Neurotoxic effects of home radon exposure on oscillatory dynamics serving attentional orienting in children and adolescents.

Radon is a naturally occurring gas that contributes significantly to radiation in the environment and is the second leading cause of lung cancer globally. Previous studies have shown that other environmental toxins have deleterious effects on brain development, though radon has not been studied as thoroughly in this context. This study examined the impact of home radon exposure on the neural oscillatory activity serving attention reorientation in youths. Fifty-six participants (ages 6-14 years) completed a classic Posner cuing task during magnetoencephalography (MEG), and home radon levels were measured for each participant. Time-frequency spectrograms indicated stronger theta (3-7 Hz, 300-800 ms), alpha (9-13 Hz, 400-900 ms), and beta responses (14-24 Hz, 400-900 ms) during the task relative to baseline. Source reconstruction of each significant oscillatory response was performed, and validity maps were computed by subtracting the task conditions (invalidly cued - validly cued). These validity maps were examined for associations with radon exposure, age, and their interaction in a linear regression design. Children with greater radon exposure showed aberrant oscillatory activity across distributed regions critical for attentional processing and attention reorientation (e.g., dorsolateral prefrontal cortex, and anterior cingulate cortex). Generally, youths with greater radon exposure exhibited a reverse neural validity effect in almost all regions and showed greater overall power relative to peers with lesser radon exposure. We also detected an interactive effect between radon exposure and age where youths with greater radon exposure exhibited divergent developmental trajectories in neural substrates implicated in attentional processing (e.g., bilateral prefrontal cortices, superior temporal gyri, and inferior parietal lobules). These data suggest aberrant, but potentially compensatory neural processing as a function of increasing home radon exposure in areas critical for attention and higher order cognition.

How the Environmental influences on Child Health Outcome (ECHO) Cohort can spur discoveries in environmental epidemiology.

NIH's Environmental influences on Child Health Outcome (ECHO) program is an innovative, large, collaborative research initiative whose mission is to enhance the health of children for generations to come. The goal of the ECHO Cohort is to examine effects of a broad array of early environmental exposures on child health and development. It includes longitudinal data and biospecimens from over 100,000 children and family members from diverse settings across the U.S. ECHO investigators have published collaborative analyses showing associations of environmental exposures--primarily in the developmentally sensitive pre-, peri-, and post-natal periods--with preterm birth and childhood asthma, obesity, neurodevelopment, and positive health. Investigators have addressed health disparities, joint effects of environmental and social determinants, and effects of mixtures of chemicals. The ECHO Cohort is now entering its second 7-year cycle (2023-2030), which will add the preconception period to its current focus on prenatal through adolescence. Through a controlled access public use database, ECHO makes its deidentified data available to the general scientific community. ECHO Cohort data provide opportunities to fill major knowledge gaps in in environmental epidemiology, and to inform policies, practices, and programs to enhance child health.

Spatiotemporal patterns of cortical microstructural maturation in children and adolescents with diffusion MRI.

Neocortical maturation is a dynamic process that proceeds in a hierarchical manner; however, the spatiotemporal organization of cortical microstructure with diffusion MRI has yet to be fully defined. This study characterized cortical microstructural maturation using diffusion MRI (fwe-diffusion tensor imaging [DTI] and neurite orientation dispersion and density imaging [NODDI] multicompartment modeling) in a cohort of 637 children and adolescents between 8 and 21 years of age. We found spatially heterogeneous developmental patterns broadly demarcated into functional domains where NODDI metrics increased, and fwe-DTI metrics decreased with age. By applying nonlinear growth models in a vertex-wise analysis, we observed a general posterior-to-anterior pattern of maturation, where the fwe-DTI measures mean diffusivity and radial diffusivity reached peak maturation earlier than the NODDI metrics neurite density index. Using non-negative matrix factorization, we found occipito-parietal cortical regions that correspond to lower order sensory domains mature earlier than fronto-temporal higher order association domains. Our findings corroborate previous histological and neuroimaging studies that show spatially varying patterns of cortical maturation that may reflect unique developmental processes of cytoarchitectonically determined regional patterns of change.

A longitudinal multi-centric cohort study assessing infant neurodevelopment delay among women with persistent postpartum depression in Nepal.

BACKGROUND: Infant neurodevelopment in the first years after birth is determined by multiple factors, including parental care and maternal mental wellbeing. In this study, we aim to assess the impact of persistent maternal depressive symptoms during the first 3 months postpartum on infant neurodevelopment at 6 months. METHODS: Using a longitudinal cohort design, 1253 mother-infant pairs were followed up at 7, 45, and 90 days to assess postpartum depressive symptoms using the Edinburgh Postnatal Depression Scale (EPDS); infants were followed up at 6 months to assess neuro-developmental status using the WHO's Infant and Young Child Development (IYCD) tool. A generalized linear regression model was used to assess the association between persistent postpartum depressive symptoms and infant neurodevelopmental delay at 6 months. A generalized linear mixed model (GLMM) with a hospital as a random intercept was used to assess the persistent postpartum depressive symptoms with an IYCD score. Linear regression was used to compare the IYCD scores between exposure groups. RESULTS: In the study population, 7.5% of mothers had persistent depressive symptoms, and 7.5% of infants had neurodevelopmental delay. Infants born to mothers with persistent depressive symptoms had a higher proportion of neurodevelopmental delay than infants born to women without persistent symptoms (48.6% vs 5.1%; p < 0.001). In the adjusted regression model, infants whose mothers had persistent depressive symptoms at 7, 45, and 90 days had a 5.21-fold increased risk of neurodevelopmental delay (aRR, 5.21; 95% CI, 3.17, 8.55). Mean scores in the motor domain (12.7 vs 15.2; p < 0.001) and language domain (6.4 vs 8.5; p < 0.001) were significant when a mother had persistent depression vs. no depression. Mean scores in the general behavioral domain (5.9 vs 10.4, p < 0.001) and the socio-emotional domain (15.4 vs 17.7; p < 0.001) were significantly different when a mother had persistent depression vs no persistent depression. CONCLUSIONS: Our results suggest that 6-month-old infants are at higher risk for neurodevelopment delays if their mother reports persistent symptoms of depression from 7 to 90 days postpartum. The neurodevelopmental delay can be observed in all functional domains. Preventive intervention to reduce maternal postpartum depression may reduce the impact on infant developmental delay.

Effect of a Center-Based Early Childhood Care and Education Program on Child Nutritional Status: A Secondary Analysis of a Stepped-Wedge Cluster Randomized Controlled Trial in Rural Sindh, Pakistan.

BACKGROUND: High-quality early childhood care and education (ECCE) programs can positively impact children's development. However, as an unintended consequence, ECCE attendance may also affect children's nutritional status. OBJECTIVE: We evaluated the effect of a center-based ECCE intervention on child nutritional outcomes in rural Pakistan. METHODS: This study utilized data from a stepped-wedge cluster randomized controlled trial of a center-based ECCE program that trained female youth to run high-quality preschools for children aged 3.5-5.5 y (Youth Leaders for Early Childhood Assuring Children are Prepared for School (LEAPS) program) in rural Sindh, Pakistan. The program did not include any school meals. A total of 99 village clusters were randomized to receive the LEAPS intervention in 3 steps, and repeated cross-sectional surveys were conducted to assess the impact on children (age: 4.5-5.5 y) at 4- time points. ITT analyses with multilevel mixed-effect models were used to estimate the effect of the intervention on child anthropometric outcomes. RESULTS: The analysis included 3858 children with anthropometric data from 4 cross-sectional survey rounds. The LEAPS intervention was found to have a positive effect on child height-for-age z score (mean difference: 0.13 z-scores; 95% confidence interval [CI]: 0.02, 0.24). However, there was a negative effect on weight-based anthropometric indicators, -0.29 weight-for-height z score (WHZ) (95% CI: -0.42, -0.15), -0.13 BMI z score (BMIZ) (95% CI: -0.23, -0.03), and -0.16 mid-upper arm circumference-for-age z score MUACZ (95% CI: -0.25, -0.05). An exploratory analysis suggested that the magnitude of the negative effect of LEAPS on WHZ, BMIZ, and weight-for-age z score (WAZ) was greater in the survey round during the COVID-19 lockdown. DISCUSSION: The LEAPS intervention positively affected child linear growth but had negative effects on multiple weight-based anthropometric measures. ECCE programs in low- and middle-income country settings should evaluate the integration of nutrition-specific interventions (eg school lunch, counseling on healthy diets) and infection control strategies to promote children's healthy growth and development. CLINICAL TRIAL REGISTRY: clinicaltrials.gov, NCT03764436, https://clinicaltrials.gov/ct2/show/NCT03764436.

Early-life stress and the gut microbiome: A comprehensive population-based investigation.

Early-life stress (ELS) has been robustly associated with a range of poor mental and physical health outcomes. Recent studies implicate the gut microbiome in stress-related mental, cardio-metabolic and immune health problems, but research on humans is scarce and thus far often based on small, selected samples, often using retrospective reports of ELS. We examined associations between ELS and the human gut microbiome in a large, population-based study of children. ELS was measured prospectively from birth to 10 years of age in 2,004 children from the Generation R Study. We studied overall ELS, as well as unique effects of five different ELS domains, including life events, contextual risk, parental risk, interpersonal risk, and direct victimization. Stool microbiome was assessed using 16S rRNA sequencing at age 10 years and data were analyzed at multiple levels (i.e. α- and ß-diversity indices, individual genera and predicted functional pathways). In addition, we explored potential mediators of ELS-microbiome associations, including diet at age 8 and body mass index at 10 years. While no associations were observed between overall ELS (composite score of five domains) and the microbiome after multiple testing correction, contextual risk - a specific ELS domain related to socio-economic stress, including risk factors such as financial difficulties and low maternal education - was significantly associated with microbiome variability. This ELS domain was associated with lower α-diversity, with ß-diversity, and with predicted functional pathways involved, amongst others, in tryptophan biosynthesis. These associations were in part mediated by overall diet quality, a pro-inflammatory diet, fiber intake, and body mass index (BMI). These results suggest that stress related to socio-economic adversity - but not overall early life stress - is associated with a less diverse microbiome in the general population, and that this association may in part be explained by poorer diet and higher BMI. Future research is needed to test causality and to establish whether modifiable factors such as diet could be used to mitigate the negative effects of socio-economic adversity on the microbiome and related health consequences.

Prenatal exposure to common infections and newborn DNA methylation: A prospective, population-based study.

BACKGROUND: Infections during pregnancy have been robustly associated with adverse mental and physical health outcomes in offspring, yet the underlying molecular pathways remain largely unknown. Here, we examined whether exposure to common infections in utero associates with DNA methylation (DNAm) patterns at birth and whether this in turn relates to offspring health outcomes in the general population. METHODS: Using data from 2,367 children from the Dutch population-based Generation R Study, we first performed an epigenome-wide association study to identify differentially methylated sites and regions at birth associated with prenatal infection exposure. We also examined the influence of infection timing by using self-reported cumulative infection scores for each trimester. Second, we sought to develop an aggregate methylation profile score (MPS) based on cord blood DNAm as an epigenetic proxy of prenatal infection exposure and tested whether this MPS prospectively associates with offspring health outcomes, including psychiatric symptoms, BMI, and asthma at ages 13-16 years. Third, we investigated whether prenatal infection exposure associates with offspring epigenetic age acceleration - a marker of biological aging. Across all analysis steps, we tested whether our findings replicate in 864 participants from an independent population-based cohort (ALSPAC, UK). RESULTS: We observed no differentially methylated sites or regions in cord blood in relation to prenatal infection exposure, after multiple testing correction. 33 DNAm sites showed suggestive associations (p < 5e10 - 5; of which one was also nominally associated in ALSPAC), indicating potential links to genes associated with immune, neurodevelopmental, and cardiovascular pathways. While the MPS of prenatal infections associated with maternal reports of infections in the internal hold out sample in the Generation R Study (R2incremental = 0.049), it did not replicate in ALSPAC (R2incremental = 0.001), and it did not prospectively associate with offspring health outcomes in either cohort. Moreover, we observed no association between prenatal exposure to infections and epigenetic age acceleration across cohorts and clocks. CONCLUSION: In contrast to prior studies, which reported DNAm differences in offspring exposed to severe infections in utero, we do not find evidence for associations between self-reported clinically evident common infections during pregnancy and DNAm or epigenetic aging in cord blood within the general pediatric population. Future studies are needed to establish whether associations exist but are too subtle to be statistically meaningful with present sample sizes, whether they replicate in a cohort with a more similar infection score as our discovery cohort, whether they occur in different tissues than cord blood, and whether other biological pathways may be more relevant for mediating the effect of prenatal common infection exposure on downstream offspring health outcomes.

Metformin in pregnancy and childhood neurodevelopmental outcomes: a systematic review and meta-analysis.

OBJECTIVE: This study aimed to examine the impact of maternal metformin use during pregnancy on offspring neurodevelopmental outcomes. DATA SOURCES: MEDLINE, Embase, and Web of Science (Core Collection) were searched from inception until July 1, 2023. STUDY ELIGIBILITY CRITERIA: Studies of women who received treatment with metformin at any stage of pregnancy for any indication with neurodevelopmental data available for their offspring were included. Studies without a control group were excluded. Randomized controlled trials, case-control, cohort, and cross-sectional studies were included in the review. METHODS: Studies were screened for inclusion and data were extracted independently by 2 reviewers. Risk of bias was assessed using a modified version of the Newcastle-Ottawa Scale for nonrandomized studies, and the Risk of Bias 2 tool for randomized trials. RESULTS: A total of 7 studies met the inclusion criteria, including a combined cohort of 14,042 children with 7641 children who were exposed and followed for up to 14 years of age. Metformin use during pregnancy was not associated with neurodevelopmental delay in infancy (relative risk, 1.09; 95% confidence interval, 0.54-2.17; 3 studies; 9668 children) or at ages 3 to 5 years (relative risk, 0.90; 95% confidence interval, 0.56-1.45; 2 studies; 6118 children). When compared with unexposed peers, metformin use during pregnancy was not associated with altered motor scores (mean difference, 0.30; 95% confidence interval, -1.15 to 1.74; 3 studies; 714 children) or cognitive scores (mean difference, -0.45; 95% confidence interval, -1.45 to 0.55; 4 studies; 734 children). Studies that were included were of high quality and deemed to be at low risk of bias. CONCLUSION: In utero exposure to metformin does not seem to be associated with adverse neurodevelopmental outcomes in children up to the age of 14 years. These findings provide reassurance to clinicians and pregnant women considering metformin use during pregnancy.

Toward a nuanced assessment of the role of intensive home visiting in improving outcomes for families: commentary on Catherine et al. (2023).

Families' experiences during the transition to parenthood and early childhood profoundly shape the lifetime trajectory of both parents and children, laying the foundation for societal inequities. Intensive home visiting programs, which aim to provide in-home support to socio-economically vulnerable parents during the transition to parenthood, are a prominent policy across the globe to provide support to less-resourced families. In this issue of the Journal of Clinical Psychology and Psychiatry, in their article titled 'Effectiveness of nurse-home visiting in improving child and maternal outcomes prenatally to age two years: A randomised controlled trial (British Columbia Healthy Connections Project)', Catherine et al. provide evidence from a randomized controlled trial of the impact of the Nurse-Family Partnership in Canada on child injury, language and behavior and birth spacing outcomes. This commentary discusses the paper's contribution and reflects on opportunities and challenges in building a nuanced understanding of the evidence-base supporting intensive home visiting programs.

Effects of engaging fathers and bundling parenting and nutrition interventions on early child development and maternal and paternal parenting in Mara, Tanzania: a factorial cluster-randomized controlled trial.

BACKGROUND: Multicomponent interventions are needed to address the various co-occurring risks that compromise early child nutrition and development. We compared the independent and combined effects of engaging fathers and bundling parenting components into a nutrition intervention on early child development (ECD) and parenting outcomes. METHODS: We conducted a 2×2 factorial cluster-randomized controlled trial across 80 villages in Mara Region, Tanzania, also known as EFFECTS (Engaging Fathers for Effective Child Nutrition and Development in Tanzania; ClinicalTrials.gov, NCT03759821). Households with children under 18 months of age residing with their mother and father were enrolled. Villages were randomly assigned to one of five groups: a nutrition intervention for mothers, a nutrition intervention for couples, a bundled nutrition and parenting intervention for mothers, a bundled intervention for couples, and a standard-of-care control. Interventions were delivered by trained community health workers through peer groups and home visits over 12 months. Mothers, fathers, and children were assessed at baseline, midline, and endline or postintervention. We used a difference-in-difference approach with intention-to-treat analysis to estimate intervention effects on ECD (Bayley Scales of Infant and Toddler Development, third edition) and maternal and paternal parenting and psychosocial well-being. RESULTS: Between October 29, 2018, and May 24, 2019, 960 households were enrolled (n = 192 per arm). Compared to nutrition interventions, bundled interventions improved children's cognitive (ß = .18 [95% CI: 0.01, 0.36]) and receptive language development (ß = .23 [0.04, 0.41]). There were no differences between interventions for other ECD domains. Compared to nutrition interventions, bundled interventions achieved additional benefits on maternal stimulation (ß = .21 [0.04, 0.38]) and availability of home learning materials (ß = .25 [0.07-0.43]) and reduced paternal parenting distress (ß = -.34 [-0.55, -0.12]). Compared to interventions with mothers only, interventions that engaged fathers improved paternal stimulation (ß = .45 [0.27, 0.63]). CONCLUSIONS: Jointly bundling parenting components into nutrition interventions while also engaging both mothers and fathers is most effective for improving maternal and paternal parenting and ECD outcomes.

Social and joint attention during shared book reading in young autistic children: a potential marker for social development.

BACKGROUND: Atypical patterns of social engagement and joint attention behaviors are diagnostic criteria for people with autism spectrum disorder. Experimental tasks using eye-tracking methodologies have, however, shown inconsistent results. The development of tasks with greater ecological validity and relevance for developmentally appropriate social milestones has been identified as important for the field. METHODS: We developed a novel, dynamic eye-tracking task emulating a shared book reading (SBR) scenario. Four SBR videos of an adult reader engaging with the viewer while reading a children's picture book and including sequenced bids for joint attention were developed. Participants included 90 children (N = 56 autistic children, N = 34 neurotypical children; aged 3-12). Social attention was also measured in a live free play task between participants and an experimenter. RESULTS: Compared to neurotypical children, autistic children displayed reduced attention to socially salient stimuli including the reader's face and picture book across SBR videos and during joint attention bids specifically. In contrast, they showed increased attention to nonsalient background stimuli compared to their neurotypical peers. These attention patterns in autistic children were associated with reduced verbal and nonverbal cognitive skills and increased symptoms associated with autism. Interestingly, positive correlations in the frequency of eye gaze between SBR and free play suggested a potential predictive value for social attention in live social interactions. CONCLUSIONS: Findings highlight the utility of SBR eye-tracking tasks in understanding underlying divergences in social engagement and joint attention between autistic and neurotypical children. This commonly practiced early childhood activity may provide insights into the relationship between social engagement and learning to reveal how such attentional patterns might influence broader developmental and educational outcomes.

Prenatal maternal infections and early childhood developmental outcomes: analysis of linked administrative health data for Greater Glasgow & Clyde, Scotland.

BACKGROUND: Previous research has linked prenatal maternal infections to later childhood developmental outcomes and socioemotional difficulties. However, existing studies have relied on retrospectively self-reported survey data, or data on hospital-recorded infections only, resulting in gaps in data collection. METHODS: This study used a large linked administrative health dataset, bringing together data from birth records, hospital records, prescriptions and routine child health reviews for 55,856 children born in Greater Glasgow & Clyde, Scotland, 2011-2015, and their mothers. Logistic regression models examined associations between prenatal infections, measured as both hospital-diagnosed prenatal infections and receipt of infection-related prescription(s) during pregnancy, and childhood developmental concern(s) identified by health visitors during 6-8 week or 27-30 month health reviews. Secondary analyses examined whether results varied by (a) specific developmental outcome types (gross-motor-skills, hearing-communication, vision-social-awareness, personal-social, emotional-behavioural-attention and speech-language-communication) and (b) the trimester(s) in which infections occurred. RESULTS: After confounder/covariate adjustment, hospital-diagnosed infections were associated with increased odds of having at least one developmental concern (OR: 1.30; 95% CI: 1.19-1.42). This was broadly consistent across all developmental outcome types and appeared to be specifically linked to infections occurring in pregnancy trimesters 2 (OR: 1.34; 95% CI: 1.07-1.67) and 3 (OR: 1.33; 95% CI: 1.21-1.47), that is the trimesters in which foetal brain myelination occurs. Infection-related prescriptions were not associated with any clear increase in odds of having at least one developmental concern after confounder/covariate adjustment (OR: 1.03; 95% CI: 0.98-1.08), but were associated with slightly increased odds of concerns specifically related to personal-social (OR: 1.12; 95% CI: 1.03-1.22) and emotional-behavioural-attention (OR: 1.15; 95% CI: 1.08-1.22) development. CONCLUSIONS: Prenatal infections, particularly those which are hospital-diagnosed (and likely more severe), are associated with early childhood developmental outcomes. Prevention of prenatal infections, and monitoring of support needs of affected children, may improve childhood development, but causality remains to be established.

Large-scale proteomics in the first trimester of pregnancy predict psychopathology and temperament in preschool children: an exploratory study.

BACKGROUND: Understanding the prenatal origins of children's psychopathology is a fundamental goal in developmental and clinical science. Recent research suggests that inflammation during pregnancy can trigger a cascade of fetal programming changes that contribute to vulnerability for the emergence of psychopathology. Most studies, however, have focused on a handful of proinflammatory cytokines and have not explored a range of prenatal biological pathways that may be involved in increasing postnatal risk for emotional and behavioral difficulties. METHODS: Using extreme gradient boosted machine learning models, we explored large-scale proteomics, considering over 1,000 proteins from first trimester blood samples, to predict behavior in early childhood. Mothers reported on their 3- to 5-year-old children's (N = 89, 51% female) temperament (Child Behavior Questionnaire) and psychopathology (Child Behavior Checklist). RESULTS: We found that machine learning models of prenatal proteomics predict 5%-10% of the variance in children's sadness, perceptual sensitivity, attention problems, and emotional reactivity. Enrichment analyses identified immune function, nervous system development, and cell signaling pathways as being particularly important in predicting children's outcomes. CONCLUSIONS: Our findings, though exploratory, suggest processes in early pregnancy that are related to functioning in early childhood. Predictive features included far more proteins than have been considered in prior work. Specifically, proteins implicated in inflammation, in the development of the central nervous system, and in key cell-signaling pathways were enriched in relation to child temperament and psychopathology measures.

Commentary: A nurturing care perspective on bundling interventions - a reflection on Jeong et al. (2023).

Bundling multiple interventions have been implemented and evaluated in response to global recognition that young children benefit from the multiple components of nurturing care. Engaging Fathers for Effective Child Nutrition and Development in Tanzania Study evaluated the impact of adding a parenting intervention to a nutrition program and involving fathers on children's development. The study found that the bundled nutrition-parenting intervention improved children's short-term cognitive and receptive language scores over the nutrition only intervention, with no difference between involving mother-father couples versus mothers only. This study adds to recommendations for future multiple component interventions, including to investigate the mechanisms driving interventions, to address the potential for both benefits and harms, to involve household and community caregivers, and to incorporate implementation research to transition evidence-based programs to scale. Expanding nurturing care through multiple component interventions has the potential to promote equity by ensuring that all children have opportunities for healthy growth and development.

"Everyone screens to some extent": Barriers and facilitators of developmental screening among children with sickle cell disease: A mixed methods study.

BACKGROUND: Developmental delays are common among children with sickle cell disease (SCD). Existing guidelines support consistent screening to increase the identification of deficits and support referral to rehabilitative interventions, yet adherence remains variable. This study sought to assess current practices and identify barriers and facilitators to improve developmental screening for children 0-3 years with SCD. PROCEDURE: A mixed methods approach, guided by the Exploration and Preparation stages of the Exploration, Preparation, Implementation, and Sustainment (EPIS) framework, assessed developmental screening practices among primary care providers and hematologists. Phase 1 included the SCD Developmental Surveillance and Screening Guideline and Practice Survey. Phase 2 included the SCD Developmental Screening Organizational Survey alongside semi-structured interviews. Descriptive and qualitative methods summarized the findings. RESULTS: Thirty-three providers from general pediatrics and hematology completed phase 1. Use of standardized developmental screening measures was variable, with the most frequently used being the Modified Checklist for Autism in Toddlers (77%) and the Ages and Stages Questionnaire (55%). Fifteen providers participated in phase 2, and reported they were most likely to engage in changes to improve their practice (mean = 4.4/5) and least likely to support spiritual health and well-being (mean = 3.5/5). Three themes emerged:(i) developmental screening is not standardized or specific to SCD, (ii) children with SCD benefit from a multidisciplinary team, and (iii) healthcare system limitations are a barrier. CONCLUSIONS: Developmental screening is inconsistent and insufficient for young children with SCD. Providers are interested in supporting children with SCD, but report a lack of standardized measures and consistent guidance as barriers.

Social inequalities in early childhood language development during the COVID-19 pandemic: a descriptive study with data from three consecutive school entry surveys in Germany.

BACKGROUND: Social health inequalities are still of great public health importance in modern societies. The COVID-19 pandemic may have affected social inequalities in people's health due to containment measures. As these measures particularly affected children, they might have been particularly vulnerable to increased social inequalities. The aim of the study was to describe health inequalities during the pandemic based on language delay (LD) in children in order to inform public health interventions for a population at risk of long-term health and education inequalities. METHODS: Data of 5-7 year old children from three consecutive school entry surveys in the German federal state of Brandenburg were used, including data compulsorily collected before the pandemic (2018/2019: n = 19,299), at the beginning of the pandemic (2019/2020: n = 19,916) and during the pandemic (2020/2021: n = 19,698). Bivariate and multivariate binary regression analyses [OR, 95% CI] cross-sectionally examined the relationship between the prevalence of LD [yes/no] and social inequalities, operationalized by family socioeconomic position [SEP low/middle/high], migration background [native-German language/non-native German language] and length of kindergarten attendance [< 4 years/ ≥ 4 years]. Factors contributing to inequality in LD were examined by socioeconomic stratification. RESULTS: Cross-sectionally, LD prevalence has decreased overall (2018/2019: 21.1%, 2019/2020: 19.2%, 2020/2021: 18.8%), and among children from both high SEP and native German-speaking families. As LD prevalence increased among children from families with low SEP and remained stable among non-native German speakers, social inequalities in LD prevalence increased slightly during the pandemic i) by low SEP (2018/2019: OR = 4.41, 3.93-4.94; 2020/2021: OR = 5.12, 4.54-5.77) and ii) by non-German native language (2018/2019: OR = 2.22, 1.86-2.66; 2020/2021: OR = 2.54, 2.19-2.95). During the pandemic, both migration background and kindergarten attendance determined LD prevalence in the high and middle SEP strata. However, the measured factors did not contribute to LD prevalence in children from families with low SEP. CONCLUSION: Social inequalities in LD increased due to opposing trends in prevalence comparing low and high SEP families. To promote health equity across the life course, early childhood should be of interest for tailored public health actions (e.g. through targeted interventions for kindergarten groups). Further analytical studies should investigate determinants (e.g., parental investment).

Longitudinal effects of prenatal substance use and environmental stressors on executive functioning in low-income African American adolescents: A latent growth modeling analysis.

Adverse prenatal substance use and environmental stressors have been linked to prefrontal cortex (PFC) impairments, the brain region that regulates executive functioning. Executive functions (e.g., inhibitory control, working memory, and cognitive flexibility) are crucial for sophisticated cognitive activities throughout child and adolescent development. There is little research on how prenatal substance use and environmental stressors longitudinally program executive functioning in children over time. We investigated the associations between prenatal/environmental stressors (i.e., maternal prenatal substance use, maternal-fetal bonding, and neighborhood disorganization) and executive function performance among low-income African American youth from age 6 until age 18. Analyses were based on four waves of data collected between 1994 and 2014 in the Memphis New Mothers Study, a longitudinal randomized controlled trial that was an intervention during pregnancy and the first two years of the child's life in low-SES women and their first-born children. Mothers and their children were followed longitudinally through 18 years post-childbirth. Prenatal substance use (e.g., prenatal smoke, alcohol, and drug use) and environmental stressor (e.g., food environment, maternal-fetal bonding and neighborhood disorganizations) evaluations were gathered from mothers and children prenatally and postnatally before the age of 4.5 years. Executive function was assessed using the Child Behavior Checklist for impulsivity and inattention, while the coding subscale of the Wechsler Intelligence Scale for Children-Third Edition, the reading recognition subtest of the Peabody Individual Achievement Test, and the digit span subtest of the Wechsler Adult Intelligence Scale were employed to assess working memory at three time periods (6, 12, and 18 years). Covariate-adjusted latent growth models estimated the associations between prenatal substance use and environmental stressors and changes in executive functioning over three time points. Prenatal smoking and alcohol use were associated with changes in impulsivity scores over 12 years. Prenatal alcohol use predicted higher inattention at baseline and a slower rate of change from ages 6 to 18. Neighborhood disorganization at ages 6 and 18 predicted higher inattention and lower working memory in youth at age 18, respectively. Our findings underscore the long-term impact of prenatal substance use exposures and neighborhood environments on cognitive development and highlight the importance of early interventions to mitigate these effects.

Gestational glyphosate exposure and early childhood neurodevelopment in a Puerto Rico birth cohort.

INTRODUCTION: N-(phosphonomethyl)glycine, or glyphosate, is a non-selective systemic herbicide widely used in agricultural, industrial, and residential settings since 1974. Glyphosate exposure has been inconsistently linked to neurotoxicity in animals, and studies of effects of gestational exposure among humans are scarce. In this study we investigated relationships between prenatal urinary glyphosate analytes and early childhood neurodevelopment. METHODS: Mother-child pairs from the PROTECT-CRECE birth cohort in Puerto Rico with measures for both maternal urinary glyphosate analytes and child neurodevelopment were included for analysis (n = 143). Spot urine samples were collected 1-3 times throughout pregnancy and analyzed for glyphosate and aminomethylphosphonic acid (AMPA), an environmental degradant of glyphosate. Child neurodevelopment was assessed at 6, 12, and 24 months using the Battelle Developmental Inventory, 2nd edition Spanish (BDI-2), which provides scores for adaptive, personal-social, communication, motor, and cognitive domains. We used multivariable linear regression to examine associations between the geometric mean of maternal urinary glyphosate analytes across pregnancy and BDI-2 scores at each follow-up. Results were expressed as percent change in BDI-2 score per interquartile range increase in exposure. RESULTS: Prenatal AMPA concentrations were negatively associated with communication domain at 12 months (%change = -5.32; 95%CI: 9.04, -1.61; p = 0.007), and communication subdomain scores at 12 and 24 months. At 24 months, four BDI-2 domains were associated with AMPA: adaptive (%change = -3.15; 95%CI: 6.05, -0.25; p = 0.038), personal-social (%change = -4.37; 95%CI: 7.48, -1.26; p = 0.008), communication (%change = -7.00; 95%CI: 11.75, -2.26; p = 0.005), and cognitive (%change = -4.02; 95%CI: 6.72, -1.32; p = 0.005). Similar trends were observed with GLY concentrations, but most confidence intervals include zero. We found no significant associations at 6 months. CONCLUSIONS: Our results suggest that gestational exposure to glyphosate is associated with adverse early neurodevelopment, with more pronounced delays at 24 months. Given glyphosate's wide usage, further investigation into the impact of gestational glyphosate exposure on neurodevelopment is warranted.

Proof of concept of the Universal Baby video innovation for early child development in Lima, Peru.

OBJECTIVE: Community-based video interventions offer an effective and potentially scalable early interaction coaching tool for caregivers living in low resource settings. We tested the Universal Baby (UB) video innovation; an early interaction coaching tool using video sourced and produced locally with early child development (ECD) expert supervision. METHODS: This proof-of-concept study enrolled 40 caregivers of children ages 10-18 months assigned to intervention and control groups by health establishments in Carabayllo, Lima, Peru. Mother/child dyads received 12 weekly group health education sessions with social support. Of those, 16 caregivers also received 6 UB videos featuring brain science education and local clips of responsive, reciprocal interaction, also known as "serve and return" interaction. Survey data assessed feasibility and acceptability of the intervention. We assessed improved quality of mother/child interaction using the Parenting Interactions with Children: Checklist of Observations Linked to Outcomes (PICCOLO). RESULTS: We found the program feasible. We successfully trained the local team to produce UB videos using locally-sourced footage and delivered the videos as part of a community-based intervention. We also found it to be acceptable in that participants enthusiastically received the UB videos, reporting they enjoyed being videotaped, and learned how to recognize and appropriately respond to their child's nuanced sounds and gestures. The median change in total PICCOLO scores favored the intervention group compared to the control group. CONCLUSIONS: UB offers great potential as a sustainable, potentially scalable, and culturally appropriate tool to promote equity for child development among young children living in low resource homes globally.

Brain volumes, behavioral inhibition, and anxiety disorders in children: results from the adolescent brain cognitive development study.

BACKGROUND: Magnetic resonance imaging (MRI) studies have identified brain changes associated with anxiety disorders (ADs), but the results remain mixed, particularly at a younger age. One key predictor of ADs is behavioral inhibition (BI), a childhood tendency for high avoidance of novel stimuli. This study aimed to evaluate the relationships between candidate brain regions, BI, and ADs among children using baseline data from the Adolescent Brain Cognitive Development (ABCD) study. METHODS: We analyzed global and regional brain volumes of 9,353 children (9-10 years old) in relation to BI and current ADs, using linear mixed models accounting for family clustering and important demographic and socioeconomic covariates. We further investigated whether and how past anxiety was related to brain volumes. RESULTS: Among included participants, 249 (2.66%) had a current AD. Larger total white matter (Beta = -0.152; 95% CI [-0.281, -0.023]), thalamus (Beta = -0.168; 95% CI [-0.291, -0.044]), and smaller hippocampus volumes (Beta = 0.094; 95% CI [-0.008, 0.196]) were associated with lower BI scores. Amygdala volume was not related to BI. Larger total cortical (OR = 0.751; 95% CI [0.580;0.970]), amygdala (OR = 0.798; 95%CI [0.666;0.956]), and precentral gyrus (OR = 0.802; 95% CI [0.661;0.973]) volumes were associated with lower odds of currently having ADs. Children with past ADs had smaller total white matter and amygdala volumes. CONCLUSIONS: The results show associations between brain volumes and both BI and ADs at an early age. Importantly, results suggest that ADs and BI have different neurobiological correlates and that earlier occurrences of ADs may influence brain structures related to BI and ADs, motivating research that can better delineate the similarities and divergence in the neurobiological underpinnings and building blocks of BI and ADs across their development in early life.