The association between micronutrient status and clinical outcomes in children with cancer undergoing treatment: A systematic review and meta-analysis

Background & aims: Micronutrient abnormalities are common in children and young people (CYP) with cancer, yet their clinical implications remain unclear. This systematic review and meta-analysis examined the prevalence of micronutrient abnormalities and their associations with treatment complications and prognostic indicator outcomes in CYP undergoing cancer therapy. Methods: We searched PubMed, EMBASE and Cochrane Library (inception–April 2025) for studies evaluating blood micronutrient status in CYP (0–21 years) with cancer. Primary outcomes were treatment-related toxicities; secondary outcomes were prognostic indicators outcomes including overall survival (OS) and event free survival (EFS). Two reviewers screened, extracted data and assessed risk of bias (JBI). Where ≥2 studies reported similar outcomes, random-effects meta-analyses pooled RRs, ORs or HRs with 95% CIs. Results: Ten studies involving 1,229 CYP were included. Micronutrient abnormalities were frequent: folate deficiency ranged from 10 to 56%, selenium 20–58%, and zinc 30–70%, with several micronutrients declining during treatment. Lower folate showed the strongest association with toxicity, with significantly increased risks of febrile neutropenia (RR 2.22), neutropenia (RR 2.30), and thrombocytopenia (RR 2.80). Lower selenium was linked to poorer survival in individual studies and consistently associated with more treatment complications, although pooled EFS estimates were non statistically significant. Zinc, vitamin B12, and copper showed no significant pooled associations with EFS, and evidence for vitamins A, C, E, and magnesium was limited or inconsistent. Conclusions: Micronutrient abnormalities, particularly low folate, selenium, and zinc, are prevalent in CYP undergoing cancer treatment, with folate showing the most consistent associations with treatment complications. This supports the need for routine monitoring; however, large international multicentre population-based and international mechanistic studies are warranted. PROSPERO Registration: Registration ID: CRD42025646467. Link: https://www.crd.york.ac.uk/PROSPERO/recorddashboard.