Cow’s milk is an important source of nutrients supporting human growth and development as well as adult health, but it can be associated with unwanted gastrointestinal (GI) symptoms. These symptoms are often attributed to lactose, but may instead be partly due to peptides released during digestion. This exploratory study aimed to compare the effects of consuming milk free of A1-type beta-casein (A1PF milk) with those of conventional cow’s milk (containing both A1- and A2-types of beta-casein) on GI symptoms in individuals who usually suffer from mild-to-moderate digestive discomfort after milk consumption. This was a single-site, double-blind, randomised, controlled, crossover study in non-regular milk drinkers (aged 18–68 years) with self-reported intolerance to cow’s milk. Participants consumed either A1PF milk or conventional milk three times per day after meals. GI symptoms, GI parameters (assessed using a SmartPill™ ingestible sensor) and blood and faecal laboratory measurements were assessed. No statistically significant between-group differences were seen in the frequency and consistency of stool; overall and individual GI symptoms; in GI parameters, including transit time; or in laboratory measurements including immunoglobulin (Ig)G, IgE, IgG1, interleukin-4, acetate, butyrate, propionate, short-chain fatty acid levels, or thiol levels. Among participants consuming A1PF milk, higher urinary galactose (U-gal) levels were correlated with smaller increases from baseline in patient-reported abdominal pain (r = − 0.296, p < 0.05); this correlation was not observed in participants consuming conventional milk. Additionally, higher U-gal levels were correlated with a greater increase in gastric transit time (r = 0.409, p < 0.05) and with a greater increase in glutathione level (r = 0.314, p < 0.05) only in participants consuming A1PF milk, but not in those consuming conventional milk. Significant correlations between higher U-gal values and changes in GI variables were seen in participants consuming A1PF milk, including increased glutathione, a smaller increase from baseline in abdominal pain, and a greater increase in gastric transit time. In terms of GI symptoms, individuals with higher baseline U-gal levels (indicating preserved lactase activity) may benefit from A1PF milk more than those with lower baseline U-gal levels. NCT06763185.

Introduction Underserved pregnant individuals experience high risk for weight gain outside clinical guidelines and adverse perinatal outcomes. The Women, Infants, and Children (WIC) federal program assists underserved pregnant individuals with supplemental nutrition. WIC is positioned to disseminate interventions promoting recommended gestational weight gain, increasing access to efficacious programs and complementing clinical care. Methods Pregnant WIC participants were randomly assigned (2019-2023) to a co-developed multicomponent e-health intervention for gestational weight gain management or usual care between 10 and 16 weeks gestation. The primary outcome (analyzed 2025) was gestational weight gain guideline attainment. Secondary weight outcomes included study-observed weight gain, weekly weight gain, deviation from guidelines, fat mass gain, and change in energy balance behaviors. Adverse perinatal outcomes were exploratory. Results Pregnant participants (n=351; 57% non-Hispanic Black) were enrolled (179 Intervention; 172 Usual Care) across 31 WIC clinics. The incidence of guideline attainment was not different between groups (both groups 17%; adjusted odds ratio, 1.05; 95% CI, 0.55 to 2.01; P=0.89). Study-observed weight gain (adjusted mean difference, -1.4 kg; 95% CI, -2.8 to -0.1; P=0.04), rate of weight gain (-0.07 kg/wk; 95% CI, -0.13 to -0.01; P=0.02), deviation from guidelines (-0.05 kg/wk; 95% CI, -0.10 to -0.00; P=0.03), and fat mass gain (-1.3 kg; 95% CI, -2.1 to -0.6; P<0.001) were lower in the Intervention Group compared to Usual Care. Change in energy intake was lower in the Intervention Group (306 kcals/day; 95% CI, -500 to -112; P=0.002). There were 43 cases (9% Intervention, 16% Usual Care) of preterm birth and 30 NICU admissions (7% Intervention, 11% Usual Care). Conclusions A remotely delivered lifestyle intervention concomitant with WIC care reduced gestational weight and fat mass gain. This approach demonstrates the potential for scalable interventions integrated into existing public health systems to expand access and inform public health strategies targeting maternal health disparities. Trial Registration Trial registration: This study is registered at www.ClinicalTrials.gov NCT04028843

Importance:Millions of children worldwide are experiencing prolonged symptoms after SARS-CoV-2 infection, yet social risk factors for developing long COVID are largely unknown. As child health is influenced by the environment in which they live and interact, adverse social determinants of health (SDOH) may contribute to the development of pediatric long COVID. Objective:To identify whether adverse SDOH are associated with increased odds of long COVID in school-aged children and adolescents in the US. Design, Setting, and Participants:This cross-sectional analysis of a multicenter, longitudinal, meta-cohort study encompassed 52 sites (health care and community settings) across the US. School-aged children (6-11 years; n = 903) and adolescents (12-17 years; n = 3681) with SARS-CoV-2 infection history were included. Those with an unknown date of first infection, history of multisystem inflammatory syndrome in children, or symptom surveys with less than 50% of questions completed were excluded. Participants were recruited via health care systems, long COVID clinics, fliers, websites, social media campaigns, radio, health fairs, community-based organizations, community health workers, and existing research cohorts from March 2022 to August 2024, and surveys were completed by caregivers between March 2022 and August 2024. Exposure:Twenty-four individual social determinant of health factors were grouped into 5 Healthy People 2030 domains: economic stability, social and community context, caregiver education access and quality, neighborhood and built environment, and health care access and quality. Latent classes were created within each domain and used in regression models. Main Outcomes and Measures:Presence of long COVID using caregiver-reported, symptom-based, age-specific research indices. Results:The mean (SD) age among 4584 individuals included in this study was 14 (3) years, and 2330 (51%) of participants were male. The number of latent classes varied by domain; the reference group was the class with the least adversity. In unadjusted analyses, most classes in each domain were associated with higher odds of long COVID. After adjusting for many factors, including age group, sex, timing of infection, referral source, and other social determinant of health domains, economic instability characterized by difficulty covering expenses, poverty, receipt of government assistance, and food insecurity were associated with an increased risk of having long COVID (class 2 adjusted odds ratio [aOR], 1.57; 95% CI, 1.18-2.09; class 4 aOR, 2.39; 95% CI, 1.73-3.30); economic instability without food insecurity (class 3) was not (aOR, 0.93; 95% CI, 0.70-1.23). Poorer social and community context (eg, high levels of discrimination and low social support) was also associated with long COVID (aOR, 2.17; 95% CI, 1.77-2.66). Sensitivity analyses stratified by age group and adjusted for race and ethnicity did not alter or attenuate these results. Conclusions and Relevance:In this study, economic instability that included food insecurity and poor social and community context were associated with greater odds of pediatric long COVID. Those with food security, despite experiencing other economic challenges, did not have greater odds of long COVID. Further study is needed to determine if addressing SDOH factors can decrease the rate of pediatric long COVID.

Introduction and Objective: Although certain glucagon-like peptide-1 receptor agonists (GLP1RA) are approved for the treatment of youth with Type 2 Diabetes Mellitus or obesity in the United States, they are increasingly used in youth with Type 1 Diabetes Mellitus (T1D) with obesity or insulin resistance at our center. We sought to understand the effects of GLP1RA use in these youth. Methods: This retrospective observational cohort study identified youth with T1D who were prescribed GLP1RA between January 1, 2019 and December 31, 2025 with at least one follow up visit. Clinical outcomes between baseline to the last visit on treatment were compared for a maximum of 4 follow up visits. Medians and interquartile ranges (IQR) were reported. Results: Eighteen patients were identified. GLP1RAs prescribed were semaglutide and liraglutide, median age at baseline was 16.65 years (IQR 15.66, 18.22), and 78% had private insurance. The median time for follow up was 283.5 days (IQR 168, 378). The median change in hemoglobin A1c (A1c) was -0.60% (-1.00, -0.20), basal insulin dose was -10.10 units (-14.50, -0.90), and body mass index (BMI) was -2.00 (-3.16, -1.05). More outcomes are included in Table 1. Conclusion: GLP1RA use in youth with T1D resulted in clinically meaningful decreases in A1c, basal insulin dose, and BMI. Prospective data in larger cohorts are needed to better understand the effectiveness of GLP1RA use in this population and risk for hypoglycemia. Disclosure E. Choi: None. A. Jergel: None. K. Cossen: None. D.S. Hsia: Advisory Panel; Current; Eli Lilly and Company. Other - I conduct clinical trials under agreements between this company and my institution.; Current; Eli Lilly and Company, Novo Nordisk.

Research shows that dietary interventions improve biomarkers of health span and aging. This paper describes the implementation and data collection methods for 4 dietary interventions and a control condition comprising the 5 arms of the Dietary Approaches to Longevity and Health (DiAL Health) Pilot study. DiAL Health is a 24-wk, randomized controlled pilot trial comparing the feasibility and preliminary efficacy of traditional and adaptive approaches to calorie restriction (CR) and time-restricted eating (TRE) on biomarkers of biological aging and health span in young, healthy adults [age: 25–49 y, body mass index (BMI): 22.0–29.9 kg/m2]. To our knowledge, this is one of the first studies to examine the effects of both CR and TRE against a usual diet and will generate preliminary data to inform a larger, longer-term comparative trial. The 2 CR arms of DiAL Health target 25% CR, whereas the 2 TRE arms promote ad libitum food intake within an 8-h daily window. Traditional CR and TRE arms will receive established interventions. The corresponding adaptive arms will receive Just-in-Time Adaptive Interventions that leverage mobile health technologies to adjust behavior and facilitate adherence with real-time or near-real-time feedback and support. Using a validated mathematical model, weight loss nomograms with measurements from internet-connected smart scales will be used to monitor dietary adherence in the adaptive CR arm. Feedograms with eating events populated by continuous glucose monitoring (CGM), the Remote Food Photography Method/SmartIntake app, and manual entry by counselors and participants will be used to monitor meal timing adherence in the adaptive TRE arm. Integration of CGM will support passive, automated detection of meal timing and eating behavior, potentially reducing reliance on self-reported measures. Findings from the DiAL Health Pilot study will inform the design and implementation of a future 5-y clinical trial evaluating personalized dietary strategies to promote longevity and improve health span.This trial was registered at clinicaltrials.gov as NCT05549362.

OBJECTIVE:To (1) describe foods offered to children and their plate waste, (2) assess how foods offered compare to the 2020 Dietary Guidelines for Americans (DGA-2020), and (3) compare foods offered with foods consumed. METHODS:We conducted a 3-day assessment with the remote food photography method (RFPM) among 38 child-caregiver dyads. Variables measured were energy, nutrients, and Healthy Eating Index-2020 scores for foods offered, consumed, and remaining as plate waste. Linear mixed models examined differences between foods offered, recommended intakes, and foods consumed. RESULTS:Foods offered exceeded the DGA-2020 (difference) for sodium (1,034.5 mg), saturated fat (2%), and added sugars (11%), and did not meet the minimum DGA-2020 threshold for fiber (-5.18 g) and calcium (-228.7 mg). Foods offered had a Healthy Eating Index-2020 score 1.3 units higher than the score of foods consumed. CONCLUSIONS AND IMPLICATIONS:Interventions that target improvements in the quality of foods offered to children are needed.

BackgroundHousehold chaos is an emerging risk factor for childhood obesity development, especially in families with lower socioeconomic status (SES). It is unclear if changes in household chaos, especially in pregnancy, may mediate the effectiveness of weight-related behavioral interventions. ObjectiveThis study aimed to describe how household chaos changed across gestation and determine whether household chaos mediated the effect of an eHealth behavioral gestational weight gain (GWG) intervention in pregnant people with low SES. MethodsPregnant people who were enrolled in the US Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) were recruited for a randomized controlled trial testing the effectiveness of an eHealth-based pragmatic intervention for GWG management. The usual care group received the standard WIC program guidance and monthly health coach support with general pregnancy recommendations. The intervention group received the standard WIC program plus health information via email and weekly health coach discussions to promote healthy eating and adequate physical activity. Weight and household chaos were measured at baseline (early pregnancy, 10+0 to 16+6 weeks gestation) and at the end of the intervention (late pregnancy, 35+0 to 37+6 weeks gestation). Household chaos changes across time were examined using a paired t test for the continuous score and using the McNemar test for household chaos category (improved or no change vs declined). Serial linear regression models and mediation analyses assessed the relationship between the intervention group (predictor), household chaos change (mediator), and GWG (outcome) with adjustment for covariates. ResultsAmong 258 participants, 53.9% (n=139) were Black, 43.4% (n=112) were nulliparous, 36.0% (n=93) were obese, and almost half (n=124, 48.1%) were classified as low household chaos at baseline. Overall, there were minimal changes in household chaos scores from early to late pregnancy (P=.34), although scores and categories tended to be higher in late pregnancy. Household chaos changes were divided; some improved or had no change (n=140, 54.3%), and some declined (n=118, 45.7%) across gestation. Household chaos did not mediate the effect of the intervention on GWG. ConclusionsIn this sample, household chaos did not change across gestation and did not explain the effect of an eHealth behavioral GWG intervention in pregnant people with lower SES. Routine-focused and multilevel interventions may improve upon these findings to support an organized home for future parent and child health. Trial RegistrationClinicalTrials.gov NCT04028843; https://www.clinicaltrials.gov/study/NCT04028843

Background Calorie restriction (CR) and time-restricted eating (TRE) consistently improve biomarkers of aging and health span, yet long-term adherence to these dietary strategies remains difficult. Technology-enabled approaches, including just-in-time adaptive interventions (JITAIs), may facilitate greater engagement by delivering personalized support in response to an individual’s real-time behavior and circumstances. Objectives The Dietary Approaches to Longevity and Health (DiAL Health) pilot trial is designed to evaluate the feasibility, acceptability, and preliminary efficacy of adaptive (JITAI-supported) compared with traditional implementations of CR and TRE and to identify outcome measures suitable for larger, long-term intervention studies. Methods This 24-wk, parallel-arm, randomized controlled pilot trial will enroll 90 healthy adults aged 22 to 45 y with a BMI of 22.0 to 29.9 kg/m2 into 1 of 5 groups: nonintervention control, traditional or adaptive TRE with an 8-h eating window, and traditional or adaptive CR targeting a 25% reduction in energy intake. Traditional interventions will emphasize in-person counseling, whereas adaptive interventions will be supported by mobile health (mHealth) technology and incorporate remote monitoring via digital tools and JITAI-based feedback to quantify eating behaviors in real time and deliver tailored adherence prompts. Results Primary feasibility outcomes include adherence, retention, and participant satisfaction. Secondary outcomes to assess preliminary clinical efficacy include Klemera–Doubal as a composite measure of biological age and the metabolic syndrome score as a marker of health span. Additional measures including patient-reported outcomes and hallmarks of aging will be collected as exploratory outcomes. Effect sizes will be estimated to guide the selection of primary end points for future large-scale trials. Conclusions The DiAL Health pilot trial will provide essential data on the comparative feasibility and potential efficacy of adaptive with those of traditional dietary strategies, informing the development of scalable interventions aimed at improving health span and delaying biological aging.This trial was registered at clinicaltrials.gov as NCT05549362.

OBJECTIVE:To evaluate the feasibility of a multi-state randomized control trial (RCT) evaluating iAmHealthy, a rurally tailored pediatric obesity treatment delivered via synchronous televideo. This study's primary outcomes included the evaluation of participant retention and the efficacy of blinding. Each intervention arm was hypothesized to retain >75% of randomized participants and preserve blinding. Additionally, the intervention's preliminary effectiveness was evaluated by comparing changes in health outcomes. METHODS:Youth aged 6-11 years with a body mass index (BMI) percentile ≥85th and their caregivers were recruited from rural communities across four states participating in the Environmental Influences on Child Health Outcomes IDeA States Pediatric Clinical Trials Network. One hundred four dyads were randomly assigned to iAmHealthy plus newsletter or newsletter-only control. Retention rates for each treatment arm were calculated. Blinding was assessed via the New Blinding Index (NBI). Child and parent BMI, child physical activity, and child dietary intake were assessed at baseline and post-treatment (6 months). RESULTS:A one-sample test of proportions indicated retention rates exceeded 75% for iAmHealthy (87%, p = .027) and control (96%, p < .001). Blinding was successful for both groups [iAmHealthy NBI = -0.12, 95% confidence interval (CI): -0.13 to 0.36; control NBI = 0.02, 95% CI: -0.24 to 0.28]. There were no significant differences in health outcomes. CONCLUSIONS:This iAmHealthy multi-state feasibility RCT demonstrated high retention and successful blinding of assessors. Although the study was not powered to detect health outcome differences, iAmHealthy exhibited a tendency toward greater improvement or attenuated declines in child health outcomes, which supports the conduct of a future fully powered RCT. CLINICALTRIALS.GOV IDENTIFIER:NCT04142034, Registered: 10-25-2019; Trial name: Feasibility Trial of the iAmHealthy Intervention; https://clinicaltrials.gov/study/NCT04142034?cond=iamhealthy&checkSpell=false&rank=1.

There is an unmet need for pharmacological therapies for children with type 2 diabetes mellitus (T2DM). We assessed the efficacy and safety of an oral dipeptidyl peptidase-4 inhibitor, alogliptin, 25 mg once daily (QD), as a potential treatment for pediatric patients with T2DM. This phase 3, 52-week, multicenter, randomized, double-blind, placebo-controlled trial was conducted in children and adolescents (10–17 years old) with T2DM. Participants had glycosylated hemoglobin (HbA1c) ≥ 6.5

BACKGROUND:The advent of highly effective pharmacotherapy that induces significant weight loss has revolutionized the treatment of obesity. Since 2020, these medications have been approved for use in children with obesity 12 years of age and older, and the American Academy of Pediatrics 2023 Clinical Practice Guidelines have endorsed their use. SOURCES OF MATERIAL:Specifically, glucagon-like peptide 1 (GLP-1) agonists and similar related nutrient stimulated hormones induce weight loss of >15% of baseline body weight in clinical trials. ABSTRACT OF FINDINGS:However, these benefits must be balanced with the known side effects and other potential unknown effects especially in growing children and adolescents. Moreover, barriers to access and long-term effects of these medications need to be addressed. CONCLUSION:In this review, we discuss important considerations for the utilization of these newer weight loss agents in the rapidly evolving landscape of weight loss pharmacotherapy in children and adolescents.

OBJECTIVE:Heterogeneity in the clinical course of type 2 diabetes in youth presenting with and without diabetic ketoacidosis (DKA) at diagnosis is not well described. We aimed to characterize if presentation of type 2 diabetes with DKA affects rates of insulin discontinuation compared with type 2 diabetes without ketosis (non-DKA). METHODS:This single-center retrospective cohort study included patients (body mass index z-score 2.4, IQR 2.07, 2.65) with a mean age of 15 years (IQR 13, 16), hospitalized for new-onset diabetes with DKA (n = 79) or non-DKA (n = 356) at an academic pediatric institution from January 2019 to December 2021 with follow-up until May 2023. All patients were initiated on insulin and titrated per their care team. Type 1 diabetes was excluded by presence of autoimmune antibodies. Primary outcomes were time to insulin discontinuation of insulin therapy and maintenance of discontinuation. RESULTS:Time to insulin discontinuation and proportion who discontinued did not differ between DKA and non-DKA groups (48.1% vs 44.7% respectively, P = .58). Trajectory analyses combining DKA and non-DKA groups identified 3 insulin discontinuation groups: early (20.1% within 2 months), late (12.5% within 6 months), and never (67.4%). Multinomial regression shows that DKA at presentation is not associated with early (P = .48) or late insulin discontinuation (P = .70) compared with never discontinuation. Insulin was restarted in 37 participants with median of 20 months (IQR 16, 24) after insulin discontinuation. CONCLUSIONS:Despite not showing differences in insulin discontinuation in youth with new-onset type 2 diabetes with and without DKA at presentation, we identified heterogeneity in duration of insulin treatment in the combined group.

Background Underserved pregnant women have a greater risk of excessive or inadequate gestational weight gain (GWG) and adverse perinatal outcomes. In the United States, the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) provides supplemental nutrition and is uniquely positioned to deliver equitable interventions that support recommended GWG. Yet to date, no randomized controlled trials have evaluated behavioral strategies for managing GWG in this setting. Objective The primary objective was to examine the effects of a statewide randomized multicomponent mobile eHealth lifestyle intervention trial on change in physical activity and sedentary time across pregnancy. The secondary objective was to explore associations between changes in physical activity, sedentary time, and GWG. Methods A total of 351 pregnant women were recruited from the Louisiana WIC clinics and were randomly assigned to a multicomponent mobile eHealth intervention for GWG management (N=179) or usual care (N=172; standard in-person WIC care) prior to 16 weeks of gestation. The multicomponent mobile intervention included daily weighing, step tracking, counseling, exercise videos, health coach interactions, and social support. For the first objective, physical activity, including movement duration and movement context, and sedentary time were assessed at baseline (early pregnancy) and at the end of the intervention (late pregnancy) using accelerometry and the Pregnancy Physical Activity Questionnaire. For the second objective, GWG was determined based on weight collected at study visits in early and late pregnancy. Linear mixed models assessed intervention effects on physical activity and GWG. Results Both the Intervention Group and the Usual Care Group significantly increased sedentary time from early to late pregnancy (adjusted effect estimate [95% CI] 62 minutes per day (42-83), P<.001 and 52 minutes per day (31-72), P<.001, respectively). Both the Intervention Group and the Usual Care Group significantly decreased moderate activity (–13 minutes per day (–20 to –6), P<.001 and –10 minutes per day (–17 to –3), P=.01, respectively) and total moderate to vigorous physical activity (–14 minutes per day (–21 to –7), P<.001 and –10 minutes per day (–18 to –3), P=.01, respectively) from early to late pregnancy. For the Pregnancy Physical Activity Questionnaire, the Intervention Group reported an increase in sports participation across pregnancy compared with the Usual Care Group (+4 metabolic equivalent task (MET)–hours per week (2-7); P=.002). There were no associations between physical activity (–7 g (–32 to 18), P=.57) or sedentary time measures (4 g (–4 to 12), P=.31) and GWG. Conclusions The first of its kind mobile eHealth multicomponent behavioral lifestyle intervention that included guidance to increase physical activity toward national guidelines did not meaningfully impact physical activity outcomes in pregnant women who were enrolled in Louisiana WIC. Trial Registration ClinicalTrials.gov NCT04028843; https://www.clinicaltrials.gov/study/NCT04028843 International Registered Report Identifier (IRRID) RR2-10.2196/18211

Introduction and Objective: Sodium-glucose cotransporter 2 inhibitors (SGLT2) were approved for the treatment of type 2 diabetes mellitus (T2DM) in youths ages 10 and older on June 20, 2023. We aimed to better understand the SGLT2 prescribing practices of pediatric endocrinologists for patients with T2DM. Methods: This retrospective cross-sectional study compared characteristics at the time of clinic visit of youths with T2DM ages 10 and older who were and were not newly prescribed SGLT2, but seen on the same clinic day, between July 1, 2022 and June 30, 2024. Wilcoxon rank sum test was used to analyze continuous variables and Pearson’s chi squared for categorical variables. Results: We identified 63 patients prescribed SGLT2 and 337 not prescribed SGLT2. Significant differences in HbA1c, use of insulin, weight z-score, history of dyslipidemia, HDL cholesterol, and use of statins were noted between the groups (Table 1). Conclusion: The findings suggest that SGLT2 are being prescribed for youths with worse glycemic control and higher risk for cardiovascular complications. There was not a difference between insurance type or Race/Ethnicity distribution, suggesting that socioeconomic status is not a primary barrier to prescription. Prospective and qualitative data would be useful in further understanding prescribing practices. E.Y. Choi: None. P.H. Nichols: None. S. Hao: None. S. Arora: None. D.S. Hsia: Advisory Panel; Eli Lilly and Company.

OBJECTIVE To compare rates of and risk factors for hospitalizations among Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE) participants taking metformin and randomly assigned to insulin glargine U-100, glimepiride, liraglutide, or sitagliptin. RESEARCH DESIGN AND METHODS Intention-to-treat (ITT) (N = 5,047) and on-assigned-treatment (AT) (N = 4,830) data sets were used. Baseline differences between those hospitalized versus those not hospitalized were assessed. Kaplan-Meier analysis was used to determine incidence for time to first hospitalization, and log-rank tests were used to determine treatment group differences. Time-to-event analyses were used to examine factors affecting subsequent hospitalization risk. RESULTS During GRADE, 1,636 participants (32.4%) were hospitalized at least once and 751 (14.9%) were hospitalized more than once. Hospitalized participants were older, less likely to be Hispanic, more likely to be White, and more likely to have a history of hypertension and had higher baseline BMI. There were no treatment group differences in incidence for time to first hospitalization in the ITT data set (P = 0.148), but a reduced hazard rate was observed for those taking liraglutide versus those taking glimepiride in the AT data set (hazard ratio 0.78 [95% CI 0.66, 0.92]; P = 0.022). Factors increasing the risk for subsequent hospitalizations included meeting the secondary outcome (HbA1c >7.5%, confirmed), each prior hospitalization, and change from assigned treatment (29%, 41%, and 56% increase in risk, respectively). Assignment to liraglutide versus glimepiride reduced this risk by 13%. CONCLUSIONS Hospitalizations were common in GRADE, and rates were nearly identical across treatment groups. The small, but significant, reduction in risk for subsequent hospitalizations among participants assigned to liraglutide versus glimepiride may influence treatment decisions in populations similar to GRADE participants.

Introduction In pregnancy, people with obesity or excess adiposity are prone to excess gestational weight gain (GWG) and have the highest risks for multiple maternal morbidities. Epidemiological studies suggest that the lowest incidence of adverse maternal and infant outcomes occurs with GWG lower than current recommendations (<5 kg) and with gestational weight maintenance, resulting in fat mass loss, in those with obesity. Data from randomised clinical trials are needed to evaluate the efficacy of a fat mass loss intervention on pregnancy outcomes. The objective of this proof-of-principle randomised controlled trial is to test the effect of a gestational fat mass loss intervention in pregnant individuals with obesity on changes in weight, fat mass and cardiometabolic disease risk factors.Methods and analysis In this two-site randomised parallel group, 100 women (30% black; 30% Hispanic) with pre-existing obesity (31.0≤body mass index≤55.0 kg/m2) are randomised to usual care (Provider Directed Group) or usual care plus a fat mass loss intervention with food provision (Weight Maintenance Group). The primary outcomes of the trial (Healthy Mamas/Mamis Saludables) are weight, fat mass (via three-compartment model) and cardiometabolic disease risk factors (ie, blood pressure, lipids, glucose, insulin) from baseline (~13 weeks gestation) to ~35 weeks gestation and at 2 weeks postpartum. Secondary aims evaluate the safety of the fat mass loss intervention during pregnancy and test the hypotheses that compared with usual care, the intervention will have no significant adverse effect on fetal growth, neonatal size, infant body composition and other adverse events. Mediators (eg, eating, activity) and moderators (eg, parity, obesity grade, race/ethnicity) of intervention effects are also examined. Finally, the study will explore the effect of prenatal fat mass loss on reducing the incidence of adverse obstetrical outcomes, including non-elective caesarean delivery, gestational diabetes, hypertension and pre-eclampsia.Ethics and dissemination The trial has been approved by the Pennington Biomedical Research Center Institutional Review Board, is monitored by an independent data and safety monitoring board and will be conducted in agreement with the Declaration of Helsinki. All results, positive, negative and inconclusive, will be disseminated at national and/or international scientific meetings and in peer-reviewed scientific journals.Trial registration number NCT04731688.

OBJECTIVE:To examine the effects of a pragmatic multicomponent eHealth intervention in pregnancy on body composition changes and subsequent associations with perinatal outcomes. METHODS:Pregnant individuals (n = 351) enrolled in Louisiana's Women, Infants, and Children program were randomly assigned to a multicomponent eHealth Intervention or Usual Care. Fat percentage, fat mass, and fat-free mass were assessed using bioelectrical impedance at trimester-specific study visits. Mixed models evaluated within- and between-group differences in body composition from early to late pregnancy: overall, by BMI, and by gestational weight gain (GWG) guideline attainment. Effects of body composition changes on perinatal outcomes was evaluated. RESULTS:Compared to Usual Care (n = 172), the Intervention Group (n = 179) had attenuated gains in fat mass, fat mass index, and fat percentage from early to late pregnancy overall, in individuals who had normal weight at enrollment, and in those who exceeded GWG guidelines (p < 0.05). No significant between-group differences in fat-free mass were observed. Fat mass change interacted with intervention effects on neonatal health outcomes (p = 0.01). CONCLUSIONS:Lifestyle interventions during pregnancy may attenuate gestational fat mass gain, particularly among women with normal weight and those who exceed GWG guidelines, with potential implications for neonatal health outcomes. TRIAL REGISTRATION:ClinicalTrials.gov identifier: NCT04028843.