Large analysis finds no clear link between rotavirus vaccination and type 1 diabetes

New research presented at the annual meeting of the European Association for the Study of Diabetes (EASD) in Milan, Italy (Sept. 28–Oct. 2), and published in Diabetologia shows that the incidence (the new case rate) of type 1 diabetes (T1D) in children ages 0.5–5 years in Norway was 11% higher following the rapid rollout and uptake of the rotavirus vaccine in September 2014. The study is by doctoral student Maria Östman, University of Oslo, Oslo, Norway, and colleagues.

Rotavirus, transmitted by the fecal-oral route, is a common virus that causes gastroenteritis. Young children, especially those under 5 years of age, are at risk of severe infections from the virus. Immunity develops with each infection, so subsequent infections are less severe. Rotavirus vaccines have effectively reduced hospitalizations and deaths from severe rotavirus infections in children.

Environmental factors, including infections, have been suspected of influencing the risk of type 1 diabetes. Previous studies of the rotavirus vaccine and the risk of type 1 diabetes have shown conflicting results.

The authors took advantage of the rapid and high uptake (92.8%) of the rotavirus vaccine among infants in Norway as a natural experiment to study the potential association between rotavirus vaccination and type 1 diabetes incidence in Norway.

In Norway, the monovalent Rotarix vaccine is included in the national childhood immunization program, as it is in the United Kingdom. Several other countries, including Germany and Italy, use both Rotarix and the pentavalent vaccine RotaTeq, while some countries, such as Finland and Iceland, implemented RotaTeq alone in their national childhood immunization programs.

Rotarix is an oral live-attenuated vaccine—a type of immunization made from a whole virus or bacterium that has been weakened in a laboratory so it does not cause severe disease. When administered, the vaccine mimics infection so that the body creates antibodies to rotavirus without causing severe disease, as the virus has been weakened.

In this cohort study, the researchers followed all children born in Norway during 2007–2019. They compared type 1 diabetes incidence in children born before and after the introduction of the rotavirus vaccine in September 2014. All children were followed from 0.5 to 5 years of age for type 1 diabetes, ensuring that the length of follow-up was equal for children born before and after the introduction of the vaccine. Data were collected until Dec. 31, 2024.

Of the 740,744 children included, 846 were diagnosed with type 1 diabetes before 5 years of age. An interrupted time series analysis comparing the predicted trend in type 1 diabetes incidence, based on observations before the rotavirus vaccine’s introduction, with the actual observed trend after its introduction showed a relative increase in type 1 diabetes incidence of 11%.

The relative hazard ratio for children fully vaccinated with two doses of the monovalent rotavirus vaccine compared with unvaccinated children was 1.17 in adjusted analyses, which, however, was not statistically significant.

The authors say, “This study found no evidence for a reduced risk of type 1 diabetes after introduction of rotavirus vaccination in infancy but found instead that the incidence of type 1 diabetes before age 5 years increased after rotavirus vaccination was introduced.”

To further assess the validity of the main result, the authors compared the incidence of type 1 diabetes among children born before and after other changes to the Norwegian Immunization Program. These changes were used as negative controls because there is no evidence that either the introduction of the hepatitis B vaccine or the switch from one pneumococcal vaccine to another would affect the incidence of type 1 diabetes.

Therefore, if the association observed after the introduction of the rotavirus vaccine reflects the true effect of rotavirus vaccination, we would not expect to see a similar association following these unrelated vaccine changes.

However, the incidence of type 1 diabetes among children born after the introduction of the hepatitis B vaccine in 2016 increased by a magnitude similar to that observed after the introduction of the rotavirus vaccine and following the switch from the 7-valent to the 13-valent pneumococcal vaccine in 2011.

The authors say these analyses indicate that the initial finding of an 11% increase in T1D incidence in children born from September 2014 to December 2019 might not be related to the rotavirus vaccine’s introduction, but to other, yet unknown changes in the environment.

T1D incidence has generally been increasing over the past decades, with some yearly fluctuation. The authors say, “We do not think any of the changes in the national vaccination program or the combination of changes explain the increase in type 1 diabetes.

“While we did our best to design our study to remove the influence of other unknown factors, there may be other unidentified factors since we see the same pattern for all changes in the national vaccination program despite our hypothesis that rotavirus vaccine would reduce the risk and the two other vaccines would not influence the risk.”

The authors also considered other potential explanations for the observed increase in the main analysis, such as the COVID-19 pandemic in 2020, after which many countries experienced an increase in the incidence of type 1 diabetes, including Norway, where there was a temporary increase in type 1 diabetes incidence in 2022 followed by a decrease.

However, a recent study on Swedish and Norwegian adolescents did not find an increase in type 1 diabetes incidence after COVID-19 infection.

The authors also considered the change to the Norwegian prenatal follow-up guidelines in June 2018, which began recommending measurement of serum ferritin concentration in the first trimester of pregnancy to determine the need for iron supplementation. From 2006–2018, the recommendation was to measure hemoglobin in week 30 of pregnancy, which is a less sensitive method. High iron levels are suspected to be associated with type 1 diabetes.

However, the authors believe the change in recommendations is not related to the increase in T1D incidence in Norway since iron levels are usually low in pregnancy. Furthermore, they do not believe it affected the study since the only children affected by the change in recommendations and included in the study were born in 2019.

The authors explain, “We do not believe that rotavirus vaccination increases the risk of type 1 diabetes. We believe there is a need for additional studies on rotavirus vaccination and type 1 diabetes in different settings with different vaccines before concluding anything. We also want to emphasize the importance of studies on other environmental factors that could have an association with type 1 diabetes.”

Provided by
European Association for the Study of Diabetes

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