Incidence rates of childhood asthma with recurrent exacerbations in the US Environmental influences on Child Health Outcomes (ECHO) program.

BACKGROUND: Descriptive epidemiological data on incidence rates (IRs) of asthma with recurrent exacerbations (ARE) are sparse. OBJECTIVES: This study hypothesized that IRs for ARE would vary by time, geography, age, and race and ethnicity, irrespective of parental asthma history. METHODS: The investigators leveraged data from 17,246 children born after 1990 enrolled in 59 US with 1 Puerto Rican cohort in the Environmental Influences on Child Health Outcomes (ECHO) consortium to estimate IRs for ARE. RESULTS: The overall crude IR for ARE was 6.07 per 1000 person-years (95% CI: 5.63-6.51) and was highest for children aged 2-4 years, for Hispanic Black and non-Hispanic Black children, and for those with a parental history of asthma. ARE IRs were higher for 2- to 4-year-olds in each race and ethnicity category and for both sexes. Multivariable analysis confirmed higher adjusted ARE IRs (aIRRs) for children born 2000-2009 compared with those born 1990-1999 and 2010-2017, 2-4 versus 10-19 years old (aIRR = 15.36; 95% CI: 12.09-19.52), and for males versus females (aIRR = 1.34; 95% CI 1.16-1.55). Black children (non-Hispanic and Hispanic) had higher rates than non-Hispanic White children (aIRR = 2.51; 95% CI 2.10-2.99; and aIRR = 2.04; 95% CI: 1.22-3.39, respectively). Children born in the Midwest, Northeast and South had higher rates than those born in the West (P < .01 for each comparison). Children with a parental history of asthma had rates nearly 3 times higher than those without such history (aIRR = 2.90; 95% CI: 2.43-3.46). CONCLUSIONS: Factors associated with time, geography, age, race and ethnicity, sex, and parental history appear to influence the inception of ARE among children and adolescents.

The Environmental Influences on Child Health Outcomes (ECHO)-Wide Cohort.

The Environmental Influences on Child Health Outcomes (ECHO)-Wide Cohort Study (EWC), a collaborative research design comprising 69 cohorts in 31 consortia, was funded by the National Institutes of Health (NIH) in 2016 to improve children's health in the United States. The EWC harmonizes extant data and collects new data using a standardized protocol, the ECHO-Wide Cohort Data Collection Protocol (EWCP). EWCP visits occur at least once per life stage, but the frequency and timing of the visits vary across cohorts. As of March 4, 2022, the EWC cohorts contributed data from 60,553 children and consented 29,622 children for new EWCP data and biospecimen collection. The median (interquartile range) age of EWCP-enrolled children was 7.5 years (3.7-11.1). Surveys, interviews, standardized examinations, laboratory analyses, and medical record abstraction are used to obtain information in 5 main outcome areas: pre-, peri-, and postnatal outcomes; neurodevelopment; obesity; airways; and positive health. Exposures include factors at the level of place (e.g., air pollution, neighborhood socioeconomic status), family (e.g., parental mental health), and individuals (e.g., diet, genomics).

Prenatal Exposure to Per- and Polyfluoroalkyl Substances and Childhood Autism-related Outcomes.

BACKGROUND: Epidemiologic evidence linking prenatal exposure to per- and polyfluoroalkyl substances (PFAS) with altered neurodevelopment is inconclusive, and few large studies have focused on autism-related outcomes. We investigated whether blood concentrations of PFAS in pregnancy are associated with child autism-related outcomes. METHODS: We included 10 cohorts from the National Institutes of Health (NIH)-funded Environmental influences on Child Health Outcomes (ECHO) program (n = 1,429). We measured 14 PFAS analytes in maternal blood collected during pregnancy; eight analytes met detection criteria for analysis. We assessed quantitative autism-related traits in children via parent report on the Social Responsiveness Scale (SRS). In multivariable linear models, we examined relationships of each PFAS (natural log-transformed) with SRS scores. We further modeled PFAS as a complex mixture using Bayesian methods and examined modification of these relationships by child sex. RESULTS: Most PFAS in maternal blood were not associated with child SRS T-scores. Perfluorononanoic acid (PFNA) showed the strongest and most consistent association: each 1-unit increase in ln-transformed PFNA was associated with greater autism-related traits (adjusted ß [95% confidence interval (CI)] = 1.5 [-0.1, 3.0]). The summed mixture, which included six PFAS detected in >70% of participants, was not associated with SRS T-scores (adjusted ß [95% highest posterior density interval] = 0.7 [-1.4, 3.0]). We did not observe consistent evidence of sex differences. CONCLUSIONS: Prenatal blood concentrations of PFNA may be associated with modest increases in child autism-related traits. Future work should continue to examine the relationship between exposures to both legacy and emerging PFAS and additional dimensional, quantitative measures of childhood autism-related outcomes.

Impact of the COVID-19 pandemic on children's sleep habits: an ECHO study.

BACKGROUND: Sleep in childhood is affected by behavioral, environmental, and parental factors. We propose that these factors were altered during the COVID-19 pandemic. This study investigates sleep habit changes during the pandemic in 528 children 4-12 years old in the US, leveraging data from the Environmental Influences on Child Health Outcomes (ECHO) Program. METHODS: Data collection occurred in July 2019-March 2020 (pre-pandemic) and two pandemic periods: December 2020-April 2021 and May-August 2021. Qualitative interviews were performed in 38 participants. RESULTS: We found no changes in sleep duration, but a shift to later sleep midpoint during the pandemic periods. There was an increase in latency at the first pandemic collection period but no increase in the frequency of bedtime resistance, and a reduced frequency of naps during the pandemic. Qualitative interviews revealed that parents prioritized routines to maintain sleep duration but were more flexible regarding timing. Children from racial/ethnic minoritized communities slept less at night, had later sleep midpoint, and napped more frequently across all collection periods, warranting in-depth investigation to examine and address root causes. CONCLUSIONS: The COVID-19 pandemic significantly impacted children sleep, but parental knowledge of the importance of sleep might have played a significant protective role. IMPACT: During the COVID-19 pandemic, US children changed their sleep habits, going to bed and waking up later, but their sleep duration did not change. Sleep latency was longer. Parental knowledge of sleep importance might have played a protective role. Regardless of data collection periods, children from racial/ethnic minoritized communities slept less and went to bed later. This is one of the first study on this topic in the US, including prospective pre-pandemic qualitative and quantitative data on sleep habits. Our findings highlight the pandemic long-term impact on childhood sleep. Results warrants further investigations on implications for overall childhood health.

Associations between area-level arsenic exposure and adverse birth outcomes: An Echo-wide cohort analysis.

BACKGROUND: Drinking water is a common source of exposure to inorganic arsenic. In the US, the Safe Drinking Water Act (SDWA) was enacted to protect consumers from exposure to contaminants, including arsenic, in public water systems (PWS). The reproductive effects of preconception and prenatal arsenic exposure in regions with low to moderate arsenic concentrations are not well understood. OBJECTIVES: This study examined associations between preconception and prenatal exposure to arsenic violations in water, measured via residence in a county with an arsenic violation in a regulated PWS during pregnancy, and five birth outcomes: birth weight, gestational age at birth, preterm birth, small for gestational age (SGA), and large for gestational age (LGA). METHODS: Data for arsenic violations in PWS, defined as concentrations exceeding 10 parts per billion, were obtained from the Safe Drinking Water Information System. Participants of the Environmental influences on Child Health Outcomes Cohort Study were matched to arsenic violations by time and location based on residential history data. Multivariable, mixed effects regression models were used to assess the relationship between preconception and prenatal exposure to arsenic violations in drinking water and birth outcomes. RESULTS: Compared to unexposed infants, continuous exposure to arsenic from three months prior to conception through birth was associated with 88.8 g higher mean birth weight (95% CI: 8.2, 169.5), after adjusting for individual-level confounders. No statistically significant associations were observed between any preconception or prenatal violations exposure and gestational age at birth, preterm birth, SGA, or LGA. CONCLUSIONS: Our study did not identify associations between preconception and prenatal arsenic exposure, defined by drinking water exceedances, and adverse birth outcomes. Exposure to arsenic violations in drinking water was associated with higher birth weight. Future studies would benefit from more precise geodata of water system service areas, direct household drinking water measurements, and exposure biomarkers.

PFAS concentrations in early and mid-pregnancy and risk of gestational diabetes mellitus in a nested case-control study within the ethnically and racially diverse PETALS cohort.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are persistent synthetic chemicals and are commonly found in everyday items. PFAS have been linked to disrupting glucose homeostasis, however, whether they are associated with gestational diabetes mellitus (GDM) risk remains inconclusive. We examined prospective associations of PFAS concentrations measured twice in pregnancy with GDM risk. METHODS: In the PETALS pregnancy cohort, a nested case-control study which included 41 GDM cases and 87 controls was conducted. PFAS analytes were measured in blood serum collected in both early and mid-pregnancy (mean [SD]: 13.9 [2.2] and 20.2 [2.2] gestational weeks, respectively), with cumulative exposure calculated by the area-under-the-curve (AUC) to integrate both the PFAS concentration and the timing of the exposure. Individual adjusted weighted unconditional logistic regression models examined seven PFAS in association with GDM risk. P-values were corrected using the false-discovery-rate (FDR). Mixture models were analyzed with Bayesian kernel machine regression (BKMR). RESULTS: PFDA, PFNA and PFOA were individually associated with higher GDM risk per interquartile range (IQR) in early pregnancy (OR [95% CI]: 1.23 [1.09, 1.38]), 1.40 [1.24, 1.58]), and 1.15 [1.04, 1.27], respectively), mid-pregnancy (1.28 [1.15, 1.43], 1.16 [1.05, 1.28], and 1.20 [1.09, 1.33], respectively), and with cumulative exposure (1.23 [1.09, 1.38], 1.21 [1.07, 1.37], and 1.19 [1.09, 1.31], respectively). PFOS in mid-pregnancy and with cumulative exposure was associated with increased GDM risk (1.41 [1.17, 1.71] and 1.33 [1.06, 1.58], respectively). PFUnDA in early pregnancy was associated with lower GDM risk (0.79 [0.64, 0.98]), whereas mid-pregnancy levels were associated with higher risk (1.49 [1.18, 1.89]). PFHxS was associated with decreased GDM risk in early and mid-pregnancy (0.48 [0.38, 0.60] and 0.48 [0.37, 0.63], respectively) and with cumulative exposure (0.49 [0.38,0.63]). PFPeA was not associated with GDM. Similar conclusions were observed in BKMR models; however, overall associations in these models were not statistically significant. CONCLUSIONS: Higher risk of GDM was consistently observed in association with PFDA, PFNA, and PFOA exposure in both early and mid-pregnancy. Results should be corroborated in larger population-based cohorts and individuals of reproductive age should potentially avoid known sources of PFAS.

Perinatal Outcomes during versus Prior to the COVID-19 Pandemic and the Role of Maternal Depression and Perceived Stress: A Report from the ECHO Program.

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..

Cardiometabolic Pregnancy Complications in Association With Autism-Related Traits as Measured by the Social Responsiveness Scale in ECHO.

Prior work has examined associations between cardiometabolic pregnancy complications and autism spectrum disorder (ASD) but not how these complications may relate to social communication traits more broadly. We addressed this question within the Environmental Influences on Child Health Outcomes program, with 6,778 participants from 40 cohorts conducted from 1998-2021 with information on ASD-related traits via the Social Responsiveness Scale. Four metabolic pregnancy complications were examined individually, and combined, in association with Social Responsiveness Scale scores, using crude and adjusted linear regression as well as quantile regression analyses. We also examined associations stratified by ASD diagnosis, and potential mediation by preterm birth and low birth weight, and modification by child sex and enriched risk of ASD. Increases in ASD-related traits were associated with obesity (ß = 4.64, 95% confidence interval: 3.27, 6.01) and gestational diabetes (ß = 5.21, 95% confidence interval: 2.41, 8.02), specifically, but not with hypertension or preeclampsia. Results among children without ASD were similar to main analyses, but weaker among ASD cases. There was not strong evidence for mediation or modification. Results suggest that common cardiometabolic pregnancy complications may influence child ASD-related traits, not only above a diagnostic threshold relevant to ASD but also across the population.

Development and validation of prediction models for gestational diabetes treatment modality using supervised machine learning: a population-based cohort study.

BACKGROUND: Gestational diabetes (GDM) is prevalent and benefits from timely and effective treatment, given the short window to impact glycemic control. Clinicians face major barriers to choosing effectively among treatment modalities [medical nutrition therapy (MNT) with or without pharmacologic treatment (antidiabetic oral agents and/or insulin)]. We investigated whether clinical data at varied stages of pregnancy can predict GDM treatment modality. METHODS: Among a population-based cohort of 30,474 pregnancies with GDM delivered at Kaiser Permanente Northern California in 2007-2017, we selected those in 2007-2016 as the discovery set and 2017 as the temporal/future validation set. Potential predictors were extracted from electronic health records at different timepoints (levels 1-4): (1) 1-year preconception to the last menstrual period, (2) the last menstrual period to GDM diagnosis, (3) at GDM diagnosis, and (4) 1 week after GDM diagnosis. We compared transparent and ensemble machine learning prediction methods, including least absolute shrinkage and selection operator (LASSO) regression and super learner, containing classification and regression tree, LASSO regression, random forest, and extreme gradient boosting algorithms, to predict risks for pharmacologic treatment beyond MNT. RESULTS: The super learner using levels 1-4 predictors had higher predictability [tenfold cross-validated C-statistic in discovery/validation set: 0.934 (95% CI: 0.931-0.936)/0.815 (0.800-0.829)], compared to levels 1, 1-2, and 1-3 (discovery/validation set C-statistic: 0.683-0.869/0.634-0.754). A simpler, more interpretable model, including timing of GDM diagnosis, diagnostic fasting glucose value, and the status and frequency of glycemic control at fasting during one-week post diagnosis, was developed using tenfold cross-validated logistic regression based on super learner-selected predictors. This model compared to the super learner had only a modest reduction in predictability [discovery/validation set C-statistic: 0.825 (0.820-0.830)/0.798 (95% CI: 0.783-0.813)]. CONCLUSIONS: Clinical data demonstrated reasonably high predictability for GDM treatment modality at the time of GDM diagnosis and high predictability at 1-week post GDM diagnosis. These population-based, clinically oriented models may support algorithm-based risk-stratification for treatment modality, inform timely treatment, and catalyze more effective management of GDM.

The Role of Childhood Asthma in Obesity Development: A Nationwide US Multicohort Study.

RATIONALE: Asthma and obesity often co-occur. It has been hypothesized that asthma may contribute to childhood obesity onset. OBJECTIVES: To determine if childhood asthma is associated with incident obesity and examine the role of asthma medication in this association. METHODS: We studied 8,716 children between ages 6 and 18.5 years who were nonobese at study entry participating in 18 US cohorts of the Environmental influences on Child Health Outcomes program (among 7,299 children with complete covariate data mean [SD] study entry age = 7.2 [1.6] years and follow up = 5.3 [3.1] years). MEASUREMENTS AND MAIN RESULTS: We defined asthma based on caregiver report of provider diagnosis. Incident obesity was defined as the first documented body mass index ≥95th percentile for age and sex following asthma status ascertainment. Over the study period, 26% of children had an asthma diagnosis and 11% developed obesity. Cox proportional hazards models with sex-specific baseline hazards were fitted to assess the association of asthma diagnosis with obesity incidence. Children with asthma had a 23% (95% confidence intervals [CI] = 4, 44) higher risk for subsequently developing obesity compared with those without asthma. A novel mediation analysis was also conducted to decompose the total asthma effect on obesity into pathways mediated and not mediated by asthma medication use. Use of asthma medication attenuated the total estimated effect of asthma on obesity by 64% (excess hazard ratios = 0.64; 95% CI = -1.05, -0.23). CONCLUSIONS: This nationwide study supports the hypothesis that childhood asthma is associated with later risk of obesity. Asthma medication may reduce this association and merits further investigation as a potential strategy for obesity prevention among children with asthma.

Associations between infant growth and pubertal onset timing in a multiethnic prospective cohort of girls.

BACKGROUND: Early puberty increases risk of adverse health conditions throughout the life course. US girls are experiencing earlier puberty without clear reasons. Studies suggest early life factors, such as infant growth, may influence pubertal timing. We assessed the associations between infant growth and onset of breast development (thelarche), pubic hair development (pubarche), and menarche in girls. METHODS: A prospective cohort of girls born at a Kaiser Permanente Northern California medical facility in 2005-11 was used. Weight-for-age z-scores were calculated at birth and 24 months. Difference in z-scores greater than 0.67 represent rapid "catch-up" growth, less than -0.67 represent delayed "catch-down" growth, and between -0.67 and 0.67 represent "normal" growth. Pubertal onset was measured using clinician-assessed sexual maturity ratings (SMRs) and defined as the age at transition from SMR 1 to SMR 2 + for both thelarche and pubarche. SMR data was collected through June 2020. Menarche was analyzed as a secondary outcome. Weibull and modified Poisson regression models were used. Models were adjusted for potential confounders. RESULTS: There were 15,196 girls included in the study. Approximately 30.2% experienced catch-up growth, 25.8% experienced catch-down growth, and 44% had normal growth. Girls with catch-up growth had increased risk of earlier thelarche (hazard ratio = 1.26, 95% confidence interval (CI): 1.18, 1.35), pubarche (1.38, 95% CI: 1.28, 1.48), and menarche (< 12y, relative risk = 1.52, 95% CI: 1.36, 1.69) compared to those with normal growth, after adjusting for covariates. These associations were partially mediated by childhood body mass index. Catch-down growth was associated with later pubertal onset. CONCLUSIONS: Girls who experience infant catch-up growth have higher risk of earlier pubertal development compared to girls with normal growth and the associations are partially explained by childhood obesity. This information may help clinicians to monitor girls who are at high risk of developing earlier.

Impaired Fasting Glucose in Pregnancy: Improved Perinatal Outcomes with Active Glycemic Management.

OBJECTIVE: This study aimed to assess the association between active glycemic management and large for gestational age (LGA) neonates and cesarean delivery (CD) among pregnant women with impaired fasting glucose (IFG). STUDY DESIGN: Retrospective cohort study using electronic health record data of women with IFG who delivered at the Kaiser Permanente Northern California from 2012 to 2017. IFG was defined as isolated fasting glucose ≥95 mg/dL. Women with gestational diabetes mellitus (GDM) or in whom GDM could not be ruled out were excluded. Baseline and treatment characteristics, and pregnancy outcomes were compared among women with IFG who participated in telephonic home glucose monitoring and glycemic management through a centralized standardized program (participants) with those who did not participate (nonparticipants). The relative risks (RRs) of perinatal complications associated with participation versus nonparticipation were estimated with Poisson's regression models. RESULTS: We identified 1,584 women meeting inclusion criteria of whom 1,151 (72.7%) were participants and 433 (27.3%) were nonparticipants. There were no differences between groups in baseline characteristics or comorbidities, except for higher mean levels of fasting glucose (FG) at the time of IFG diagnosis in participants than in nonparticipants (98.9 vs. 98.0 mg/dL, p = 0.01). Participants received hypoglycemic medications more frequently than nonparticipants (68.2 vs. 0.9%, p < 0.01). The rate of LGA was significantly lower in participants compared with nonparticipants (19.1 vs. 25.0%, p = 0.01). After adjusting for age, race/ethnicity, education, body mass index, and level of FG impairment, the RR for LGA for participants compared with nonparticipants was 0.68, 95% CI: 0.55-0.84. The risk of CD did not differ significantly by participation status, in unadjusted or adjusted analyses. CONCLUSION: Active standardized glycemic management was associated with a decreased risk of LGA for women with IFG. This finding supports an active glycemic management strategy for patients with IFG during pregnancy to reduce the risk of LGA, similar to GDM management. KEY POINTS: · Pregnant women with IFG have increased rates of LGA.. · Active management of IFG is associated with a decreased LGA.. · Treatment of IFG like GDM may improve perinatal outcomes..

Improving clinical utility of GAD65 autoantibodies by electrochemiluminescence assay and clinical phenotype when identifying autoimmune adult-onset diabetes.

AIMS/HYPOTHESIS: It is important to differentiate the two major phenotypes of adult-onset diabetes, autoimmune type 1 diabetes and non-autoimmune type 2 diabetes, especially as type 1 diabetes presents in adulthood. Serum GAD65 autoantibodies (GADA) are the most sensitive biomarker for adult-onset autoimmune type 1 diabetes, but the clinical value of GADA by current standard radiobinding assays (RBA) remains questionable. The present study focused on the clinical utility of GADA differentiated by a new electrochemiluminescence (ECL) assay in patients with adult-onset diabetes. METHODS: Two cohorts were analysed including 771 diabetic participants, 30-70 years old, from the Action LADA study (n = 6156), and 2063 diabetic participants, 20-45 years old, from the Diabetes in Young Adults (DiYA) study. Clinical characteristics of participants, including requirement of early insulin treatment, BMI and development of multiple islet autoantibodies, were analysed according to the status of RBA-GADA and ECL-GADA, respectively, and compared between these two assays. RESULTS: GADA was the most prevalent and predominant autoantibody, >90% in both cohorts. GADA positivity by either RBA or ECL assay significantly discriminated clinical type 1 from type 2 diabetes. However, in both cohorts, participants with ECL-GADA positivity were more likely to require early insulin treatment, have multiple islet autoantibodies, and be less overweight (for all p < 0.0001). However, clinical phenotype, age at diagnosis and BMI independently improved positive predictive value (PPV) for the requirement of insulin treatment, even augmenting ECL-GADA. Participants with GADA detectable by RBA, but not confirmed by ECL, had a phenotype more similar to type 2 diabetes. These RBA-GADA positive individuals had lower affinity GADA compared with participants in which GADA was confirmed by ECL assay. CONCLUSIONS/INTERPRETATION: Detection of GADA by ECL assay, given technical advantages over RBA-GADA, identified adult-onset diabetes patients at higher risk of requiring early insulin treatment, as did clinical phenotype, together allowing for more accurate clinical diagnosis and management.

Exercise During the First Trimester and Infant Size at Birth: Targeted Maximum Likelihood Estimation of the Causal Risk Difference.

This cohort study sought to estimate the differences in risk of delivering infants who were small or large for gestational age (SGA or LGA, respectively) according to exercise during the first trimester of pregnancy (vs. no exercise) among 2,286 women receiving care at Kaiser Permanente Northern California in 2013-2017. Exercise was assessed by questionnaire. SGA and LGA were determined by the sex- and gestational-age-specific birthweight distributions of the 2017 US Natality file. Risk differences were estimated by targeted maximum likelihood estimation, with and without data-adaptive prediction (machine learning). Analyses were also stratified by prepregnancy weight status. Overall, exercise at the cohort-specific 75th percentile was associated with an increased risk of SGA of 4.5 (95% CI: 2.1, 6.8) per 100 births, and decreased risk of LGA of 2.8 (95% CI: 0.5, 5.1) per 100 births; similar findings were observed among the underweight and normal-weight women, but no associations were found among those with overweight or obesity. Meeting Physical Activity Guidelines was associated with increased risk of SGA and decreased risk of LGA but only among underweight and normal-weight women. Any vigorous exercise reduced the risk of LGA in underweight and normal-weight women only and was not associated with SGA risk.

Understanding childhood obesity in the US: the NIH environmental influences on child health outcomes (ECHO) program.

BACKGROUND: Few resources exist for prospective, longitudinal analysis of the relationships between early life environment and later obesity in large diverse samples of children in the United States (US). In 2016, the National Institutes of Health launched the Environmental influences on Child Health Outcomes (ECHO) program to investigate influences of environmental exposures on child health and development. We describe demographics and overweight and obesity prevalence in ECHO, and ECHO's potential as a resource for understanding how early life environmental factors affect obesity risk. METHODS: In this cross-sectional study of 70 extant US and Puerto Rico cohorts, 2003-2017, we examined age, race/ethnicity, and sex in children with body mass index (BMI) data, including 28,507 full-term post-birth to <2 years and 38,332 aged 2-18 years. Main outcomes included high BMI for age <2 years, and at 2-18 years overweight (BMI 85th to <95th percentile), obesity (BMI ≥ 95th percentile), and severe obesity (BMI ≥ 120% of 95th percentile). RESULTS: The study population had diverse race/ethnicity and maternal demographics. Each outcome was more common with increasing age and varied with race/ethnicity. High BMI prevalence (95% CI) was 4.7% (3.5, 6.0) <1 year, and 10.6% (7.4, 13.7) for 1 to <2 years; overweight prevalence increased from 13.9% (12.4, 15.9) at 2-3 years to 19.9% (11.7, 28.2) at 12 to <18 years. ECHO has the statistical power to detect relative risks for 'high' BMI ranging from 1.2 to 2.2 for a wide range of exposure prevalences (1-50%) within each age group. CONCLUSIONS: ECHO is a powerful resource for understanding influences of chemical, biological, social, natural, and built environments on onset and trajectories of obesity in US children. The large sample size of ECHO cohorts adopting a standardized protocol for new data collection of varied exposures along with longitudinal assessments will allow refined analyses to identify drivers of childhood obesity.

Comparative Effectiveness of 2 Diabetes Prevention Lifestyle Programs in the Workplace: The City and County of San Francisco Diabetes Prevention Trial.

INTRODUCTION: Data on the comparative effectiveness of Diabetes Prevention Programs (DPPs) in the workplace are limited. METHODS: Between September 2015 and July 2016, employees of the City and County of San Francisco who were at risk for type 2 diabetes (N = 158) were randomly assigned to one of 2 DPP-derived programs recognized by the Centers for Disease Control and Prevention: an in-person YMCA-DPP (n = 78) or an online virtual lifestyle management DPP (VLM-DPP) offered through Canary Health (n = 80). The primary outcome was change in body weight assessed at 6 and 12 months. Follow-up ended in August 2017. RESULTS: Both the YMCA-DPP and VLM-DPP yielded a significant reduction in percentage body weight at 6 months. For the YMCA-DPP, mean percentage change at 6 months was -2.70% (95% confidence interval [CI], -3.91% to -1.48%) and at 12 months was -2.46% (95% CI, -4.24% to -0.68%). For the VLM-DPP, mean percentage change at 6 months was -2.41% (95% CI, -4.07% to -0.77%) and at 12 months was -1.59% (95% CI, -3.51% to 0.33%). The mean between-condition difference at 6 months was -0.25% (95% CI, -2.04% to 1.55%) and at 12 months was -0.84% (95% CI, -3.03% to 1.34%). No significant differences were observed between conditions. The YMCA-DPP had a slightly higher reduction in waist circumference than VLM-DDP at 6 months (mean between-condition difference -2.00 cm [95% CI, -4.24 to 0.25 cm]). Participant engagement, expressed as mean number of completed core program sessions, was significantly higher for the YMCA-DPP than the VLM-DPP. Participants of the YMCA-DPP completed an average of 10.2 sessions (95% CI, 9.0 to 11.4), and participants of the VLM-DPP completed an average of 5.9 sessions (95% CI, 4.7 to 7.1). The adjusted mean between-condition difference was 4.2 sessions (95% CI, 2.54 to 5.99). CONCLUSION: Both the YMCA-DPP and VLM-DPP yielded weight loss at 6 months, which was maintained at 12 months in the YMCA-DPP. The workplace may be an effective setting to offer DPPs.

Plasma phospholipid n-3 and n-6 polyunsaturated fatty acids in relation to cardiometabolic markers and gestational diabetes: A longitudinal study within the prospective NICHD Fetal Growth Studies.

BACKGROUND: Despite dietary recommendations of polyunsaturated fatty acids (PUFAs) for cardiometabolic health, n-3 and n-6 PUFAs and their interplay in relation to diabetes risk remain debated. Importantly, data among pregnant women are scarce. We investigated individual plasma phospholipid n-3 and n-6 PUFAs in early to midpregnancy in relation to subsequent risk of gestational diabetes mellitus (GDM). METHODS AND FINDINGS: Within the National Institute of Child Health and Human Development (NICHD) Fetal Growth Studies-Singleton Cohort (n = 2,802), individual plasma phospholipid n-3 and n-6 PUFAs levels were measured at gestational weeks (GWs) 10-14, 15-26, 23-31, and 33-39 among 107 GDM cases (ascertained on average at GW 27) and 214 non-GDM controls. Conditional logistic regression was used, adjusting for major risk factors for GDM. After adjusting for covariates, individual n-3 eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA) were inversely correlated with insulin-resistance markers, whereas individual n-6 dihomo-gamma-linolenic acid (DGLA) was positively correlated with insulin-resistance markers. At GW 15-26, a standard deviation (SD) increase in total n-3 PUFAs and individual n-3 DPA was associated with a 36% (adjusted odds ratio 0.64; 95% CI 0.42-0.96; P = 0.042) and 33% (0.67; 95% CI 0.45-0.99; P = 0.047) lower risk of GDM, respectively; however, the significance did not persist after post hoc false-discovery rate (FDR) correction (FDR-corrected P values > 0.05). Associations between total n-6 PUFAs and GDM were null, whereas associations with individual n-6 PUFAs were differential. Per SD increase, gamma-linolenic acid (GLA) at GWs 10-14 and DGLA at GWs 10-14 and 15-26 were significantly associated with a 1.40- to 1.95-fold higher risk of GDM, whereas docosatetraenoic acid (DTA) at GW 15-26 was associated with a 45% (0.55; 95% CI 0.37-0.83) lower risk of GDM (all FDR-corrected P values < 0.05). Null associations were observed for linoleic acid (LA) in either gestational window in relation to risk of GDM. Women with high (≥median) n-3 PUFAs and low (

Associations of Maternal Gestational Weight Gain and Obesity With the Timing of Pubertal Onset in Daughters.

Early puberty is associated with adverse health outcomes, but little is known regarding early-life determinants influencing pubertal timing. We examined the associations between maternal gestational weight gain (GWG) and the timing of the onset of breast development (thelarche) and pubic hair development (pubarche) in a cohort of 2,070 girls born in a Kaiser Permanente Northern California facility between 2005 and 2006. Using Weibull regression models accommodating interval censoring and adjusting for important confounders, we found that excess GWG was associated with increased risk of early thelarche (hazard ratio (HR) = 1.50, 95% confidence interval (CI): 1.26, 1.78) and early pubarche (HR = 1.35, 95% CI: 1.10, 1.66). Inadequate GWG was associated with early thelarche (HR = 1.36, 95% CI: 1.08, 1.71). The associations between excess or inadequate GWG and risk of earlier thelarche were stronger if mothers were obese before or at the beginning of pregnancy (body mass index ≥30 kg body weight per m height squared) (HR = 2.01, 95% CI: 1.53, 2.63; HR = 2.08, 95% CI: 1.45, 2.98, respectively). Similar associations were found for pubarche outcome. Inclusion of girls' prepubertal body mass index slightly attenuated these associations, but they remained significant. Monitoring of maternal weight before and throughout pregnancy might help prevent early pubertal onset and subsequent negative health outcomes.

A Randomized Study of Values Affirmation to Promote Interest in Diabetes Prevention Among Women With a History of Gestational Diabetes.

OBJECTIVE: The objective of this study was to test whether 2 interventions promote interest in diabetes prevention among women with a history of gestational diabetes mellitus, who face high lifetime risk for diabetes. RESEARCH DESIGN AND METHODS: We designed an email outreach message promoting an existing preventive lifestyle program. The message incorporated values affirmation, a theory-based intervention that can improve openness to health information but typically relies on a writing exercise less practical in health care settings. In a 3-arm randomized study, 237 women with elevated body mass index and a history of gestational diabetes mellitus were randomized to read an outreach message containing either no affirmation (control) or 1 of 2 affirmations, streamlined to remove the typical writing exercise: either a values affirmation prompting reflection on any personal value, or a parenting affirmation prompting reflection on caregiving-related values. Outcomes included demonstrating interest in the lifestyle program (seeking information about it or intending to join) and seeking publicly-available health information about diabetes prevention. RESULTS: Compared with control, participants randomized to the values affirmation more frequently demonstrated interest in the lifestyle program (59.0% vs. 74.4%; adjusted relative risk: 1.31; 95% confidence interval: 1.04-1.66) and sought information about diabetes prevention (59.0% vs. 73.4%; adjusted relative risk: 1.22; 95% confidence interval: 0.97-1.54). The parenting affirmation yielded no significant differences in either outcome. CONCLUSIONS: A streamlined values affirmation, designed for feasibility in a health care setting, can promote interest in diabetes prevention among women at high risk. Research is needed to evaluate its effects on diabetes prevention program enrollment and clinical outcomes.

Gestational weight gain and optimal wellness (GLOW): rationale and methods for a randomized controlled trial of a lifestyle intervention among pregnant women with overweight or obesity.

BACKGROUND: Excess gestational weight gain (GWG) is common among women with overweight or obesity, increasing their risks for pregnancy complications, delivering a large infant, and postpartum weight retention. To date, only intensive interventions have had success and few interventions have been designed for implementation in healthcare settings. METHODS: We describe the development, rationale, and methods of GLOW (GestationaL Weight Gain and Optimal Wellness), a randomized controlled trial evaluating the efficacy of a lifestyle intervention to prevent excess GWG among racially/ethnically diverse women with overweight or obesity in an integrated healthcare delivery system. Participants in Kaiser Permanente Northern California will be randomized, within 2 weeks of completing a study baseline clinic visit at 10 weeks' gestation, to either usual medical care or a multi-component pregnancy lifestyle intervention adapted from the Diabetes Prevention Program (target N = 400). Informed by focus groups with patients and designed to be feasible in a clinical setting, the intervention will include 13 weekly individual sessions (11 delivered by telephone) focused on behavior change for weight management, healthy eating, physical activity, and stress management. Outcomes will be assessed in women and their infants from randomization to 12 months postpartum. The primary outcome is GWG. Secondary outcomes include changes in diet and physical activity during pregnancy and infant birthweight. Exploratory outcomes include cardiometabolic profile assessed via pregnancy blood samples and cord blood samples; and postpartum weight retention and infant anthropometrics up to 12 months of age. The trial includes systematic approaches to enhance intervention fidelity, intervention adherence, and participant retention in trial assessments. DISCUSSION: GLOW is among few trials targeting excess GWG among diverse women with overweight or obesity in a healthcare setting, with long-term maternal and infant outcomes assessed up to 12 months after delivery. This evaluation of a multi-component intervention is designed to produce generalizable results to inform potential adoption of the intervention in clinical settings. TRIAL REGISTRATION: ClinicalTrials.gov ( NCT02130232 ): submitted April 30, 2014; posted May 5, 2014.