Abstract
Premature infants are vulnerable to severe respiratory syncytial virus (RSV) lower respiratory tract infection (LRTI) resulting in hospitalisation and the potential for longer-term respiratory morbidity. Whilst the severity and consequence of RSV LRTI are generally accepted and recognised in infants born ≤32 weeks gestational age (GA), there is less acknowledgment of the potential consequences in infants born 33–35 weeks GA. However, there is a growing body of evidence suggesting that infants born between 33 and 35 weeks GA may be equally at risk for RSV LRTI as infants born <32 weeks GA. Interrupted lung development and an immature immune system have been linked with an increased susceptibility for RSV LRTI, along with other environmental, social, and physiological risk factors. Currently, the only effective method of preventing RSV LRTI is prophylaxis with palivizumab. Often with limited healthcare resources, identifying infants at greatest risk of RSV LRTI who would potentially benefit most from prophylaxis is highly desirable, particularly in the 33–35-week GA group. The purpose of this article is to examine the causes and consequences of RSV LRTI in infants born 33–35 weeks GA, and look at the potential for using risk factors to identify high risk infants and, thereby, optimise prophylaxis. The causes and consequences of RSV LRTI in infants born 33–35 weeks GAA were determined via literature review. A number of underlying risk factors that significantly increase the risk of severe RSV LRTI and subsequent hospitalisation in this group of infants have been identified, most notably from the FLIP and PICNIC studies. A European predictive model based on the risk factors in the FLIP study has recently been developed and validated, which will aid identification of infants born between 33 and 35 weeks GA with the highest risk of RSV hospitalisation. Implementation of this model and prophylaxis of infants born between 33 and 35 weeks GA should be a national or regional decision, taken in perspective of other public health needs.
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References
Horn SD, Smout RJ (2003) Effect of prematurity on respiratory syncytial virus hospital resource use and outcomes. J Pediatr 143:S133–S141
Willson DF, Landrigan CP, Horn SD, Smouht RJ (2003) Complications in infants hospitalized for bronchiolitis or respiratory syncytial virus pneumonia. J Pediatr 143(Suppl 1):S142–S149
Boyce TG, Mellen BG, Mitchel EF et al (2000) Rates of hospitalisation for respiratory syncytial virus infection among children in Medicaid. J Pediatr 137:865–870
Imaizumi S, Agarwal S, Pereira G (2001) Severity of respiratory syncytial virus (RSV) infection in hospitalized premature infants: the effect of gestational age and immune prophylaxis with palivizumab. APS/SPR/APA Annual Meeting, Baltimore, MD
IMpact-RSV Study Group (1998) Palivizumab, a humanized respiratory syncytial virus monoclonal antibody, reduces hospitalisation from respiratory syncytial virus infection in high-risk infants. Pediatrics 102:531–537
Feltes TF, Cabalka AK, Meissner C, Cardiac Synagis Study Group et al (2003) Palivizumab prophylaxis reduces hospitalisation due to respiratory syncytial virus in young children with hemodynamically significant congenital heart disease. J Pediatr 143:532–540
Langston C, Kidaa K, Reed M, Thurlbeck WM (1984) Human lung growth in late gestation and in the neonate. Am Rev Respir Dis 129:607–613
Friedrich L, Stein RT, Pitrez PMC et al (2006) Reduced lung function in healthy preterm infants in the first months of life. Am J Respir Crit Care Med 173:442–447
Handforth J, Friedland JS, Sharland M (2000) Basic epidemiology and immunopathology of RSV in children. Paediatr Respir Rev 1:210–214
Aujard Y, Faroux B (2002) Risk factors for severe respiratory syncytial virus infection in infants. Respir Med 96(Suppl B):S9–S14
Mussi-Pinhata MM, Gonçlaves AL (1989) Serum immunoglobulin levels and incidence of infection during the first year of life in full-term and preterm infants. J Trop Pediatr 35:147–153
Ballow M, Cates KL, Rowe JC et al (1986) Development of the immune system in very low weight (less than 1500g) premature infants: concentrations of plasma immunoglobulins and patterns of infections. Pediatr Res 20:899–904
Karron RA, Singleton RJ, Bulkow L et al (1999) Severe respiratory syncytial virus disease in Alaska native children. RSV Alaska Study Group. J Infect Dis 180:41–49
Yeung CY, Hobbs JR (1968) Serum-γG-globulin levels in normal, premature, post-mature, and “small-for-dates” newborn babies. Lancet 291:1167–70
Bont L, Kimpen JL (2002) Immunological mechanisms of severe respiratory syncytial virus bronchiolitis. Intensive Care Med 28:616–621
Culley FJ, Pollot J, Openshaw PJM (2002) Age at first viral infection determines the pattern of T cell-mediated disease during reinfection in adulthood. J Exp Med 10:1381–1386
Carbonell-Estrany X, Figueras-Aloy J, Law BJ, Infection Respiratonia Infantil por Virus Respiratorio, Pediatric Investigators Collaborative Network on Infections in Canada Study (2004) Identifying risk factors for severe respiratory syncytial virus among infants born after 33 through 35 completed weeks of gestation: different methodologies yield consistent findings. Pediatr Infect Dis J 23(Suppl 11):S193–201
Simoes EAF (2002) Immunoprophylaxis of respiratory syncytial virus: global experience. Respire Res 3(Suppl 1):S26–S33
Resch B, Pasnocht A, Gusenleitner W, Műller W (2005) Rehospitalisations for respiratory disease and respiratory syncytial virus infection in preterm infants of 29–36 weeks gestational age. J Infect 50:397–403
Navas L, Wang E, de Carvalho V, Robsinson J (1992) Improved outcome of respiratory syncytial virus infection in a high-risk hospitalized population of Canadian children. J Pediatr 121:348–354
Purcell K, Fergie J (2004) Driscoll Children’s Hospital respiratory syncytial virus database. Pediatr Infect Dis J 23:418–423
Greensill J, McNamara PS, Dove W et al (2003) Human metapneumovirus in severe respiratory syncytial virus bronchiolitis. Emerg Infect Dis 9:372–375
van Woensel JBM, Bos AP, Lutter R et al (2006) Absence of human metapneumovirus co-infection in cases of severe respiratory syncytial virus infection. Pediatr Pulmonol 41:872–874
Semple MG, Cowell A, Dove W et al (2005) Dual infection of infants by human metapneumovirus and human respiratory syncytial virus is strongly associated with severe bronchiolitis. J Infect Dis 191:382–386
Greenough A, Alexander J, Burgess S et al (2004) Health care utilisation of prematurely born, preschool children related to hospitalisation for RSV infection. Arch Dis Child 89:673–678
Sampalis JS (2003) Morbidity and mortality after RSV-associated hospitalizations among premature Canadian infants. J Pediatr 143:S150–S156
Bont L, Steijn M, van Aalderen WM (2004) Impact of wheezing after respiratory syncytial virus infection on health-related quality of life. Pediatr Infect Dis J 23:414–417
Figueras-Aloy J, Carbonell-Estrany X, Quero J, IRIS Study Group (2004) Case-control study of the risk factors linked to respiratory syncytial virus infection requiring hospitalisation in premature infants born at a gestational age of 33–35 weeks in Spain. Pediatr Infect Dis J 23:815–820
Law BJ, Langley JM, Allen U et al (2004) The pediatric investigators collaborative network on infections in Canada study of predictors of hospitalisation for respiratory syncytial virus infection for infants born at 33 through 35 completed weeks of gestation. Pediatr Infect Dis J 23:806–814
Doering G, Gusenleitner W, Belohradsky BH et al (2006) The risk of respiratory syncytial virus-related hospitalisations in preterm infants of 29 to 35 weeks gestational age. Pediatr Infect Dis J 25:1188–1190
Liese JG, Grill E, Fischer B, Munich RSV Study Group et al (2003) Incidence and risk factors of respiratory syncytial virus-related hospitalizations in premature infants in Germany. Eur J Pediatr 162:230–236
Rossi GA, Medici MC, Arcangeletti MC et al, Osservatorio RSV Study Group (2007) Risk factors for severe RSV-induced lower respiratory tract infection over four consecutive epidemics. Eur J Pediatr 166(12):1267–1272
Simon A, Khurana K, Wilkesmann A et al (2006) Nosocomial respiratory syncytial virus infection: impact of prospective surveillance and targeted infection control. Int J Hyg Environ Health 209:317–324
Thorburn K, Kerr S, Taylor N et al (2004) RSV outbreak in a paediatric intensive care unit. J Hosp Infect 57:194–201
Macartney KK, Gorelick MH, Manning ML et al (2000) Nosocomial respiratory syncytial virus infections: the cost-effectiveness and cost-benefit of infection control. Pediatrics 106:520–526
Isaacs D, Dickson H, O’Callaghan C et al (1991) Handwashing and cohorting in prevention of hospital acquired infections with respiratory syncytial virus. Arch Dis Child 66:227–231
Pedraz C, Carbonell-Estrany X, Figueras-Aloy J, Quero J, IRIS Study Group (2003) Effectiveness of palivizumab prophylaxis in decreasing syncytial virus hospitalizations in premature infants. Pediatr Infect Dis J 22:823–827
Lacaze-Masmonteil T, Seindenberg J, Mitchell I (2003) Evaluation of the safety of palivizumab in the second season of exposure in young children at risk for severe respiratory syncytial virus infection. Drug Saf 26:283–291
Sorrentino M, Powers T (2000) Effectiveness of palivizumab: evaluation of outcomes from the 1998 to 1999 respiratory syncytial virus season. The Palivizumab outcomes study group. Pediatr Infect Dis J 19:1068–71
Cohen AH, Sorrentino M, Powers T (2000) Effectiveness of palivizumab for preventing serious RSV disease. J Respir Dis 2(suppl):S30–S32
Groothuis JR, Northern Hemisphere Expanded Access Study Group (2001) Safety and tolerance of palivizumab administration in a large northern hemisphere trial. Pediatr Infect Dis J 20:628–630
Oh PI, Lanctjt KL, Yoon A, Composs Investigators et al (2002) Palivizumab prophylaxis for respiratory syncytial virus in Canada: utilization and outcomes. Pediatr Infect Dis J 21:512–518
Palivizumab Outcomes Registry Study Group (2003) Palivizumab prophylaxis of respiratory syncytial virus disease in 2000–2001: results from the Palivizumab Outcomes registry. Pediatr Pulmono 35:484–489
Sigurs N, Gustafsson PM, Bjarnason R et al (2005) Severe respiratory syncytial virus bronchiolitis in infancy and asthma and allergy at age 13. Am J Respir Crit Care Med 171:137–141
Henderson K, Hilliard TN, Sherriff A et al (2005) Hospitalization for RSV bronchiolitis before 12 months of age and subsequent asthma, atopy and wheeze: a longitudinal birth cohort study. Pediatr Allergy Immunol 16:386–392
Stein RT, Sherril D, Morgan W et al (1999) Respiratory syncytial virus in early life and risk of wheeze and allergy by age 13 years. Lancet 354:541–545
Korppi M, Piippo-Savolainen E, Korhonen K, Remes S (2004) Respiratory morbidity 20 years after RSV infection in infancy. Pediatr Pulmonol 38:155–160
Hyvarinen M, Piippo-Savolainen E, Korhonen K, Korppi M (2005) Teenage asthma after severe infantile bronchiolitis or pneumonia. Acta Paediatr 94:1378–1383
Broughton S, Bhat R, Roberts A et al (2006) Diminished lung function, RSV infection and respiratory morbidity in prematurely born infants. Arch Dis Child 91:26–30
Simoes EAF, Groothuis JR, Carbonell-Estrany X et al (2007) Palivizumab prophylaxis, respiratory syncytial virus, and subsequent recurrent wheezing. J Pediatrics 151:34–42
Lázaro y de Mercado P, Figueras Aloy J, Domenech Martínez E et al (2006) La eficiencia (coste-efectividad) de palivizumab como profilaxis para la infeccion por virus respiratorio sincitial en prematuros de 32–35 semanas en España. An Pediatr (Barc) 65:316–324
Nuijten MJC, Wittenberg W, Lebmeier M (2007) Cost effectiveness of palivizumab for respiratory syncytial virus prophylaxis in high-risk children: a UK analysis. Pharmacoeconomics 25:55–71
Devlin N, Parkin D (2004) Does NICE have a cost-effectiveness threshold and what other factors influence its decisions? A binary choice analysis. Health Econ 13:437–452
Martin JA, Hamilton BE, Sutton PD et al (2006) Final data for 2004. Natl Vital Stat Rep 55:1–101
Figueras AJ, Quero J, Domenech E, Comite de Estandares de la Sociedad Espanola de Neonatologia (2005) Recommendations for the prevention of respiratory syncytial virus infection. An Pediatr (Barc) 63:357–362
Rondini G, Macagno F, Barberi I (2004) Raccomandazioni della Società Italiana di Neonatologia per la prevenzione delle malattie da virus respiratorio sinciziale (VRS). Acta Neonatologica 1:1–11
Deutsche Gesellschaft für Pädiatrische Infektiologie (DGPI) (2006) Stellungnahme zur Prophylaxe von schweren RSV-Erkrankungen bei Risikokindern mit Palivizumab. http://www.dgpi.de/pdf/Leitlinie_Palivizumab_27Okt2006.pdf. Cited 4 December 2006
Committee on Infectious Diseases and Committee on Fetus and Newborn for the American Academy of Pediatrics (2003) Revised indications for the use of palivizumab and respiratory syncytial virus immune globulin intravenous for the prevention of respiratory syncytial virus infections. Pediatrics 112:1442–1446
Simoes EAF, Carbonell-Estrany X, Fullarton JF, Liese J (2007) A European predictive model for respiratory syncytial virus (RSV) hospitalisation of premature infants born at 33–35 weeks of gestational age (wGA). Presented at the 25th international congress of pediatrics, Athens, Greece, 25–30 August 2007
Medici MC, Arcangeletti MC, Rossi GA, Osservatorio VRS Study Group et al (2006) Four-year incidence of respiratory syncytial virus infection in infants and young children referred to emergency departments for lower respiratory tract diseases in Italy: the “Osservatorio VRS” study (2000–2004). New Microbiol 29:35-43
Acknowledgements
We are grateful to Dr Andrew Campbell, of Abbott Laboratories, for his contribution to the concept and structure of this paper and much stimulating discussion in the field of RSV and its management. Strategen Ltd. provided medical writing assistance, which was funded by Abbott Laboratories, Abbott Park, Illinois.
Contributors
XCE proposed the concept and structure of the review. All authors contributed to the interpretation of the evidence and the development of the manuscript.
Competing interests
XCE, LB, GD, J-BG, and ML have acted as expert advisors and speakers for Abbott Laboratories and have received honoraria in this regard.
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Carbonell-Estrany, X., Bont, L., Doering, G. et al. 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 (2008). https://doi.org/10.1007/s10096-008-0520-8
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DOI: https://doi.org/10.1007/s10096-008-0520-8