Reference Curves for Metabolic Syndrome Indicators in Children and Adolescents: A Global Systematic Review

We aimed to summarise recent evidence on age- and sex-specific reference curves for metabolic syndrome (MetS) indicators in paediatric populations.

There is a lack of consensus regarding diagnostic thresholds for MetS in children and adolescents, leading to challenges in its early identification and intervention. A systematic search was performed in PubMed/Medline, Web of Science and Scopus, covering the period between January 2018 and February 2025. Three researchers evaluated 8,529 studies according to the inclusion criteria. Finally, 46 articles that reported reference values for at least one metabolic indicator: waist circumference, fasting glucose, glycated haemoglobin, homeostatic model assessment for insulin resistance, high-density lipoprotein cholesterol, triglycerides, systolic or diastolic blood pressure, in children aged 0 to 18 years were included in the review and data synthesis. The age-specific trends in each MetS indicator were assessed by calculating the median reference curves along with the lower and upper percentile bounds. Overall, there has been a substantial heterogeneity in the reported reference values for waist circumference and glucose metabolism biomarkers. Comparatively smaller variations were observed for blood pressure and lipid parameters. Limited data were available for young age groups (0-4 years) and there have been substantial differences in study methodologies including study design, assays and statistical approaches used to derive reference curves. This systematic review highlighted the substantial inconsistencies in the reported reference curves for MetS indicators in children and adolescents. There is a pressing need for deriving harmonized reference curves for paediatric MetS from diverse populations.