Paediatric Rotavirus Vaccination, Coeliac Disease and Type 1 Diabetes in Children: A Population-Based Cohort Study

Background: Rotavirus infection has been proposed as a risk factor for coeliac disease (CD) and type 1 diabetes (T1D). The UK introduced infant rotavirus vaccination in 2013. We therefore investigated whether rotavirus vaccination prevents CD and T1D in the UK. Methods: A cohort study of children born between 2010 and 2015 was conducted using primary care records from the Clinical Practice Research Datalink. Children were followed-up from three months to seven years old, with censoring for outcome, death or leaving the practice. CD was defined as diagnosis of CD or the prescription of gluten-free goods. T1D was defined as a T1D diagnosis. The exposure was rotavirus vaccination, defined as one or more doses. Mixed-effects Cox regression was used to estimate Hazard ratios (HR) and 95% confidence intervals (CIs). Models were adjusted for potential confounders and included random intercepts for general practices. Findings: There were 880 629 children in the cohort (48·8% female). A total of 343 113 (39·0%) participants received rotavirus vaccine; among those born after the introduction of rotavirus vaccination, 93·4% were vaccinated. Study participants contributed 4 526 794 person-years, with median follow-up 5·85 person-years. There were 1 657 CD cases, an incidence of 36·6 cases per 100 000 person-years. Compared with unvaccinated children the adjusted HR for a CD was 1·03 (95% CI 0·84-1·26) for vaccinated children. Females had a 40% higher hazard than males. T1D was recorded for 733 participants, an incidence of 16·2 cases per 100 000 person-years. In adjusted analysis rotavirus vaccination was not associated with risk of T1D (HR 0·9, 95% CI 0·69-1·20). Interpretation: This study did not provide evidence that rotavirus vaccination prevents CD or T1D, nor is it associated with increased risk, delivering further evidence of rotavirus vaccine safety. Funding: This study is funded by the National Institute for Health Research. Declaration of Interests: DH and MIG report grants on the topic of rotavirus vaccines, outside of the submitted work, from GlaxoSmithKline Biologicals, Sanofi Pasteur and Merck and Co (Kenilworth, New Jersey, US) after the closure of Sanofi Pasteur-MSD in December 2016. MIG also reports personal fees for consultancy, outside the submitted work, from GlaxoSmithKline Biologicals. TI and KF have nothing to disclose. Ethics Approval Statement: Ethical approval for this research was given by the Independent Scientific and Ethical Committee (ISAC) of the CPRD (reference 20_024RA2). CPRD obtains annual rolling ethical approval (reference number 05/MRE04/87) and no additional ethical approval was required for this project which meets ISAC requirements.