This systematic review aims to synthesize scientific evidence on the effects of oral nutritional supplementation (ONS) on health-related outcomes and nutritional biomarkers among children and adolescents with undernutrition. The review protocol was reported following the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) guidelines. A comprehensive keyword and reference search was conducted in seven electronic bibliographic databases: PubMed, Academic Search Complete, Academic Search Premier, CINAHL, Global Health, Web of Science, and Scopus. We identified 14 peer-reviewed articles reporting results from 13 unique studies (eight randomized controlled trials, four pre-post studies, and one observational study). Study participants were recruited from 14 countries/regions, with ages ranging from 1 to 14 years. Outcomes of interest include health-related outcomes (acute diseases and infections) and nutritional biomarkers (e.g., serum iron and zinc). Six of the eight studies examining acute diseases/infections and five of the seven examining nutritional biomarkers reported statistically significant improvement in some, but not all, outcomes. A meta-analysis of three studies found that ONS interventions reduce the incidence of upper respiratory tract infection (URTI) by 39% (95% CI, 0.42-0.91) in children at nutritional risk when compared to dietary counseling (DC) alone. This systematic review suggests that ONS interventions can improve certain health-related outcomes and nutritional biomarkers in undernourished children and adolescents. Specifically, the use of ONS significantly reduces the risk of URTI, highlighting its potential to enhance immune function and break the cycle of undernutrition and infection.
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