliability, Pearson correlations to evaluate relationships with other relevant variables, and analyses of variance to identify regional, age, and sex differences. Mokken analysis resulted in a moderately strong, unidimensional scale that retained nine of the original 10 items. We detected small to moderate positive associations with depression, anxiety, and general stress, and negative associations with life satisfaction. Adult caregivers had the highest PTSS scores, followed by adolescents, pregnant/postpartum individuals, and children. Caregivers of younger children, females, and older youth had higher PTSS scores compared to caregivers of older children, males, and younger youth, respectively. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

The role of prenatal violence exposure in the development of disparities in children's adiposity from birth to middle childhood.

OBJECTIVE: This study examined whether women's exposure to multiple types of violence during childhood and pregnancy was associated with children's BMI trajectories and whether parenting quality moderated those associations. METHODS: A cohort of 1288 women who gave birth between 2006 and 2011 self-reported their exposure to childhood traumatic events, intimate partner violence (IPV), and residential address (linked to geocoded index of violent crime) during pregnancy. Children's length/height and weight at birth and at age 1, 2, 3, 4 to 6, and 8 years were converted to BMI z scores. Observed mother-child interactions were behaviorally coded during a dyadic teaching task. RESULTS: Covariate-adjusted growth mixture models identified three trajectories of children's BMI from birth to 8 years old: Low-Stable (17%), Moderate-Stable (59%), and High-Rising (22%). Children whose mothers experienced more types of IPV during pregnancy were more likely to be in the High-Rising than the Low-Stable (odds ratio [OR] = 2.62; 95% CI: 1.27-5.41) trajectory. Children whose mothers lived in higher crime neighborhoods were more likely to be in the High-Rising than the Low-Stable (OR = 1.11; 95% CI:1.03-1.17) or Moderate-Stable trajectories (OR = 1.08; CI: 1.03-1.13). Main effects of childhood traumatic events and moderation by parenting were not detected. CONCLUSIONS: Maternal experiences of violence during pregnancy increase children's risk for developing overweight, highlighting intergenerational transmission of social adversity in children's health.

Protective factors in the relationship between perceived discrimination and risky drinking among American Indian adolescents.

INTRODUCTION: The relationship between perceived discrimination and risky drinking among American Indian (AI) youth is understudied, and the potential protective factors that may buffer this association are unknown. Therefore, the objective of this study was to examine protective factors across individual, family, school, peer, and cultural domains of the social ecology that might attenuate the relationship between perceived discrimination and risky drinking among AI adolescents. METHOD: Data were from the Substance Use Among American Indian Youth Study (Swaim and Stanley, 2018, 2021). AI youth who have used alcohol in their lifetime (n = 2516 within 62 schools) had an average age of 15.16 years (SD = 1.75) and 55.5% were female. Five sets of linear regressions were conducted. Risky drinking was regressed on demographic variables, alcohol use frequency, perceived discrimination, one protective factor (religiosity, parental monitoring, peer disapproval of alcohol use, school engagement, and ethnic identity), and one two-way interaction between perceived discrimination and the protective factor. RESULTS: Prevalence of risky drinking among lifetime drinkers was 40.1%. There were positive associations between perceived discrimination and risky drinking in all models (Bs range from.20 to.23; p <.001). Parental monitoring had a negative association with risky drinking (B = -0.255, p <.001). Religiosity was the only statistically significant moderator (B = -0.08, p = 0.01), indicating that religiosity weakened the relation between perceived discrimination and risky drinking. CONCLUSIONS: Religiosity may represent an important protective factor that could help guide efforts to prevent risky drinking in the face of discrimination among AI adolescents.

Association of Gestational Diabetes Mellitus and Perinatal Maternal Depression with Early Childhood Behavioral Problems: An Environmental Influences on Child Health Outcomes (ECHO) Study.

This study examined the association of gestational diabetes mellitus (GDM), prenatal, and postnatal maternal depressive symptoms with externalizing, internalizing, and autism spectrum problems on the Preschool Child Behavior Checklist in 2379 children aged 4.12 ± 0.60 (48% female; 47% White, 32% Black, 15% Mixed Race, 4% Asian, <2% American Indian/Alaskan Native, <2% Native Hawaiian; 23% Hispanic). Data were collected from the NIH Environmental influences on Child Health Outcomes (ECHO) Program from 2009-2021. GDM, prenatal, and postnatal maternal depressive symptoms were each associated with increased child externalizing and internalizing problems. GDM was associated with increased autism behaviors only among children exposed to perinatal maternal depressive symptoms above the median level. Stratified analyses revealed a relation between GDM and child outcomes in males only.

A Comparison of Task-Based and Questionnaire Assessments of Executive Control Aspects in Relation to Adolescent Marijuana Initiation.

Prior research has linked deficits in executive control (EC) to marijuana use in adolescents but has relied either primarily on adolescent self-report of EC or tasked-based EC, and focused on limited aspects of EC, usually inhibitory control. We examined unique associations of three established aspects of EC (inhibitory control, working memory, and flexible shifting) assessed with both performance on laboratory tasks and self-report in relation to marijuana initiation. Participants were 260 youth (ages 14-18 years) from a small Midwestern city in the United States enrolled in the adolescent phase (beginning in 2017) of an ongoing study of EC development recruited originally between 2006 and 2012 (46% male, 72% European American). The three aspects of executive control were measured in a laboratory setting with well-established performance-based measures and with a psychometrically-sound self-report survey instrument. Youth also provided self-report of marijuana initiation in a phone survey administered during their laboratory visit. Multiple logistic regression analysis indicated that flexible shifting as measured by a performance-based task was negatively and uniquely associated with marijuana initiation (AOR = 0.68, 95% CI = 0.48 - 0.91), and self-reported deficits in inhibitory control were positively associated with marijuana initiation (AOR = 1.92, 95% CI = 1.15 - 3.21). Although larger-scale longitudinal research is needed, findings of this study suggest that screening efforts to identify youth at risk of marijuana initiation might rely on more cost-effective self-report assessment of inhibitory control, but further valuable information can come from more resource-intensive but sensitive performance-based assessment of flexible shifting.

Does preschool executive control mediate the impact of early environmental unpredictability and deprivation on the general factor of psychopathology a decade later?

BACKGROUND: Although deprivation has been consistently shown to increase risk for psychopathology through impaired executive control, the unique effects of other dimensions of early adversity, such as unpredictability, on executive control development are poorly understood. The current study evaluated whether deprivation and/or unpredictability early in life have unique effects on the general factor of psychopathology through impaired preschool executive control. METHODS: Participants included 312 children (51% female) oversampled for greater sociodemographic risk. Preschool executive control was measured using a battery of nine developmentally appropriate executive control tasks. Dimensions of adversity were measured with observational and caregiver assessments, and psychopathology was measured with caregiver and child reports. RESULTS: In separate models, both deprivation and unpredictability had significant indirect effects on the adolescent general factor of psychopathology through impaired preschool executive control. However, when both dimensions of adversity were included simultaneously, early life deprivation, but not unpredictability, was uniquely associated with the general factor of psychopathology in adolescence through impaired preschool executive control. CONCLUSIONS: Preschool executive control appears to be a transdiagnostic mechanism through which deprivation, but not unpredictability, increases risk for the general factor of psychopathology in adolescence. Results elucidate potential transdiagnostic targets for intervention efforts aimed at reducing the development and maintenance of psychopathology across the life span.

Intergenerational transmission of stress: Multi-domain stressors from maternal childhood and pregnancy predict children's mental health in a racially and socioeconomically diverse, multi-site cohort.

PURPOSE: Despite growing recognition that unfortunately common maternal stress exposures in childhood and pregnancy may have intergenerational impacts on children's psychiatric health, studies rarely take a life course approach. With child psychopathology on the rise, the identification of modifiable risk factors is needed to promote maternal and child well-being. In this study, we examined associations of maternal exposure to childhood traumatic events (CTE) and pregnancy stressful life events (PSLE) with child mental health problems in a large, sociodemographically diverse sample. METHODS: Participants were mother-child dyads in the ECHO-PATHWAYS consortium's harmonized data across three U.S. pregnancy cohorts. Women completed questionnaires regarding their own exposure to CTE and PSLE, and their 4-6-year-old child's mental health problems using the Child Behavior Checklist (CBCL). Regression analyses estimated associations between stressors and child total behavior problems, adjusting for confounders. RESULTS: Among 1948 dyads (child age M = 5.13 (SD = 1.02) years; 38% Black, 44% White; 8.5% Hispanic), maternal history of CTE and PSLE were independently associated with children's psychopathology: higher CTE and PSLE counts were related to higher total problems ([ßCTE = 0.11, 95% CI [.06, .16]; ßSLE = 0.21, 95% CI [.14, 0.27]) and greater odds of clinical levels of problems (ORCTE = 1.41; 95% CI [1.12, 1.78]; ORPSLE = 1.36; 95% CI [1.23, 1.51]). Tests of interaction showed PSLEs were more strongly associated with child problems for each additional CTE experienced. CONCLUSION: Findings confirm that maternal exposure to CTE and PSLE are independently associated with child mental health, and history of CTE exacerbates the risk associated with PSLE, highlighting intergenerational risk pathways for early psychopathology. Given the prevalence of these exposures, prevention and intervention programs that reduce childhood trauma and stress during pregnancy will likely positively impact women's and their children's health.

Social Network Analysis of Diffusion Among American Indian Youth in a Culturally Adapted, Family-focused Prevention Program.

Diffusion can contribute to the spread of preventive intervention effects from participants to non-participants, but best practices for randomized trials prevent contamination of conditions. These practices conflict with cultural values of community benefit, which are salient among American Indians. This study embedded social network measures within a randomized trial of the Bii-Zin-Da-De-Dah (BZDDD) family-focused prevention program to characterize youth's social networks, describe the nature and content of sharing, and test for diffusion effects on cultural engagement (ethnic identification, cultural socialization, cultural practices) and substance use. Participants were 256 American Indian youths enrolled in the trial who provided self-reports of their social networks and indicated whether specific program content was shared with or received from others, while completing cultural engagement and substance use questionnaires across three waves. Results indicated that social networks were comprised mainly of peers and same-age family members (e.g., cousins). Program sharing was not uncommon. For example, 51% of responding intervention youth reported talking with non-participants about BZDDD at wave 2, typically (53%) with similar-age friends and family who were, most often (71%), out of the home. Evidence for diffusion effects was limited, but did indicate that control youth who had some exposure to BZDDD had a significantly higher average cultural/ethnic identity scale score at wave 2 and were more likely to ask an elder for advice than control youth who had no BZDDD exposure in adjusted analyses. Findings illustrate the value of measuring and testing for potential effects of diffusion in prevention trials with American Indians.

Differences in Emotional and Behavioral Problems of Students over Time: A 22-Year Cross-Sectional Cohort Study.

Levels of emotional and behavioral problems in children and adolescents demonstrate secular changes over time, warranting ongoing investigation. Prior studies examining secular trends in a range of such problems have been conducted in the U.S. and internationally. Research in this area generally has not fully considered the school setting. This study compared emotional and behavioral problems across two cohorts of students in the U.S. assessed over a 22-year time period as part of measurement development efforts for the Scales for Assessing Emotional Disturbance Rating Scale (SAED-RSRS; Epstein et al., 2020). Specifically, analyses drew from data collected via teacher report on matched cohorts of students for the 1998 (data collected from 1996 to 1997; n = 1,148) and 2020 (data collected from 2016 to 2018; n = 1,148) editions of the SAED-RS. After establishing measurement invariance across cohorts and testing for gender differences, structural equation modeling revealed statistically significant cohort mean differences on two of the five factors of the SAED-RS, suggesting increases over time in Inability to Learn (ß = 0.09, p = .024) and Physical Symptoms and Fears (ß = 0.14, p = .005) that were comparable for girls and boys. There were no statistically significant differences on the remaining factors: Relationship Problems, Inappropriate Behavior, and Unhappiness/Depression. Supplemental item-level tests revealed differences on 8 of the 39 SAED-RS items. Findings suggest increases in specific problem areas that could benefit from ongoing monitoring and targeted interventions to support contemporary students.

A Multi-Cohort Examination of the Independent Contributions of Maternal Childhood Adversity and Pregnancy Stressors to the Prediction of Children's Anxiety and Depression.

Women's social experiences can have long-term implications for their offspring's health, but little is known about the potential independent contributions of multiple periods of stress exposures over time. This study examined associations of maternal exposure to adversity in childhood and pregnancy with children's anxiety and depression symptoms in a large, sociodemographically diverse sample. Participants were 1389 mother-child dyads (child age M = 8.83 years; SD = 0.66; 42% Black, 42% White; 6% Hispanic) in the ECHO-PATHWAYS Consortium's three U.S. pregnancy cohorts. Women reported their exposure to childhood traumatic events (CTE) and pregnancy stressful life events (PSLE). Children self-reported on their symptoms of anxiety and depression at age 8-9 years. Regression analyses estimated associations between maternal stressors and children's internalizing problems, adjusting for confounders, and examined child sex as a modifier. Exploratory interaction analyses examined whether geospatially-linked postnatal neighborhood quality buffered effects. In adjusted models, PSLE counts positively predicted levels of children's anxiety and depression symptoms ([ßAnxiety=0.08, 95%CI [0.02, 0.13]; ßDepression=0.09, 95%CI [0.03, 0.14]); no significant associations were observed with CTE. Each additional PSLE increased odds of clinically significant anxiety symptoms by 9% (95%CI [0.02, 0.17]). Neither sex nor neighborhood quality moderated relations. Maternal stressors during pregnancy appear to have associations with middle childhood anxiety and depression across diverse sociodemographic contexts, whereas maternal history of childhood adversity may not. Effects appear comparable for boys and girls. Policies and programs addressing prevention of childhood internalizing symptoms may benefit from considering prenatal origins and the potential two-generation impact of pregnancy stress prevention and intervention.

Childhood executive control and adolescent substance use initiation: the mediating roles of physical and relational aggression and prosocial behavior.

Although predictive associations between childhood executive control (EC) and adolescent substance use have been established in prior research, the developmental pathways involved in these long-term links have not been well understood. The goal of the current study was to investigate the degree to which aggressive behaviors, including both physical and relational aggression, and prosocial behaviors in elementary school operate as developmental pathways between preschool EC and adolescent substance use, while accounting for participants' age, sex, family history of substance use, and family socioeconomic status. Participants were 329 youth (49% male; 63.6% European American) who were recruited to participate in a study between 2006 and 2012 while youth were in preschool and elementary school and followed into adolescence. The sample was recruited from a small Midwestern city in the United States. EC was assessed with performance-based tasks when children were 5 years 3 months. Youth behaviors with peers were reported by teachers when participants were in elementary school. Self-reports of the substance use initiation (e-cigarettes, cigarettes, alcohol, and marijuana) were obtained in adolescence via phone surveys. Mediation analyses revealed a statistically significant indirect effect from preschool EC to adolescent substance use through youth's engagement in relational aggression in elementary school (b = > -0.22 [-0.51; -0.08]; ß = > -0.18). Our results suggest that developmental pathways to adolescent substance use may begin in preschool, setting the stage for susceptibility to engagement in relational aggression, which increases, in turn, youth's likelihood for substance use initiation in adolescence.

Placental transcriptomic signatures of spontaneous preterm birth.

BACKGROUND: Spontaneous preterm birth accounts for most preterm births and leads to significant morbidity in the newborn and childhood period. This subtype of preterm birth represents an increasing proportion of all preterm births when compared with medically indicated preterm birth, yet it is understudied in omics analyses. The placenta is a key regulator of fetal and newborn health, and the placental transcriptome can provide insight into pathologic changes that lead to spontaneous preterm birth. OBJECTIVE: This analysis aimed to identify genes for which placental expression was associated with spontaneous preterm birth (including early preterm and late preterm birth). STUDY DESIGN: The ECHO PATHWAYS consortium extracted RNA from placental samples collected from the Conditions Affecting Neurocognitive Development and Learning in Early Childhood and the Global Alliance to Prevent Prematurity and Stillbirth studies. Placental transcriptomic data were obtained by RNA sequencing. Linear models were fit to estimate differences in placental gene expression between term birth and spontaneous preterm birth (including gestational age subgroups defined by the American College of Obstetricians and Gynecologists). Models were adjusted for numerous confounding variables, including labor status, cohort, and RNA sequencing batch. This analysis excluded patients with induced labor, chorioamnionitis, multifetal gestations, or medical indications for preterm birth. Our combined cohort contained gene expression data for 14,023 genes in 48 preterm and 540 term samples. Genes and pathways were considered statistically significantly different at false discovery rate-adjusted P value of <.05. RESULTS: In total, we identified 1728 genes for which placental expression was associated with spontaneous preterm birth with more differences in expression in early preterm samples than late preterm samples when compared with full-term samples. Of those, 9 genes were significantly decreased in both early and late spontaneous preterm birth, and the strongest associations involved placental expression of IL1B, ALPL, and CRLF1. In early and late preterm samples, we observed decreased expression of genes involved in immune signaling, signal transduction, and endocrine function. CONCLUSION: This study provides a comprehensive assessment of the differences in the placental transcriptome associated with spontaneous preterm birth with robust adjustment for confounding. Results of this study are in alignment with the known etiology of spontaneous preterm birth, because we identified multiple genes and pathways for which the placental and chorioamniotic membrane expression was previously associated with prematurity, including IL1B. We identified decreased expression in key signaling pathways that are essential for placental growth and function, which may be related to the etiology of spontaneous preterm birth. We identified increased expression of genes within metabolic pathways associated exclusively with early preterm birth. These signaling and metabolic pathways may provide clinically targetable pathways and biomarkers. The findings presented here can be used to understand underlying pathologic changes in premature placentas, which can inform and improve clinical obstetrics practice.

Gestational diabetes mellitus, prenatal maternal depression, and risk for postpartum depression: an Environmental influences on Child Health Outcomes (ECHO) Study.

BACKGROUND: Prior research has demonstrated bidirectional associations between gestational diabetes mellitus (GDM) and perinatal maternal depression. However, the association between GDM, prenatal depression, and postpartum depression (PPD) has not been examined in a prospective cohort longitudinally. METHODS: Participants in the current analysis included 5,822 women from the National Institutes of Health's Environmental influences on Child Health Outcomes (ECHO) Research Program: N = 4,606 with Neither GDM nor Prenatal Maternal Depression (Reference Category); N = 416 with GDM only; N = 689 with Prenatal Maternal Depression only; and N = 111 with Comorbid GDM and Prenatal Maternal Depression. The PROMIS-D scale was used to measure prenatal and postnatal maternal depressive symptoms. Primary analyses consisted of linear regression models to estimate the independent and joint effects of GDM and prenatal maternal depression on maternal postpartum depressive symptoms. RESULTS: A higher proportion of women with GDM were classified as having prenatal depression (N = 111; 21%) compared to the proportion of women without GDM who were classified as having prenatal depression (N = 689; 13%), however this finding was not significant after adjustment for covariates. Women with Comorbid GDM and Prenatal Maternal Depression had significantly increased postpartum depressive symptoms measured by PROMIS-D T-scores compared to women with Neither GDM nor Prenatal Maternal Depression (mean difference 7.02, 95% CI 5.00, 9.05). Comorbid GDM and Prenatal Maternal Depression was associated with an increased likelihood of PPD (OR 7.38, 95% CI 4.05, 12.94). However, women with GDM only did not have increased postpartum PROMIS-D T-scores or increased rates of PPD. CONCLUSIONS: Our findings underscore the importance of universal depression screening during pregnancy and in the first postpartum year. Due to the joint association of GDM and prenatal maternal depression on risk of PPD, future studies should examine potential mechanisms underlying this relation.

Prenatal metabolomic profiles mediate the effect of maternal obesity on early childhood growth trajectories and obesity risk: the Conditions Affecting Neurocognitive Development and Learning in Early Childhood (CANDLE) Study.

BACKGROUND: Maternal prepregnancy obesity is an important risk factor for offspring obesity, which may partially operate through prenatal programming mechanisms. OBJECTIVES: The study aimed to systematically identify prenatal metabolomic profiles mediating the intergenerational transmission of obesity. METHODS: We included 450 African-American mother-child pairs from the Conditions Affecting Neurocognitive Development and Learning in Early Childhood (CANDLE) Study pregnancy cohort. LC-MS was used to conduct metabolomic profiling on maternal plasma samples of the second trimester. The childhood growth outcomes of interest included BMI trajectories from birth to age 4 y (rising-high-, moderate-, and low-BMI trajectories) as well as overweight/obesity (OWO) risk at age 4 y. Mediation analysis was conducted to identify metabolite mediators linking maternal OWO and childhood growth outcomes. The potential causal effects of maternal OWO on metabolite mediators were examined using the Mendelian randomization (MR) method. RESULTS: Among the 880 metabolites detected in the maternal plasma during pregnancy, 14 and 11 metabolites significantly mediated the effects of maternal prepregnancy OWO on childhood BMI trajectories and the OWO risk at age 4 y, respectively, and 5 mediated both outcomes. The MR analysis suggested 6 of the 20 prenatal metabolite mediators might be causally influenced by maternal prepregnancy OWO, most of which are from the pathways related to the metabolism of amino acids (hydroxyasparagine, glutamate, and homocitrulline), sterols (campesterol), and nucleotides (N2,N2-dimethylguanosine). CONCLUSIONS: Our study provides further evidence that prenatal metabolomic profiles might mediate the effect of maternal OWO on early childhood growth trajectories and OWO risk in offspring. The metabolic pathways, including identified metabolite mediators, might provide novel intervention targets for preventing the intrauterine development of obesity in the offspring of mothers with obesity.

A Permutation Test-Based Approach to Strengthening Inference on the Effects of Environmental Mixtures: Comparison between Single-Index Analytic Methods.

BACKGROUND: Optimization of mixture analyses is critical to assess potential impacts of human exposures to multiple pollutants. Single-index regression methods quantify total mixture association and chemical component contributions. Single-index methods include several variants of quantile g-computation (QGC) and weighted quantile sum regression (WQSr), though each has limitations. OBJECTIVES: We developed a novel permutation test for WQSr and compared its performance to extant versions of WQSr and QGC in simulation studies and an analysis of prenatal phthalates and childhood cognition. METHODS: WQSr uses ensemble nonlinear optimization to identify weights for mixture exposures in an index associated with the outcome in a prespecified direction, with ensembles based on bootstrap resampling (WQSBS) or random subsetting of exposures (WQSRS). Statistical significance can be assessed without splitting the data (Nosplit), by splitting the data into training and test sets (Split), by repeatedly holding out test sets (RH), or by using a novel permutation test (PT) to obtain a more accurate p-value. QGC instead provides a sum mixture coefficient and component coefficients with no constraints on direction. In simulations, we compared false positive rates (FPR) and power to detect true associations and accuracy in estimating mixture weights. We also estimated associations between prenatal phthalate mixtures and childhood IQ in the Conditions Affecting Neurocognitive Development and Learning in Early Childhood cohort using each method. RESULTS: FPR was well controlled at ≤7% in all but the Nosplit WQSr variants. Among these methods, the WQSBS and WQSRS PT variants had the highest power (89%-98%), with lower power for QGC (85%-93%) and RH (60%-97%) or Split WQSr variants (40%-78%). WQSr methods estimated mixture weights 2-4 times more accurately than the QGC method. Coefficients for mixture associations with full scale IQ varied 3- to 4-fold across analytic methods. DISCUSSION: WQSr paired with our novel permutation test best balanced power and false positive rate when assessing a mixture effect. As new methods develop, each should be examined for performance and applicability. https://doi.org/10.1289/EHP10570.

The roles of sleep and executive function in adolescent nighttime eating.

Nighttime eating has been associated with obesity, inflammation, and poor nutritional intake, yet correlates of this behavior are understudied in pediatric populations and among adolescents in particular. The current study examines modifiable factors related to nighttime eating, including sleep parameters and regulatory abilities-as well as the interplay between these constructs-in adolescents. A total of 223 adolescents (Mage = 15.32 years, 52.9 % female, 15.7 % classified as overweight, 21.1 % had obesity) wore ActiGraph devices to measure sleep and were instructed to complete three 24-h dietary recall measures over a two-week period. Participants also completed self-report measures of executive function. Greater variability in sleep duration was consistently associated with higher average calorie, sugar, and fat consumption after 8, 9, and 10 PM. The main effect of global executive function on all nighttime eating measures was nonsignificant, and executive function did not moderate relationships between sleep parameters and nighttime eating measures. Since adolescents' eating habits may set the stage for lifelong dietary practices, efforts to ensure consistent sleep duration may reduce risk for nighttime eating in this nutritionally vulnerable population.