Comparative safety of the 20-valent and the 13-valent pneumococcal vaccines in infants and toddlers: a systematic review and meta-analysis of randomized trials.
Ubaldo Helena Beckhäuser HB, Braga Maria Clara Abreu Vianna MCAV, Silva Elisama da Costa EDC, Lima Lenita de Melo LM
This systematic review and meta-analysis aimed to compare the safety of the 20-valent pneumococcal conjugate vaccine versus the 13-valent pneumococcal vaccine in healthy infants and toddlers. We searched PubMed, Scopus, Embase, and Cochrane on January 20, 2026, for randomized controlled trials comparing the 20-valent pneumococcal conjugate vaccine with the 13-valent pneumococcal conjugate vaccine in healthy infants and toddlers (0-3 years). We computed risk ratios with 95% confidence intervals for all outcomes, using a random-effects model. Heterogeneity was assessed using I2 statistics. Five randomized clinical trials were included, comprising 5,604 patients, of whom 3,059 received the 20-valent pneumococcal conjugate vaccine. There were no significant differences between the 20-valent pneumococcal conjugate vaccine and the 13-valent pneumococcal conjugate vaccine in adverse event incidence after doses 1-3 (risk ratio 1.00; 95%CI 0.92-1.10; p=0.952; I2=0%), or after dose 4 (risk ratio 0.90; 95%CI 0.76-1.07; p=0.238; I2=36%). Similarly, no significant differences were observed in serious adverse events, fever, irritability, and injection site pain. The 20-valent pneumococcal conjugate vaccine was associated with a higher incidence of decreased appetite after doses 2 (risk ratio 1.13, 95%CI 1.02-1.24; p=0.019) and 3 (risk ratio 1.34, 95%CI 1.14-1.58; p<0.001). In contrast, a significantly lower risk of local redness was observed with the 20-valent pneumococcal conjugate vaccine after dose 2 (risk ratio 0.93; 95%CI 0.86-0.99; p=0.034). The 20-valent pneumococcal conjugate vaccine demonstrated a safety profile largely comparable to the 13-valent pneumococcal conjugate vaccine, supporting its use in routine pediatric immunization programs.