Mineralocorticoid receptor antagonist monotherapy in pediatric non-classical 11ß-hydroxylase deficiency.

OBJECTIVES: Congenital adrenal hyperplasia (CAH) is an uncommon genetic disorder which affects cortisol production in the adrenal glands. It is usually treated with glucocorticoids. We present a case of non-classical CAH caused by the partial deficiency of 11 beta-hydroxylase (11ßOH) which was treated with aldosterone antagonist (eplerenone) monotherapy. CASE PRESENTATION: An adolescent male was diagnosed with 11 beta-hydroxylase deficiency (11ßOHD) at 13 years of age when he presented with hypertension, fatigue and headaches. He was initially treated with glucocorticoids, but requested an alternative therapy. Eplerenone was commenced at 25 mg with subsequent dose increases to 100 mg daily. His hypertension was controlled on this regimen, achieving a 24 h average blood pressure of 124/81 mmHg. CONCLUSIONS: CAH caused by 11ßOHD is a known cause of hypertension. It is usually managed with glucocorticoids, and antihypertensives are added if blood pressure remains uncontrolled. In this case, glucocorticoid therapy was not tolerated and treatment with aldosterone antagonist monotherapy was effective in controlling his hypertension.

Exploring height outcomes with adjuvant aromatase inhibition in growth hormone-deficient male survivors of childhood cancer.

BACKGROUND: Aromatase inhibitors (AI) may improve height in short stature conditions; however, the effect in childhood cancer survivors (CCS) is unknown. We assessed final adult height (FAH) in CCS treated with AI and GH compared with those treated with GH alone. METHODS: Retrospective cohort study of GH-deficient male CCS treated between 2007 and 2023. FAH was noted as the height at the fusion of growth plates or 18 years of age. Multivariable linear regression was used to examine treatment association with FAH, adjusting for other risk factors. RESULTS: Ninety-two patients were included; 70 were treated with GH and 22 with combination AI/GH. The mean age at GH initiation did not differ between groups. The mean age at AI initiation was 13.7 ± 1.9 years. A greater proportion of patients in the AI/GH group were treated with stem cell transplantation, abdominal radiation, total body irradiation, and cis-retinoic acid (p < .01). Multivariable linear regression demonstrated no significant treatment association with FAH Z-score (ß = 0.04, 95% CI: -0.9 to 0.9). History of spinal radiation (ß = -0.93, 95% CI: -1.7 to -0.2), lower starting height Z-score (ß = -0.8, 95% CI: -1.2 to -0.4), and greater difference between bone age and chronological age (ß = -0.3, 95% CI: -0.5 to -0.07) were associated with lower FAH Z-score. CONCLUSIONS: Adjuvant AI was not associated with increased FAH in male CCS compared with GH monotherapy. Future work is needed to determine the optimal adjunctive treatment to maximize FAH for this population.

Approach to the Patient: Investigation of Pediatric Hypoglycemia in the Emergency Department-A Practical Algorithm.

Hypoglycemia in the pediatric population tends to present in the newborn period or during metabolic crisis triggered by prolonged fasting and intercurrent illness. Current recommendations to investigate all children presenting with hypoglycemia for the first time are cumbersome and costly but necessary to identify those with serious conditions who predispose to hypoglycemia. We describe a practical and cost-effective method of evaluating children who present to the emergency department with previously undiagnosed hypoglycemia. Glucose and point-of-care (POC) beta-hydroxybutyrate levels should be measured on all children with a low screening POC glucose level, and a full history and physical examination will identify those requiring further investigation. This approach is suggested to identify patients with serious and life-threatening disease with the same fidelity as the currently recommended approach of performing a critical sample on all children with hypoglycemia. Our streamlined approach will reduce the cost to approximately 10% of the current approach per patient diagnosed with a serious underlying disease. Further, children without underlying hypoglycemia-predisposing disorders will be identified and discharged without unnecessary intervention.

Approaches to Measuring Beta Cell Reserve and Defining Partial Clinical Remission in Paediatric Type 1 Diabetes.

CONTEXT: Type 1 diabetes (T1D) results from the autoimmune T-cell mediated destruction of pancreatic beta cells leading to insufficient insulin secretion. At the time of diagnosis of T1D, there is residual beta cell function that declines over the subsequent months to years. Recent interventions have been approved to preserve beta cell function in evolving T1D. OBJECTIVE: The aim of this review is to summarise the approaches used to assess residual beta cell function in evolving T1D, and to highlight potential future directions. METHODS: Studies including subjects aged 0 to 18 years were included in this review. The following search terms were used; "(type 1 diabetes) and (partial remission)" and "(type 1 diabetes) and (honeymoon)". References of included studies were reviewed to determine if additional relevant studies were eligible. RESULTS: There are numerous approaches to quantifying beta cell reserve in evolving T1D. These include c-peptide measurement after a mixed meal or glucagon stimuli, fasting c-peptide, the urinary c-peptide/creatinine ratio, insulin dose-adjusted haemoglobin A1c, and other clinical models to estimate beta cell function. Other biomarkers may have a role, including the proinsulin/c-peptide ratio, cytokines, and microRNA. Studies using thresholds to determine if residual beta cell function is present often differ in values used to define remission. CONCLUSIONS: As interventions are approved to preserve beta cell function, it will become increasingly necessary to quantify residual beta cell function in research and clinical contexts. In this report, we have highlighted the strengths and limitations of the current approaches.

Growth Hormone Treatment for Non-GHD Disorders: Excitement Tempered by Biology.

The success of growth hormone (GH) replacement in children with classical GH deficiency has led to excitement that other causes of short stature may benefit similarly. However, clinical experience has shown less consistent and generally less dramatic effects on adult height, perhaps not surprising in light of increased understanding of GH and growth plate biology. Nonetheless, clinical demand for GH treatment continues to grow. Upon the 20th anniversary of the US Food and Drug Administration's approval of GH treatment for idiopathic short stature, this review will consider the factors underlying the expansion of GH treatment, the biological mechanisms of GH action, the non-GH-deficient uses of GH as a height-promoting agent, biological constraints to GH action, and future directions.

International Newborn Screening Practices for the Early Detection of Congenital Adrenal Hyperplasia.

INTRODUCTION: Newborn screening (NBS) programmes vary internationally in their approach to screening. Guidelines for congenital adrenal hyperplasia (CAH) screening recommend the use of two-tier testing and gestational age cutoffs to minimise false-positive results. The aims of this study were to describe (1) the approaches; (2) protocols used; and (3) available outcomes for CAH screening internationally. METHODS: All members of the International Society for Neonatal Screening were asked to describe their CAH NBS protocols, with an emphasis on the use of second-tier testing, 17-hydroxyprogesterone (17OHP) cutoffs, and gestational age and birth weight adjustments. If available, screening outcomes were requested. RESULTS: Representatives from 23 screening programmes provided data. Most (n = 14; 61%) recommend sampling at 48-72 h of life. Fourteen (61%) use single-tier testing and 9 have a two-tier testing protocol. Gestational age cutoffs are used in 10 programmes, birth weight cutoffs in 3, and a combination of both in 9. One programme does not use either method of adjusting 17OHP cutoffs. Case definition of a positive test and the response to a positive test differed between programmes. CONCLUSIONS: We have demonstrated significant variation across all aspects of NBS for CAH, including timing, the use of single versus two-tier testing and cutoff interpretation. Collaboration between international screening programmes and implementation of new techniques to improve screen efficacy will facilitate ongoing expansion and quality improvement in CAH NBS.

Adolescents' Experiences of Transition to Self-Management of Type 1 Diabetes: Systematic Review and Future Directions.

PURPOSE: The purpose of this systematic literature review was to explore studies that report the experiences of adolescents, their families, and health care professionals of adolescents' transition to self-management of type 1 diabetes (T1DM). METHODS: SocINDEX, PsycInfo, APA PsycArticles, and MEDLINE electronic databases were searched. Studies reporting on experiences of transition to self-management of T1DM for adolescents, their parents, siblings, and health care professionals published between January 2010 amd December 2021 were included. The Mixed Methods Appraisal Tool guided trustworthiness and relevance of selected studies. RESULTS: A total of 29 studies met the inclusion criteria. Findings indicate that adolescents' experiences of transitioning to self-management of T1DM are interconnected with the supports provided by others (eg, family, teachers, friends). Considering interdependence and collective lived experiences is essential to developing effective and personalized family, peer, and social interventions to facilitate transition and to avoid negative outcomes in later life. The renegotiation of roles within the network of supports that impact adolescents' transition and adolescents' self-negotiation have been neglected. CONCLUSION: Transition to self-management of T1DM is a dynamic and iterative process comprising of continuous shifts between interdependence and independence, making it challenging for all involved. A number of research gaps and avenues for future research are outlined.

The impact of fear of hypoglycaemia on sleep in adolescents with type 1 diabetes.

AIMS: Fear of hypoglycaemia (FOH) can contribute to impaired sleep for adults with type 1 diabetes (T1D) and parents of children with T1D, although it is unknown how FOH may affect sleep for adolescents with T1D. This study examines the relationship between adolescent FOH and sleep and assessed the influences of continuous glucose monitor (CGM) and insulin pump use. METHODS: Adolescents ages 14-18 years with T1D completed questionnaires evaluating FOH (Child Hypoglycemia Fear Survey) and sleep (Pittsburgh Sleep Quality Index, PSQI). Analyses included linear and logistic regression, t-tests and Fisher's exact tests. RESULTS: Participants included 95 adolescents (52 female) with a median (IQR) age of 16.5 (15.3-17.7) years and a T1D duration of 5.7 (2.5-9.6) years. Analyses showed increased FOH-Worry subscale scores were associated with reduced sleep duration (ß = -0.03, p = 0.042, adjusting for BMI z-score, race and ethnicity) and increased sleep disturbances (OR = 1.1, p = 0.038, adjusting for race and ethnicity). Frequent CGM users had longer sleep duration (average 7.5 h) compared with infrequent or non-CGM users (average = 6.8 h; p = 0.029), and pump users had overall improved sleep health as determined by PSQI score (p = 0.019). Technology use did not have significant interactions in the relationships between FOH and sleep duration or sleep disturbances. CONCLUSIONS: Worrying about hypoglycaemia was associated with impaired sleep for adolescents with T1D. Diabetes technology users have some sleep improvements, but CGM and pump use do little to alter the relationship between FOH and sleep outcomes.

Racial Disparities in Technology Use in Children With Type 1 Diabetes: A Qualitative Content Analysis of Parents' Perspectives.

PURPOSE: The purpose of the study was to describe differences in non-Hispanic Black (NHB) and non-Hispanic White (NHW) parents' perceptions of factors that influence the use of diabetes technology. METHODS: Focus groups were conducted with parents of NHB and NHW children at a pediatric diabetes center in the Northeast United States. Kilbourne's health disparities framework informed the focus group guide and a priori coding for directed content analysis. Further analysis allowed subcategories to emerge inductively. RESULTS: Twenty-one parents participated. Five subcategories emerged, describing differences in NHB and NHW parent decisions regarding diabetes technology: (1) child's choice, (2) shame versus pride, (3) pros and cons of technology, (4) time frame, and (5) blood glucose indications of readiness. NHB parents feared technology malfunction, worried that visible devices could worsen experienced stigma of diabetes diagnosis, and described the diabetes team as gatekeepers, who changed eligibility criteria for diabetes technology use for their research purposes. In contrast, NHW parents reported diabetes team expectation of diabetes technology use and did not report provider-related barriers. CONCLUSION: This study adds to existing literature advancing our understanding of the patient and provider mechanisms underlying racial disparities in diabetes technology use. This understanding may guide development of interventions focused on patients, providers, and structural factors to improve equity in use of diabetes technology by youth with type 1 diabetes.

Perspectives of Pediatric Community Health Workers: Roles, Successes, and Challenges.

This multicenter qualitative study described the roles of 10 pediatric community health workers (CHWs) in their own words through exploration of the role features, successes, and challenges in pediatric health care settings across three urban U.S. cities (Philadelphia, New York City, and Cincinnati). Individual, semi-structured telephone interviews were conducted. Interviews described prominent features of the pediatric CHW role, which included taking a family-centered approach to goal setting and determining support needed, ensuring family goals stayed at the center of the work, and acting as a trusted figure for families to talk openly with. CHWs described their role as rewarding, believing in the work, and feeling a sense of fulfillment, and felt successful when families had positive outcomes, including when barriers were eliminated, resources were obtained, or independence was demonstrated by families. Challenges CHWs faced in their roles included establishing trust with families, managing the ever-changing family circumstances many families experience due to socioeconomic barriers, and managing limitations of protocol and restrictions within their roles. This study demonstrated numerous considerations for CHW practice in pediatric health care settings, in addition to considerations for pediatric-specific CHW program development and management. The primary policy implication of this study included a basis for increased funding for CHW programs in pediatric health care settings. This study also demonstrated a need for further research on the change CHWs effect within child and family systems outside of health care, such as schools and child welfare agencies.

Underrepresented Voices: Impacts of Social Determinants of Health on Type 1 Diabetes Family Management in Single-Parent, Black Families.

OBJECTIVES: Social determinants of health (SDOH) impact families' ability to manage chronic illnesses such as type 1 diabetes (T1D). Black, single parents have unique SDOH-related resource needs and concerns when caring for a child with a chronic illness, yet their voices are underrepresented in the pediatric T1D literature. The aim of this qualitative study was to identify and explore the SDOH that influence T1D management in Black, single-parent families. METHODS: In this 2-phase qualitative study we used content analysis to explore themes derived from 3 nominal group technique sessions and semistructured interviews, with 20 self-identified Black, single parents of a child with T1D. RESULTS: Parents encountered various SDOH-related issues that negatively influenced management of their children's T1D. Six major themes emerged from the parent-generated list of SDOH-related barriers: 1) lack of parent and child emotional and physical support systems, 2) maintaining parent and child's physical and mental health, 3) pain management with medication administration, 4) clinical team empathy, 5) provider communication, and 6) economic burden of food costs. CONCLUSIONS: These exploratory findings contribute to the knowledge base required to guide development of culturally relevant, individual- and population-level interventions for racially and compositionally minority families, to increase health equity and address racial health disparities in T1D. Routine assessment of family social support context and resources, better integration of community-level social services into clinical health encounters and clinician bias and communication training are advised starting points to address the specific needs of racial and ethnic minority families experiencing the greatest social and clinical challenges.

Novel PTH Gene Mutations Causing Isolated Hypoparathyroidism.

CONTEXT: Parathyroid hormone (PTH) gene mutations represent a rare cause of familial isolated hypoparathyroidism (FIH). These defects can cause hypoparathyroidism with increased or decreased serum levels of PTH through 1) impaired PTH synthesis; 2) induction of parathyroid cell apoptosis; or 3) secretion of bioinactive PTH molecules. Eight pathogenic mutations of this gene have been described previously. OBJECTIVE: Through describing 2 novel mutations of the PTH gene, we aim to extend the molecular basis for FIH and further refine the proposed mechanisms by which PTH mutations cause hypoparathyroidism. METHODS: Proband case reports were compiled with extended family analysis. The probands in both kindreds presented before age 10 days with hypocalcemia and elevated phosphate levels. Proband A had low PTH levels, whereas these levels were elevated in Proband B. Proband B was initially diagnosed with pseudohypoparathyroidism. Methylation analysis was performed of CpG dinucleotides within 3 GNAS differentially methylated regions; whole-genome sequencing; and PTH infusion with analysis of nephrogenous 3',5'-cyclic adenosine 5'-monophosphate. RESULTS: Proband A had a novel heterozygous sequence change in exon 2 of the PTH gene, c.46_47delinsAA (p.Ala16Lys), and proband B had a novel homozygous nucleotide transition in PTH exon 3 (c.128G > A; p.G43E) that led to replacement of glycine by glutamic acid at position 12 of PTH 1-84. PTH 1-34 infusion demonstrated that renal responsiveness to PTH was intact and not antagonized by circulating bioinactive PTH. CONCLUSION: PTH gene mutations are uncommon causes of hypoparathyroidism, but can be misdiagnosed as disorders of gland development or receptor function if PTH levels are decreased or elevated, respectively. Genetic testing should be considered early in the diagnostic approach to these presentations.

Influence of social determinants of health barriers to family management of type 1 diabetes in Black single parent families: A mixed methods study.

OBJECTIVE: US disparities in pediatric type 1 diabetes treatment and outcomes are increasing disproportionately among Black youth and compounded for youth from single parent homes. Despite worsened outcomes, Black youth from single parent homes and their caregivers are underrepresented in pediatric type 1 diabetes research. The purpose of this study was to understand the social determinants of health (SDOH) barriers that may contribute to health disparities and family management in Black youth with type 1 diabetes from single parent homes. RESEARCH DESIGN AND METHODS: A three-phase mixed methods study with self-identified Black single parents of youth with type 1 diabetes from an urban US pediatric diabetes center was conducted. Focus groups and interviews informed development of a parent-generated survey of SDOH barriers to diabetes management. Survey results are presented. RESULTS: A resulting 71 item parent-generated survey was administered to 105 parents. Among all items, most problematic SDOH barriers included lack of social support, managing parent/child diabetes-related stress, difficulties accessing diabetes supplies, pain management, cost of food and diabetes camp, need to take time off from work, lack of skilled school staff, school absences and unsafe neighborhoods. Structural racism related to child welfare reporting, and police targeting were also notable concerns. CONCLUSIONS: There is a critical need for clinical, community, and policy-related research and interventions, designed to reduce type 1 diabetes racial health disparities by addressing the impacts of SDOH as drivers of family management outcomes among Black youth from single parent families.

The Bihormonal Bionic Pancreas Improves Glycemic Control in Individuals With Hyperinsulinism and Postpancreatectomy Diabetes: A Pilot Study.

OBJECTIVE: To determine whether the bihormonal bionic pancreas (BHBP) improves glycemic control and reduces hypoglycemia in individuals with congenital hyperinsulinism (HI) and postpancreatectomy diabetes (PPD) compared with usual care (UC). RESEARCH DESIGN AND METHODS: Ten subjects with HI and PPD completed this open-label, crossover pilot study. Coprimary outcomes were mean glucose concentration and time with continuous glucose monitoring (CGM) glucose concentration <3.3 mmol/L. RESULTS: Mean (SD) CGM glucose concentration was 8.3 (0.7) mmol/L in the BHBP period versus 9 (1.8) mmol/L in the UC period (P = 0.13). Mean (SD) time with CGM glucose concentration <3.3 mmol/L was 0% (0.002) in the BHBP period vs. 1.3% (0.018) in the UC period (P = 0.11). CONCLUSIONS: Relative to UC, the BHBP resulted in comparable glycemic control in our population.

Early Racial/Ethnic Disparities in Continuous Glucose Monitor Use in Pediatric Type 1 Diabetes.

Racial-ethnic disparities in technology use have been described in children with type 1 diabetes (T1D). It is not known whether these emerge early in disease management. This single-center retrospective study examined disparities in continuous glucose monitor (CGM) initiation and durability in the first-year after diagnosis of T1D in children. Of 345 eligible children, 46% started CGM within their first year. In non-Hispanic white (NHW) children, 51% started using CGM versus 28% of non-Hispanic black (NHB) children (P = 0.006). After stratifying by commercial/government insurance, a proxy for socioeconomic status, this difference persisted among those with commercial insurance. One-year post-CGM initiation, 96% (125/130) of NHW children were using CGM versus 73% (11/15) of NHB children (P = 0.003). Disparities in CGM use emerge early in care of children with T1D, with lower rates of initiation and sustained use of CGM in NHB children. Strategies addressing causes of these disparities should begin early in T1D management.

The presentation of congenital adrenal hyperplasia in an unscreened population.

BACKGROUND: The aim of this study was to describe the incidence and spectrum of early clinical presentations of congenital adrenal hyperplasia (CAH) in an unscreened population. METHODS: A national retrospective observational study was undertaken to identify all children diagnosed with CAH in the Republic of Ireland, between January 2005 and December 2019. Reporting clinicians completed anonymized clinical questionnaires. RESULTS: There were 103 cases of CAH reported and 69 cases met the study inclusion criteria. The estimated annualized incidence of CAH in the Republic of Ireland was 1:14,754 or 0.07 cases per 1,000 live births. Forty-seven children presented clinically in the first six months of life, but only 17 of these had a confirmed diagnosis by day 10. Of these early presentations, there were 28 infants with salt-wasting, 15 females presented with virilized genitalia and four infants were detected due to a family history of CAH. Female infants presented at a median age of 0 days [IQR 0-1] and males at 14 days [IQR 9-21]. Seventy-eight percent of salt-wasting presentations occurred after day 10. Delays in clinical presentation, biochemical diagnosis and treatment initiation were identified. CONCLUSIONS: The incidence of CAH is higher in Ireland than in other unscreened populations. In the absence of screening, clinicians should be aware of the possibility of CAH and appropriate investigations should be urgently requested. Life-threatening salt-wasting is the most frequent clinical presentation and many cases could be detected prior to decompensation if newborn screening were introduced.

Sarcopenia and preserved bone mineral density in paediatric survivors of high-risk neuroblastoma with growth failure.

BACKGROUND: Survival from paediatric high-risk neuroblastoma (HR-NBL) has increased, but cis-retinoic acid (cis-RA), the cornerstone of HR-NBL therapy, can cause osteoporosis and premature physeal closure and is a potential threat to skeletal structure in HR-NBL survivors. Sarcopenia is associated with increased morbidity in survivors of paediatric malignancies. Low muscle mass may be associated with poor prognosis in HR-NBL patients but has not been studied in these survivors. The study objective was to assess bone density, body composition and muscle strength in HR-NBL survivors compared with controls. METHODS: This prospective cross-sectional study assessed areal bone mineral density (aBMD) of the whole body, lumbar spine, total hip, femoral neck, distal 1/3 and ultradistal radius and body composition (muscle and fat mass) using dual-energy X-ray absorptiometry (DXA) and lower leg muscle strength using a dynamometer. Measures expressed as sex-specific standard deviation scores (Z-scores) included aBMD (adjusted for height Z-score), bone mineral apparent density (BMAD), leg lean mass (adjusted for leg length), whole-body fat mass index (FMI) and ankle dorsiflexion peak torque adjusted for leg length (strength-Z). Muscle-specific force was assessed as strength relative to leg lean mass. Outcomes were compared between HR-NBL survivors and controls using Student's t-test or Mann-Whitney U test. Linear regression models examined correlations between DXA and dynamometer outcomes. RESULTS: We enrolled 20 survivors of HR-NBL treated with cis-RA [13 male; mean age: 12.4 ± 1.6 years; median (range) age at therapy initiation: 2.6 (0.3-9.1) years] and 20 age-, sex- and race-matched controls. Height-Z was significantly lower in HR-NBL survivors compared with controls (-1.73 ± 1.38 vs. 0.34 ± 1.12, P < 0.001). Areal BMD-Z, BMAD-Z, FMI-Z, visceral adipose tissue and subcutaneous adipose tissue were not significantly different in HR-NBL survivors compared with controls. Compared with controls, HR-NBL survivors had lower leg lean mass-Z (-1.46 ± 1.35 vs. - 0.17 ± 0.84, P < 0.001) and strength-Z (-1.13 ± 0.86 vs. - 0.15 ± 0.71, P < 0.001). Muscle-specific force was lower in HR-NBL survivors compared with controls (P < 0.05). CONCLUSIONS: Bone mineral density and adiposity are not severely impacted in HR-NBL survivors with growth failure, but significant sarcopenia persists years after treatment. Future studies are needed to determine if sarcopenia improves with muscle-specific interventions in this population of cancer survivors.

Safety and Efficacy of Glucagon-Like Peptide-1 Receptor Agonists in Children and Adolescents with Obesity: A Meta-Analysis.

OBJECTIVES: To determine the weight, body mass index (BMI), cardiometabolic, and gastrointestinal effects of glucagon-like peptide-1 (GLP-1) receptor agonists in children with obesity. STUDY DESIGN: Web of Science, PubMed/MEDLINE, and Scopus databases from 01/01/1994-01/01/2021 for randomized control trials examining the weight, BMI, cardiometabolic, or gastrointestinal effects of GLP-1 receptor agonists in children and adolescents with obesity. Data were extracted by 2 independent surveyors and a random effects model was applied to meta-analyze generic inverse variance outcomes. Primary outcomes were related to weight and cardiometabolic profile, and secondary outcomes of interest were gastrointestinal-related treatment-emergent adverse events. RESULTS: Nine studies involving 574 participants were identified, of which 3 involved exenatide and 6 involved liraglutide. GLP-1 receptor agonists use caused a modest reduction in body weight (mean difference [MD] -1.50 [-2.50,-0.50] kg, I2 64%), BMI (MD -1.24 [-1.71,-0.77] kg/m2, I2 0%), and BMI z score (MD -0.14 [-0.23,-0.06], I2 43%). Glycemic control was improved in children with proven insulin resistance (glycated hemoglobin A1c MD -1.05 [-1.93,-0.18] %, I2 76%). Although no lipid profile improvements were noted, a modest decrease in systolic blood pressure was detected (MD -2.30 [-4.11,-0.49] mm Hg; I2 0%). Finally, analysis of gastrointestinal-related treatment-emergent adverse events revealed an increased risk of nausea (risk ratio 2.11 [1.44, 3.09]; I2 0%), without significant increases in other gastrointestinal symptoms. CONCLUSIONS: This meta-analysis indicates that GLP-1 receptor agonists are safe and effective in modestly reducing weight, BMI, glycated hemoglobin A1c, and systolic blood pressure in children and adolescents with obesity in a clinical setting, albeit with increased rates of nausea. PROSPERO ID: CRD42020195869.