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This document summarizes a study on the relationship between atopic dermatitis (AD) and IgE-mediated food allergy (FA) in children. The study found that children with AD were more likely to develop FA, and vice versa. However, the study had limitations, such as not assessing the severity of AD and having a small sample size for cases of FA. The findings suggest that AD and FA may be related and further research is needed to understand and address these conditions. [Extracted from the article]

Importance: Limited access to healthy foods, resulting from residence in neighborhoods with low food access, is a public health concern. The contribution of this exposure in early life to child obesity remains uncertain., Objective: To examine associations of neighborhood food access during pregnancy or early childhood with child body mass index (BMI) and obesity risk., Design, Setting, and Participants: Data from cohorts participating in the US nationwide Environmental Influences on Child Health Outcomes consortium between January 1, 1994, and March 31, 2023, were used. Participant inclusion required a geocoded residential address in pregnancy (mean 32.4 gestational weeks) or early childhood (mean 4.3 years) and information on child BMI., Exposures: Residence in low-income, low-food access neighborhoods, defined as low-income neighborhoods where the nearest supermarket is more than 0.5 miles for urban areas or more than 10 miles for rural areas., Main Outcomes and Measures: BMI z score, obesity (age- and sex-specific BMI ≥95th percentile), and severe obesity (age- and sex-specific BMI ≥120% of the 95th percentile) from age 0 to 15 years., Results: Of 28 359 children (55 cohorts; 14 657 [51.7%] male and 13 702 [48.3%] female; 590 [2.2%] American Indian, Alaska Native, Native Hawaiian, or Other Pacific Islander; 1430 [5.4%] Asian; 4034 [15.3%] Black; 17 730 [67.2%] White; and 2592 [9.8%] other [unspecified] or more than 1 race; 5754 [20.9%] Hispanic and 21 838 [79.1%] non-Hispanic) with neighborhood food access data, 23.2% resided in low-income, low-food access neighborhoods in pregnancy and 24.4% in early childhood. After adjusting for individual sociodemographic characteristics, residence in low-income, low-food access (vs non-low-income, low-food access) neighborhoods in pregnancy was associated with higher BMI z scores at ages 5 years (β, 0.07; 95% CI, 0.03-0.11), 10 years (β, 0.11; 95% CI, 0.06-0.17), and 15 years (β, 0.16; 95% CI, 0.07-0.24); higher obesity risk at 5 years (risk ratio [RR], 1.37; 95% CI, 1.21-1.55), 10 years (RR, 1.71; 95% CI, 1.37-2.12), and 15 years (RR, 2.08; 95% CI, 1.53-2.83); and higher severe obesity risk at 5 years (RR, 1.21; 95% CI, 0.95-1.53), 10 years (RR, 1.54; 95% CI, 1.20-1.99), and 15 years (RR, 1.92; 95% CI, 1.32-2.80). Findings were similar for residence in low-income, low-food access neighborhoods in early childhood. These associations were robust to alternative definitions of low income and low food access and additional adjustment for prenatal characteristics associated with child obesity., Conclusions: Residence in low-income, low-food access neighborhoods in early life was associated with higher subsequent child BMI and higher risk of obesity and severe obesity. We encourage future studies to examine whether investments in neighborhood resources to improve food access in early life would prevent child obesity.

Aim: To develop an automated computable phenotype (CP) algorithm for identifying diabetes cases in children and adolescents using electronic health records (EHRs) from the UF Health System., Materials and Methods: The CP algorithm was iteratively derived based on structured data from EHRs (UF Health System 2012-2020). We randomly selected 536 presumed cases among individuals aged <18 years who had (1) glycated haemoglobin levels ≥ 6.5%; or (2) fasting glucose levels ≥126 mg/dL; or (3) random plasma glucose levels ≥200 mg/dL; or (4) a diabetes-related diagnosis code from an inpatient or outpatient encounter; or (5) prescribed, administered, or dispensed diabetes-related medication. Four reviewers independently reviewed the patient charts to determine diabetes status and type., Results: Presumed cases without type 1 (T1D) or type 2 diabetes (T2D) diagnosis codes were categorized as non-diabetes/other types of diabetes. The rest were categorized as T1D if the most recent diagnosis was T1D, or otherwise categorized as T2D if the most recent diagnosis was T2D. Next, we applied a list of diagnoses and procedures that can determine diabetes type (e.g., steroid use suggests induced diabetes) to correct misclassifications from Step 1. Among the 536 reviewed cases, 159 and 64 had T1D and T2D, respectively. The sensitivity, specificity, and positive predictive values of the CP algorithm were 94%, 98% and 96%, respectively, for T1D and 95%, 95% and 73% for T2D., Conclusion: We developed a highly accurate EHR-based CP for diabetes in youth based on EHR data from UF Health. Consistent with prior studies, T2D was more difficult to identify using these methods., (© 2024 John Wiley & Sons Ltd.)

Background: A major challenge in epidemiology is knowing when an exposure effect is large enough to be clinically important, in particular how to interpret a difference in mean outcome in unexposed/exposed groups. Where it can be calculated, the proportion/percentage beyond a suitable cut-point is useful in defining individuals at high risk to give a more meaningful outcome. In this simulation study we compute differences in outcome means and proportions that arise from hypothetical small effects in vulnerable sub-populations., Methods: Data from over 28,000 mother/child pairs belonging to the Environmental influences on Child Health Outcomes Program were used to examine the impact of hypothetical environmental exposures on mean birthweight, and low birthweight (LBW) (birthweight < 2500g). We computed mean birthweight in unexposed/exposed groups by sociodemographic categories (maternal education, health insurance, race, ethnicity) using a range of hypothetical exposure effect sizes. We compared the difference in mean birthweight and the percentage LBW, calculated using a distributional approach., Results: When the hypothetical mean exposure effect was fixed (at 50, 125, 167 or 250g), the absolute difference in % LBW (risk difference) was not constant but varied by socioeconomic categories. The risk differences were greater in sub-populations with the highest baseline percentages LBW: ranging from 3.1-5.3 percentage points for exposure effect of 125g. Similar patterns were seen for other mean exposure sizes simulated., Conclusions: Vulnerable sub-populations with greater baseline percentages at high risk fare worse when exposed to a small insult compared to the general population. This illustrates another facet of health disparity in vulnerable individuals., (© 2024. The Author(s).)

Background/objectives: Prenatal exposure to ambient air pollution is associated with adverse cardiometabolic outcomes in childhood. We previously observed that prenatal black carbon (BC) was inversely associated with adiponectin, a hormone secreted by adipocytes, in early childhood. Changes to DNA methylation have been proposed as a potential mediator linking in utero exposures to lasting health impacts., Methods: Among 532 mother-child pairs enrolled in the Colorado-based Healthy Start study, we performed an epigenome-wide association study of the relationship between prenatal exposure to a component of air pollution, BC, and DNA methylation in cord blood. Average pregnancy ambient BC was estimated at the mother's residence using a spatiotemporal prediction model. DNA methylation was measured using the Illumina 450K array. We used multiple linear regression to estimate associations between prenatal ambient BC and 429,246 cysteine-phosphate-guanine sites (CpGs), adjusting for potential confounders. We identified differentially methylated regions (DMRs) using DMRff and ENmix-combp. In a subset of participants (n = 243), we investigated DNA methylation as a potential mediator of the association between prenatal ambient BC and lower adiponectin in childhood., Results: We identified 44 CpGs associated with average prenatal ambient BC after correcting for multiple testing. Several genes annotated to the top CpGs had reported functions in the immune system. There were 24 DMRs identified by both DMRff and ENmix-combp. One CpG (cg01123250), located on chromosome 2 and annotated to the UNC80 gene, was found to mediate approximately 20% of the effect of prenatal BC on childhood adiponectin, though the confidence interval was wide (95% CI: 3, 84)., Conclusions: Prenatal BC was associated with DNA methylation in cord blood at several sites and regions in the genome. DNA methylation may partially mediate associations between prenatal BC and childhood cardiometabolic outcomes., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Researchers often aim to assess whether repeated measures of an exposure are associated with repeated measures of an outcome. A question of particular interest is how associations between exposures and outcomes may differ over time. In other words, researchers may seek the best form of a temporal model. While several models are possible, researchers often consider a few key models. For example, researchers may hypothesize that an exposure measured during a sensitive period may be associated with repeated measures of the outcome over time. Alternatively, they may hypothesize that the exposure measured immediately before the current time period may be most strongly associated with the outcome at the current time. Finally, they may hypothesize that all prior exposures are important. Many analytic methods cannot compare and evaluate these alternative temporal models, perhaps because they make the restrictive assumption that the associations between exposures and outcomes remains constant over time. Instead, we provide a tutorial describing four temporal models that allow the associations between repeated measures of exposures and outcomes to vary, and showing how to test which temporal model is best supported by the data. By finding the best temporal model, developmental psychopathology researchers can find optimal windows for intervention.

Our objective was to interrogate mesenchymal stem cell (MSC) lipid metabolism and gestational exposures beyond maternal body mass that may contribute to child obesity risk. MSCs were cultured from term infants of mothers with obesity (n = 16) or normal weight (n = 15). In MSCs undergoing myogenesis in vitro, we used lipidomics to distinguish phenotypes by unbiased cluster analysis and lipid challenge (24-hour excess fatty acid [24hFA]). We measured MSC AMP-activated protein kinase (AMPK) activity and fatty acid oxidation (FAO), and a composite index of maternal glucose, insulin, triglycerides, free fatty acids, TNF-α, and high-density lipoprotein and total cholesterol in fasting blood from mid and late gestation (~17 and ~27 weeks, respectively). We measured child adiposity at birth (n = 29), 4-6 months (n = 29), and 4-6 years (n = 13). Three MSC clusters were distinguished by triacylglycerol (TAG) stores, with greatest TAGs in Cluster 2. All clusters increased acylcarnitines and TAGs with 24hFA, although Cluster 2 was more pronounced and corresponded to AMPK activation and FAO. Maternal metabolic markers predicted MSC clusters and child adiposity at 4-6 years (both highest in Cluster 3). Our data support the notion that MSC phenotypes are predicted by comprehensive maternal metabolic milieu exposures, independent of maternal BMI, and suggest utility as an at-birth predictor for child adiposity, although validation with larger longitudinal samples is warranted.

Background: Prenatal fish intake is a key source of omega-3 (ω-3) polyunsaturated fatty acids needed for brain development, yet intake is generally low, and studies addressing associations with autism spectrum disorder (ASD) and related traits are lacking., Objective: This study aimed to examine associations of prenatal fish intake and ω-3 supplement use with both autism diagnosis and broader autism-related traits., Methods: Participants were drawn from 32 cohorts in the Environmental influences on Child Health Outcomes Cohort Consortium. Children were born between 1999 and 2019 and part of ongoing follow-up with data available for analysis by August 2022. Exposures included self-reported maternal fish intake and ω-3/fish oil supplement use during pregnancy. Outcome measures included parent report of clinician-diagnosed ASD and parent-reported autism-related traits measured by the Social Responsiveness Scale (SRS)-second edition (n = 3939 and v3609 for fish intake analyses, respectively; n = 4537 and n = 3925 for supplement intake analyses, respectively)., Results: In adjusted regression models, relative to no fish intake, fish intake during pregnancy was associated with reduced odds of autism diagnosis (odds ratio: 0.84; 95% confidence interval [CI]: 0.77, 0.92), and a modest reduction in raw total SRS scores (β: -1.69; 95% CI: -3.3, -0.08). Estimates were similar across categories of fish consumption from "any" or "less than once per week" to "more than twice per week." For ω-3 supplement use, relative to no use, no significant associations with autism diagnosis were identified, whereas a modest relation with SRS score was suggested (β: 1.98; 95% CI: 0.33, 3.64)., Conclusions: These results extend previous work by suggesting that prenatal fish intake, but not ω-3 supplement use, may be associated with lower likelihood of both autism diagnosis and related traits. Given the low-fish intake in the United States general population and the rising autism prevalence, these findings suggest the need for better public health messaging regarding guidelines on fish intake for pregnant individuals., Competing Interests: Conflicts of interest The authors report no conflicts of interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Given prior literature focused on the Developmental Origins of Health and Disease framework, there is strong rationale to hypothesize that reducing depression in the prenatal period will cause improvements in offspring cardiometabolic health. The current review outlines evidence that prenatal depression is associated with offspring cardiometabolic risk and health behaviors. We review evidence of these associations in humans and in nonhuman animals at multiple developmental periods, from the prenatal period (maternal preeclampsia, gestational diabetes), neonatal period (preterm birth, small size at birth), infancy (rapid weight gain), childhood and adolescence (high blood pressure, impaired glucose-insulin homeostasis, unfavorable lipid profiles, abdominal obesity), and into adulthood (diabetes, cardiovascular disease). In addition to these cardiometabolic outcomes, we focus on health behaviors associated with cardiometabolic risk, such as child eating behaviors, diet, physical activity, and sleep health. Our review focuses on child behaviors (e.g., emotional eating, preference for highly palatable foods, short sleep duration) and parenting behaviors (e.g., pressuring child to eat, modeling of health behaviors). These changes in health behaviors may be detected before changes to cardiometabolic outcomes, which may allow for early identification of and prevention for children at risk for poor adult cardiometabolic outcomes. We also discuss the methods of the ongoing Care Project, which is a randomized clinical trial to test whether reducing prenatal maternal depression improves offspring's cardiometabolic health and health behaviors in preschool. The goal of this review and the Care Project are to inform future research, interventions, and policies that support prenatal mental health and offspring cardiometabolic health. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Background: Studies of childhood diet diversity and allergic disease have not examined additional associations with an offspring allergy-linked maternal diet index during pregnancy. We studied both associations in a pre-birth cohort., Methods: Offspring allergic disease diagnoses were obtained from electronic medical records. Maternal and infant diet were self-reported. Adjusted parametric Weibull time-to-event models assessed associations between maternal diet index, infant diet diversity and time to development of allergic rhinitis, atopic dermatitis, asthma, wheeze, IgE-mediated food allergy, and a combined outcome of any allergic disease except for wheeze., Results: Infant diet diversity at 1 year was associated with the risk of the combined outcome between 1 and 4 years of age (p = .002). While both maternal diet index and infant diet diversity at 1 year were associated with the risk of the combined outcome between 1 and 4 years of age (both p < .05), infant diet diversity at 1 year did not modify the association between maternal diet index and the risk of the combined outcome between 1 and 4 years of age (p = .5). The group with the lowest risk of the combined allergy outcome had higher maternal diet index and higher infant diet diversity., Conclusions: The novel finding that both maternal diet index during pregnancy and infant diet diversity at 12 months are associated with the risk of a combined allergic disease outcome points to two targets for preventive interventions: maternal diet index scores during pregnancy and offspring diet diversity during infancy., (© 2024 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Background: Certain endocrine-disrupting chemicals (EDCs) are widespread in consumer products and may alter glucose metabolism. However, the impact of EDC exposures on glucose and insulin regulation during pregnancy is incompletely understood, despite potential adverse consequences for maternal and infant health. We estimated associations between 37 urinary biomarkers of EDCs and glucose-insulin traits among pregnant women., Methods: Seventeen phthalate or phthalate substitute metabolites, six environmental phenols, four parabens, and ten organophosphate ester metabolites were quantified in mid-pregnancy urine from 298 participants in the Healthy Start Study. Fasting blood glucose, insulin, and hemoglobin A1c were assessed concurrently, and Homeostasis Model Assessment 2-Insulin Resistance (HOMA2-IR) was calculated. Gestational diabetes diagnoses and screening results were obtained from medical records for a subset of participants. We estimated associations between each EDC and outcome separately using linear and robust Poisson regression models and analyzed EDC mixture effects., Results: The EDC mixture was positively associated with glucose, insulin, and HOMA2-IR, although overall associations were attenuated after adjustment for maternal BMI. Two mixture approaches identified di(2-ethylhexyl) phthalate (DEHP) metabolites as top contributors to the mixture's positive associations. In single-pollutant models, DEHP metabolites were positively associated with fasting glucose, fasting insulin, and HOMA2-IR even after adjustment for maternal BMI. For example, each interquartile range increase in log 2 -transformed mono(2-ethyl-5-oxohexyl) phthalate was associated with 2.4 mg/dL (95% confidence interval (CI): 1.1, 3.6) higher fasting glucose, 11.8% (95%CI: 3.6, 20.5) higher fasting insulin, and 12.3% (95%CI: 4.2, 21.1) higher HOMA2-IR. Few EDCs were associated with hemoglobin A1c or with a combined outcome of impaired glucose tolerance or gestational diabetes., Discussion: Exposures to phthalates and particularly DEHP during pregnancy are associated with altered glucose-insulin regulation. Disruptions in maternal glucose metabolism during pregnancy may contribute to adverse pregnancy outcomes including gestational diabetes and fetal macrosomia, and associated long-term consequences for maternal and child health., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: This study seeks to characterize cardiovascular health (CVH) from early childhood to late adolescence and identify sociodemographic correlates of high CVH that serve as levers for optimizing CVH across early life., Methods and Results: Among 1530 youth aged 3 to 20 years from 2 cohorts in the ECHO (Environmental Influences on Child Health Outcomes) consortium, we first derived CVH scores on the basis of the Life's Essential 8 construct comprising 4 behavioral (nicotine use/exposure, physical activity, sleep, and diet) and 4 health factors (body mass index, blood pressure, non-high-density lipoprotein cholesterol, and fasting glucose) during early childhood (mean age, 3.5 years), middle childhood (8.0 years), early adolescence (13.3 years), and late adolescence (17.8 years). Next, we used generalized regression to estimate the probability of high (versus not high) CVH with respect to sociodemographic characteristics. Overall CVH score was stable across life stages: 81.2±7.6, 83.3±8.0, and 81.7±8.9 of 100 possible points in early childhood, middle childhood, and early adolescence, respectively. Accordingly, during these life stages, most children (63.3%-71.5%) had high CVH (80 to <100). However, CVH declined by late adolescence, with an average score of 75.5±10.2 and 39.4% high CVH. No children had optimal CVH (score=100) at any time. Correlates of high CVH include non-Hispanic White race and ethnicity, maternal college education, and annual household income >$70 000. These associations were driven by behavioral factors., Conclusions: Although most youth maintained high CVH across childhood, the decline by late adolescence indicates that cardiovascular disease prevention should occur before the early teen years. Disparities in high CVH over time with respect to sociodemographic characteristics were explained by behavioral factors, pointing toward prevention targets.

Tracking trajectories of body size in children provides insight into chronic disease risk. One measure of pediatric body size is body mass index (BMI), a function of height and weight. Errors in measuring height or weight may lead to incorrect assessment of BMI. Yet childhood measures of height and weight extracted from electronic medical records often include values which seem biologically implausible in the context of a growth trajectory. Removing biologically implausible values reduces noise in the data, and thus increases the ease of modeling associations between exposures and childhood BMI trajectories, or between childhood BMI trajectories and subsequent health conditions. We developed open-source algorithms (available on github) for detecting and removing biologically implausible values in pediatric trajectories of height and weight. A Monte Carlo simulation experiment compared the sensitivity, specificity and speed of our algorithms to three published algorithms. The comparator algorithms were selected because they used trajectory information, had open-source code, and had published verification studies. Simulation inputs were derived from longitudinal epidemiological cohorts. Our algorithms had higher specificity, with similar sensitivity and speed, when compared to the three published algorithms. The results suggest that our algorithms should be adopted for cleaning longitudinal pediatric growth data., (© 2024. The Author(s).)

Past studies support the hypothesis that the prenatal period influences childhood growth. However, few studies explore the joint effects of exposures that occur simultaneously during pregnancy. To explore the feasibility of using mixtures methods with neighborhood-level environmental exposures, we assessed the effects of multiple prenatal exposures on body mass index (BMI) from birth to age 24 months. We used data from two cohorts: Healthy Start (n = 977) and Maternal and Developmental Risks from Environmental and Social Stressors (MADRES; n = 303). BMI was measured at delivery and 6, 12, and 24 months and standardized as z-scores. We included variables for air pollutants, built and natural environments, food access, and neighborhood socioeconomic status (SES). We used two complementary statistical approaches: single-exposure linear regression and quantile-based g-computation. Models were fit separately for each cohort and time point and were adjusted for relevant covariates. Single-exposure models identified negative associations between NO 2 and distance to parks and positive associations between low neighborhood SES and BMI z-scores for Healthy Start participants; for MADRES participants, we observed negative associations between O 3 and distance to parks and BMI z-scores. G-computations models produced comparable results for each cohort: higher exposures were generally associated with lower BMI, although results were not significant. Results from the g-computation models, which do not require a priori knowledge of the direction of associations, indicated that the direction of associations between mixture components and BMI varied by cohort and time point. Our study highlights challenges in assessing mixtures effects at the neighborhood level and in harmonizing exposure data across cohorts. For example, geospatial data of neighborhood-level exposures may not fully capture the qualities that might influence health behavior. Studies aiming to harmonize geospatial data from different geographical regions should consider contextual factors when operationalizing exposure variables., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Sheena E. Martenies reports financial support was provided by National Institutes of HealthOffice of the Director. Dana Dabelea reports financial support was provided by National Institutes of HealthOffice of the Director. Dana Dabelea reports financial support was provided by National Institute of Diabetes and Digestive and Kidney Diseases. Carrie V. Breton, Theresa M. Bastain, Rima Habre, and Shohreh F. Farzan report financial support was provided by National Institutes of HealthOffice of the Director. Carrie V. Breton and Theresa M. Bastain report financial support was provided by National Institute of Environmental Health Sciences. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Maternal metabolism during pregnancy shapes offspring health via in utero programming. In the Healthy Start study, we identified five subgroups of pregnant women based on conventional metabolic biomarkers: Reference ( n = 360); High HDL-C ( n = 289); Dyslipidemic-High TG ( n = 149); Dyslipidemic-High FFA ( n = 180); Insulin Resistant (IR)-Hyperglycemic ( n = 87). These subgroups not only captured metabolic heterogeneity among pregnant participants but were also associated with offspring obesity in early childhood, even among women without obesity or diabetes. Here, we utilize metabolomics data to enrich characterization of the metabolic subgroups and identify key compounds driving between-group differences. We analyzed fasting blood samples from 1065 pregnant women at 18 gestational weeks using untargeted metabolomics. We used weighted gene correlation network analysis (WGCNA) to derive a global network based on the Reference subgroup and characterized distinct metabolite modules representative of the different metabolomic profiles. We used the mummichog algorithm for pathway enrichment and identified key compounds that differed across the subgroups. Eight metabolite modules representing pathways such as the carnitine-acylcarnitine translocase system, fatty acid biosynthesis and activation, and glycerophospholipid metabolism were identified. A module that included 189 compounds related to DHA peroxidation, oxidative stress, and sex hormone biosynthesis was elevated in the Insulin Resistant-Hyperglycemic vs. the Reference subgroup. This module was positively correlated with total cholesterol (R:0.10; p -value < 0.0001) and free fatty acids (R:0.07; p -value < 0.05). Oxidative stress and inflammatory pathways may underlie insulin resistance during pregnancy, even below clinical diabetes thresholds. These findings highlight potential therapeutic targets and strategies for pregnancy risk stratification and reveal mechanisms underlying the developmental origins of metabolic disease risk.

Purpose: Adiponectin is a potent uterine tocolytic that decreases with gestational age, suggesting it could be a maternal metabolic quiescence factor. Maternal stress can influence preterm birth risk, and adiponectin levels may be stress-responsive. We characterized associations between adiponectin and glucocorticoids with preterm birth and modeled their predictive utility. We hypothesized maternal plasma adiponectin and cortisol are inversely related and lower adiponectin and higher cortisol associate with preterm birth., Methods: We performed a nested case-control study using biobanked fasting maternal plasma. We included low-risk singleton pregnancies, and matched 1:3 (16 preterm, 46 term). We quantified total, high (HMW), and low molecular weight (LMW) adiponectin using ELISA. We validated an HPLC-MS/MS serum assay for use in plasma, to simultaneously measure cortisol, cortisone, and five related steroid hormones. We used linear/logistic regression to compare group means and machine learning for predictive modeling., Results: The preterm group had lower mean LMW adiponectin (3.07 μg/mL vs. 3.81 μg/mL at 15w0d, P=0.045) and higher mean cortisone (34.4 ng/mL vs. 29.0 ng/mL at 15w0d, P=0.031). The preterm group had lower cortisol-to-cortisone and lower LMW adiponectin-to-cortisol ratios. We found HMW adiponectin, cortisol-to-cortisone ratio, cortisone, maternal height, age, and pre-pregnancy BMI most strongly predicted preterm birth (AUROC=0.8167). In secondary analyses, we assessed biomarker associations with maternal self-reported psychosocial stress. Lower perceived stress associated with a steeper change in cortisone in the term group., Conclusion: Overall, metabolic and stress biomarkers associated with preterm birth in this healthy cohort. We identify a possible mechanistic link between maternal stress and metabolism for pregnancy maintenance., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com. See the journal About page for additional terms.)

Adult-onset diabetes increases one's risk of neurodegenerative disease including Alzheimer's disease (AD); however, the risk associated with youth-onset diabetes (Y-DM) remains underexplored. We quantified plasma biomarkers of neurodegeneration and AD in participants with Y-DM from the SEARCH cohort at adolescence and young adulthood (Type 1, n = 25; Type 2, n = 25; 59% female; adolescence, age = 15 y/o [2.6]; adulthood, age = 27.4 y/o [2.2]), comparing them with controls (adolescence, n = 25, age = 14.8 y/o [2.7]; adulthood, n = 21, age = 24.9 y/o [2.8]). Plasma biomarkers, including glial fibrillary acidic protein (GFAP), neurofilament light chain protein (NfL), phosphorylated tau-181 (pTau181), and amyloid beta (Aβ40, Aβ42), were measured via Simoa. A subset of participants (n = 7; age = 27.5 y/o [5.7]) and six controls (age = 25.1 y/o [4.5]) underwent PET scans to quantify brain amyloid and tau densities in AD sensitive brain regions. Y-DM adolescents exhibited lower plasma levels of Aβ40, Aβ42, and GFAP, and higher pTau181 compared to controls ( p < 0.05), a pattern persisting into adulthood ( p < 0.001). All biomarkers showed significant increases from adolescence to adulthood in Y-DM ( p < 0.01), though no significant differences in brain amyloid or tau were noted between Y-DM and controls in adulthood. Preliminary evidence suggests that preclinical AD neuropathology is present in young people with Y-DM, indicating a potential increased risk of neurodegenerative diseases., Competing Interests: Conflicts of Interest: The authors declare no conflicts of interest.

Aims: To examine, among youth and young adults (YYA) with type 1 diabetes (T1D), the association of household food insecurity (HFI) with: 1) HbA 1c and 2) episodes of diabetic ketoacidosis (DKA) and severe hypoglycemia., Methods: HFI was assessed using the U.S. Household Food Security Survey Module in SEARCH for Diabetes in Youth participants with T1D between 2016 and 2019. Linear and logistic regression models adjusted for age, diabetes duration, sex, race, ethnicity, clinic site, parent/participant education, household income, health insurance, and diabetes technology use., Results: Of 1830 participants (mean age 20.8 ± 5.0 years, 70.0 % non-Hispanic White), HbA 1c was collected for 1060 individuals (mean HbA1c 9.2 % ± 2.0 %). The prevalence of HFI was 16.4 %. In the past 12 months, 18.2 % and 9.9 % reported an episode of DKA or severe hypoglycemia, respectively. Compared to participants who were food secure, HFI was associated with a 0.33 % (95 % CI 0.003, 0.657) higher HbA 1c level. Those with HFI had 1.58 (95 % CI 1.13, 2.21) times the adjusted odds of an episode of DKA and 1.53 (95 % CI 0.99, 2.37) times the adjusted odds of an episode of severe hypoglycemia as those without HFI., Conclusions: HFI is associated with higher HbA 1c levels and increased odds of DKA in YYA with T1D., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Synthetic oxytocin (sOT) is frequently administered during parturition. Studies have raised concerns that fetal exposure to sOT may be associated with altered brain development and risk of neurodevelopmental disorders. In a large and diverse sample of children with data about intrapartum sOT exposure and subsequent diagnoses of two prevalent neurodevelopmental disorders, i.e., attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD), we tested the following hypotheses: (1) Intrapartum sOT exposure is associated with increased odds of child ADHD or ASD; (2) associations differ across sex; (3) associations between intrapartum sOT exposure and ADHD or ASD are accentuated in offspring of mothers with pre-pregnancy obesity., Methods: The study sample comprised 12,503 participants from 44 cohort sites included in the Environmental Influences on Child Health Outcomes (ECHO) consortium. Mixed-effects logistic regression analyses were used to estimate the association between intrapartum sOT exposure and offspring ADHD or ASD (in separate models). Maternal obesity (pre-pregnancy BMI ≥ 30 kg/m 2 ) and child sex were evaluated for effect modification., Results: Intrapartum sOT exposure was present in 48% of participants. sOT exposure was not associated with increased odds of ASD (adjusted odds ratio [aOR] 0.86; 95% confidence interval [CI], 0.71-1.03) or ADHD (aOR 0.89; 95% CI, 0.76-1.04). Associations did not differ by child sex. Among mothers with pre-pregnancy obesity, sOT exposure was associated with lower odds of offspring ADHD (aOR 0.72; 95% CI, 0.55-0.96). No association was found among mothers without obesity (aOR 0.97; 95% CI, 0.80-1.18)., Conclusions: In a large, diverse sample, we found no evidence of an association between intrapartum exposure to sOT and odds of ADHD or ASD in either male or female offspring. Contrary to our hypothesis, among mothers with pre-pregnancy obesity, sOT exposure was associated with lower odds of child ADHD diagnosis., (© 2024. The Author(s).)

Background: Phthalate exposure may contribute to hypertensive disorders of pregnancy (HDP), including preeclampsia/eclampsia (PE/E), but epidemiologic studies are lacking., Objectives: To evaluate associations of pregnancy phthalate exposure with development of PE/E and HDP., Methods: Using data from 3,430 participants in eight Environmental influences on Child Health Outcomes (ECHO) Program cohorts (enrolled from 1999 to 2019), we quantified concentrations of 13 phthalate metabolites (8 measured in all cohorts, 13 in a subset of four cohorts) in urine samples collected at least once during pregnancy. We operationalized outcomes as PE/E and composite HDP (PE/E and/or gestational hypertension). After correcting phthalate metabolite concentrations for urinary dilution, we evaluated covariate-adjusted associations of individual phthalates with odds of PE/E or composite HDP via generalized estimating equations, and the phthalate mixture via quantile-based g-computation. We also explored effect measure modification by fetal sex using stratified models. Effect estimates are reported as odds ratios (OR) with 95% confidence intervals (95% CIs)., Results: In adjusted analyses, a doubling of mono-benzyl phthalate (MBzP) and of mono (3-carboxypropyl) phthalate (MCPP) concentrations was associated with higher odds of PE/E as well as composite HDP, with somewhat larger associations for PE/E. For example, a doubling of MCPP was associated with 1.12 times the odds of PE/E (95%CI 1.00, 1.24) and 1.02 times the odds of composite HDP (95%CI 1.00, 1.05). A quartile increase in the phthalate mixture was associated with 1.27 times the odds of PE/E (95%CI 0.94, 1.70). A doubling of mono-carboxy isononyl phthalate (MCiNP) and of mono-carboxy isooctyl phthalate (MCiOP) concentrations were associated with 1.08 (95%CI 1.00, 1.17) and 1.11 (95%CI 1.03, 1.19) times the odds of PE/E. Effect estimates for PE/E were generally larger among pregnancies carrying female fetuses., Discussion: In this study, multiple phthalates were associated with higher odds of PE/E and HDP. Estimates were precise and some were low in magnitude. Interventions to reduce phthalate exposures during pregnancy may help mitigate risk of these conditions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Estimates for the effects of environmental exposures on health outcomes, including secondhand smoke (SHS) exposure, often present considerable variability across studies. Knowledge of the reasons behind these differences can aid our understanding of effects in specific populations as well as inform practices of combining data from multiple studies., Objectives: This study aimed to assess the presence of effect modification by measured sociodemographic characteristics on the effect of SHS exposure during pregnancy on birth weights that may drive differences observed across cohorts. We also aimed to quantify the extent to which differences in the cohort mean effects observed across cohorts in the Environmental influences on Child Health Outcomes (ECHO) consortium are due to differing distributions of these characteristics., Methods: We assessed the presence of effect modification and transportability of effect estimates across five ECHO cohorts in a total of 6,771 mother-offspring dyads. We assessed the presence of effect modification via gradient boosting of regression trees based on the H-statistic. We estimated individual cohort effects using linear models and targeted maximum likelihood estimation (TMLE). We then estimated transported effects from one cohort to each of the remaining cohorts using a robust nonparametric estimation approach relying on TMLE estimators and compared them to the original effect estimates for these cohorts., Results: Observed effect estimates varied across the five cohorts, ranging from significantly lower birth weight associated with exposure [ - 167.3 g ; 95% confidence interval (CI): - 270.4 , - 64.1 ] to higher birth weight with wide CIs, including the null ( 42.4 g ; 95% CI: - 15.0 , 99.8). Transported effect estimates only minimally explained differences in the point estimates for two out of the four cohort pairs., Discussion: Our findings of weak to moderate evidence of effect modification and transportability indicate that unmeasured individual-level and contextual factors and sources of bias may be responsible for differences in the effect estimates observed across ECHO cohorts. https://doi.org/10.1289/EHP13961.

Background: Limited access to healthy foods, resulting from residence in neighborhoods with low-food access or from household food insecurity, is a public health concern. Contributions of these measures during pregnancy to birth outcomes remain understudied., Objectives: We examined associations between neighborhood food access and individual food insecurity during pregnancy with birth outcomes., Methods: We used data from 53 cohorts participating in the nationwide Environmental Influences on Child Health Outcomes-Wide Cohort Study. Participant inclusion required a geocoded residential address or response to a food insecurity question during pregnancy and information on birth outcomes. Exposures include low-income-low-food-access (LILA, where the nearest supermarket is >0.5 miles for urban or >10 miles for rural areas) or low-income-low-vehicle-access (LILV, where few households have a vehicle and >0.5 miles from the nearest supermarket) neighborhoods and individual food insecurity. Mixed-effects models estimated associations with birth outcomes, adjusting for socioeconomic and pregnancy characteristics., Results: Among 22,206 pregnant participants (mean age 30.4 y) with neighborhood food access data, 24.1% resided in LILA neighborhoods and 13.6% in LILV neighborhoods. Of 1630 pregnant participants with individual-level food insecurity data (mean age 29.7 y), 8.0% experienced food insecurity. Residence in LILA (compared with non-LILA) neighborhoods was associated with lower birth weight [β -44.3 g; 95% confidence interval (CI): -62.9, -25.6], lower birth weight-for-gestational-age z-score (-0.09 SD units; -0.12, -0.05), higher odds of small-for-gestational-age [odds ratio (OR) 1.15; 95% CI: 1.00, 1.33], and lower odds of large-for-gestational-age (0.85; 95% CI: 0.77, 0.94). Similar findings were observed for residence in LILV neighborhoods. No associations of individual food insecurity with birth outcomes were observed., Conclusions: Residence in LILA or LILV neighborhoods during pregnancy is associated with adverse birth outcomes. These findings highlight the need for future studies examining whether investing in neighborhood resources to improve food access during pregnancy would promote equitable birth outcomes., (Copyright © 2024 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Objective: To assess associations between distal symmetric polyneuropathy (DSPN) and Diabetes Prevention Program (DPP) treatment groups, diabetes status or duration, and cumulative glycemic exposure approximately 21 years after DPP randomization., Research Design and Methods: In the DPP, 3,234 adults ≥25 years old at high risk for diabetes were randomized to an intensive lifestyle (ILS), metformin, or placebo intervention to prevent diabetes. After the DPP ended, 2,779 joined the Diabetes Prevention Program Outcomes Study (DPPOS). Open-label metformin was continued, placebo was discontinued, ILS was provided in the form of semiannual group-based classes, and all participants were offered quarterly lifestyle classes. Symptoms and signs of DSPN were assessed in 1,792 participants at DPPOS year 17. Multivariable logistic regression models were used to evaluate DSPN associations with treatment group, diabetes status/duration, and cumulative glycemic exposure., Results: At 21 years after DPP randomization, 66% of subjects had diabetes. DSPN prevalence did not differ by initial DPP treatment assignment (ILS 21.5%, metformin 21.5%, and placebo 21.9%). There was a significant interaction between treatment assignment to ILS and age (P < 0.05) on DSPN. At DPPOS year 17, the odds ratio for DSPN in comparison with ILS with placebo was 17.4% (95% CI 3.0, 29.3) lower with increasing 5-year age intervals. DSPN prevalence was slightly lower for those at risk for diabetes (19.6%) versus those with diabetes (22.7%) and was associated with longer diabetes duration and time-weighted HbA1c (P values <0.001)., Conclusions: The likelihood of DSPN was similar across DPP treatment groups but higher for those with diabetes, longer diabetes duration, and higher cumulative glycemic exposure. ILS may have long-term benefits on DSPN for older adults., (© 2024 by the American Diabetes Association.)

Objective: We sought to evaluate the impact of the coronavirus disease 2019 (COVID-19) pandemic on perinatal outcomes while accounting for maternal depression or perceived stress and to describe COVID-specific stressors, including changes in prenatal care, across specific time periods of the pandemic., Study Design: Data of dyads from 41 cohorts from the National Institutes of Health Environmental influences on Child Health Outcomes Program ( N  = 2,983) were used to compare birth outcomes before and during the pandemic ( n  = 2,355), and a partially overlapping sample ( n  = 1,490) responded to a COVID-19 questionnaire. Psychosocial stress was defined using prenatal screening for depression and perceived stress. Propensity-score matching and general estimating equations with robust variance estimation were used to estimate the pandemic's effect on birth outcomes., Results: Symptoms of depression and perceived stress during pregnancy were similar prior to and during the pandemic, with nearly 40% of participants reporting mild to severe stress, and 24% reporting mild depression to severe depression. Gestations were shorter during the pandemic ( B  =  - 0.33 weeks, p  = 0.025), and depression was significantly associated with shortened gestation ( B  =  - 0.02 weeks, p  = 0.015) after adjustment. Birth weights were similar ( B  =  - 28.14 g, p  = 0.568), but infants born during the pandemic had slightly larger birth weights for gestational age at delivery than those born before the pandemic ( B  = 0.15 z-score units, p  = 0.041). More women who gave birth early in the pandemic reported being moderately or extremely distressed about changes to their prenatal care and delivery (45%) compared with those who delivered later in the pandemic. A majority (72%) reported somewhat to extremely negative views of the impact of COVID-19 on their life., Conclusion: In this national cohort, we detected no effect of COVID-19 on prenatal depression or perceived stress. However, experiencing the COVID-19 pandemic in pregnancy was associated with decreases in gestational age at birth, as well as distress about changes in prenatal care early in the pandemic., Key Points: · COVID-19 was associated with shortened gestations.. · Depression was associated with shortened gestations.. · However, stress during the pandemic remained unchanged.. · Most women reported negative impacts of the pandemic.., Competing Interests: C.M. served as Chair of the Data Safety Monitoring Board (DSMB) for an Aerogen-supported trial: A Partially-Blind, Randomized, Controlled, Parallel-Group Dose Ranging Study to Determine the Efficacy, Safety and Tolerability of AeroFactTM (SF-RI 1 surfactant for inhalation combined with a dedicated drug delivery system) in Preterm Infants at Risk for Worsening Respiratory Distress Syndrome; Chair of the DSMB for the NIH RCT evaluating Sildenafil in Preterm Infants with Pulmonary Hypertension. J.N. served on the Advisory Board for the Twin Life Study (Germany); received royalties or licenses from Macmillan and consulting fees from the University of Southern California. J.H. served on the New York State Drinking Water Quality Council. The other authors have no conflicts of interest to disclose., (Thieme. All rights reserved.)

Background: Islet autoantibodies form the foundation for type 1 diabetes (T1D) diagnosis and staging, but heterogeneity exists in T1D development and presentation. We hypothesized that autoantibodies can identify heterogeneity before, at, and after T1D diagnosis, and in response to disease-modifying therapies., Methods: We systematically reviewed PubMed and EMBASE databases (6/14/2022) assessing 10 years of original research examining relationships between autoantibodies and heterogeneity before, at, after diagnosis, and in response to disease-modifying therapies in individuals at-risk or within 1 year of T1D diagnosis. A critical appraisal checklist tool for cohort studies was modified and used for risk of bias assessment., Results: Here we show that 152 studies that met extraction criteria most commonly characterized heterogeneity before diagnosis (91/152). Autoantibody type/target was most frequently examined, followed by autoantibody number. Recurring themes included correlations of autoantibody number, type, and titers with progression, differing phenotypes based on order of autoantibody seroconversion, and interactions with age and genetics. Only 44% specifically described autoantibody assay standardization program participation., Conclusions: Current evidence most strongly supports the application of autoantibody features to more precisely define T1D before diagnosis. Our findings support continued use of pre-clinical staging paradigms based on autoantibody number and suggest that additional autoantibody features, particularly in relation to age and genetic risk, could offer more precise stratification. To improve reproducibility and applicability of autoantibody-based precision medicine in T1D, we propose a methods checklist for islet autoantibody-based manuscripts which includes use of precision medicine MeSH terms and participation in autoantibody standardization workshops., (© 2024. The Author(s).)

Aims: Suboptimal glycaemic control in children and adolescents with type 1 diabetes is prevalent and associated with increased risk of diabetes-related complications and mortality later in life. First, we aimed to identify distinct glycated haemoglobin (HbA1c) trajectories in children and adolescents (2-19 years) with type 1 diabetes. Second, we examined their associations with clinical and socio-demographic factors., Methods: Data were obtained from the Danish Registry of Childhood and Adolescent Diabetes (DanDiabKids) comprising all Danish children and adolescents diagnosed with type 1 diabetes from 1996 to 2019. Subgroups of distinct mean trajectories of HbA1c were identified using data-driven latent class trajectory modelling., Results: A total of 5889 children (47% female) had HbA1c measured a median of 6 times (interquartile range 3-8) and contributing to 36,504 measurements. We identified four mean HbA1c trajectories, referred to as 'Stable but elevated HbA1c' (83%), 'Increasing HbA1c' (5%), 'Late HbA1c peak' (7%), and 'Early HbA1c peak' (5%). Compared to the 'Stable but elevated HbA1c' group, the three other groups presented rapidly deteriorating glycaemic control during late childhood or adolescence, had higher HbA1c at study entry, and included fewer pump users, higher frequency of inadequate blood glucose monitoring, more severe hypoglycaemic events, lower proportions with Danish origin, and worse educational status of parents. The groups also represented significant differences by healthcare region., Conclusions: Children and adolescents with type 1 diabetes experience heterogenous trajectories with different timings and magnitudes of the deterioration of HbA1c levels, although the majority follow on average a stable, yet elevated HbA1c trajectory. The causes and long-term health implications of these heterogenous trajectories need to be addressed., (© 2023 Diabetes UK.)

Aims: Determining diabetes type in children has become increasingly difficult due to an overlap in typical characteristics between type 1 diabetes (T1D) and type 2 diabetes (T2D). The Diabetes Study in Children of Diverse Ethnicity and Race (DISCOVER) programme is a National Institutes of Health (NIH)-supported multicenter, prospective, observational study that enrols children and adolescents with non-secondary diabetes. The primary aim of the study was to develop improved models to differentiate between T1D and T2D in diverse youth., Materials and Methods: The proposed models will evaluate the utility of three existing T1D genetic risk scores in combination with data on islet autoantibodies and other parameters typically available at the time of diabetes onset. Low non-fasting serum C-peptide (<0.6 nmol/L) between 3 and 10 years after diabetes diagnosis will be considered a biomarker for T1D as it reflects the loss of insulin secretion ability. Participating centres are enrolling youth (<19 years old) either with established diabetes (duration 3-10 years) for a cross-sectional evaluation or with recent onset diabetes (duration 3 weeks-15 months) for the longitudinal observation with annual visits for 3 years. Cross-sectional data will be used to develop models. Longitudinal data will be used to externally validate the best-fitting model., Results: The results are expected to improve the ability to classify diabetes type in a large and growing subset of children who have an unclear form of diabetes at diagnosis., Conclusions: Accurate and timely classification of diabetes type will help establish the correct clinical management early in the course of the disease., (© 2023 John Wiley & Sons Ltd.)

Objectives. To examine whether a previously reported association between airborne lead exposure and children's cognitive function replicates across a geographically diverse sample of the United States. Methods. Residential addresses of children (< 5 years) were spatially joined to the Risk-Screening Environmental Indicators model of relative airborne lead toxicity. Cognitive outcomes for children younger than 8 years were available for 1629 children with IQ data and 1476 with measures of executive function (EF; inhibitory control, cognitive flexibility). We used generalized linear models using generalized estimating equations to examine the associations of lead, scaled by interquartile range (IQR), accounting for individual- and area-level confounders. Results. An IQR increase in airborne lead was associated with a 0.74-point lower mean IQ score (b = -0.74; 95% confidence interval = -1.00, -0.48). The association between lead and EF was nonlinear and was modeled with a knot at the 97.5th percentile of lead in our sample. Lead was significantly associated with lower mean inhibitory control but not with cognitive flexibility. This effect was stronger among males for both IQ and inhibitory control. Conclusions. Early-life exposure to airborne lead is associated with lower cognitive functioning. ( Am J Public Health. 2024;114(3):309-318. https://doi.org/10.2105/AJPH.2023.307519).

Background: The 2017-2018 U.S. PFAS exposure burden calculator was designed to provide a summary exposure score for per- and polyfluoroalkyl substances (PFAS) mixtures using targeted PFAS analyte data. Its aim was to place PFAS burden score estimates onto a common scale based on nationally representative U.S. reference ranges from 2017 to 2018, enabling comparisons of overall PFAS burden scores across studies even if they did not measure the same set of PFAS analytes., Objective: To use the U.S. PFAS exposure burden calculator for comparing the same mixture of PFAS compounds in similarly aged adolescents and their associations with cardiometabolic outcomes in the HOME Study and NHANES between 2015 and 2018., Methods: We applied the PFAS burden calculator to 8 PFAS analytes measured in the serum of adolescents from the HOME Study (Cincinnati, Ohio; age range 11-14 years; years: 2016-2019; n = 207) and NHANES (US; age range 12-14 years; years 2015-2018; n = 245). We used the non-parametric Mann-Whitney U test and chi-squared test to compare the two study samples. In both studies, we examined associations of PFAS burden scores with the same cardiometabolic outcomes, adjusted for the same core set of covariates using regression analyses. We conducted sensitivity analyses to verify robustness of exposure-outcome associations, by accounting for measurement error of PFAS burden scores., Results: PFAS burden scores were significantly different (p = 0.004) between the HOME Study (median: 0.00, interquartile range - 0.37, 0.34) and the NHANES samples (median: 0.04, IQR -0.11, 0.54), while no significant difference was found for PFAS summed concentrations (p = 0.661). In the HOME Study, an interquartile (IQR) increase in PFAS burden score was associated with higher total cholesterol [7.0 mg/dL, 95% CI: 0.6, 13.4]; HDL [2.8 mg/dL, 95% CI: 0.4, 5.2]; LDL [5.9 mg/dL, 95% CI: 0.5, 11.3], insulin [0.1 log(mIU/L), 95% CI: 0.01, 0.2], and HOMA-IR [0.1, 95% CI: 0.01, 0.2]. In NHANES, an IQR increase in PFAS burden score was associated with higher diastolic blood pressure [2.4 mmHg, 95% CI: 0.4, 4.4] but not with other outcomes. Sensitivity analyses in the HOME Study and NHANES were consistent with the main findings., Conclusions: Performance of the U.S. PFAS exposure burden calculator was similar in a local versus national sample of adolescents, and may be a useful tool for the assessment of PFAS mixtures across studies., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Shelley H. Liu reports financial support was provided by National Institute of Child Health and Human Development. Shelley H. Liu reports financial support was provided by National Institute of Environmental Health Sciences. Jessie Buckley reports financial support was provided by National Institute of Environmental Health Sciences. Joseph Braun reports financial support was provided by National Institute of Environmental Health Sciences. J.M.B. has been compensated for serving as an expert witness for plaintiffs in litigation over PFAS contaminated drinking water., (Copyright © 2023. Published by Elsevier Inc.)

Objective: n -3 fatty acid consumption during pregnancy is recommended for optimal pregnancy outcomes and offspring health. We examined characteristics associated with self-reported fish or n -3 supplement intake., Design: Pooled pregnancy cohort studies., Setting: Cohorts participating in the Environmental influences on Child Health Outcomes (ECHO) consortium with births from 1999 to 2020., Participants: A total of 10 800 pregnant women in twenty-three cohorts with food frequency data on fish consumption; 12 646 from thirty-five cohorts with information on supplement use., Results: Overall, 24·6 % reported consuming fish never or less than once per month, 40·1 % less than once a week, 22·1 % 1-2 times per week and 13·2 % more than twice per week. The relative risk (RR) of ever ( v . never) consuming fish was higher in participants who were older (1·14, 95 % CI 1·10, 1·18 for 35-40 v . <29 years), were other than non-Hispanic White (1·13, 95 % CI 1·08, 1·18 for non-Hispanic Black; 1·05, 95 % CI 1·01, 1·10 for non-Hispanic Asian; 1·06, 95 % CI 1·02, 1·10 for Hispanic) or used tobacco (1·04, 95 % CI 1·01, 1·08). The RR was lower in those with overweight v . healthy weight (0·97, 95 % CI 0·95, 1·0). Only 16·2 % reported n -3 supplement use, which was more common among individuals with a higher age and education, a lower BMI, and fish consumption (RR 1·5, 95 % CI 1·23, 1·82 for twice-weekly v . never)., Conclusions: One-quarter of participants in this large nationwide dataset rarely or never consumed fish during pregnancy, and n -3 supplement use was uncommon, even among those who did not consume fish.

Using data from a longitudinal cohort of children, we examined whether epigenetic age acceleration (EAA) was associated with pubertal growth and whether these associations were mediated by adiposity. We examined associations between EAA at approximately 10 years of age with pubertal growth metrics, including age at peak height velocity (PHV), PHV, and sex steroid levels and whether these associations were mediated by measures of adiposity including body mass index (BMI) and MRI-assessed visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT). Children (n = 135) with accelerated EAA had higher PHV (β 0.018, p = 0.0008) although the effect size was small. The association between EAA and age at PHV was not significant (β  - 0.0022, p = 0.067). Although EAA was associated with higher BMI (β 0.16, p = 0.0041), VAT (β 0.50, p = 0.037), and SAT (β 3.47, p = 0.0076), BMI and VAT did not mediate associations between EAA and PHV, while SAT explained 8.4% of the association. Boys with higher EAA had lower total testosterone (β  - 12.03, p = 0.0014), but associations between EAA and other sex steroids were not significant, and EAA was not associated with sex steroid levels in girls. We conclude that EAA did not have strong associations with either age at onset of puberty or pubertal growth speed, although associations with growth speed were statistically significant. Studies with larger sample sizes are needed to confirm this pattern of associations., (© 2024. The Author(s).)

Maternal educational attainment (MEA) shapes offspring health through multiple potential pathways. Differential DNA methylation may provide a mechanistic understanding of these long-term associations. We aimed to quantify the associations of MEA with offspring DNA methylation levels at birth, in childhood and in adolescence. Using 37 studies from high-income countries, we performed meta-analysis of epigenome-wide association studies (EWAS) to quantify the associations of completed years of MEA at the time of pregnancy with offspring DNA methylation levels at birth (n = 9 881), in childhood (n = 2 017), and adolescence (n = 2 740), adjusting for relevant covariates. MEA was found to be associated with DNA methylation at 473 cytosine-phosphate-guanine sites at birth, one in childhood, and four in adolescence. We observed enrichment for findings from previous EWAS on maternal folate, vitamin-B 12 concentrations, maternal smoking, and pre-pregnancy BMI. The associations were directionally consistent with MEA being inversely associated with behaviours including smoking and BMI. Our findings form a bridge between socio-economic factors and biology and highlight potential pathways underlying effects of maternal education. The results broaden our understanding of bio-social associations linked to differential DNA methylation in multiple early stages of life. The data generated also offers an important resource to help a more precise understanding of the social determinants of health., (© 2023. The Author(s).)

Background: Typically, child exposure to food insecurity is assessed by caregiver reports of household food security. Child report has the potential for greater accuracy because it pertains only to the child whose experiences may differ from caregiver reports., Objective: We assessed if adolescent-reported food insecurity was associated with levels of hemoglobin A 1c (HbA 1c ), acute diabetes-related complications, depressive symptoms, and disordered eating behaviors in adolescents with type 1 diabetes, independently from household food security., Methods: In a cross-sectional analysis of the multicenter SEARCH for Diabetes in Youth Cohort Study (phase 4, 2016-2019) including 601 adolescents aged 10-17 y with type 1 diabetes and their caregivers, household food security, and adolescent-reported food security were assessed using the 18-item Household Food Security Survey Module and the 6-item Child Food Security Assessment questionnaire. Age-stratified (10-13 and 14-17) regression models were performed to estimate independent associations, adjusting for sociodemographics, clinical factors, and household food security., Results: Food insecurity was reported by 13.1% (n = 79) of adolescents and 15.6% (n = 94) of caregivers. Among adolescent-caregiver dyads, 82.5% (n = 496) of reports were concordant and 17.5% (n = 105) discordant, Cohen's κ= 0.3. Adolescent-reported food insecurity was not independently associated with HbA 1c , diabetic ketoacidosis, and severe hypoglycemia, including in age-stratified analyses. Adolescent-reported food insecurity was independently associated with elevated odds of depressive symptoms [odds ratio (OR): 3.6; 95% confidence interval (CI): 1.3, 10.3] and disordered eating behaviors (OR: 2.5, 95% CI: 1.4, 4.6) compared with adolescents reporting food security; these associations remained in both age groups for disordered eating behaviors and in the older group for depressive symptoms., Conclusions: Adolescents with type 1 diabetes may experience food insecurity differently than caregivers. Adolescent-reported food insecurity was independently associated with depressive symptoms and disordered eating behaviors and thus may be an important attribute to assess in addition to household food security in adolescents with type 1 diabetes., (Copyright © 2023 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)