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. 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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Free PMC article

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

Xavier Carbonell-Estrany et al. PLoS One. .
Free PMC article


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.

Conflict of interest statement

Competing Interests: This study was funded by AbbVie Farmacéutica S.L.U. Madrid, Spain. In addition Xavier Carbonell-Estrany and Eduardo G. Pérez-Yarza have acted as expert advisors and speakers for AbbVie and have received honoraria in this regard. For the remaining authors none was declared. This does not alter the authors’ adherence to PLOS ONE policies on sharing data and materials.


Fig 1
Fig 1. Schematic of Study Design.
*children: allergic dermatitis, allergic rhinitis, allergic conjunctivitis, or contact dermatitis; parents/siblings: asthma, food allergy, pollen allergy, mite allergy, contact dermatitis, or allergic dermatitis. **TNO-AZL preschool children Quality of Life questionnaire: a 43-item questionnaire consisting of 12 multi (3–7) item scales that cover the domains of physical (sleeping, appetite, respiratory problems, digestive problems, skin problems, motor functioning), social (social functioning, problem behaviour), cognitive (communication), and emotional functioning (anxiety, positive mood, liveliness). Scale scores are calculated by adding up the item scores within the scales, and transforming the crude scale scores linearly to a 0–100 scale, with higher scores indicating better quality of life28,29,30. †Parents/legal guardians had to provide additional permissions for lung function and skin prick tests to be performed. ‡FEV1, FVC, FEF25-75.
Fig 2
Fig 2. Respiratory scores for TAPQOL questionnaire through 6 years of age.
†Scores range from 0–100, where higher scores indicate better quality of life for patients. Mann-Whitney U test. SD: standard deviation, NS: not significant. Patient numbers at years 2 and 3 reflect patients entering the study at different ages. For each patient, the mean score was calculated across the years they completed the questionnaire (e.g. if TAPQOL completed from 2 to 6 years, mean was calculated over 5 years).

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    1. Simões EA. Respiratory syncytial virus infection. Lancet. 1999;354: 847–852. - PubMed
    1. Hall CB, Weinberg GA, Iwane MK, Blumkin AK, Edwards KM, Staat MA, et al. The burden of respiratory syncytial virus infection in young children. N Engl J Med. 2009;360: 588–598. 10.1056/NEJMoa0804877 - DOI - PMC - PubMed
    1. Figueras-Aloy J, Carbonell-Estrany X, Quero-Jiménez J, Fernández-Colomer B, Guzmán-Cabañas J, Echaniz-Urcelay I, et al. FLIP-2 Study: risk factors linked to respiratory syncytial virus infection requiring hospitalization in premature infants born in Spain at a gestational age of 32 to 35 weeks. Pediatr Infect Dis J. 2008;27: 788–793. 10.1097/INF.0b013e3181710990 - DOI - PubMed
    1. Law BJ, Langley JM, Allen U, Paes B, Lee DS, Mitchell I, et al. The Pediatric Investigators Collaborative Network on Infections in Canada study of predictors of hospitalization for respiratory syncytial virus infection for infants born at 33 through 35 completed weeks of gestation. Pediatr Infect Dis J. 2004;23: 806–814. - PubMed
    1. Liese JG, Grill E, Fischer B, Roeckl-Wiedmann I, Carr D, Belohradsky BH, et al. Incidence and risk factors of respiratory syncytial virus-related hospitalizations in premature infants in Germany. Eur J Pediatr. 2003. 162:230–236. - PubMed

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This study was funded by AbbVie Farmacéutica S.L.U. Madrid, Spain. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.