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Maternal metabolic factors during pregnancy predict early childhood growth trajectories and obesity risk: the CANDLE Study.
BackgroundWe investigated the individual and additive effects of three modifiable maternal metabolic factors, including pre-pregnancy overweight/obesity, gestational weight gain (GWG), and gestational diabetes mellitus (GDM), on early childhood growth trajectories and obesity risk.MethodsA total of 1425 mother-offspring dyads (953 black and 472 white) from a longitudinal birth cohort were included in this study. Latent class growth modeling was performed to identify the trajectories of body mass index (BMI) from birth to 4 years in children. Poisson regression models were used to examine the associations between the maternal metabolic risk factors and child BMI trajectories and obesity risk at 4 years.ResultsWe identified three discrete BMI trajectory groups, characterized as rising-high-BMI (12.6%), moderate-BMI (61.0%), or low-BMI (26.4%) growth. Both maternal pre-pregnancy obesity (adjusted relative risk [adjRR] = 1.96; 95% confidence interval [CI]: 1.36-2.83) and excessive GWG (adjRR = 1.71, 95% CI: 1.13-2.58) were significantly associated with the rising-high-BMI trajectory, as manifested by rapid weight gain during infancy and a stable but high BMI until 4 years. All three maternal metabolic indices were significantly associated with childhood obesity at age 4 years (adjRR for pre-pregnancy obesity = 2.24, 95% CI: 1.62-3.10; adjRR for excessive GWG = 1.46, 95% CI: 1.01-2.09; and adjRR for GDM = 2.14, 95% = 1.47-3.12). In addition, risk of rising-high BMI trajectory or obesity at age 4 years was stronger among mothers with more than one metabolic risk factor. We did not observe any difference in these associations by race.ConclusionMaternal pre-pregnancy obesity, excessive GWG, and GDM individually and jointly predict rapid growth and obesity at age 4 years in offspring, regardless of race. Interventions targeting maternal obesity and metabolism may prevent or slow the rate of development of childhood obesity
Participation in the special supplemental nutrition program for women, infants, and children is not associated with early childhood socioemotional development: Results from a longitudinal cohort study
AbstractSocioemotional development in early childhood has long-term impacts on health status and social outcomes, and racial and socioeconomic disparities in socioemotional skills emerge early in life. The Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) is an early childhood nutrition intervention with the potential to ameliorate these disparities. Our objective was to assess the impact of WIC on early socioemotional development in a longitudinal study. We examined the association between WIC participation and scores on the Brief Infant Toddler Social Emotional Assessment (BITSEA) in 327 predominantly African American mother–child dyads who were participants in the longitudinal Conditions Affecting Neurocognitive Development in Early Life (CANDLE) Study (Memphis, TN). To account for selection bias, we used within-child fixed effects to model the variability in each child's BITSEA scores over two measurement occasions (ages 12 and 24months). Final models were adjusted for time-varying characteristics including child age, maternal stress, mental health, child abuse potential, marital status, and food stamp participation. In fully adjusted models, we found no statistically significant effect of WIC on change in socioemotional development (β=0.22 [SD=0.39] and β=−0.58 [SD=0.79] for BITSEA Competence and Problem subdomains, respectively). Using rigorous methods and a longitudinal study design, we found no significant association between WIC and socioemotional development in a high needs population. This finding suggests that early childhood interventions that more specifically target socioemotional development are necessary if we are to reduce racial disparities in socioemotional skills and prevent poor social and health outcomes across the life course
Second-Trimester Placental and Thyroid Hormones Are Associated With Cognitive Development From Ages 1 to 3 Years
Adequate maternal thyroid hormone (TH) is necessary for fetal brain development. The role of placental human chorionic gonadotropin (hCG) in ensuring the production of TH is less well understood. The objective of the study was to evaluate 1) associations of placental hCG and its subunits, and maternal TH in the second trimester, and 2) the single and joint effects of TH and placental hormones on cognitive development and communication at ages 1 and 3 years. Fifty individuals (5%) were selected from the CANDLE (Conditions Affecting Neurocognitive Development and Early Learning) pregnancy cohort in Memphis, Tennessee, with recruitment from 2006 to 2011, to equally represent male and female fetuses. Participants were 68% Black and 32% White. Hormones measured were maternal thyroid (thyrotropin [TSH] and free thyroxine [FT4]) and placental hormones (hCG, its hyperglycosylated form [hCG-h], and free alpha- [hCG alpha] and beta-subunits [hCG beta]) in maternal serum (17-28 weeks). The primary outcome measurement was the Bayley Scales of Infant and Toddler Development. All forms of hCG were negatively associated with FT4 and not associated with TSH. hCG alpha was associated with cognitive development at age 1 year and jointly interacted with TSH to predict cognitive development at age 3 years. This pilot study added insight into the thyrotropic actions of hCG in the second trimester, and into the significance of this mechanism for brain development. More research is warranted to elucidate differences between hCG alpha, hCG beta, and hCG-h in relation to TH regulation and child brain function.Peer reviewe
Maternal exposure to childhood traumatic events, but not multi-domain psychosocial stressors, predict placental corticotrophin releasing hormone across pregnancy
Maternal psychosocial stress increases the risk of adverse birth and postnatal outcomes for the mother and child, but the role of maternal exposure to childhood traumatic events (CTE) and multi-domain psychosocial stressors for the level and rise of placental Corticotrophin-Releasing Hormone (pCRH) across pregnancy has been understudied. In a sociodemographically and racially diverse sample of 1303 women (64% Black, 36% White/others) with low-medical risk pregnancies at enrollment from Shelby County, Tennessee, USA, blood samples were drawn twice, corresponding roughly to second and third trimester, and extracted prior to conducting radioimmune assays for pCRH. Mothers reported CTE (physical abuse, sexual abuse, or family violence, in childhood), adulthood traumatic events, and interpersonal violence during pregnancy. Neighborhood crime/deprivation was derived using geospatially-linked objective databases. General linear and mixed models tested associations between stress exposure variables and pCRH levels and rate of rise, adjusting for obstetric/clinical/health related factors. Maternal CTE did not predict pCRH levels at time 1, but positively predicted levels at time 2, and the rate of rise in pCRH across pregnancy. Race did not moderate this association. No additional maternal stress exposures across adulthood or during pregnancy predicted pCRH outcomes. Findings indicate that childhood violence or abuse exposure can become biologically embedded in a manner predicting later prenatal physiology relevant for maternal and offspring health, and that such embedding may be specific to childhood, but not adulthood, stress. Findings also highlight the placental-fetal unit as a mechanistic pathway through which intergenerational transmission of the adverse effects of childhood adversities may occur.publishedVersio
Association of Atopic Dermatitis and Mental Health Outcomes Across Childhood: A Longitudinal Cohort Study.
IMPORTANCE: Research has highlighted associations between atopic dermatitis (AD) and mental health conditions in adults. However, literature on the development of mental health comorbidities in children is limited despite the large burden of pediatric AD worldwide. OBJECTIVE: To examine the association between AD and internalizing behaviors and symptoms of depression at multiple points across childhood and adolescence and to explore potential mediating factors, including asthma/rhinitis, sleep, and inflammation. DESIGN, SETTING, AND PARTICIPANTS: This longitudinal, population-based birth cohort study included children followed up from birth for a mean (SD) duration of 10.0 (2.9) years from the UK Avon Longitudinal Study of Parents and Children. Data were collected from September 6, 1990, to December 31, 2009. Data were analyzed from August 30, 2019, to July 30, 2020. EXPOSURES: Annual period prevalence of AD assessed at 11 points from 6 months to 18 years of age, measured by standardized questions about flexural dermatitis. MAIN OUTCOMES AND MEASURES: Symptoms of depression, measured using child-reported responses to the Short Moods and Feelings Questionnaire at 5 points from 10 to 18 years of age and internalizing behaviors, measured by maternal report of the Emotional Symptoms subscale of the Strength and Difficulties Questionnaire at 7 points from 4 to 16 years of age. RESULTS: Among the 11 181 children included in the analysis (5721 male [51.2%]), the period prevalence of symptoms of depression ranged from 6.0% to 21.6%; for internalizing behaviors, from 10.4% to 16.0%. Although mild to moderate AD was not associated with symptoms of depression, it was associated with internalizing behaviors as early as 4 years of age (mean increased odds of 29%-84% across childhood in adjusted models). Severe AD was associated with symptoms of depression (adjusted odds ratio, 2.38; 95% CI, 1.21-4.72) and internalizing symptoms (adjusted odds ratio, 1.90; 95% CI, 1.14-3.16). Sleep quality mediated some of this association, but it was not explained by differences in sleep duration, asthma/rhinitis, or levels of inflammatory markers (interleukin 6 and C-reactive protein). CONCLUSIONS AND RELEVANCE: Within this population-based birth cohort study in the UK, severe AD was associated with symptoms of depression and internalizing behaviors throughout childhood and adolescence. Risk of internalizing symptoms was increased even for children with mild AD beginning early in childhood, highlighting the importance of behavioral and mental health awareness in this population
Measurement Bias in Caregiver-Report of Early Childhood Behavior Problems across Demographic Factors in an Echo-Wide Diverse Sample
BACKGROUND: Research and clinical practice rely heavily on caregiver-report measures, such as the Child Behavior Checklist 1.5-5 (CBCL/1.5-5), to gather information about early childhood behavior problems and to screen for child psychopathology. While studies have shown that demographic variables influence caregiver ratings of behavior problems, the extent to which the CBCL/1.5-5 functions equivalently at the item level across diverse samples is unknown.
METHODS: Item-level data of CBCL/1.5-5 from a large sample of young children (
RESULTS: Items with the most impactful DIF across child and caregiver groupings were identified for Internalizing, Externalizing, and total Problems. The robust item sets, excluding the high DIF items, showed good reliability and high correlation with the original Internalizing and total Problems scales, with lower reliability for Externalizing. Language version of CBCL administration, education level and sex of the caregiver respondent showed the most significant impact on MI, followed by child age. Sensitivity analyses revealed that child race has a unique impact on DIF over and above socioeconomic status.
CONCLUSIONS: The CBCL/1.5-5, a caregiver-report measure of early childhood behavior problems, showed bias across demographic groups. Robust item sets with less DIF can measure Internalizing and total Problems equally as well as the full item sets, with slightly lower reliability for Externalizing, and can be crosswalked to the metric of the full item set, enabling calculation of normed T scores based on more robust item sets
Associations Between Cortical Thickness and Reasoning Differ by Socioeconomic Status in Development
Although lower socioeconomic status (SES) is generally negatively associated with performance on cognitive assessments, some children from lower-SES backgrounds perform as well as their peers from higher-SES backgrounds. Yet little research has examined whether the neural correlates of individual differences in cognition vary by SES. The current study explored whether relationships between cortical structure and fluid reasoning differ by SES in development. Fluid reasoning, a non-verbal component of IQ, is supported by a distributed frontoparietal network, with evidence for a specific role of rostrolateral prefrontal cortex (RLPFC). In a sample of 115 4–7-year old children, bilateral thickness of RLPFC differentially related to reasoning by SES: thicker bilateral RLPFC positively correlated with reasoning ability in children from lower-SES backgrounds, but not in children from higher-SES backgrounds. Similar results were found in an independent sample of 59 12–16-year old adolescents. Furthermore, young children from lower-SES backgrounds with strong reasoning skills were the only group to show a positive relationship between RLPFC thickness and age. In sum, we found that relationships between cortical thickness and cognition differ by SES during development
An epigenetic clock for gestational age at birth based on blood methylation data
Background: Gestational age is often used as a proxy for developmental maturity by clinicians and researchers alike. DNA methylation has previously been shown to be associated with age and has been used to accurately estimate chronological age in children and adults. In the current study, we examine whether DNA methylation in cord blood can be used to estimate gestational age at birth. Results: We find that gestational age can be accurately estimated from DNA methylation of neonatal cord blood and blood spot samples. We calculate a DNA methylation gestational age using 148 CpG sites selected through elastic net regression in six training datasets. We evaluate predictive accuracy in nine testing datasets and find that the accuracy of the DNA methylation gestational age is consistent with that of gestational age estimates based on established methods, such as ultrasound. We also find that an increased DNA methylation gestational age relative to clinical gestational age is associated with birthweight independent of gestational age, sex, and ancestry. Conclusions: DNA methylation can be used to accurately estimate gestational age at or near birth and may provide additional information relevant to developmental stage. Further studies of this predictor are warranted to determine its utility in clinical settings and for research purposes. When clinical estimates are available this measure may increase accuracy in the testing of hypotheses related to developmental age and other early life circumstances
Life satisfaction for adolescents with developmental and behavioral disabilities during the COVID-19 pandemic
Background: This study aimed to identify contextual factors associated with life satisfaction during the COVID-19 pandemic for adolescents with mental, emotional, behavioral, and developmental (MEBD) disabilities. Methods: Data were collected from a sample of 1084 adolescents aged 11–21 years from April 2020 to August 2021. This cross-sectional study used a sequential machine learning workflow, consisting of random forest regression and evolutionary tree regression, to identify subgroups of adolescents in the Environmental influences on Child Health Outcomes (ECHO) consortium who demonstrated enhanced vulnerability to lower life satisfaction as described by intersecting risk factors, protective factors, and MEBD disabilities. Results: Adolescents with a history of depression, anxiety, autism, and attention-deficit/hyperactivity disorder were particularly susceptible to decreased life satisfaction in response to unique combinations of stressors experienced during the COVID-19 pandemic. These stressors included decreased social connectedness, decreased family engagement, stress related to medical care access, pandemic-related traumatic stress, and single-caregiver households. Conclusion: Findings from this study highlight the importance of interventions aimed specifically at increasing adolescent social connectedness, family engagement, and access to medical support for adolescents with MEBD disabilities, particularly in the face of stressors, such as a global pandemic. Impact: Through a machine learning process, we identified contextualized risks associated with life satisfaction among adolescents with neurodevelopmental disabilities during the COVID-19 pandemic.The COVID-19 pandemic resulted in large-scale social disruptions for children and families. Such disruptions were associated with worse mental health outcomes in the general pediatric population, but few studies have examined specific subgroups who may be at heightened risk. We endeavored to close that gap in knowledge.This study highlights the importance of social connectedness, family engagement, and access to medical support as contributing factors to life satisfaction during the COVID-19 pandemic for adolescents with neurodevelopmental disabilities
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