Children of Diabetic Mothers Have Greater Risk of Developing Multiple Sclerosis

Nete Nielson, PhD

An original version of this article was published online by sister publication NeurologyLive.

Data from a Danish nationwide register-based cohort study demonstrated an increased risk of developing multiple sclerosis (MS) in the children of mothers with diabetes, corroborating the view that has been shown in previous studies.

A team of investigators led by Nete Nielsen, PhD, adjunct associate professor, Statens Serum Institut, pooled all 1,633,436 singletons born in Denmark between 1978-2008 to examine MS risk in offspring of diabetic mothers.

The analysis included overall data and data according to type of maternal diabetes mellitus (pregestational or gestational), as well as examined MS risk among offspring of diabetic fathers.

They found that the individuals whose mothers had pregestational diabetes had a 2.3-fold increased risk of MS compared with that among individuals with nondiabetic mothers (hazard ratio [HR], 2.25; 95% CI, 1.35–3.75).

The study authors noted, “regardless of the mechanism, our study suggests that the contribution of maternal diabetes mellitus to the absolute risk of MS in their offspring is only modest.”

They noted that in a prior work from 2005, the estimated sporadic absolute risk of MS among women and men in Denmark was 0.5% and 0.3%, respectively.

"With a roughly 2.3-fold increased relative risk, cautious estimates of the absolute (lifetime) risk of developing MS among daughters and sons of diabetic mothers are therefore likely in the order of 1.2% and 0.7%, respectively,” Nielsen and colleagues wrote.

For mothers with gestational diabetes, the MS risk was deemed statistically non-significant (HR, 1.03; 95% CI, 0.49–2.16).

Offspring of diabetic fathers also showed statistically non-significant results (HR, 1.40; 95% CI, 0.78–2.54).

The study had a total of 2332 MS cases identified, 1634 among females and 698 among males. Information about parental diabetes diagnoses were obtained from the Danish National Patient Register (NPR).

Using Cox proportional hazards regression analysis, the investigators found that the MS risk among cohort members whose mothers were recorded in the NPR as obese before or during pregnancy was 65% higher than that among other cohort members using the initial unadjusted analyses (HR, 1.65; 95% CI, 1.05–2.60).

Furthermore, they found a statistically significant association between birth weight and MS risk (test for homogeneity, P = .004).

They noted though that “another limitation is incomplete information concerning obesity in the NPR. However, while not all cases of obesity in the general population are recorded in the NPR, we believe that obese pregnant women are likely to have their obesity recorded in the NPR during the course of pregnancy.”

Additional analyses included comparison between MS risk between individuals exposed to maternal pregestational diabetes mellitus and nondiabetic mothers.

All told, the relative risk of MS among those exposed to pregestational type 1 diabetes and type 2 diabetes showed HRs of 2.21 (95%, 1.28–3.83) and 2.57 (95% CI, 0.64–10.6), respectively, compared with individuals born to nondiabetic mothers.

Cohort members who were born to mothers (n = 25,598) or fathers (n = 17,316) who had been diagnosed with any autoimmune disease other than diabetes and MS either before or during pregnancy were not any unusual risk of developing MS (maternal exposure: HR, 1.40; 95% CI, 0.92–2.13; paternal exposure: HR, 1.01; 95% CI, 0.57–1.78).

Mothers with pregestational inflammatory bowel diseases (IBD) were at a 2.1-fold increased risk of MS (HR, 2.12; 95% CI, 1.14–3.94) when restricting the analyses to IBD alone.

However, there was no unusual risk of MS for children of fathers with IBD (HR, 1.42; 95% CI, 0.64–3.17) nor children of mothers with gestational IBD (HR, 0.93; 95% CI, 0.13–6.62).

"An advantage of our study is that we relied on routinely collected patient information about the exposure variable, diagnoses of parental diabetes, obtained from records of the Danish NPR, thereby eliminating any potential influence of differential recall problems that may have influenced findings in prior studies relying on self-reported data,” Nielsen and team wrote.

The study, "Maternal diabetes and risk of multiple sclerosis in the offspring: A Danish nationwide register-based cohort study," was published online in Multiple Sclerosis Journal.