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

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J Pediatr. 2019 Dec 3. pii: S0022-3476(19)31457-X. doi: 10.1016/j.jpeds.2019.10.046. [Epub ahead of print] Maternal Infection in Pregnancy and Childhood Leukemia: A Systematic Review and Meta-analysis.

He JR¹, Ramakrishnan R², Hirst JE³, Bonaventure A⁴, Francis SS⁵, Paltiel O⁶, H?berg SE⁷, Lemeshow S⁸, Olsen S⁹, Tikellis G¹⁰, Magnus P⁷, Murphy MFG³, Wiemels JL¹¹, Linet MS¹², Dwyer T¹³.
Author information

1 Nuffield Department of Women's and Reproductive Health, University of Oxford, Oxford, UK; Division of Birth Cohort Study, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China; The George Institute for Global Health, University of Oxford, Oxford, UK. 2 Nuffield Department of Women's and Reproductive Health, University of Oxford, Oxford, UK; The George Institute for Global Health, University of Oxford, Oxford, UK; University of New South Wales, Sydney, Australia. 3 Nuffield Department of Women's and Reproductive Health, University of Oxford, Oxford, UK. 4 Department of Health Sciences, University of York, York, UK; Department of Non-Communicable Disease Epidemiology, London School of Hygiene & Tropical Medicine, London, UK. 5 Division of Epidemiology, School of Community Health Sciences, University of Nevada, Reno, NV. 6 Braun School of Public Health, Hadassah-Hebrew University Medical Center, Jerusalem, Israel. 7 Centre for Fertility and Health, Norwegian Institute of Public Health, Oslo, Norway. 8 Division of Biostatistics, College of Public Health, Ohio State University, Columbus, OH. 9 Center for Fetal Programming, Department of Epidemiology Research, State Serum Institute, Copenhagen, Denmark. 10 Population Epidemiology, Murdoch Children's Research Institute, Royal Children's Hospital, University of Melbourne, Melbourne, Australia. 11 Department of Preventative Medicine, University of Southern California, Los Angeles, CA. 12 Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD. 13 Nuffield Department of Women's and Reproductive Health, University of Oxford, Oxford, UK; The George Institute for Global Health, University of Oxford, Oxford, UK. Electronic address: terence.dwyer@georgeinstitute.ox.ac.uk.

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.
Copyright ? 2019 Elsevier Inc. All rights reserved.


KEYWORDS:

Prenatal; childhood cancer; in utero

PMID: 31810630 DOI: 10.1016/j.jpeds.2019.10.046