Secondary Causes Of Obesity In Children: An Umbrella Review

Abstract

Background: A basic energy imbalance drives most childhood obesity. However, secondary causes account for a highly specific minority of cases that require targeted medical care. Researchers have published numerous systematic reviews on specific subtypes of secondary obesity in children; however, no review has synthesized this evidence at the review level.

Objectives: We conducted a umbrella review of existing studies to determine the prevalence, clinical features, diagnostic methods, and management plans for secondary causes of childhood obesity.

Methods: We searched the PubMed/MEDLINE, Web of Science, Scopus, and Embase databases for systematic reviews, meta-analyses, and clinical guidelines published between January 2000 and December 2025. We focused only on children and adolescents (aged 0–18 years). We checked the quality of their methods using AMSTAR-2, and then we ran a narrative synthesis across the reviews for each specific cause.

Results: We identified 30 eligible reviews, providing data from > 15,000 children. We grouped the findings into five main categories: monogenic obesity (MC4R deficiency accounts for 2–5% of severe early-onset cases), genetic syndromes (Prader-Willi syndrome occurs in 1 out of every 15,000–25,000 children), hypothalamic obesity (occurs in 25–60% of patients after craniopharyngioma), obesity caused by medications (affects 15–30% of children taking atypical antipsychotics), and endocrine causes (less than 1%). The AMSTAR-2 ratings varied from low to high quality. We found the strongest and most consistent evidence for using growth hormone therapy in Prader-Willi syndrome and for managing weight spikes associated with antipsychotics.

Conclusions: This umbrella review proves that secondary causes account for 5–10% of childhood obesity and demand highly tailored treatment plans. Specific drugs (e.g., setmelanotide, recombinant leptin, and growth hormone) offer significant benefits for certain subtypes. Physicians should apply a strict red-flag checklist to identify such cases. Future reviews should incorporate the latest genomic data as precision medicine improves.