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.

The Environmental Influences on Child Health Outcome (ECHO) program at the National Institutes of Health 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 program is to examine effects of a broad array of early environmental exposures on child health and development. The information includes longitudinal data and biospecimens from more than 100 000 children and family members from diverse settings across the United States ECHO investigators have published collaborative analyses showing associations of environmental exposures-primarily in the developmentally sensitive pre-, peri-, and postnatal 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 environmental epidemiology and to inform policies, practices, and programs to enhance child health. This article is part of a Special Collection on Environmental Epidemiology.

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.

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.

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.

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.

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.

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.

The interplay of maternal and paternal postpartum depressive symptoms with children's internalizing and externalizing symptoms from childhood to adolescence: does socioeconomic status matter? A longitudinal cohort study.

BACKGROUND: Maternal postpartum depression is an important risk factor for internalizing and externalizing problems in children. The role of concurrent paternal depression remains unclear, especially by socioeconomic status. This study examined independent and interactive associations of postpartum maternal and paternal depression with children's internalizing/externalizing symptoms throughout childhood and adolescence (ages 3.5-17 years). METHODS: We used data from the Québec Longitudinal Study of Child Development, a representative birth cohort (1997-1998) in Canada. Data included self-reported maternal and paternal depressive symptoms at 5 months' postpartum using the Center for Epidemiologic Studies Depression Scale. Internalizing and externalizing symptoms in children were reported by parents, teachers and children/adolescents using the Social Behaviour Questionnaire (ages 3.5-13 years) and the Mental Health and Social Inadaptation Assessment for Adolescents (ages 15-17 years). We used three-level mixed effects modelling to test associations after adjusting for confounding factors. RESULTS: With 168 single-parent families excluded, our sample consisted of 1,700 families with useable data. Of these, 275 (16.2%) families reported maternal depression (clinically elevated symptoms), 135 (7.9%) paternal depression and 39 (2.3%) both. In families with high socioeconomic status, maternal depression was associated with greater child internalizing (ß = .34; p < .001) and externalizing symptoms (ß = .22; p = .002), regardless of the presence/absence of paternal depression. In families with low socioeconomic status, associations with symptoms were stronger with concurrent paternal depression (internalizing, ß = .84, p < .001; externalizing, ß = .71, p = .003) than without (internalizing, ß = .30, p < .001; externalizing, ß = .24, p = .002). CONCLUSIONS: Maternal depression increases the risk for children's internalizing/externalizing problems in all socioeconomic contexts. In families with low socioeconomic status, risks were exacerbated by concurrent paternal depression. Postpartum depression, especially in low socioeconomic environments, should be a primary focus to optimize mental health across generations.

Childhood Developmental Milestones and Risk of Adult Cerebrovascular Disease: The Northern Finland Birth Cohort 1966.

INTRODUCTION: To the best of our knowledge, no previous studies have examined the relationship between childhood developmental milestones and risk of adulthood cerebrovascular disease (CeVD). We studied whether the risk of adult CeVD is associated with delayed attainment of motor and language milestones. METHODS: Within the Northern Finland Birth Cohort 1966, a total of 11,688 persons were followed from birth to either death, moving abroad or 54 years of age. CeVD diagnoses, i.e., ischemic and hemorrhagic strokes and transient ischemic attacks, were extracted from national registers with diagnostic coding based on recommendations of the World Health Organization. Cox proportional hazard models stratified by sex were used to estimate associations of motor development and language milestones between ages 0 and 4 years and adult CeVD women-to-men relative hazard ratios (RHRs) were estimated for each developmental milestone. Analyses were adjusted for family socioeconomic status and birth weight for gestational age. RESULTS: Altogether 498 (4.3%) CeVDs were recorded during follow-up. Among both sexes, later turning from back to tummy was associated with ischemic CeVD in adulthood with an adjusted hazard ratio (aHR) of 1.25 and 95% confidence interval (CI) 1.06-1.46 for men and an aHR: 1.20 (CI: 1.02-1.42) for women per 1 month delay in achievement. Delayed overall motor development, modeled by motor milestone principal component score, was related to increased risk of ischemic CeVD (aHR: 1.50; CI: 1.03-2.19) among men. Later achievement of making sounds was associated with any CeVD (aHR: 2.74; CI: 1.39-5.40) and especially ischemic CeVD (aHR: 3.41; CI: 1.65-7.06) among men with women-to-men RHR's of 0.17 (95% CI: 0.04-0.81) for any CeVD and RHR 0.18 (95% CI: 0.04-0.89) for ischemic stroke indicating risk to be lower in women compared to men. CONCLUSIONS: These findings suggest that later achievement of childhood milestones could be a predictor for development of CeVD risk. The results point toward a common neurodevelopmental background and could in part explain lifetime CeVD risk accumulation.

The Grenada Learning and Memory Scale: Psychometric features and normative data in Caribbean preschool children.

OBJECTIVE: Neuropsychological assessment of preschool children is essential for early detection of delays and referral for intervention prior to school entry. This is especially pertinent in low- and middle-income countries (LMICs), which are disproportionately impacted by micronutrient deficiencies and teratogenic exposures. The Grenada Learning and Memory Scale (GLAMS) was created for use in limited resource settings and includes a shopping list and face-name association test. Here, we present psychometric and normative data for the GLAMS in a Grenadian preschool sample. METHODS: Typically developing children between 36 and 72 months of age, primarily English speaking, were recruited from public preschools in Grenada. Trained Early Childhood Assessors administered the GLAMS and NEPSY-II in schools, homes, and clinics. GLAMS score distributions, reliability, and convergent/divergent validity against NEPSY-II were evaluated. RESULTS: The sample consisted of 400 children (190 males, 210 females). GLAMS internal consistency, inter-rater agreement, and test-retest reliability were acceptable. Principal components analysis revealed two latent factors, aligned with expected verbal/visual memory constructs. A female advantage was observed in verbal memory. Moderate age effects were observed on list learning/recall and small age effects on face-name learning/recall. All GLAMS subtests were correlated with NEPSY-II Sentence Repetition, supporting convergent validity with a measure of verbal working memory. CONCLUSIONS: The GLAMS is a psychometrically sound measure of learning and memory in Grenadian preschool children. Further adaptation and scale-up to global LMICs are recommended.

Engaging Family Members to Support Exclusive Breastfeeding, Responsive care, and Antiretroviral Therapy Adherence Among Families with Children who are HIV-Exposed and Uninfected.

Children who are HIV-exposed and uninfected (CHEU) are at increased risk for poor growth, health, and development compared to children who are HIV-unexposed and uninfected. To support families with CHEU, we assessed the acceptability of engaging family members to support women living with HIV (WLWH) with exclusive breastfeeding (EBF) and antiretroviral therapy (ART) adherence and to engage in responsive infant caregiving. We conducted trials of improved practices, a consultative research approach, that follows participants over time as they try recommended behaviors. We enrolled postpartum women in Lusaka, Zambia, who identified home supporters. At visit 1, WLWH were interviewed about current practices. At visit 2, WLWH and home supporters received tailored EBF, responsive care, and ART adherence counseling. At visit 3, WLWH and home supporters were interviewed about their experiences trying recommended practices for 2-3 weeks. Interview transcripts were analyzed thematically. Participants included 23 WLWH, 15 male partners, and 8 female family members. WLWH reported several barriers to EBF. The most common were fear of HIV transmission via breastfeeding-despite high ART adherence-and insufficient breastmilk. After counseling, WLWH reported less fear of HIV transmission and improved breastfeeding practices. Home supporters reported providing WLWH increased support for EBF and ART adherence and practicing responsive caregiving. Both male and female home supporters appreciated being included in counseling and more involved in caregiving, and WLWH valued the increased support. Families with CHEU need focused support. Tailored counseling and family support for WLWH show promise for improving EBF, responsive caregiving, and ART adherence.

"I was very scared when I found out my son had sickle cell": Caregiver knowledge and attitudes toward early intervention for young children with sickle cell disease: Implications for policy and practice from a multi-site study.

OBJECTIVE: This study characterized caregivers' beliefs related to early intervention services for children with sickle cell disease (SCD) to gain an indepth understanding of caregivers' experiences and desires for early intervention services. METHODS: Both qualitative and quantitative data were collected from caregivers of children aged 0-4 years with SCD across two sites in the United States. Caregivers completed the Knowledge of Infant Development Inventory, a custom survey about their experiences with early intervention, and a qualitative interview. RESULTS: A total of 127 caregivers were approached, 47 participated in surveys, and 20 completed interviews. Caregivers expressed varying levels of confidence and understanding of developmental milestones across sites. Interviews highlighted three main themes: fear of SCD-related complications, variable buy-in to early intervention, and the importance of provider-caregiver relationships. While some caregivers appreciated early intervention, others questioned its necessity. Caregivers communicated interest in connecting with other families facing similar challenges, emphasizing the need for increased awareness of available resources. CONCLUSIONS: Fear about their child's well-being was expressed by many caregivers, emphasizing the need for a supportive healthcare team that can help families connect with preventive interventions. While about a quarter of children had been referred to rehabilitation services, caregivers were unaware of the elevated risk for developmental delay, which diminished caregiver interest in participating in programs like early intervention. This study underscores the importance of addressing knowledge gaps and overcoming barriers to enhance care for families affected by SCD.

Language and communication development and school readiness of children raised by grandparents or in multi-generational homes.

BACKGROUND: One in ten U.S. children lives with a grandparent, and more foster children are being placed in kinship care. OBJECTIVES: Our objective was to compare early language and communication development and school readiness among children raised by grandparents (alone or in multigenerational households) to children raised by parents. METHODS: We included in this cross-sectional study children ages 1-5 years from the 2016-2020 National Survey of Children's Health to examine healthy and ready to learn school readiness outcomes and binary language and communication development (2018-2020 data only) by caregiver type (parent, multigenerational, and grandparent-only) with survey-weighted log-binomial regression adjusted for confounders. We stratified by survey years pre-COVID-19 pandemic versus during. RESULTS: Among 33,342 children, 86.0% (SE = 0.51) of children were 'On-Track' for language and communication development; only 37.2% (SE = 0.68) were 'On-Track' overall for school readiness. Children raised by grandparents or in multigenerational households were more often 'On-Track' for school readiness than children raised by parents, but only upon adjustment for covariates (adjusted prevalence ratio (aPR) for grandparent-only 1.13, 95% confidence interval (CI) 1.11, 1.15; aPR for multigenerational 1.13, CI 1.12, 1.15). Smaller and less consistent differences in prevalence were observed for the other outcomes (language and communication development, school readiness domains of early learning skills, social-emotional development, self-regulation development and physical well-being and motor development). A disparity in school readiness may have emerged during the COVID-19 pandemic; children in grandparent-only households had a lower prevalence of being 'On-Track' for school readiness (aPR 0.71, 95% CI 0.69, 0.73) compared to children in parent households, whereas children in multigenerational households continued to be more often school-ready than children in parent households. CONCLUSION: Large proportions of children across caregiver types were not fully prepared for school. Consideration of key covariates is important because socio-economic disadvantage may mask other advantages grandparent-led and multigenerational households offer children's early development.