Maternal diabetes mellitus, particularly type 2 and type 1, is associated with an increased epilepsy risk in offspring, a Canadian population study found.

The findings suggest that prenatal metabolic and inflammatory exposures may contribute to this development, according to epidemiologist-biostatistician Bénédicte Driollet, PhD, and colleagues writing in Pediatrics.

“Given the ongoing rise in diabetes prevalence among women, the close monitoring of young children exposed to maternal diabetes for early neurological signs of epilepsy might be warranted,” Driollet, of the Department of Epidemiology, Biostatistics, and Occupational Health at McGill University in Montreal, Quebec, Canada, and co-authors wrote.

This seizure disorder is common among children, with a prevalence ranging from 5.2 to 8.9 per 1000.

Evidence of an association between maternal diabetes and neurodevelopmental disorders in offspring, particularly epilepsy, remains limited and heterogeneous, however. Moreover, most studies have not distinguished between diabetes subtypes — type 1, type 2, and gestational diabetes — which have distinct etiologies.

“While maternal diabetes is well recognized as a risk factor for adverse perinatal outcomes and congenital anomalies, its association with long-term neurologic outcomes such as epilepsy has received comparatively less attention in fetal medicine, neonatology, and medical education,” Driollet told Medscape Medical News.

In Canada, clinical discussions and follow-up largely focus on pregnancy and neonatal outcomes, while potential long-term neurologic outcomes in offspring, such as epilepsy, are not routinely addressed in standard prenatal care, she said.

Driollet’s group estimated the crude and adjusted association among type 1, type 2, and gestational diabetes and epilepsy in children younger than 18 years in a retrospective birth cohort of all in-hospital live births from 2002 to 2018 in Ontario, Canada’s most populous province. They linked births with population-based maternal and child health records up to March 2020.

A diagnosis of epilepsy was defined as at least one inpatient hospitalization and diagnosis or three or more outpatient diagnoses on the basis of physician claims separated by at least 30 days within 2 years of age 18.

Among 2,105,553 children, 160,644 (7.6%) were exposed to maternal diabetes: 0.3% to type 1, 1.2% to type 2, and 6.1% to gestational diabetes. Over a median follow-up of 10.2 years, 17,853 epilepsy cases were diagnosed. After adjusting for maternal socioeconomic and clinical characteristics, children exposed to maternal diabetes, including gestational diabetes, had an increased risk for epilepsy in all diabetes subcategories compared with those unexposed.

Adjusted hazard ratios were as follows: type 2, 1.40 (95% CI, 1.24-1.58); type 1, 1.32 (95% CI, 1.03-1.69); and gestational diabetes, 1.14 (95% CI, 1.07-1.22).

Women with type 2 or gestational diabetes shared similar characteristics: They tended to be older at delivery — more likely to be immigrants, including refugees — and had a greater number of previous children — especially women with type 2 diabetes. These mothers were also more likely to reside in ethnically diverse and socioeconomically deprived areas than were women with type 1 or those without diabetes.

Several studies have reported associations between maternal diabetes and neurodevelopmental conditions including attention-deficit/hyperactivity disorder and autism spectrum disorder, suggesting broad effects of the intrauterine metabolic environment on brain development, Driollet said.

For mothers with diabetes, the best advice remains preconception counseling, optimization of glycemic control before and during pregnancy, and close multidisciplinary care, she added. “These measures are known to improve maternal and neonatal outcomes and may also reduce longer-term risks for the child.”

Offering a nonparticipant’s perspective on the findings, Elham Abushanab, MD, neurologist at the Cleveland Clinic’s Epilepsy Center in Cleveland, found the connection interesting but stressed that this was an associative, not a causative, study. “And other prenatal factors in mothers — including obesity, hypertension, and ongoing stress and anxiety — could equally be contributing to their children’s risk for epilepsy and other neurodevelopmental problems,” she told Medscape Medical News.

In her neurology practice, Abushanab always asks mothers of children with epilepsy about their prenatal and gestational history. Good glycemic control before and during pregnancy is always recommended for this and other reasons. “For mothers with diabetes and other metabolic disorders, I advise close monitoring of their children,” she said. And while epilepsy typically shows up in early childhood, she found it interesting that maternal short-term gestational diabetes was associated with a much later, adolescent onset.

Going forward, said Driollet, research should focus on disentangling causal mechanisms, the role of glycemic control and timing of exposure, differences by diabetes type, and potential preventive strategies. “Longitudinal studies with detailed metabolic and neurodevelopmental data are particularly needed.”

This study was supported by the Institute for Clinical Evaluative Sciences, funded by the Ontario Ministry of Health (MOH) and the Ministry of Long-Term Care, and the Canadian Institutes of Health Research. Parts of this material are based on data and information provided by the MOH, the Canadian Institute for Health Information, and Immigration, Refugees and Citizenship Canada. The authors declared having no relevant conflicts of interest.