Maternal hormonal contraception use and childhood cancer risk: a systematic review and meta-analysis

Observational studies have linked maternal hormonal contraception use to childhood cancer risk, but findings are inconsistent. A systematic review was conducted of this potential relationship. A systematic search was performed in PubMed, Embase, Scopus, Cochrane, and Web of Science databases until April 9, 2025. Studies reporting maternal hormonal contraception use before or during pregnancy and childhood cancer risk (0-19 years) were eligible. We included studies providing risk estimates in English or Scandinavian languages. Newcastle-Ottawa Scale was used to assess study quality. Meta-analysis using fixed and random effects was used to pool relative risks (RRs) with 95% confidence intervals (CIs) for childhood cancer according to maternal hormonal contraception use (1) up to or during pregnancy, and (2) exclusively during pregnancy. We included 27 studies (24 case-control and 3 cohort), totaling 11,067 childhood cancer cases. Maternal hormonal contraception use up to and during pregnancy increased risk of any childhood cancer (RR = 1.18; 95% CI = 1.10-1.26), leukemia (RR = 1.24; 95% CI = 1.06-1.45), and lymphoid leukemia (RR = 1.17; 95% CI = 1.06-1.28). Exposures during pregnancy showed higher risk estimate for any cancer (RR = 1.32; 95% CI = 1.12-1.56) and leukemia (RR = 1.63; 95% CI = 1.07-2.49). Most studies were moderate (70%) or high (26%) quality. Maternal hormonal contraception use may increase childhood cancer risk, particularly for leukemia, and during pregnancy. Further prospective studies are needed, focusing on specific hormonal contraception substances and exposure timing.