For any cancer type, researchers found that children exposed to gestational diabetes have around 20% more risk for developing a cancer before age 14.

“As clinicians, we still do not fully understand the cause of most childhood cancers, which makes prevention very challenging,” explains Nathalie Auger, MD. “It is important to identify potential risk factors, especially those that can be modified. Adult studies suggest that high blood sugar may be a cancer risk factor. Similarly, in utero exposure to high sugar levels may be carcinogenic to children. Gestational diabetes mellitus, which can often be prevented and controlled, is thus an interesting and potentially modifiable exposure to study.”

For a paper published in Diabetes Care, Dr. Auger and colleagues examined the link between gestational diabetes and early versus late childhood cancer. “The few prior studies of the association between gestational diabetes and childhood cancer have been inconclusive,” she says. “Many of the studies did not stratify by the age at which cancer developed. We hypothesized that the carcinogenic effect of in utero hyperglycemia may fade after birth and, therefore, only impact cancer in early childhood.”

Children Exposed to Gestational Diabetes in Utero Have 20% Higher Cancer Risk

To assess their hypothesis, the researchers conducted a retrospective cohort study of more than 1 million children born in Quebec between 2006 and 2019. They used a centralized database to identify all children hospitalized before age 14. “Children are linked with their mother’s health file, so we were able to know who was exposed to gestational diabetes in utero,” Dr. Auger says. “We then stratified our analyses by the age at which cancer occurred to verify if there was an association with gestational diabetes, controlling for potential confounding factors.”

Dr. Auger and colleagues found that 8.2% of children in the study cohort were exposed to gestational diabetes. During 7.6 million person-years of follow-up, 1,702 children developed cancer. “We observed that for any cancer type, children exposed to gestational diabetes have around 20% more risk for developing a cancer before age 14,” Dr. Auger adds. “For leukemia, the most common cancer in children, the risk can increase up to 38% to 90%, depending on the leukemia subtype. Results were not statically significant for solid tumors, but our research nevertheless suggests that children exposed to gestational diabetes could have a greater risk (Table).”

Gestational diabetes was most strongly linked with cancer at the youngest ages and decreased as children got older, according to the study team. In children younger than 2, gestational diabetes was associated with 1.47 times greater risk for any cancer, 1.61 times greater risk for blood cancer, and 1.44 times greater risk for solid cancer, when compared with no gestational diabetes. However, no significant link was observed between gestational diabetes and blood or solid cancers beyond age 2, with no associations seen among participants older than 6.

Screening for and Controlling Gestational Diabetes Is Critical

General practitioners, endocrinologists, and obstetricians/gynecologists should view this study as a critical reason to screen and control gestational diabetes in pregnant women, Dr. Auger notes. “Controlling hyperglycemia in pregnancy will not only optimize fetal growth but may also reduce the risk for childhood cancer,” she says. “While one study is not enough to change practice, physicians should be aware that gestational diabetes may be a risk factor for childhood cancer. Physicians should consider motivating their patients to properly manage their blood sugar during pregnancy.”

The study team notes that researchers still do not understand how hyperglycemia sparks carcinogenesis in utero, adding that the molecular biology involved in the association will be an interesting avenue for future research. “The better we understand the pathways, the more likely we can find ways to prevent childhood cancer,” Dr. Auger says. “There may also be a threshold of exposure below which there is no risk for cancer. Future studies that have detailed information on blood sugar levels during pregnancy would help answer this question.”

 

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