In the main intention-to-treat analysis age at first hospitalization within the period from randomization to 12?months of age is analyzed according to randomization group. BS-181 HCl The current vaccine was introduced in Denmark in 1987 as a one-shot measles-mumps-rubella vaccine at 15?months, a timing chosen to avoid inhibition of the infants immune response by maternal antibodies. One generation later, the MMR vaccinated mothers have lower antibody levels compared to the naturally infected, and their infants are already susceptible at 6?months of age or earlier, thus increasing the risk of epidemics. Methods The Danish MMR trial is usually a double-blind randomized clinical trial recruiting between March 2019 and December 2021 with last patient last visit in February 2022. Altogether The plaque reduction neutralization test (PRNT), which steps the serum dilution capable of preventing 50% of plaque formation induced by measles computer virus in cell cultures, has been considered the most reliable criterion for the serological evaluation of measles immunity. For PRNT, the protective cut-off dilution is usually defined to be >?120 [15, 18]. A frequency of 95% seroconversion rate, i.e., children mounting a protective level of humoral immunity according to the abovementioned cutoff value after MMR-vaccination at 6?months of age, will be considered sufficient to implement primary MMR immunization at 6?months in the Danish vaccination program [15, 19]. Statistically significant 20% decrease in hospitalization due to contamination from 6 to 12?months of age in children randomized to receive MMR at 6?months compared to children receiving placebo. The framework of the trial is usually equivalence with regard to the first co-primary outcome concerning specific immunity. The WHO has well-defined criteria for sufficient antibody response as a measurement of both IgG, IgM, and plaque reduction neutralization test (PRNT) [15]. Secondary outcomes include immunogenicity of MMR-vaccination measured as IgM and IgG antibodies against measles, mumps, and rubella 1?month following randomization in infants randomized to MMR-vaccine, and 1?month following routine MMR-vaccination at 15?months of age. Maternal antibodies quantified by measles neutralizing antibodies and IgG and IgM to measles, mumps, and rubella prior to randomization will be evaluated. The secondary outcomes also contain other indirect effects of early vaccination including HMOX1 infectious disease hospitalizations within the first 24?months of life and incidence of asthmatic bronchitis and BS-181 HCl atopic dermatitis. Use of prescribed medication will be assessed regarding anti-asthmatics, topical treatment against atopic dermatitis, and antibiotics. In explorative analyses, cellular immunity against measles after early MMR vaccination and again after routine MMR vaccination at 15?months of age is evaluated as activated (interferon gamma producing) T cells recognizing selected measles-epitopes through ELIspot analyses [20]. Maternal antibodies, stress, and BS-181 HCl pollution have the potential to interfere with the immune response. Antibodies are assessed by blood samples from both infant and mother; pollution markers are tested in blood and urine, and acute and chronic stress markers are tested in blood, saliva, and hair. Furthermore, genetic association studies are planned based on buccal swaps to detect genes involved in the immune response to vaccination and stress response. Data collection All data are joined directly into and stored in the e-crf and anonymized prior to publication of results. Background informationA structured interview focusing on demographics, parental immunization against MMR, and risk factors such as atopic disposition and parental smoking habits as well as exposure to wild-type MMR is usually filled electronically by the BS-181 HCl parents prior to randomization. Register-based dataHospitalizations are identified using the Danish National Patient Registry. All Danish citizens have a unique social security number (CPR) that can be BS-181 HCl used to link data from the national Danish health registers at an individual level. The Danish Register of Medicinal Product Statistics contains CPR-number-based information about sale of all prescribed medicines in Denmark. The included children are followed in these registries until 24?months of age for breastfeeding, hospitalizations, and total medication use, including use of antibiotics, anti-asthmatics, and topical medication against eczema. Clinical and paraclinical data At inclusion (children participating.