A systematic review and meta-analysis of adverse events following measles-containing vaccines in infants less than 12 months of age.

Background: Lowering the age for receiving the first dose of a measles-containing vaccine (MCV1) has been suggested to close the emerging immunity gap in infants. However, tolerability remains one of the main concerns for vaccine-hesitant parents. We conducted a systematic review and meta-analysis of reactogenicity following MCV1 in infants under 12 months of age.

Methods: We searched EMBASE and PubMed in February 2021. The search was updated in February 2024. With exception of case reports, we included all English-written original studies published >1985 that contained frequency measures on adverse events (AEs) within 56 days following MCV1 in infants <12 months of age. We identified all common AEs and their frequencies and combined these across studies in a meta-analysis. The effect of measles strain and vaccine valency was also evaluated.

Findings: We included 24 studies for analysis: 18 randomized controlled trials (RCTs), three interventional studies, and three observational studies. Only one RCT was placebo-controlled. Commonly reported AEs were injection site reactions, fever, rash, gastrointestinal symptoms, respiratory tract symptoms, conjunctivitis, and symptoms related to the general condition of the infant. The frequency of any AE was generally <10 %; however, the placebo-controlled trial showed no difference between MCV1 and placebo-injected infants. Edmonston B strains and measles-mumps-rubella-varicella vaccine (MMRV) were associated with a higher rate of high fever >39 °C.

Interpretation: Most AEs occurred in <10 % of infants receiving MCV1 at < 12 months of age. The placebo-controlled trial suggested no excess reactogenicity following early MCV. Measles strain and vaccine valency may affect AE risks, but other factors such as socioeconomic status, race, and setting could also explain this finding, as these were not equally distributed between studies. Caution is advised when interpreting findings from studies without a placebo group.