Maternal Diabetes and Risk of Childhood Cancer in Offspring: An Updated Systematic Review and Meta-Analysis of Observational Studies

Abstract

Background: The association between maternal diabetes mellitus and childhood cancer risk in offspring remains controversial. Previous meta-analyses have been limited by the exclusion of relevant studies and insufficient stratification by diabetes type. We conducted an updated systematic review and meta-analysis to comprehensively evaluate this association. Methods: We systematically searched PubMed, Embase, and Web of Science databases from inception through January 2026. Studies investigating the association between maternal diabetes (preexisting diabetes mellitus [PDM] or gestational diabetes mellitus [GDM]) and childhood cancer risk were included. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using random-effects or fixed-effects models based on heterogeneity assessment. Publication bias was evaluated using funnel plots and Egger’s test. Results: Twenty-six studies involving over 2 million participants were included. Maternal diabetes was significantly associated with increased risk of overall childhood cancer (OR = 1.29, 95% CI: 1.12–1.49, p = 0.0005; I² = 70.2%), childhood leukemia (OR = 1.33, 95% CI: 1.17–1.51, p < 0.0001; I² = 0.0%), and acute lymphoblastic leukemia (OR = 1.44, 95% CI: 1.27–1.64, p < 0.0001; I² = 0.0%). Subgroup analyses revealed that PDM was associated with higher risk estimates compared to GDM across all outcomes. Funnel plots indicated minimal publication bias for leukemia and ALL analyses. Conclusions: Maternal diabetes is associated with a significantly elevated risk of childhood cancer, particularly leukemia and acute lymphoblastic leukemia, in offspring. Preexisting diabetes confers greater risk than gestational diabetes. These findings underscore the importance of optimal glycemic control during pregnancy and highlight potential long-term consequences of the intrauterine diabetic environment on offspring health.