Secondary Causes of Obesity in Children: A Systematic Review and Meta-Analysis
DOI:
https://doi.org/10.64149/Keywords:
childhood obesity; secondary obesity; monogenic obesity; Prader-Willi syndrome; hypothalamic obesity; meta-analysis; systematic review; growth hormone; ROBINS-I; MC4R.Abstract
Background: Secondary causes account for a clinically insignificant minority of childhood obesity; however, prevalence estimates, diagnostic yields, and management outcomes across specific etiological subtypes have not been quantitatively synthesized from primary study data.
Objectives: To conduct a systematic review and meta-analysis of primary studies examining the prevalence, clinical features, diagnostic approaches, and management outcomes of secondary causes of obesity in children and adolescents aged 0–18 years.
Methods: PubMed/MEDLINE, Web of Science, Scopus, and Embase were searched from January 2000 to December 2025. Only primary studies (cohort studies, randomized controlled trials, cross-sectional studies, clinical trials, and case series with ≥5 patients) were included. Two reviewers independently screened studies and extracted data. Risk of bias was assessed using ROBINS-I for observational studies and Cochrane RoB 2 for the RCT. Random-effects meta-analyses were performed for outcomes reported in ≥2 studies, and heterogeneity was quantified using I² and Cochran’s Q. Publication bias was assessed using Egger’s test with k≥3.
Results: Twelve primary studies (N > 3,000 children) met the inclusion criteria. The meta-analysis demonstrated a pooled MC4R deficiency prevalence of 3.6% (95% CI 2.1–5.4%; I²=41%) among children with severe early-onset obesity. Next-generation sequencing yielded a genetic diagnosis in 9.5% (95% CI 7.2–12.1%; I²=28%). Growth hormone therapy in Prader-Willi syndrome significantly reduced body mass index SDS (pooled MD −0.82; 95% CI −1.14 to −0.50; I²=19%). Hypothalamic obesity developed in 42.5% (95% CI 27.1–58.7%; I²=67%) of children following craniopharyngioma treatment. Leptin/leptin-receptor replacement therapy produced marked weight reduction (pooled MD −8.4 kg; 95% CI −12.1 to −4.7; I²=0%). The risk of bias was low in four studies and moderate in eight.
Conclusions: This meta-analysis provides precise pooled estimates for the prevalence and treatment effects of major secondary obesity subtypes in children. Growth hormone therapy in PWS achieves consistent, clinically meaningful BMI SDS reduction. Genetic testing in children with severe early-onset obesity yields a diagnosis in approximately 1 in 10 children. Future adequately powered RCTs are urgently needed to evaluate hypothalamic obesity and novel targeted pharmacotherapies.
