Meta-analysis links maternal infection in pregnancy to childhood ALL risk

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Pediatric blood & cancer Published May 1, 2026 Medically reviewed May 1, 2026 Study authors: Chen Xi, Wang Shiping, Yu Weixia, Liu Minghong, Cai Jianzheng, Wang Haifang PubMed ↗ DOI ↗ By Dr. Amelia Tan, PhD · Internal Medicine & Chronic Disease

Key Takeaway

Consider maternal influenza prevention during pregnancy to potentially reduce childhood ALL risk, but interpret associational findings cautiously.

This systematic review and meta-analysis synthesized 26 studies from PubMed, Web of Science, Embase, and Cochrane Library to evaluate the association between maternal infection during pregnancy and risk of childhood acute lymphoblastic leukemia (ALL) in offspring.

Any maternal infection was associated with a pooled adjusted odds ratio of 1.18 (95% CI: 1.03-1.35). The most robust association was observed for influenza (OR 1.90; 95% CI: 1.27-2.83). Borderline significant associations were found for Epstein-Barr virus (OR 1.45; 95% CI: 1.00-2.09) and respiratory tract infections (OR 1.18; 95% CI: 1.00-1.39). Combined genitourinary infections showed a significant but likely artifactual signal (OR 1.44; 95% CI: 1.03-2.01), not replicated in tract-specific analyses.

Limitations include potential confounding, particularly for genitourinary infections, and the observational nature of included studies. Sensitivity analyses and GRADE assessment were used to evaluate evidence certainty.

Clinically, these findings underscore the importance of influenza prevention and timely management of prenatal infections, though causality cannot be inferred from this association.

Study Details

Study typeMeta analysis

EvidenceLevel 1

PublishedMay 2026

PMID41834321

View Original Abstract ↓

OBJECTIVE: To systematically evaluate the association between maternal infection during pregnancy and the risk of childhood acute lymphoblastic leukemia (ALL) in offspring through a comprehensive meta-analysis of adjusted and pathogen-specific data. METHODS: We systematically searched PubMed, Web of Science, Embase, and Cochrane Library from inception to January 7, 2025. Two reviewers performed data extraction and assessed study quality using the Joanna Briggs Institute (JBI) checklist. Pooled odds ratios (ORs) were calculated for any infection, specific pathogen infection, and anatomical sites of infection. Sensitivity analyses and the GRADE approach were employed to evaluate the robustness and certainty of the evidence. RESULTS: A total of 26 studies were included. The pooled adjusted OR for "any infection" was 1.18 (95% confidence interval [CI]: 1.03-1.35) after sensitivity analysis. Influenza demonstrated the most robust association (adjusted odds ratio [OR] 1.90; 95% CI: 1.27-2.83). In contrast, Epstein-Barr virus (adjusted OR 1.45; 95% CI: 1.00-2.09) and respiratory tract infections (adjusted OR 1.18; 95% CI: 1.00-1.39) showed only borderline significance. Analysis by anatomical site revealed a significant but likely artifactual signal for combined genitourinary infections (OR 1.44; 95% CI: 1.03-2.01), which was not replicated in more populous, tract-specific syntheses. CONCLUSIONS: Maternal infections during pregnancy, particularly influenza, are associated with an increased risk of childhood ALL, and borderline associations were observed for EBV and respiratory infections. The observed risk from genitourinary infections may have come from confounding. These findings emphasize the clinical importance of influenza prevention and the timely management of prenatal infections.