Maternal Infection in Pregnancy and Childhood Leukemia: A Systematic Review and Meta-analysis

Jian Rong He, Rema Ramakrishnan, Jane E. Hirst, Audrey Bonaventure, Stephen S. Francis, Ora Paltiel, Siri E. Håberg, Stanley Lemeshow, Sjurdur Olsen, Gabriella Tikellis, Per Magnus, Michael F.G. Murphy, Joseph L. Wiemels, Martha S. Linet, Terence Dwyer*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

20 Scopus citations


Objective: To summarize the published evidence regarding the association between maternal infection during pregnancy and childhood leukemia. Study design: In this systematic review and meta-analysis (PROSPERO number, CRD42018087289), we searched PubMed and Embase to identify relevant studies. We included human studies that reported associations of at least one measure of maternal infection during pregnancy with acute lymphoblastic leukemia (ALL) or all childhood leukemias in the offspring. One reviewer extracted the data first using a standardized form, and the second reviewer independently checked the data for accuracy. Two reviewers used the Newcastle-Ottawa Scale to assess the quality of included studies. We conducted random effects meta-analyses to pool the ORs of specific type of infection on ALL and childhood leukemia. Results: This review included 20 studies (ALL, n = 15; childhood leukemia, n = 14) reported in 32 articles. Most (>65%) included studies reported a positive association between infection variables and ALL or childhood leukemia. Among specific types of infection, we found that influenza during pregnancy was associated with higher risk of ALL (pooled OR, 3.64; 95% CI, 1.34-9.90) and childhood leukemia (pooled OR, 1.77; 95% CI, 1.01-3.11). Varicella (pooled OR, 10.19; 95% CI, 1.98-52.39) and rubella (pooled OR, 2.79; 95% CI, 1.16-6.71) infections were also associated with higher childhood leukemia risk. Conclusions: Our findings suggest that maternal infection during pregnancy may be associated with a higher risk of childhood leukemia.

Original languageAmerican English
Pages (from-to)98-109.e8
JournalJournal of Pediatrics
StatePublished - Feb 2020
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2019 Elsevier Inc.


  • Prenatal
  • childhood cancer
  • in utero


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