BACKGROUND: Preterm infants are at high risk of developing respiratory syncytial virus (RSV)-associated lower respiratory tract infection (LRTI). This observational epidemiologic study evaluated RSV disease burden and risk factors for RSV-associated LRTI hospitalization in preterm infants 33 weeks+0 days to 35 weeks+6 days gestational age not receiving RSV prophylaxis. METHODS: Preterm infants ≤6 months of age during RSV season (1 October 2013-30 April 2014) were followed at 72 sites across 23 countries from September 2013-July 2014 (study period). RSV testing was performed according to local clinical practice. Factors related to RSV-associated hospitalization for LRTI were identified using multivariable logistic regression with backward selection. RESULTS: Of the 2390 evaluable infants, 204 and 127 were hospitalized for LRTI during the study period and RSV season, respectively. Among these subjects, 64/204 and 46/127, respectively, were hospitalized for confirmed RSV LRTI. Study period and RSV season normalized RSV hospitalization rates (per 100 infant years) were 4.1 and 6.1, respectively. Factors associated with an increased risk of RSV-related LRTI hospitalization in multivariable analyses were smoking of family members (P<0.0001), non-hemodynamically significant congenital heart disease diagnosis (P = 0.0077), maternal age of ≤25 years at delivery (P = 0.0009), low maternal educational level (P = 0.0426), household presence of children aged 4 to 5 years (P = 0.0038), age on 1 October ≤3 months (P = 0.0422), and presence of paternal atopy (P<0.0001). CONCLUSIONS: During the 2013-2014 RSV season across 23 countries, for preterm infants 33-35 weeks gestation ≤6 months old on 1 October not receiving RSV prophylaxis, confirmed RSV LRTI hospitalization incidence was 4.1 per 100 infant years during the study period and 6.1 per 100 infant years during the RSV season. This study enhances the findings of single-country studies of common risk factors for severe RSV infection in preterm infants and suggests that combinations of 4-6 risk factors may be used to accurately predict risk of RSV hospitalization. These findings may be useful in the identification of infants most at risk of severe RSV infection.

Biostatistics GKM Gesellschaft für Therapieforschung mbH Munich Germany

Data and Statistical Sciences AbbVie Deutschland GmbH and Co KG Ludwigshafen Germany

Department of Pediatrics Akershus University Hospital Lørenskog Norway

Department of Pediatrics and Adolescent Medicine American University of Beirut Riad El Solh Beirut Lebanon

Department of Pediatrics Geneva Medical School and University Hospitals of Geneva Geneva Switzerland

Department of Woman and Child Health Karolinska Institutet Stockholm Sweden

Inserm U930 Université François Rabelais and Department of Neonatology University Hospital Clocheville Tours France

Institute for the Care of Mother and Child 3rd Faculty of Medicine Charles University Prague Czech Republic

Neonatology AbbVie Inc North Chicago IL United States of America

Neonatology and HIV AbbVie Ltd Dublin Ireland

Virology AbbVie Inc North Chicago IL United States of America

Zobrazit více v PubMed

American Academy of Pediatrics (2012) Respiratory syncytial virus In: Pickering LK, Baker CJ, Kimberlin DW, Long SS, editors. Red Book: 2012 Report of the Committee on Infectious Diseases. 29th ed. Elk Grove Village, IL: American Academy of Pediatrics; pp. 609–617.

World Health Organization (2010) ICD-10 International statistical classification of diseases and related health problems (10th Revision). PubMed

American Academy of Pediatrics (AAP) Committee on Fetus and Newborn and American College of Obstetricians and Gynecologists ACOG Committee on Obstetric Practice (2012) Standard Terminology for Reporting of Reproductive Health Statistics in the United States. Guidelines for Perinatal Care. pp. 497–418.

Garcia CG, Bhore R, Soriano-Fallas A, Trost M, Chason R, Ramilo O, et al. (2010) Risk factors in children hospitalized with RSV bronchiolitis versus non-RSV bronchiolitis. Pediatrics 126: e1453–1460. 10.1542/peds.2010-0507 PubMed DOI PMC

Weisman L (2003) Populations at risk for developing respiratory syncytial virus and risk factors for respiratory syncytial virus severity: infants with predisposing conditions. Pediatr Infect Dis J 22: S33–37; discussion S37-39. PubMed

Meert K, Heidemann S, Abella B, Sarnaik A (1990) Does prematurity alter the course of respiratory syncytial virus infection? Crit Care Med 18: 1357–1359. PubMed

Resch B, Gusenleitner W, Muller W (2002) The impact of respiratory syncytial virus infection: a prospective study in hospitalized infants younger than 2 years. Infection 30: 193–197. PubMed

Holman RC, Shay DK, Curns AT, Lingappa JR, Anderson LJ (2003) Risk factors for bronchiolitis-associated deaths among infants in the United States. Pediatr Infect Dis J 22: 483–490. PubMed

Blencowe H, Cousens S, Oestergaard MZ, Chou D, Moller AB, Narwal R, et al. (2012) National, regional, and worldwide estimates of preterm birth rates in the year 2010 with time trends since 1990 for selected countries: a systematic analysis and implications. Lancet 379: 2162–2172. 10.1016/S0140-6736(12)60820-4 PubMed DOI

Carbonell-Estrany X, Bont L, Doering G, Gouyon JB, Lanari M (2008) Clinical relevance of prevention of respiratory syncytial virus lower respiratory tract infection in preterm infants born between 33 and 35 weeks gestational age. Eur J Clin Microbiol Infect Dis 27: 891–899. 10.1007/s10096-008-0520-8 PubMed DOI

Blanken MO, Koffijberg H, Nibbelke EE, Rovers MM, Bont L, Dutch RSV Neonatal Network (2013) Prospective validation of a prognostic model for respiratory syncytial virus bronchiolitis in late preterm infants: a multicenter birth cohort study. PLoS ONE 8: e59161 10.1371/journal.pone.0059161 PubMed DOI PMC

Ambrose CS, Anderson EJ, Simoes EA, Wu X, Elhefni H, Park CL, et al. (2014) Respiratory syncytial virus disease in preterm infants in the U.S. born at 32–35 weeks gestation not receiving immunoprophylaxis. Pediatr Infect Dis J 33: 576–582. 10.1097/INF.0000000000000219 PubMed DOI PMC

Figueras-Aloy J, Carbonell-Estrany X, Quero-Jimenez J, Fernandez-Colomer B, Guzman-Cabanas J, Echaniz-Urcelay I, et al. (2008) 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 27: 788–793. 10.1097/INF.0b013e3181710990 PubMed DOI

Gijtenbeek RG, Kerstjens JM, Reijneveld SA, Duiverman EJ, Bos AF, Vrijlandt EJ (2015) RSV infection among children born moderately preterm in a community-based cohort. Eur J Pediatr 174: 435–442. 10.1007/s00431-014-2415-2 PubMed DOI

Law BJ, Langley JM, Allen U, Paes B, Lee DS, Mitchell I, et al. (2004) 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 23: 806–814. PubMed

Liese JG, Grill E, Fischer B, Roeckl-Wiedmann I, Carr D, Belohradsky BH, et al. (2003) Incidence and risk factors of respiratory syncytial virus-related hospitalizations in premature infants in Germany. Eur J Pediatr 162: 230–236. PubMed

Simoes EA, Carbonell-Estrany X, Fullarton JR, Liese JG, Figueras-Aloy J, Doering G, et al. (2008) A predictive model for respiratory syncytial virus (RSV) hospitalisation of premature infants born at 33–35 weeks of gestational age, based on data from the Spanish FLIP Study. Respir Res 9: 78 10.1186/1465-9921-9-78 PubMed DOI PMC

(2008) Konsensuspapier zur Prophylaxe der RSV-Infektion mit Palivizumab und Post-RSV-Atemwegserkrankung. Monatsschr Kinderheilkd 156: 381–383.

Figueras Aloy J, Carbonell Estrany X, Comite de Estandares de la Sociedad Espanola de Neonatologia (2010) [Recommendations for the use of palivizumab in the prevention of respiratory syncytial virus infection in late preterm infants (32(1) to 35(0) weeks of gestation)]. An Pediatr (Barc) 73: 98 e91-94. PubMed

Robinson JL (2011) Canadian Paediatric Society, Infectious Diseases and Immunization Committee. Preventing respiratory syncytial virus infections. Paediatr Child Health 16: 488–490. PubMed PMC

German Society for Paediatric Infectious Diseases (DGPI), German Society of Pediatric Cardiology (DGPK), Society of Pediatric Pneumology (GPP), Society of Neonatology and Pediatric Intensive Care Medicine (GNPI), Professional Association of Child and Adolescent Physicians (BVKJ) (2012) [Guideline for the Prevention of Serious Illnesses by Respiratory Syncytial Virus in Children at Risk]. Available: http://www.awmf.org/uploads/tx_szleitlinien/048-012l_S2k_Prophylaxe_von_schweren_RSV-Erkrankungen_bei_Risikokindern_07-2012-12-2016.pdf. Accessed 2015 June 22.

Samson L (2009) Prevention of respiratory syncytial virus infection. Paediatr Child Health 14: 521–532. PubMed PMC

Hall CB, Weinberg GA, Iwane MK, Blumkin AK, Edwards KM, Staat MA, et al. (2009) The burden of respiratory syncytial virus infection in young children. N Engl J Med 360: 588–598. 10.1056/NEJMoa0804877 PubMed DOI PMC

The IMpact-RSV Study Group (1998) Palivizumab, a Humanized Respiratory Syncytial Virus Monoclonal Antibody, Reduces Hospitalization From Respiratory Syncytial Virus Infection in High-risk Infants. Pediatrics 102: 531–537. PubMed

Steyerberg EW (2009) Clinical Prediction Models: A Practical Approach to Development, Validation, and Updating: Springer.

Fenton TR, Kim JH (2013) A systematic review and meta-analysis to revise the Fenton growth chart for preterm infants. BMC Pediatr 13: 59 10.1186/1471-2431-13-59 PubMed DOI PMC

Cilla G, Sarasua A, Montes M, Arostegui N, Vicente D, Perez-Yarza E, et al. (2006) Risk factors for hospitalization due to respiratory syncytial virus infection among infants in the Basque Country, Spain. Epidemiol Infect 134: 506–513. PubMed PMC

Holberg CJ, Wright AL, Martinez FD, Ray CG, Taussig LM, Lebowitz MD (1991) Risk factors for respiratory syncytial virus-associated lower respiratory illnesses in the first year of life. Am J Epidemiol 133: 1135–1151. PubMed

Zhang XB, Liu LJ, Qian LL, Jiang GL, Wang CK, Jia P, et al. (2014) Clinical characteristics and risk factors of severe respiratory syncytial virus-associated acute lower respiratory tract infections in hospitalized infants. World J Pediatr 10: 360–364. 10.1007/s12519-014-0513-x PubMed DOI

Sommer C, Resch B, Simoes EA (2011) Risk factors for severe respiratory syncytial virus lower respiratory tract infection. Open Microbiol J 5: 144–154. 10.2174/1874285801105010144 PubMed DOI PMC

Adler NE, Boyce T, Chesney MA, Cohen S, Folkman S, Kahn RL, et al. (1994) Socioeconomic status and health. The challenge of the gradient. Am Psychol 49: 15–24. PubMed

Feltes TF, Cabalka AK, Meissner HC, Piazza FM, Carlin DA, Top FH Jr., et al. (2003) Palivizumab prophylaxis reduces hospitalization due to respiratory syncytial virus in young children with hemodynamically significant congenital heart disease. J Pediatr 143: 532–540. PubMed

Feltes TF, Sondheimer HM, Tulloh RM, Harris BS, Jensen KM, Losonsky GA, et al. (2011) A randomized controlled trial of motavizumab versus palivizumab for the prophylaxis of serious respiratory syncytial virus disease in children with hemodynamically significant congenital heart disease. Pediatr Res 70: 186–191. 10.1038/pr.2011.411 PubMed DOI