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Meta-Analysis
. 2020 Feb:217:98-109.e8.
doi: 10.1016/j.jpeds.2019.10.046. Epub 2019 Dec 4.

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

Jian-Rong He  1 , Rema Ramakrishnan  2 , Jane E Hirst  3 , Audrey Bonaventure  4 , Stephen S Francis  5 , Ora Paltiel  6 , Siri E Håberg  7 , Stanley Lemeshow  8 , Sjurdur Olsen  9 , Gabriella Tikellis  10 , Per Magnus  7 , Michael F G Murphy  3 , Joseph L Wiemels  11 , Martha S Linet  12 , Terence Dwyer  13
Affiliations
Meta-Analysis

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

Jian-Rong He et al. J Pediatr. 2020 Feb.

Abstract

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.

Keywords: Prenatal; childhood cancer; in utero.

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Conflict of interest statement

The other authors declare no conflicts of interest.

Figures

Figure 1.
Figure 1.
Study selection flow chart.
Figure 2.
Figure 2.
Qualitative summary of a proxy of any infection for A, ALL and B, all childhood leukemias. EBV, Epstein-Barr virus; HHV-6, human herpesvirus type 6.
Figure 3.
Figure 3.
Meta-analysis of specific type of infection for ALL (A, nonlaboratory data; B, laboratory data). The study of Fine et al 1985 used both self-report or medical record data for CMV.
Figure 4.
Figure 4.
Meta-analysis of specific type of infection for all childhood leukemias (A, nonlaboratory data; B, laboratory data). The study of Fine et al 1985 used both self-report or medical record data for CMV.
Figure 5.
Figure 5.
Funnel plots of influenza for A, ALL and B, all childhood leukemias.
See this image and copyright information in PMC

Comment in

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