Adverse Events Following Varicella-Containing Vaccination in Healthy Children: A Systematic Review and Meta-Analysis

Background: Varicella-containing vaccines have substantially reduced the burden of varicella worldwide; however, comprehensive evidence on adverse events following vaccination in children remains important for vaccine safety monitoring, vaccine confidence and immunization policy. We aimed to systematically evaluate the incidence of adverse events following licensed varicella-containing vaccination in healthy children. Methods: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) evaluating monovalent varicella vaccines or measles-mumps-rubella-varicella (MMRV) vaccines in healthy children aged ≥12 months and <12 years. Eight databases were searched from 1 January 2000 to 17 July 2026. Studies using active safety monitoring and reporting extractable adverse event counts with corresponding denominators were included. Pooled incidence proportions among vaccinated children were estimated using generalized linear mixed models with random effects. Subgroup analyses were performed by vaccine type, vaccination dose, and World Health Organization region. Risk of bias was assessed using the Cochrane Risk of Bias 2 tool, and certainty of evidence was evaluated using the GRADE approach. Results: Forty-three RCTs involving 31,915 vaccinated children were included. Fever was the most frequently reported common adverse event, with a pooled incidence of 11.58% (95% confidence interval [CI], 6.79-19.07%). Pooled incidences were 2.74% (95% CI, 1.10-6.67%) for redness/erythema, 2.19% (95% CI, 0.93-5.06%) for pain, and 0.82% (95% CI, 0.33-1.98%) for swelling. Compared with monovalent varicella vaccines, MMRV vaccines showed higher pooled incidences of fever (43.44% vs. 5.29%), redness/erythema (16.50% vs. 0.69%), pain (12.27% vs. 0.91%), and swelling (7.02% vs. 0.30%); however, these estimates were based on between-study comparisons and should not be interpreted as causal effects of vaccine type. Rare serious adverse events were uncommon, including febrile seizures (0.0989%) and anaphylaxis (0.0343%), with no observed cases of encephalitis. Conclusions: Varicella-containing vaccines were generally well tolerated in children, with most observed adverse events being uncommon and rare serious adverse events infrequently reported. Continued safety surveillance remains important, particularly for rare serious adverse events.