gms | German Medical Science

Introduction: Infections during pregnancy might elevate the risk of childhood cancer by affecting foetal immunity and genetics. Existing evidence, predominantly focused on leukaemia, is inconclusive. Therefore, we conducted a systematic review and meta-analysis investigating the association between prenatal infections and diverse childhood cancers, to enhance understanding of childhood cancer aetiology.

Methods: We systematically searched PubMed and Web of Science up to November 30, 2023. Our study protocol was preregistered in PROSPERO (ID: CRD42023483706). Eligible studies included original human epidemiological studies on maternal infections during pregnancy and childhood cancer, with appropriate reference groups. We evaluated study quality and risk of bias using a self-developed scoring tool. Pooled odds ratios (ORs) and 95% confidence intervals (95%CIs) were calculated using random-effect models. Heterogeneity was examined in subgroups based on study characteristics, confounder control, exposure and outcome assessment. Publication bias was assessed using Egger tests and funnel plots.

Results: Forty-three studies (36 case-control and 7 cohort studies) involving 7,550,298 participants were included with 20 analyses of 8 different infections and 6 diverse childhood cancers. Prenatal infections were associated with increased overall cancer risk (OR=1.37, 95%CI: 1.17-1.61). Viral infections showed elevated risks for leukaemia (OR=1.44, 95%CI: 1.02-2.02) and acute lymphoblastic leukaemia (ALL) (OR=1.70, 95%CI: 1.18-2.43). Influenza exhibited increased risks of leukaemia (OR=1.70, 95%CI: 1.07-2.72) and ALL (OR=2.62, 95%CI: 1.35-5.11). Genitourinary tract infections were associated with increased risks of leukaemia (OR=1.72, 95%CI: 1.25-2.38) and solid tumors (OR=1.98, 95%CI: 1.12-3.52). Other analyses showed no significant associations. Subgroup analyses revealed varying heterogeneity. Significant publication bias was observed in analyses on overall infections and all cancers.

Conclusion: The observed findings show that infections during pregnancy are associated with increased childhood cancer risk, especially viral and genitourinary tract infections. However, varying heterogeneity, methodological constraints, and publication bias, warrant cautious interpretation. Large cohort studies with valid assessments of maternal infection and detailed confounder information are needed to underpin these associations.

The authors declare that they have no competing interests.

The authors declare that an ethics committee vote is not required.