Measles-mumps-rubella vaccination at 6 months of age and the risk of atopic disease in the first year of life: Results from a Danish placebo-controlled randomised trial

Background: In observational studies, childhood vaccinations have been associated with atopic diseases. However, results are conflicting and evidence from randomised trials is lacking. Methods: Atopic disease after interventional measles-mumps-rubella (MMR) vaccine was a pre-planned secondary outcome of the MMR trial, a randomised, double-blind, placebo-controlled trial in 6540 Danish infants in the high-income setting of Denmark. At two hospitals, infants 5–7 months of age were randomly assigned 1:1 to receive an intramuscular injection with M-M-R VaxPro or placebo (solvent only). Randomisation was stratified by site, sex, and prematurity (< 37 weeks of gestation). The infants were followed up in the Danish health registries to detect eczema, asthma-like disease, and allergic rhinoconjunctivitis, the composite outcome of the three diseases being the primary endpoint of the present study. The trial was registered in the EU Clinical Trials Registry (2016-001901-18) and ClinicalTrials.gov (NTC03780179). Findings: Between April 2019 and October 2021, 6540 infants were randomised (3266 MMR and 3274 placebo). There was no difference in the rate of atopic disease before 12 months of age between the MMR and placebo group (76 events MMR vs. 77 placebo), resulting in a hazard ratio of 0·98 (95% confidence interval 0·72 to 1·35). Secondary analyses with follow-up until 24 months of age yielded essentially identical results. Interpretation: Based on trial data in 6540 Danish infants randomised to MMR or placebo at 5–7 months, no association between MMR and atopic disease in early childhood was observed.