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PLoS One. 2015 May 8;10(5):e0125422. doi: 10.1371/journal.pone.0125422. eCollection 2015.

Long-Term Burden and Respiratory Effects of Respiratory Syncytial Virus Hospitalization in Preterm Infants-The SPRING Study.

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Neonatology Service, Hospital Clinic, Institut d'Investigacions Biomediques August Pi Suñer (IDIBAPS), Barcelona, Spain.
Division of Pediatric Respiratory Medicine, Hospital Universitario Donostia-Instituto Biodonostia, San Sebastián, Spain; Biomedical Research Centre Network for Respiratory Diseases (CIBERES), San Sebastián, Spain; Department of Pediatrics, University of the Basque Country (UPV/EHU), San Sebastián, Spain.
Neonatology Unit, Hospital Universitario La Paz, Madrid, Spain.
Neonatology Service, Hospital Universitario Reina Sofía, Córdoba, Spain.
Health Outcomes Research Department, 3D Health Research, Barcelona, Spain.
Neonatology Division, Instituto de Investigación Sanitaria Gregorio Marañón, Hospital General Universitario "Gregorio Marañón", Madrid, Spain.


The health status of premature infants born 321-350 weeks' gestational age (wGA) hospitalized for RSV infection in the first year of life (cases; n = 125) was compared to that of premature infants not hospitalized for RSV (controls; n = 362) through 6 years. The primary endpoints were the percentage of children with wheezing between 2-6 years and lung function at 6 years of age. Secondary endpoints included quality of life, healthcare resource use, and allergic sensitization. A significantly higher proportion of cases than controls experienced recurrent wheezing through 6 years of age (46.7% vs. 27.4%; p = 0.001). The vast majority of lung function tests appeared normal at 6 years of age in both cohorts. In children with pulmonary function in the lower limit of normality (FEV1 Z-score [-2; -1]), wheezing was increased, particularly for cases vs. controls (72.7% vs. 18.9%, p = 0.002). Multivariate analysis revealed the most important factor for wheezing was RSV hospitalization. Quality of life on the respiratory subscale of the TAPQOL was significantly lower (p = 0.001) and healthcare resource utilization was significantly higher (p<0.001) in cases than controls. This study confirms RSV disease is associated with wheezing in 32-35 wGA infants through 6 years of age.

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