Maternal Medication Use and Childhood Cancer in Offspring-Systematic Review and Considerations for Researchers.

Sarah Hjorth,Maarit K Leinonen,Caroline H Hemmingsen,Anne Broe,Hedvig Nordeng,Marie Hargreave,Lina S Mørch,Susanne K Kjaer,Anton Pottegaard,Justine Bénévent

doi:10.1093/aje/kwab154

Abstract

Cancer is an important cause of childhood mortality, yet the etiology is largely unknown. A combination of pre- and postnatal factors is thought to be implicated, including maternal medication use. We aimed to provide: 1) a systematic review of peer-reviewed publications on associations between maternal medication use and childhood cancer, with a focus on study design and methodology; and 2) suggestions for how to increase transparency, limit potential biases, and improve comparability in studies on maternal medication use and childhood cancer. We conducted a systematic search in the PubMed, Embase, Scopus, Cochrane, and Web of Science databases to June 8, 2020. Altogether, 112 studies were identified. The reviewed studies were heterogeneous in study design, exposure, and outcome classification. In 21 studies (19%), the outcome was any childhood cancer. Of the 91 papers that reported on specific types of cancer, 62% did not report the cancer classification system. The most frequently investigated medication groups were sex hormones (46 studies, excluding fertility medications), and antiinfectives (37 studies). Suggestions for strengthening future pharmacoepidemiologic studies on maternal medication use and childhood cancer relate to choice of cancer classification system, exposure windows, and methods for identification of, and control for, potential confounders.

Highlights

1.1 Medication use during pregnancy1.1.1 Prevalence of medication use during pregnancyPregnancy is a period of many physiological changes in the maternal body [14]
Paper v used Poisson regression to estimate crude incidence rate ratios (IRRs) and incidence rate differences (IRDs) of childhood leukaemia with 95% confidence intervals (CI) comparing children prenatally exposed to nitrofurantoin, and children prenatally exposed to pivmecillinam
Neurodevelopment was assessed using 27 different psychometric instruments completed by health care professionals, 15 different psychometric instruments completed by parents, and five different psychometric instruments completed by teachers, not counting different versions of the same instrument (S4 Table)

Summary

Introduction

1.1 Medication use during pregnancy1.1.1 Prevalence of medication use during pregnancyPregnancy is a period of many physiological changes in the maternal body [14]. The aims were I: to describe the current literature, identify knowledge gaps and provide suggestions on how to improve the validity in future studies; II: to understand the patterns of analgesic and antibiotic use before, during, and after pregnancy, III: to investigate the association between prenatal exposure to non-steroidal anti-inflammatory drugs (NSAIDs) and child Attention-Deficit/Hyperactivity Disorder (ADHD); and IV: to investigate the association between prenatal exposure to nitrofurantoin and childhood leukaemia. Studies have suggested increased risks of childhood leukaemia after prenatal exposure to antibiotics, nitrofurantoin These findings may be related to the underlying maternal infection. The only large study to investigate at the individual antibiotic substance level and specific types of childhood cancers, found associations with leukaemia for exposure to some commonly used antibiotics, including nitrofurantoin (HR 1.56, 95% CI 1.02-2.37), when compared to unexposed children (7). The objective of the present study was to investigate the risk of childhood leukaemia after prenatal exposure to nitrofurantoin compared to pivmecillinam

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Conclusion