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Efficacy and Safety of GLP-1 RAs in Children and Adolescents With Obesity or Type 2 Diabetes: A Systematic Review and Meta-Analysis

Author/s: 
Pareeta Kotecha, Wenxi Huang, Ya-Yun Yeh

Importance Obesity affects 1 in 5 children and adolescents, increasing the risk of type 2 diabetes (T2D). Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are among the few pharmacotherapy options available for this population, necessitating a comprehensive evaluation of efficacy and safety.

Objective To assess the efficacy and safety of GLP-1 RAs in children and adolescents (<18 years) with obesity, prediabetes, or T2D.

Data Sources A systematic search was conducted in PubMed, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) for randomized clinical trials (RCTs) published from inception until February 28, 2025. Data analysis was completed from January 2025 to April 2025.

Study Selection RCTs comparing GLP-1 RAs to placebo in children and adolescents with obesity, overweight, prediabetes, or T2D with reported safety and efficacy data were included.

Data Extraction and Synthesis Two reviewers independently extracted data on sample size, population, interventions, follow-up, and outcomes. Risk of bias was assessed using version 2 of the Cochrane risk of bias tool (RoB2). Efficacy outcomes (except lipids) were analyzed as estimated treatment differences, lipids as estimated treatment ratios, and safety via rate ratios. A random-effects inverse variance model was used for all outcomes.

Main Outcomes and Measures The primary efficacy outcomes were change in hemoglobin A1c (HbA1c) (in percentage points), fasting glucose (in milligrams per deciliter), body weight (in kilograms), body mass index (BMI, calculated as weight in kilograms divided by height in meters squared), BMI z scores or percentiles, BMI standard deviation score (SDS), lipid outcomes, and blood pressure. Exploratory efficacy outcomes included obstructive sleep apnea and metabolic dysfunction–associated steatohepatitis or metabolic dysfunction–associated steatotic liver disease. Safety outcomes included gastrointestinal adverse effects (GI AEs), infections, hepatobiliary disorders, suicidal ideation or behaviors, depression, hypoglycemia, and adverse event discontinuations.

Results A total of 18 RCTs (11 in obesity, 6 in T2D, and 1 in prediabetes) with 1402 participants (838 GLP-1 RA users and 564 placebo) were included (mean [range] age, 13.7 [6-17] years; 831 female participants (59.3%); median [IQR] treatment duration, 0.51 [0.25-1.00] years). GLP-1 RAs significantly reduced HbA1c (−0.44%; 95% CI, −0.68% to −0.21%), fasting glucose (−9.92 mg/dL; 95% CI, −16.20 to −3.64), body weight (−3.02 kg; 95% CI, −4.98 to −1.06), BMI (−1.45; 95% CI, −2.40 to −0.49), BMI SDS (−0.20; 95% CI, −0.36 to −0.05), BMI percentile (−7.24%; 95% CI, −12.97% to −1.51%), and systolic blood pressure (−2.73 mm Hg; 95% CI, −4.04 to −1.43) and increased GI AE (log[rate ratio] [RR], 0.75). Other AEs, including suicidal ideation or behaviors, showed no significant differences.

Conclusions and Relevance In this systematic review and meta-analysis of 18 trials, GLP-1 RAs significantly improved glycemic, weight, and cardiometabolic outcomes in children and adolescents with T2D or obesity. Available data over a relatively short follow-up suggested suicidal ideation or behaviors were not significantly different, although GI AEs warrant attention in long-term management.

2024 edition of the Rourke Baby Record

Author/s: 
Anne Rowan-Legg, Patricia Li, Bruce Kwok, Leslie Rourke, Denis Leduc, James Rourke, Imaan Bayoumi

Objective: To assist busy primary care providers caring for infants and young children and their families by providing them with the most recent recommendations and supportive evidence included in the 2024 edition of the Rourke Baby Record (RBR).

Quality of evidence: Articles from pediatric preventive care literature (January 2019 to March 2023) were reviewed for relevance and quality of evidence. When available, evidence from systematic reviews, relevant clinical guidelines, and clinical trials were incorporated. In the absence of high-level evidence, observational studies and expert opinion on the topic were included. Primary research studies were reviewed and critically appraised using a modified protocol.

Main message: Notable updates in the 2024 edition of the RBR include the promotion of early relational health for families; identification of targeted support and resources as opposed to labelling of high-risk groups; guidance on culturally safe care; clarification and evidence-based adjustments of the age of achievement of some developmental surveillance milestones; recommendations on plant-based beverages, vegetarian, and vegan diets; screening considerations for iron deficiency; dangers of ingestion of button batteries and cannabis edibles; literacy and socioemotional benefits of reading, singing, and storytelling; the importance of unstructured outdoor play; the environment's effect on children's health; the significance of sentinel injuries; acholic stools; and the normal presence and abnormal persistence of developmental (primitive) reflexes.

Conclusion: Building on its 40-year history, the 2024 RBR provides freely available, evidence-informed recommendations to guide clinicians in providing effective, up-to-date, and comprehensive preventive pediatric care. Despite the challenging and evolving landscape of primary health care delivery, the RBR will continue to support primary care providers.

Keywords 

2024 edition of the Rourke Baby Record

Author/s: 
Anne Rowan-Legg, Patricia Li, Bruce Kwok, Leslie Rourke, Denis Leduc, James Rourke, Imaan Bayoumi

Objective: To assist busy primary care providers caring for infants and young children and their families by providing them with the most recent recommendations and supportive evidence included in the 2024 edition of the Rourke Baby Record (RBR).

Quality of evidence: Articles from pediatric preventive care literature (January 2019 to March 2023) were reviewed for relevance and quality of evidence. When available, evidence from systematic reviews, relevant clinical guidelines, and clinical trials were incorporated. In the absence of high-level evidence, observational studies and expert opinion on the topic were included. Primary research studies were reviewed and critically appraised using a modified protocol.

Main message: Notable updates in the 2024 edition of the RBR include the promotion of early relational health for families; identification of targeted support and resources as opposed to labelling of high-risk groups; guidance on culturally safe care; clarification and evidence-based adjustments of the age of achievement of some developmental surveillance milestones; recommendations on plant-based beverages, vegetarian, and vegan diets; screening considerations for iron deficiency; dangers of ingestion of button batteries and cannabis edibles; literacy and socioemotional benefits of reading, singing, and storytelling; the importance of unstructured outdoor play; the environment's effect on children's health; the significance of sentinel injuries; acholic stools; and the normal presence and abnormal persistence of developmental (primitive) reflexes.

Conclusion: Building on its 40-year history, the 2024 RBR provides freely available, evidence-informed recommendations to guide clinicians in providing effective, up-to-date, and comprehensive preventive pediatric care. Despite the challenging and evolving landscape of primary health care delivery, the RBR will continue to support primary care providers.

Keywords 

Addictive Screen Use Trajectories and Suicidal Behaviors, Suicidal Ideation, and Mental Health in US Youths

Author/s: 
Yunyu Xiao, PhD, Yuan Meng, PhD, Timothy T. Brown, PhD

Importance: Increasing child and adolescent use of social media, video games, and mobile phones has raised concerns about potential links to youth mental health problems. Prior research has largely focused on total screen time rather than longitudinal addictive use trajectories.

Objectives: To identify trajectories of addictive use of social media, mobile phones, and video games and to examine their associations with suicidal behaviors and ideation and mental health outcomes among youths.

Design, setting, and participants: Cohort study analyzing data from baseline through year 4 follow-up in the Adolescent Brain Cognitive Development Study (2016-2022), with population-based samples from 21 US sites.

Exposures: Addictive use of social media, mobile phones, and video games using validated child-reported measures from year 2, year 3, and year 4 follow-up surveys.

Main outcomes and measures: Suicidal behaviors and ideation assessed using child- and parent-reported information via the Kiddie Schedule for Affective Disorders and Schizophrenia. Internalizing and externalizing symptoms were assessed using the parent-reported Child Behavior Checklist.

Results: The analytic sample (n = 4285) had a mean age of 10.0 (SD, 0.6) years; 47.9% were female; and 9.9% were Black, 19.4% Hispanic, and 58.7% White. Latent class linear mixed models identified 3 addictive use trajectories for social media and mobile phones and 2 for video games. Nearly one-third of participants had an increasing addictive use trajectory for social media or mobile phones beginning at age 11 years. In adjusted models, increasing addictive use trajectories were associated with higher risks of suicide-related outcomes than low addictive use trajectories (eg, increasing addictive use of social media had a risk ratio of 2.14 [95% CI, 1.61-2.85] for suicidal behaviors). High addictive use trajectories for all screen types were associated with suicide-related outcomes (eg, high-peaking addictive use of social media had a risk ratio of 2.39 [95% CI, 1.66-3.43] for suicidal behaviors). The high video game addictive use trajectory showed the largest relative difference in internalizing symptoms (T score difference, 2.03 [95% CI, 1.45-2.61]), and the increasing social media addictive use trajectory for externalizing symptoms (T score difference, 1.05 [95% CI, 0.54-1.56]), compared with low addictive use trajectories. Total screen time at baseline was not associated with outcomes.

Conclusions and relevance: High or increasing trajectories of addictive use of social media, mobile phones, or video games were common in early adolescents. Both high and increasing addictive screen use trajectories were associated with suicidal behaviors and ideation and worse mental health.

Has This Child Experienced Physical Abuse? The Rational Clinical Examination Systematic Review

Author/s: 
Sonal N Shah, Hiu-Fai Fong, Suzanne B Haney, Mary Clyde Pierce, Nancy S Harper, Mark I Neuman

Importance: Nearly 100 000 children experience physical abuse each year in the US. Among approximately 2000 annual deaths related to child maltreatment, more than 40% resulted from physical abuse, and half of those children were younger than 1 year. Many of these young children had unidentified abusive injuries before the fatal event.

Objective: To determine the accuracy of clinical and radiologic findings for identifying physical abuse among children who have sustained an injury.

Data Sources and Study Selection: MEDLINE, PubMed Central, and Embase were searched for articles published from 1970 to September 2024. Three authors identified studies describing clinical and radiologic characteristics in children and adolescents undergoing assessment for physical abuse.

Data Extraction and Synthesis: The number of children with and without each clinical or radiologic finding, and the presence or absence of physical abuse, which had been determined by expert panels, predefined criteria, or standardized scales that quantify the level of concern for abuse, were recorded.

Main Outcomes and Measures: The sensitivity, specificity, and likelihood ratios (LRs) of each finding for the presence of physical abuse were calculated and the range or calculated summary measures were reported when the finding was evaluated in more than 1 study.

Results: Of 7378 unique articles, 18 studies met inclusion criteria. The prevalence of physical abuse in these 18 studies ranged from 5% to 79%. Studies that were focused on skin findings in children evaluated for trauma showed that the presence of oral injury such as a torn frenulum (positive LR, 6.6 [95% CI, 3.2-14.0]), bruising on the buttocks (positive LR range, 15-83) or neck (positive LR range, 2.2-84), patterned bruises (positive LR range, 2.0-66), and subconjunctival hemorrhage (positive LR range, 5.4-130) were associated with increased likelihood of physical abuse. In studies of hospitalized children with head injury, the presence of retinal hemorrhages (positive LR, 11.0 [95% CI, 4.0-32.0]), seizures (positive LR, 3.9 [95% CI, 2.4-6.5]), hypoxic ischemic injury (positive LR, 3.4 [95% CI, 1.8-6.4]), or a subdural hematoma (positive LR, 3.2 [95% CI, 2.6-3.8]) increased the likelihood of physical abuse. In studies examining children who underwent skeletal surveys, a single fracture (positive LR, 5.9 [95% CI, 2.9-12.0]) or multiple fractures (positive LR, 3.8 [95% CI, 2.4-6.0]) increased the likelihood of physical abuse.

Conclusions and Relevance: A detailed physical examination that reveals oral injury, bruises on the buttocks or neck, patterned bruises, and subconjunctival hemorrhage in young children should alert clinicians to the possibility of physical abuse. Findings on neuroimaging and ophthalmologic evaluation in infants and young children with head trauma can help clinicians determine the likelihood of physical abuse.

Has This Child Experienced Physical Abuse?: The Rational Clinical Examination Systematic Review

Author/s: 
Sonal N Shah, Hiu-Fai Fong, Suzanne B Haney, Nancy S Harper, Mary Clyde Pierce, Mark I Neuman

Importance: Nearly 100 000 children experience physical abuse each year in the US. Among approximately 2000 annual deaths related to child maltreatment, more than 40% resulted from physical abuse, and half of those children were younger than 1 year. Many of these young children had unidentified abusive injuries before the fatal event.

Objective: To determine the accuracy of clinical and radiologic findings for identifying physical abuse among children who have sustained an injury.

Data sources and study selection: MEDLINE, PubMed Central, and Embase were searched for articles published from 1970 to September 2024. Three authors identified studies describing clinical and radiologic characteristics in children and adolescents undergoing assessment for physical abuse.

Data extraction and synthesis: The number of children with and without each clinical or radiologic finding, and the presence or absence of physical abuse, which had been determined by expert panels, predefined criteria, or standardized scales that quantify the level of concern for abuse, were recorded.

Main outcomes and measures: The sensitivity, specificity, and likelihood ratios (LRs) of each finding for the presence of physical abuse were calculated and the range or calculated summary measures were reported when the finding was evaluated in more than 1 study.

Results: Of 7378 unique articles, 18 studies met inclusion criteria. The prevalence of physical abuse in these 18 studies ranged from 5% to 79%. Studies that were focused on skin findings in children evaluated for trauma showed that the presence of oral injury such as a torn frenulum (positive LR, 6.6 [95% CI, 3.2-14.0]), bruising on the buttocks (positive LR range, 15-83) or neck (positive LR range, 2.2-84), patterned bruises (positive LR range, 2.0-66), and subconjunctival hemorrhage (positive LR range, 5.4-130) were associated with increased likelihood of physical abuse. In studies of hospitalized children with head injury, the presence of retinal hemorrhages (positive LR, 11.0 [95% CI, 4.0-32.0]), seizures (positive LR, 3.9 [95% CI, 2.4-6.5]), hypoxic ischemic injury (positive LR, 3.4 [95% CI, 1.8-6.4]), or a subdural hematoma (positive LR, 3.2 [95% CI, 2.6-3.8]) increased the likelihood of physical abuse. In studies examining children who underwent skeletal surveys, a single fracture (positive LR, 5.9 [95% CI, 2.9-12.0]) or multiple fractures (positive LR, 3.8 [95% CI, 2.4-6.0]) increased the likelihood of physical abuse.

Conclusions and relevance: A detailed physical examination that reveals oral injury, bruises on the buttocks or neck, patterned bruises, and subconjunctival hemorrhage in young children should alert clinicians to the possibility of physical abuse. Findings on neuroimaging and ophthalmologic evaluation in infants and young children with head trauma can help clinicians determine the likelihood of physical abuse.

Efficacy of interventions for the treatment of irritable bowel syndrome, functional abdominal pain-not otherwise specified, and abdominal migraine in children: a systematic review and network meta-analysis

Author/s: 
Vasiliki Sinopoulou, Jip Groen, Morris Gordon, Ed Mougey, James P Franciosi, Tim G J de Meij, Merit M Tabbers, Marc A Benninga

Background: Many treatments for abdominal pain-related disorders of gut-brain interaction (AP-DGBI) in children have been studied. We aimed to assess the efficacy and safety of all known treatment options for paediatric AP-DGBI.

Methods: For this systematic review and network meta-analysis, we searched Embase, MEDLINE, and CENTRAL databases from inception to Jan 16, 2025, for published randomised controlled trials. We included trials of any treatment for AP-DGBIs (irritable bowel syndrome, functional abdominal pain-not otherwise specified, and abdominal migraine, excluding functional dyspepsia) in children aged 4-18 years. We excluded randomised controlled trials that solely included children with functional dyspepsia, but we included studies in which children with functional dyspepsia were included alongside children with the other AP-DGBI diagnoses and outcome data could not be separated. Data extraction and quality appraisal were performed in duplicate. The primary outcome for this network meta-analysis was author-defined treatment success. Network meta-analysis methodology was used within a frequentist framework using multivariate meta-analysis and outcomes were assessed using the Grading of Recommendations, Assessment, Development and Evaluation methodology. Clinical relevance of effect sizes was interpreted according to consensus definitions.

Findings: Of 19 337 records identified through the database search, 155 records representing 91 original randomised controlled trials were included in the network meta-analysis: these 91 trials comprised 7226 participants (4119 females and 2673 males). 12 studies assessed dietary treatments (n=730), 25 assessed pharmacological treatments (n=2140), 23 assessed probiotic treatments (n=1762), and 35 assessed psychosocial treatments (n=2952). Two treatments were probably more effective for treatment success than control treatments (moderate certainty): hypnotherapy (risk ratio [RR] 4·99 [95% CI 2·15 to 11·57]; large effect size) and cognitive behavioural therapy (CBT; RR 1·99 [95% CI 1·33 to 2·98]; moderate effect size). All other treatments evaluated for treatment success were either not effective or the data were of very low certainty and thus no conclusions could be made.

Interpretation: Hypnotherapy and CBT show moderate certainty for treatment efficacy with clinically relevant effect sizes. No conclusions can be made about the other therapies and treatment success due to very low evidence certainty. Future randomised controlled trials should focus on improving the evidence certainty for those other therapies with regard to core AP-DGBI outcomes.

Funding: None.

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