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

2026-06
Clinical nutrition (Edinburgh, Scotland) 61
- Hala AbuSalameh
- Ruijie Li
- Nubia Maria de Oliveira
- Judy Schoeman
- Minke Huibers
- Mirjam van den Brink
- Amy L Lovell
- Paul C Rogers
- Raquel Revuelta Iniesta

PubMed: 41967219
DOI: 10.1016/j.clnu.2026.106653

Study Design

Type: Meta-Analysis
Population: children and young people (CYP) with cancer undergoing cancer therapy
Methods: systematic review and meta-analysis searching PubMed, EMBASE and Cochrane Library; random-effects meta-analyses pooled RRs, ORs or HRs with 95% CIs

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.

Research Insights

Copper→Improved Event-Free Survival
Zinc, vitamin B12, and copper showed no significant pooled associations with EFS
Effect
Neutral
Effect size
Small
Selenium→Improved Event-Free Survival
Zinc, vitamin B12, and copper showed no significant pooled associations with EFS
Effect
Neutral
Effect size
Small
Selenium→Improved Overall Survival
Lower selenium was linked to poorer survival in individual studies
Effect
Beneficial
Effect size
Moderate
Selenium→Reduced Treatment Complications
consistently associated with more treatment complications
Effect
Beneficial
Effect size
Moderate
Vitamin B12→Improved Event-Free Survival
Zinc, vitamin B12, and copper showed no significant pooled associations with EFS
Effect
Neutral
Effect size
Small
Vitamin B9→Reduced Febrile Neutropenia Risk
lower folate showed the strongest association with toxicity, with significantly increased risks of febrile neutropenia (RR 2.22)
Effect
Harmful
Effect size
Large
Vitamin B9→Reduced Neutropenia Risk
lower folate showed the strongest association with toxicity, with significantly increased risks of ... neutropenia (RR 2.30)
Effect
Harmful
Effect size
Large
Vitamin B9→Reduced Thrombocytopenia Risk
lower folate showed the strongest association with toxicity, with significantly increased risks of ... thrombocytopenia (RR 2.80)
Effect
Harmful
Effect size
Large
Zinc→Improved Event-Free Survival
Zinc, vitamin B12, and copper showed no significant pooled associations with EFS
Effect
Neutral
Effect size
Small

Adverse Events Reported

Vitamin B9→febrile neutropenia
Lower folate showed the strongest association with toxicity, with significantly increased risks of febrile neutropenia (RR 2.22)
Finding
Increased risk
Magnitude
RR 2.22
Significant
Yes
Vitamin B9→neutropenia
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).
Finding
Increased risk
Magnitude
RR 2.30
Significant
Yes
Vitamin B9→thrombocytopenia
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).
Finding
Increased risk
Magnitude
RR 2.80
Significant
Yes
Selenium→treatment complications
Lower selenium was linked to poorer survival in individual studies and consistently associated with more treatment complications
Finding
Increased risk
Copper→treatment complications
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.
Finding
Reported
Zinc→treatment complications
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.
Finding
Reported
Vitamin B12→treatment complications
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.
Finding
Reported