Objectives: A systematic literature review and meta-analysis was performed to evaluate the impact of prophylaxis with palivizumab on mortality and morbidity associated with respiratory syncytial virus infection in infants at high risk (≤ 35 wks of gestational age, chronic lung disease, or congenital heart disease).

Data sources: MEDLINE, EMBASE, and Current Contents were used. MEDLINE was searched from January 1, 1990 to May 16, 2007. The bibliographies of accepted studies and recent reviews and proceedings from the past 2 yrs were searched to identify additional relevant studies.

Study selection: Randomized controlled trials and prospective or retrospective cohort studies evaluating all-cause and respiratory syncytial virus-specific mortality, respiratory syncytial virus hospitalizations, and health care use in infants at high risk for respiratory syncytial virus infection receiving prophylaxis with palivizumab.

Data extraction: Data elements from each accepted study were extracted by one researcher and confirmed by a second researcher. Differences were resolved before data entry and analysis.

Data synthesis: A total of 2473 citations were screened and ten comparative studies of palivizumab prophylaxis evaluating >15,000 infants were included. Comparisons of mortality and hospitalization outcomes between infant groups using prophylaxis and not using prophylaxis were made using meta-analyses.

Conclusions: Prophylaxis and nonprophylaxis infant groups appeared to be comparable at baseline. All-cause mortality during the respiratory syncytial virus season was 12 of 6380 (0.19%) for infants with prophylaxis vs. 33 of 8182 (0.53%) for infants without prophylaxis (Peto odds ratio, 0.30; 95% confidence interval, 0.17-0.55). Only five respiratory syncytial virus-specific deaths were reported, and the majority of the studies did not report respiratory syncytial virus-related deaths. The rate of respiratory syncytial virus hospitalization was significantly lower among preterm infants with prophylaxis compared with those without prophylaxis (4.1% vs. 10.4%; odds ratio, 0.35; 95% confidence interval, 0.25-0.47). Prophylaxis with palivizumab was associated with a reduction in all-cause mortality and respiratory syncytial virus hospitalization among preterm infants at high risk. Additional research on cause of death among infants at high risk is needed.