Hydrolyzed Rice Formula for the Management of Cow’s Milk Allergy in Infants and Young Children: A Systematic Review of Randomized Controlled Trials

Background/Objectives: Hydrolyzed rice formula (HRF) is an alternative to extensively hydrolyzed cow’s milk formula (eHF) or soy formula for infants with cow’s milk allergy (CMA). We evaluated its effects on acquisition of tolerance to cow’s milk protein, growth, safety, and tolerability in infants and young children with confirmed CMA. Methods: PubMed, Embase, and CENTRAL were searched through 26 May 2026 without language restrictions (PROSPERO CRD420261445267). Risk of bias was assessed using the Cochrane Risk of Bias 2 tool for tolerance acquisition and growth, and certainty of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) for tolerance acquisition. Owing to heterogeneity, results were synthesized narratively. Results: Four RCTs (321 participants; range, 16–108) were included. Two reported tolerance acquisition, assessed at 12 months of age in one trial and during 12 months of follow-up in the other. Estimates were imprecise and in opposite directions: RR 0.84 (95% CI 0.53–1.32; 18/41 vs. 21/40) and RR 1.35 (95% CI 0.95–1.91; 26/36 vs. 22/41). Certainty of evidence was very low. Growth did not differ significantly between HRF and eHF in two trials. In another trial, an unadjusted advantage for HRF and casein hydrolysate over soy formula did not persist after correction for multiple comparisons. Allergic reactions were rare, with no clear differences in adverse events between formulas. Conclusions: Available evidence does not establish whether HRF is equivalent, superior, or inferior to eHF or soy formula for tolerance acquisition or growth in infants with CMA. Adequately powered RCTs using standardized outcome definitions are needed.