The link between gestational diabetes and childhood cancer

“As clinicians, we still don’t fully understand the cause of most childhood cancers, which makes prevention very difficult,” says Nathalie Auger, MD. “It is important to identify potential risk factors, especially those that can be changed. Studies in adults suggest that high blood sugar may be a risk factor for cancer. Likewise, in utero exposure to high levels of sugar may be carcinogenic to children. Gestational diabetes mellitus, which can often be prevented and controlled, is therefore an interesting and potentially modifiable exposure to study.

For an article published in Diabetic Treatments, Dr. Auger and his colleagues examined the link between gestational diabetes and early and late childhood cancer. “The few previous studies on the association between gestational diabetes and childhood cancer have been inconclusive,” she says. “Many studies have not stratified by the age at which the cancer developed. We hypothesized that the carcinogenic effect of in utero high blood sugar may subside after birth and therefore affect cancer only in infancy.

Children exposed to gestational diabetes in utero Have a 20% higher risk of cancer

To test their hypothesis, the researchers conducted a retrospective cohort study of more than one million children born in Quebec between 2006 and 2019. They used a centralized database to identify all children hospitalized before the age of 14 years old. “Children are linked to their mother’s health record, so we were able to find out who was at risk for gestational diabetes in utero“says Dr. Auger. “We then stratified our analyzes by the age at which the cancer occurred to test whether there was an association with gestational diabetes, controlling for potential confounders.”

Dr. Auger and his colleagues found that 8.2% of children in the study cohort were at risk for gestational diabetes. During 7.6 million person-years of follow-up, 1,702 children developed cancer. “We observed that for any type of cancer, children exposed to gestational diabetes have about a 20% increased risk of developing cancer before the age of 14,” adds Dr. Auger. “For leukemia, the most common cancer in children, the risk can increase by as much as 38% to 90%, depending on the leukemia subtype. The results were not statistically significant for solid tumors, but our research nonetheless suggests that children exposed to gestational diabetes may be at higher risk. (Table).”

Gestational diabetes was most strongly linked to cancer in younger ages and decreased as the children got older, according to the study team. In children under 2 years of age, gestational diabetes was associated with a 1.47 times higher risk of any cancer, 1.61 times higher risk of blood cancer and 1.44 times higher risk of solid cancer, compared to the absence of gestational diabetes. However, no significant association was observed between gestational diabetes and blood or solid cancers beyond the age of 2 years, and no association was observed in participants older than 6 years.

Screening and control of gestational diabetes is essential

General practitioners, endocrinologists and obstetricians/gynaecologists should consider this study as a key reason for screening and controlling gestational diabetes in pregnant women, notes Dr. Auger. “Controlling high blood sugar during pregnancy will not only optimize fetal growth, but may also reduce the risk of childhood cancer,” she says. “Although a single study is not enough to change practice, physicians should be aware that gestational diabetes can be a risk factor for childhood cancer. Physicians should consider motivating their patients to properly manage their blood sugar during pregnancy.

Study team notes researchers still don’t understand how high blood sugar triggers 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 we can find ways to prevent cancer in children,” says Dr. Auger. “There may also be an exposure threshold below which there is no risk of cancer. Future studies with detailed information on blood sugar levels during pregnancy would help answer this question.

Harry D. Gonzalez