Comparison of the vitamin D level between children with and without cow's milk protein allergy: a systematic review with meta-analysis.

Background: Vitamin D plays an important role in modulating immune responses, which may be associated with cow's milk protein allergy (CMPA). This meta-analysis aimed to comprehensively compare the vitamin D level between children with CMPA and healthy controls.

Methods: Studies comparing the vitamin D level between children with CMPA and healthy controls were comprehensively searched in PubMed, Web of Science, Embase, Wan Fang, CNKI, and VIP until April 2025.

Results: A total of 12 studies, involving 605 children with confirmed CMPA (CMPA group) and 558 healthy controls (control group) were included. The vitamin D level was lower in the CMPA group than in the control group [standardized mean difference (SMD) (95% confidence interval): -1.229 (-2.117, -0.340), P = 0.007]. Regarding subgroup analysis, the vitamin D level was lower in the CMPA group than in the control group in studies using mass spectrometry or automated immunoassay (P = 0.042), and was of no difference in those using enzyme-linked immunosorbent assay (P = 0.200) or chemiluminescence (P = 0.097). Moreover, the vitamin D level was lower in the CMPA group than in the control group in studies conducted in Asia (P < 0.001) or South America (P = 0.041), but not in studies conducted in Europe (P = 0.500). All included studies were high-quality. No publication bias was found. Sensitivity analyses indicated high robustness of the results.

Conclusion: Vitamin D is decreased in children with CMPA, indicating its potential association with CMPA. These findings may enhance the understanding of CMPA and guide the prevention or management of CMPA in children.