Citations

Childhood obesity has assumed epidemic proportions; it results from a complex interplay of genetic, physiological, socioeconomic, and environmental factors. It is associated with numerous short- and long-term health complications, including cardiometabolic and psychosocial consequences. While lifestyle modifications remain the cornerstone of treatment, their overall impact is modest. As a result, pharmacotherapy is increasingly recommended as an adjunct in selected pediatric patients, particularly those with severe or refractory obesity. In recent years, several anti-obesity medications, including glucagon-like peptide-1 (GLP-1) receptor agonists, have shown promise in pediatric populations, particularly adolescents. However, the pharmacologic options remain limited for younger children. This review summarizes current evidence on the efficacy and safety of available anti-obesity medications in children and adolescents, offering practical, age-based strategies to guide the appropriate clinical use of these medications as part of a comprehensive obesity-management plan.

It is unknown how many children with obesity are offered treatments aligned with clinical practice guidelines. This study examined electronic medical record data from a Midwest, USA, health system to quantify referrals to obesity treatment among patients 2–17 years old with obesity presenting for well-child visits in 2022 and/or 2023. Mixed-effects logistic regression models tested associations of referral placement with child characteristics, the Area Deprivation Index, and distance to specialty care. Of 14,893 patients, 591 (4.0%) received a referral. Referrals were associated with severe obesity ( p < 0.001), older age ( p < 0.001), proximity to specialty care ( p < 0.001), number of well-visits ( p ≤ 0.001), and identification with a minoritized race or ethnicity ( p < 0.05–0.001). Findings indicate a large gap from the current state of referrals to alignment with practice guidelines for pediatric obesity. Furthermore, research needs to explore and address barriers to referrals and treatment access.

Background: Pharmacological options for severe obesity in early childhood are limited. While lisdexamfetamine is approved for attention-deficit/hyperactivity disorder (ADHD) and binge eating disorder, its role in managing obesity in children without these conditions has not been well studied. This case series assessed the effect of lisdexamfetamine on weight in young children with severe obesity but without ADHD or binge eating disorder. Methods: We conducted a retrospective chart review of six children with severe obesity treated with lisdexamfetamine for weight management. Demographic, anthropometric, and metabolic data were collected. One patient had Prader–Willi syndrome (PWS); the others had no known syndromic obesity. Results: Median age at treatment initiation was 6.5 years (range: 4.5–14), with equal male and female distribution. Median treatment duration was 12 months (range: 12–24), and mean maximum tolerated lisdexamfetamine dose was 35 mg (range: 10–60). In patients without syndromic obesity (n = 5) including one child with hypothalamic obesity, lisdexamfetamine significantly reduced body mass index (BMI) percent of the 95th percentile at 12 months (median change –24%, range: −18 to −28, p = 0.031), equating to a 13.8% reduction in BMI. Height percentile remained unchanged ( p = 0.59). The patient with PWS did not achieve lasting weight loss. Three children reported decreased appetite. Conclusions: Lisdexamfetamine was associated with weight loss in young children with severe obesity without genetic syndromes. Further studies are warranted to assess the long-term efficacy and safety of lisdexamfetamine in the management of pediatric obesity.

Abstract There is limited data on the effect of antiobesity medications in individuals with Bardet-Biedl syndrome (BBS). Here, we present a case of an adult with BBS who experienced significant weight loss following treatment with a combination of topiramate and phentermine. A 31-year-old female with BBS, with homozygous pathogenic variant in the BBS2 gene, presented with obesity, dyslipidemia, and obstructive sleep apnea. At 29 years of age, her body mass index (BMI) was 43.3 kg/m2 (reference range 18.5-24.9 kg/m2), and she was initiated on 50 mg topiramate daily for migraine prophylaxis. With lifestyle modifications, BMI dropped to 40.5 kg/m2. Subsequently, phentermine 30 mg daily was added. Eight months after adding phentermine, BMI significantly decreased to 31.5 kg/m² (27% decrease in BMI), with improvement in glycemic and lipid parameters. She developed paranoia due to a social stressor prompting a brief hold of phentermine and resumption at a lower dose. This case highlights the weight loss response with phentermine and topiramate combination therapy in a patient with BBS. Further research is needed to explore the efficacy and safety of conventional antiobesity medications in isolation, as sequential or combination therapy to setmelanotide, to most effectively impact weight and metabolic burden in patients with BBS.

We assessed associations of pediatrician demographic characteristics with patient satisfaction (PS) scores. We performed a retrospective analysis of PS scores among pediatricians at a single academic institution and their associations with individual demographic features including gender, race, and geographic location of medical school education. We analyzed PS survey results for 153 pediatricians, 48.4% of whom were female. Males received higher scores in 4 out of 10 questions including “Likelihood of your recommending this care provider to others” ( P = .007). We observed similar findings for white pediatricians compared to Black, Indigenous, and People of Color (BIPOC) ( P = .033) and US medical school graduates compared to international school graduates ( P = .044). Overall, we observed that pediatricians who are female, BIPOC, or international medical school graduates receive lower PS scores than their counterparts. The impact of potential survey responder bias should be acknowledged when interpreting PS scores for pediatricians.

SummaryObjectiveTo examine change in weight status following initiation of lisdexamfetamine in children with attention deficit hyperactivity disorder (ADHD) and overweight or obesity.Study DesignA retrospective chart review included children aged 2 to <18 years treated with lisdexamfetamine for ADHD. Body mass index (BMI) data for up to 2 years after initiation of lisdexamfetamine were analysed using linear mixed effects models with autoregressive‐1 correlation structure on time of follow‐up per patient.ResultsThe analysis included 330 children ≤18 years, median age 10 years (interquartile range 8.1–13) comprising 55 children with severe obesity, 88 with mild‐moderate obesity, 131 with overweight and 56 with healthy weight, 68% male and 32% female. At 2 years after initiation of lisdexamfetamine in the severe obesity group, the BMI Z‐score decreased by −0.41 (95% confidence intervals [CI] [−0.57, −0.25], p < 0.001) and BMI percent of the 95th percentile decreased by −11.2% (95% CI [−15.8 to −6.7], p < 0.001). In the mild–moderate obesity group, BMI Z‐score decreased by −0.44 (95% CI [−0.56, −0.31], p < 0.001) and BMI% of the 95th percentile decreased by −11.1% at 24 months (95% CI [−13.9 to −8.4], p < 0.001). In the mild–moderate obesity and overweight groups, younger children (ages 4–10) showed greater reduction in their BMI (p < 0.001 and p = 0.029, respectively).ConclusionReduction in BMI for age was noted for up to 2 years following initiation of lisdexamfetamine in children with ADHD and overweight and obesity. Further studies are warranted to study the weight loss effect of lisdexamfetamine in children with obesity.

Abstract Context Pituitary adenomas and cysts are rare in pediatric patients and improved understanding can guide management recommendations. Objective To report incidence, presentation, management, and outcomes in a pediatric population-based cohort with pituitary adenomas and cysts, and to explore the relationship between these lesions and brain magnetic resonance imaging (MRI) rates, as well as lesion size and headaches with disease progression. Methods In this retrospective cohort study of pediatric patients (≤18 years) with incident pituitary adenomas and cysts in Olmsted County, MN, from 1976 to 2021, 234 unique patients were identified using diagnostic codes through the Rochester Epidemiology Project, with 37 confirmed cases of pituitary adenoma or cyst included. Incidence rates were calculated using census data. Descriptive statistics were used for extracted clinical data. Results Incidence of pediatric adenomas and cysts was 2.29 cases per 100 000 person-years. Of the 37 cases, 68% were nonfunctioning adenomas or cysts, 27% were prolactinomas, and there was 1 each of growth hormone (GH)– and thyrotropin (TSH)-secreting adenomas. Median lesion diameter was 5.5 mm (IQR, 4.0-8.0). Median follow-up was 7.4 years (IQR, 4.5-15.4). Four patients had disease progression which stabilized with second-line therapy. Brain MRI rates did not correlate with lesion incidence. No clinically meaningful relationship was found between lesion size or headache and disease progression. Conclusion Pituitary adenomas and cysts are rare in pediatric patients. Most are small, nonfunctioning, and stable on long-term follow-up. Larger studies on small nonfunctioning pituitary lesions are needed to enhance understanding of their natural history and develop long-term management recommendations.

AbstractPediatric obesity, characterized by a body mass index (BMI) at or above the 95th percentile for age, affects a substantial number of children and adolescents worldwide. Metabolic dysfunction‐associated steatotic liver disease (MASLD), formerly known as nonalcoholic fatty liver disease, represents a prominent hepatic manifestation of obesity and metabolic syndrome, emerging as the most prevalent hepatic disorder among pediatric patients and a significant contributor to liver transplantation in adults. The escalating prevalence of pediatric MASLD mirrors the alarming rise in childhood obesity rates over recent decades. While lifestyle modifications focusing on dietary changes and increased physical activity constitute the cornerstone of MASLD management, achieving and maintaining significant weight reduction remains challenging. Moreover, disease progression often persists despite standard‐of‐care interventions, warranting exploration into alternative therapeutic strategies. Pharmacological interventions, particularly, glucagon‐like peptide‐1 receptor agonists (GLP‐1RA), have shown promise in addressing pediatric obesity and its associated comorbidities, including MASLD. Recent studies have demonstrated the efficacy of GLP‐1RA in inducing weight loss and improving liver enzyme levels, suggesting a potential role in halting disease progression, and reducing the risk of major adverse liver outcomes. This review provides a comprehensive overview of the current pharmacotherapy landscape for pediatric MASLD, with a focus on novel agents such as GLP‐1RA. Furthermore, the manuscript proposes a practical algorithm to assist in integrating GLP‐1RA into the clinical management of pediatric patients with obesity and MASLD. Despite promising results, further research is warranted to elucidate the long‐term efficacy and safety of GLP‐1RA in pediatric populations.

Abstract Context Variants in melanocortin 4 receptor (MC4R) pathway-related genes have been associated with obesity. The association of these variants with cardiometabolic parameters are not fully known. Objective We compared the severity of obesity and cardiometabolic risk markers in children with MC4R pathway-related clinically reported genetic variants relative to children without these variants. Methods A retrospective chart review was performed in children with obesity who underwent multigene panel testing for monogenic obesity. Results Data on a total of 104 children were examined, with 93 (89%) identified as White. Thirty-nine (37.5%) patients had clinically reported variants in the MC4R pathway, and the remaining 65 patients did not have reported MC4R pathway-related variants. Among the MC4R-related variants, PCSK1 risk alleles were most common, reported in 15 children (14%). The maximum body mass index percent of the 95th percentile was not different between groups (P = .116). Low-density lipoprotein cholesterol (LDL-C) was not different between groups (P = .132). However, subgroup analysis demonstrated higher LDL cholesterol in children with the PCSK1 c.661A&gt;G risk allele relative to those with MC4R-related variant of uncertain significance (P = .047), negative genetic testing (P = .012), and those with non-MC4R related variants (P = .048). The blood pressure, fasting glucose, hemoglobin A1C, total cholesterol, alanine transaminase, and high-density lipoprotein cholesterol were not different between groups. Conclusion Variants in the MC4R pathway-related genes were not associated with severity of obesity and cardiometabolic risk markers except for the c.661A&gt;G PCSK1 risk allele, which was associated with higher LDL-C levels.

SummaryObjectiveRising prevalence of obesity has led to increased rates of prediabetes and diabetes mellitus (DM) in children. This study compares rates of prediabetes and diabetes using two recommended screening tests (fasting plasma glucose [FPG] and haemoglobin A1c [HbA1c]).Study DesignData were collected prospectively from 37 multi‐component paediatric weight management programs in POWER (Paediatric Obesity Weight Evaluation Registry).ResultsFor this study, 3962 children with obesity without a known diagnosis of DM at presentation and for whom concurrent measurement of FPG and HbA1c were available were evaluated (median age 12.0 years [interquartile range, IQR 9.8, 14.6]; 48% males; median body mass index 95th percentile [%BMIp95] 134% [IQR 120, 151]). Notably, 10.7% had prediabetes based on FPG criteria (100–125 mg/dL), 18.6% had prediabetes based on HbA1c criteria (5.7%–6.4%), 0.9% had DM by FPG abnormality (≥126 mg/dL) and 1.1% had DM by HbA1c abnormality (≥6.5%). Discordance between the tests was observed for youth in both age groups (10–18 years [n = 2915] and age 2–9 years [n = 1047]).ConclusionThere is discordance between FPG and HbA1c for the diagnosis of prediabetes and DM in youth with obesity. Further studies are needed to understand the predictive capability of these tests for development of DM (in those diagnosed with prediabetes) and cardiometabolic risk.