Maternal diabetes and risk of childhood malignancies in the offspring: a systematic review and meta-analysis of observational studies.

Abstract

Diabetes mellitus (DM) is widely recognized as a risk factor for diverse cancers in adults. However, the association between maternal diabetes and risk of childhood cancer in the offspring has so far not been well studied. We thus conducted a meta-analysis to evaluate the role of maternal diabetes on the risk of childhood cancer. We performed a comprehensive literature search to identify eligible studies published up to June 20, 2020, including the PubMed, Web of science and Embase databases. Summary odds ratios (OR) and 95% confidence intervals (CI) were computed using a random-effects model (I2 ≥ 25%) or a fixed-effect model (I2 < 25%). Totally, sixteen case-control and six cohort studies on the risk of childhood cancer associated with maternal diabetes were included. Overall, children of diabetic women had a significantly increased risk in childhood malignancy (OR, 1.30; 95% CI, 1.10-1.53). Notably, a significantly elevated risk of childhood cancer in the offspring was found for women with pre-existing diabetes (OR, 1.41; 95% CI, 1.17-1.70), but not for women with gestational diabetes mellitus (GDM) (OR, 1.10; 95% CI, 0.94-1.28). For site-specific cancers, maternal diabetes was associated with a higher risk of leukemia in offspring (OR, 1.30; 95% CI, 1.15-1.48), especially for acute lymphoblastic leukemia (OR, 1.44; 95% CI, 1.27-1.64). However, no significant associations were observed between maternal diabetes and the risk of lymphomas and retinoblastoma. Our meta-analysis indicates that maternal diabetes is associated with an increased risk of childhood cancer in the offspring, particularly for acute lymphoblastic leukemia. Future study should investigate the underlying biological mechanisms behind the association.