Lafond, Kathryn E.Nair, HarishRasooly, Mohammad HafizValente, FatimaGuzman, GuiselleCoulibaly, DaoudaArmero, JulioJima, DaddiHowie, Stephen R. C.Ampofo, WilliamMena, RicardoChadha, MandeepSampurno, Ondri DwiEmukule, Gideon O.Nurmatov, ZuridinCorwin, AndrewHeraud, Jean MichelNoyola, Daniel E.Cojocaru, RaduNymadawa, PagbajabynBarakat, AmalAdedeji, AdebayoVon Horoch, MartaOlveda, RemigioNyatanyi, ThierryMmbaga, VidaChittaganpitch, MalineeNguyen, Tran HienTheo, AndrosWhaley, MelissaAzziz-Baumgartner, EduardoBresee, JosephCampbell, HarryWiddowson, Marc-AlainBooy, Robert2016-08-012016-08-012016-03-24Lafond KE, Nair H, Rasooly MH, Valente F, Booy R, Rahman M, et al. (2016) Global Role and Burden of Influenza in Pediatric Respiratory Hospitalizations, 1982–2012: A Systematic Analysis. PLoS Med 13(3): e1001977. DOI: 10.1371/journal.pmed.1001977.1549-1277 (print)1549-1676 (online)10.1371/journal.pmed.1001977http://hdl.handle.net/2263/56142S1 Appendix. Summary of published articles included in the analyses, with reference list.S2 Appendix. Summary of influenza-associated ALRI and total number of influenza-associated hospitalizations in children 0–5 mo and 6–11 mo, with reference list.S1 Data. Analysis dataset.S1 Fig. Forest plot of data sources with PCR testing for pooled estimate, children <6 mo.S2 Fig. Forest plot of data sources with PCR testing for pooled estimate, children <1 y.S3 Fig. Forest plot of data sources with PCR testing for pooled estimate, children <2 y.S4 Fig. Forest plot of data sources with PCR testing for pooled estimate, children <5 y.S5 Fig. Forest plot of data sources with PCR testing for pooled estimate, children <18 y.S6 Fig. Forest plot of data sources with PCR testing for pooled estimate, children 5–17 y.S1 PRISMA checklist.S1 Table. Literature search methodology and results, by database.BACKGROUND The global burden of pediatric severe respiratory illness is substantial, and influenza viruses contribute to this burden. Systematic surveillance and testing for influenza among hospitalized children has expanded globally over the past decade. However, only a fraction of the data has been used to estimate influenza burden. In this analysis, we use surveillance data to provide an estimate of influenza-associated hospitalizations among children worldwide. METHODS AND FINDINGS We aggregated data from a systematic review (n = 108) and surveillance platforms (n = 37) to calculate a pooled estimate of the proportion of samples collected from children hospitalized with respiratory illnesses and positive for influenza by age group (<6 mo, <1 y, <2 y, <5 y, 5–17 y, and <18 y). We applied this proportion to global estimates of acute lower respiratory infection hospitalizations among children aged <1 y and <5 y, to obtain the number and per capita rate of influenza-associated hospitalizations by geographic region and socio-economic status. Influenza was associated with 10% (95% CI 8%–11%) of respiratory hospitalizations in children <18 y worldwide, ranging from 5% (95% CI 3%–7%) among children <6 mo to 16% (95% CI 14%–20%) among children 5–17 y. On average, we estimated that influenza results in approximately 374,000 (95% CI 264,000 to 539,000) hospitalizations in children <1 y—of which 228,000 (95% CI 150,000 to 344,000) occur in children <6mo—and 870,000 (95% CI 610,000 to 1,237,000) hospitalizations in children <5 y annually. Influenza- associated hospitalization rates were more than three times higher in developing countries than in industrialized countries (150/100,000 children/year versus 48/100,000). However, differences in hospitalization practices between settings are an important limitation in interpreting these findings. CONCLUSIONS Influenza is an important contributor to respiratory hospitalizations among young children worldwide. Increasing influenza vaccination coverage among young children and pregnant women could reduce this burden and protect infants <6 mo.enThe work is made available under the Creative Commons CC0 license.InfluenzaChildrenRespiratory hospitalizationsBurdenArticle