A Comparison of Amino Acid-Based, Hydrolyzed, and Soy-Based Formulas on Growth of Pediatric Patients with Cow’s Milk Allergy: A Systematic Review and Meta-Analysis of Clinical Trials

Background: Some studies have explored the effects of amino acid-based formulas (AAF), extensively hydrolyzed formulas (EHF), and soy-based formulas (SF) on growth indices, weight-for-age z-scores, length-for-age z-scores, and weight in children with cow's milk allergy (CMA). Aims: This review aimed to evaluate and differentiate the effectiveness of AAF, EHF, and SF on growth parameters in children with CMA. Methods: A systematic review was conducted in three databases-PubMed, Web of Science, and Scopus-up to March 2023 to identify eligible studies. Eight articles were analyzed in this study. Effect sizes were reported as weighted mean difference with 95% confidence intervals (CI). Statistical heterogeneity between studies was assessed using Cochran's Q-test. The risk of bias was evaluated using the ROBINS-I tool. Results: A total of eight studies, encompassing 469 participants, met the inclusion criteria. The meta-analysis demonstrated a significant positive effect of the AAF and EHF on weight and weight-for-age z-scores, while no significant changes were observed for length-for-age z-scores. Furthermore, pooled effect sizes indicated that AAF had a more pronounced impact in weight-for-age z-scores (+0.30) compared with EHF (+0.25). Soy-based formulas had negligible effects on growth parameters. Conclusion: The findings suggest that AAF and EHF are more effective in improving growth parameters, particularly weight-for-age z-scores, in children with CMA compared with SF. Among the formulas studied, AAF showed the greatest positive impact on weight-for-age z-scores. These results highlight the importance of formula selection for optimizing growth outcomes in children with CMA.