Maternal Gestational, Pregestational Diabetes Risk Factors for ALL in Offspring

Characteristics of the diabetic intrauterine environment may promote the development of acute lymphoblastic leukemia (ALL) in offspring, according to the results of a study examining the link between maternal diabetes and risk for childhood ALL.

“In this nationwide register-based cohort study, we found that the risk of childhood ALL in children born to women with pregestational or gestational diabetes was 2.9- and 1.7-fold increased, respectively,” wrote Signe Holst Søegaard, of the department of epidemiology research, Statens Serum Institut, Copenhagen, and colleagues in the British Journal of Cancer.

According to the study, the risk factors for childhood ALL are largely unknown. Research has shown that there is intrauterine development of preleukemic cell clones, and that ALL risk may be increased in children born to women with diabetes.

With this study, Søegaard and colleagues wanted to examine if risk for ALL varied by the type of maternal diabetes. They looked at associations between maternal pregestational diabetes or gestational diabetes and offspring risk of childhood ALL in a registry that included all single children born in Denmark between 1996 and 2015 (n = 1,187,482).

In the cohort, 492 children developed ALL before age 15. This was an annual incidence of 4.4 per 100,000 person years. In total, 5,409 children were born from women who had pregestational diabetes. Of these children, 6 developed ALL, all of whom had mothers diagnosed with diabetes before age 30. The researchers found that of the 24,306 children born to women with gestation diabetes, 14 developed ALL.

“The observed association with pregestational diabetes in our study is likely attributable to type 1 diabetes because the vast majority of these women had received insulin as first-time antidiabetic treatment and were diagnosed before age 30 years,” the researchers wrote. “However, the fact that gestational diabetes was also associated with offspring ALL risk suggests that the association with maternal diabetes is not exclusively related to the autoimmunity of type 1 diabetes.”

An adjusted model showed that childhood ALL risk among children born to women with pregestational or gestational diabetes was almost threefold higher and twofold higher, respectively, compared with children born to women without diabetes. Paternal diabetes did not alter risk for ALL in offspring.

“The increased ALL risk in children born to women with diabetes is unlikely to reflect shared genetic risk factors; rather it may reflect that circumstances characteristic of diabetic pregnancies such as intrauterine hyperglycemia promote offspring ALL development,” the researchers wrote. “In support hereof, we observed that children born to women with pregestational diabetes who developed ALL weighed on average 400 g more than those who did not, suggesting that maternal hyperglycemia was more pronounced in the former.”