Effect of Fortified Formula on Growth and Nutritional Status in Young Children: A Systematic Review and Meta-Analysis

Previous reviews of the effect of young child formulas on health outcomes in infants and toddlers have been inconclusive. In this study, we undertook a contemporary synthesis of studies investigating the effects of consuming fortified milk beverages (compared to cow's milk or unfortified comparator formula) on growth and/or nutritional status in children 1-3 years of age. Five electronic databases were searched (PubMed, Web of Science, Scopus, ProQuest, and Cochrane Library) for randomised controlled trials comparing fortified milk against control milk in young children (9-48 months), published between January 1990 and June 2022. Outcomes were growth, body composition, biochemical markers, and/or nutritional status. Mean differences (MD) were pooled using random-effects meta-analysis where there were >= 3 studies. The risk of bias was assessed using the Cochrane Risk of Bias 2.0 tool. Nineteen articles (12 studies; n = 4795) met the inclusion criteria. Heterogeneity was substantial, likely attributable to considerable variation in study characteristics. Fortified milk was associated with increased weight gain (MD = 0.14 kg [95% CI 0.06, 021], p = 0.0003) compared with control milk. Subgroup analyses demonstrated increases in weight in lower-income countries, and in studies with intervention periods > 6 months. There were no effects of fortified milks on other anthropometric measures. Haemoglobin (MD = 3.76 g/L [95% CI 0.17, 7.34], p = 0.04) and ferritin (MD = 0.01 nmol/L [95% CI 0.00, 0.02], p = 0.02) concentrations were increased in infants consuming fortified milks. Fortified milk beverages appear to offer a safe and acceptable source of complementary nutrition as a short-term strategy for addressing nutritional deficits and may modestly promote weight gain in vulnerable populations when provided for periods > 6 months. This study was prospectively registered with PROSPERO (CRD42022339920) and funded by the Infant Nutrition Council.