New research to be 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 (the journal of EASD) shows that incidence (the new case rate) of type 1 diabetes (T1D) in children aged 0.5-5 years in Norway was 11% higher following the rapid roll out and uptake of the rotavirus vaccine in September 2014. The study is by PhD student Maria Östman, University of Oslo, Oslo, Norway, and colleagues.
Rotavirus transmitted by the faecal–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 efficiently reduced hospitalisation and mortality of severe rotavirus infections in children.
Environmental factors, including infections have been suspected to influence the risk of type 1 diabetes. Previous studies of rotavirus vaccine and 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 programme; similar to the UK. Several other countries use both Rotarix® and the pentavalent vaccine RotaTeq®, for example Germany and Italy, while some countries implemented RotaTeq® alone in their national childhood immunization programmes, such as Finland and Iceland.
Rotarix is an oral live-attenuated vaccine - a type of immunisation 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 it 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 compared to after introduction of the rotavirus vaccine in September 2014. All children were followed from 0.5 to 5 years of age for type 1 diabetes, making sure that the length of follow-up was equal for children born before and after introduction of vaccine. Data was collected until 31st of December 2024.
Of 740,744 included children, 846 were diagnosed with type 1 diabetes before 5 years of age. Interrupted time series, comparing the predicted trend of type 1 incidence based on observations before rotavirus vaccine introduction to the actual observed trend after vaccine introduction showed a relative increase of type 1 diabetes of 11%.
The relative hazard ratio for fully vaccinated with two doses of the monovalent rotavirus vaccine compared to non-vaccinated 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 diabetes before age five 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 Immunisation Programme. 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 a 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 was increased by a similar magnitude 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 indicates that the initial findings of an 11% increase in incidence in T1D in children born from September 2014 to December 2019 might not be related to the rotavirus vaccine introduction, but to other yet unknown changes in the environment.
T1D incidence has been generally increasing over the past decades, with some yearly fluctuation. The authors say "We do not think any of the changes in the national vaccination programme neighter or the combination of changes explained 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 programme despite our hypothesis that rotavirus vaccine would reduce the risk and the two other vaccines would not influence the risk."
The authors also considered potential other 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 of the Norwegian prenatal follow-up guidelines in June 2018, that started recommending measurement of ferritin concentration in serum in the first trimester of pregnancy to determine the need for iron supplement. In 2006–2018 the recommendation was measurement of haemoglobin in week 30 of the 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 emphasise the importance of studies on other environmental factors that could have association with type 1 diabetes."
