Advanced search
Publication Cover
Expert Review of Respiratory Medicine Volume 9, 2015 - Issue 6
Submit an article Journal homepage
682
Views
13
CrossRef citations to date
0
Altmetric
Reviews

Risk of respiratory syncytial virus infection in preterm infants: reviewing the need for prevention

Haben Y AbrahaMedical Outcomes and Research in Economics (MORE®) Research Group, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada
,
Krista L LanctôtMedical Outcomes and Research in Economics (MORE®) Research Group, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada
&
Bosco PaesDivision of Neonatology, Department of Pediatrics, McMaster University, Hamilton, Ontario, CanadaCorrespondence[email protected]
Pages 779-799 | Published online: 12 Oct 2015

References

  • Papers of special note have been highlighted as:
  • * of interest
  • ** of significant interest
  • Chanock R, Roizman B, Myers R. Recovery from infants with respiratory illness of a virus related to chimpanzee coryza agent (CCA). I. Isolation, properties and characterization. Am J Hyg. 1957;66:281–290.
  • Glezen WP, Taber LH, Frank AL, et al. Risk of primary infection and reinfection with respiratory syncytial virus. Am J Dis Child. 1986;140:543–546.
  • Nair H, Nokes DJ, Gessner BD, et al. Global burden of acute lower respiratory infections due to respiratory syncytial virus in young children: a systematic review and meta-analysis. Lancet. 2010;375:1545–1555.
  • Hall CB, Weinberg GA, Iwane MK, et al. The burden of respiratory syncytial virus infection in young children. N Engl J Med. 2009;360:588–598.

*  A large population-based study confirming that prematurity and infants <2 years of age especially those aged <6 months are good predictors of RSV-hospitalization

  • Borchers AT, Chang C, Gershwin ME, et al. Respiratory syncytial virus – a comprehensive review. Clin Rev Allergy Immunol. 2013;45:331–379.
  • Arruda E, Jones MH, Escremim de Paula F, et al. The burden of single virus and viral coinfections on severe lower respiratory tract infections among preterm infants: a prospective birth cohort study in Brazil. Pediatr Infect Dis J. 2014;33:997–1003.
  • Meyerholz DK, Grubor B, Fach SJ, et al. Reduced clearance of respiratory syncytial virus infection in a preterm lamb model. Microbes Infect. 2004;6:1312–1319.
  • McLellan KE, Schwarze J, Beattie T. Chest auscultatory signs in infants presenting to A&E with bronchiolitis. Eur J Emerg Med. 2014;21:436–441.
  • Tregoning JS, Schwarze J. Respiratory viral infections in infants: causes, clinical symptoms, virology, and immunology. Clin Microbiol Rev. 2010;23:74–98.
  • Ralston S, Hill V. Incidence of apnea in infants hospitalized with respiratory syncytial virus bronchiolitis: a systematic review. J Pediatr. 2009;155:728–733.
  • Hall CB, Simoes EA, Anderson LJ. Clinical and epidemiologic features of respiratory syncytial virus. Curr Top Microbiol Immunol. 2013;372:39–57.
  • Basile V, Di Mauro A, Scalini E, et al. Lung ultrasound: a useful tool in diagnosis and management of bronchiolitis. BMC Pediatr. 2015;15:63.
  • Stokes KL, Currier MG, Sakamoto K, et al. The respiratory syncytial virus fusion protein and neutrophils mediate the airway mucin response to pathogenic respiratory syncytial virus infection. J Virol. 2013;87:10070–10082.
  • Mejias A, Dimo B, Suarez NM, et al. Whole blood gene expression profiles to assess pathogenesis and disease severity in infants with respiratory syncytial virus infection. PLoS Med. 2013;10:e1001549.

**  An excellent study indicating that whole blood RNA transcriptional profiles of infants may better define severe RSV infection, improve the understanding of disease pathogenesis and permit identification of potential therapeutic or preventive targets

  • Sow FB, Gallup JM, Krishnan S, et al. Respiratory syncytial virus infection is associated with an altered innate immunity and a heightened pro-inflammatory response in the lungs of preterm lambs. Respir Res. 2011;12:106.
  • Resch B, Resch E, Muller W. Should respiratory care in preterm infants include prophylaxis against respiratory syncytial virus infection? The case in favour. Paediatr Respir Rev. 2013;14:130–136.
  • Resch B, Gusenleitner W, Muller WD, et al. Observational study of respiratory syncytial virus-associated hospitalizations and use of palivizumab in premature infants aged 29–32 weeks. Eur J Clin Microbiol Infect Dis. 2006;25:120–122.
  • Stevens TP, Sinkin RA, Hall CB, et al. Respiratory syncytial virus and premature infants born at 32 weeks’ gestation or earlier: hospitalization and economic implications of prophylaxis. Arch Pediatr Adolesc Med. 2000;154:55–61.
  • Law BJ, Langley JM, Allen U, 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.
  • Palivizumab, a humanized respiratory syncytial virus monoclonal antibody, reduces hospitalization from respiratory syncytial virus infection in high-risk infants. Pediatrics. 1998;102:531–537.

**  A landmark trial demonstrating the safety and efficacy of palivizumab in reducing RSV-hospitalization in preterm infants and those with bronchopulmonary dysplasia. This led to universal indications for RSV prophylaxis

  • Boyce TG, Mellen BG, Mitchel EF Jr., et al. Rates of hospitalization for respiratory syncytial virus infection among children in medicaid. J Pediatr. 2000;137:865–870.
  • Gijtenbeek RG, Kerstjens JM, Reijneveld SA, et al. RSV infection among children born moderately preterm in a community-based cohort. Eur J Pediatr. 2015;174:435–442.
  • Resch B, Gusenleitner W, Muller W. The impact of respiratory syncytial virus infection: a prospective study in hospitalized infants younger than 2 years. Infection. 2002;30:193–197.
  • Gouyon JB, Roze JC, Guillermet-Fromentin C, et al. Hospitalizations for respiratory syncytial virus bronchiolitis in preterm infants at <33 weeks gestation without bronchopulmonary dysplasia: the CASTOR study. Epidemiol Infect. 2013;141:816–826.
  • Ambrose CS, Anderson EJ, Simoes EA, et al. Respiratory syncytial virus disease in preterm infants in the U.S. born at 32–35 weeks gestation not receiving immunoprophylaxis. Pediatr Infect Dis J. 2014;33:576–582.
  • Horn SD, Smout RJ. Effect of prematurity on respiratory syncytial virus hospital resource use and outcomes. J Pediatr. 2003;143:S133–41.
  • Willson DF, Landrigan CP, Horn SD, et al. Complications in infants hospitalized for bronchiolitis or respiratory syncytial virus pneumonia. J Pediatr. 2003;143:S142–9.
  • Law B, Macdonald N, Langley J, et al. Severe respiratory syncytial virus infection among otherwise healthy prematurely born infants: what are we trying to prevent? Paediatr Child Health. 1998;3:402–404.
  • Ochoa TJ, Bautista R, Davila C, et al. Respiratory syncytial virus-associated hospitalizations in pre-mature infants in Lima, Peru. Am J Trop Med Hyg. 2014;91:1029–1034.
  • Gil-Prieto R, Gonzalez-Escalada A, Marin-Garcia P, et al. Respiratory syncytial virus bronchiolitis in children up to 5 years of age in Spain: epidemiology and comorbidities: an observational study. Medicine (Baltimore). 2015;94:e831.
  • Sampalis JS. Morbidity and mortality after RSV-associated hospitalizations among premature Canadian infants. J Pediatr. 2003;143:S150–S156.
  • Drysdale SB, Alcazar-Paris M, Wilson T, et al. Viral lower respiratory tract infections and preterm infants’ healthcare utilisation. Eur J Pediatr. 2015; 174:209–215.
  • Shefali-Patel D, Paris MA, Watson F, et al. RSV hospitalisation and healthcare utilisation in moderately prematurely born infants. Eur J Pediatr. 2012;171:1055–1061.
  • Cane PA, Pringle CR. Respiratory syncytial virus heterogeneity during an epidemic: analysis by limited nucleotide sequencing (SH gene) and restriction mapping (N gene). J Gen Virol. 1991;72(Pt 2):349–357.
  • Panayiotou C, Richter J, Koliou M, et al. Epidemiology of respiratory syncytial virus in children in Cyprus during three consecutive winter seasons (2010–2013): age distribution, seasonality and association between prevalent genotypes and disease severity. Epidemiol Infect. 2014;142:2406–2411.
  • Esposito S, Piralla A, Zampiero A, et al. Characteristics and their clinical relevance of respiratory syncytial virus types and genotypes circulating in northern Italy in five consecutive winter seasons. PLoS One. 2015;10:e0129369.
  • Mu Y, Zeng J, Chen Q, et al. New method for the visual detection of human respiratory syncytial virus using reverse transcription loop-mediated amplification. J Virol Methods. 2014;206:84–88.
  • Gilca R, De Serres G, Tremblay M, et al. Distribution and clinical impact of human respiratory syncytial virus genotypes in hospitalized children over 2 winter seasons. J Infect Dis. 2006;193:54–58.
  • Papadopoulos NG, Gourgiotis D, Javadyan A, et al. Does respiratory syncytial virus subtype influences the severity of acute bronchiolitis in hospitalized infants? Respir Med. 2004;98:879–882.
  • Martinello RA, Chen MD, Weibel C, et al. Correlation between respiratory syncytial virus genotype and severity of illness. J Infect Dis. 2002;186:839–842.
  • Hornsleth A, Klug B, Nir M, et al. Severity of respiratory syncytial virus disease related to type and genotype of virus and to cytokine values in nasopharyngeal secretions. Pediatr Infect Dis J. 1998;17:1114–1121.
  • Robinson J, Le Saux N. Preventing hospitalizations for respiratory syncytial virus infection. Paediatr Child Health. 2015;20:321–326.
  • Carbonell-Estrany X, Quero J, Bustos G, et al. Rehospitalization because of respiratory syncytial virus infection in premature infants younger than 33 weeks of gestation: a prospective study. IRIS Study Group. Pediatr Infect Dis J. 2000;19:592–597.
  • Liese JG, Grill E, Fischer B, et al. Incidence and risk factors of respiratory syncytial virus-related hospitalizations in premature infants in Germany. Eur J Pediatr. 2003;162:230–236.
  • Groothuis JR, Gutierrez KM, Lauer BA. Respiratory syncytial virus infection in children with bronchopulmonary dysplasia. Pediatrics. 1988;82:199–203.
  • Navas L, Wang E, de Carvalho V, et al. Improved outcome of respiratory syncytial virus infection in a high-risk hospitalized population of Canadian children. Pediatric Investigators Collaborative Network on Infections in Canada. J Pediatr. 1992;121:348–354.
  • Flamant C, Hallalel F, Nolent P, et al. Severe respiratory syncytial virus bronchiolitis in children: from short mechanical ventilation to extracorporeal membrane oxygenation. Eur J Pediatr. 2005;164:93–98.
  • Byington CL, Wilkes J, Korgenski K, et al. Respiratory syncytial virus-associated mortality in hospitalized infants and young children. Pediatrics. 2015;135:e24–31.
  • Tempia S, Walaza S, Viboud C, et al. Mortality associated with seasonal and pandemic influenza and respiratory syncytial virus among children <5 years of age in a high HIV prevalence setting–South Africa, 1998–2009. Clin Infect Dis. 2014;58:1241–1249.
  • Nair H, Simoes EA, Rudan I, et al. Global and regional burden of hospital admissions for severe acute lower respiratory infections in young children in 2010: a systematic analysis. Lancet. 2013;381:1380–1390.
  • Welliver RC Sr., Checchia PA, Bauman JH, et al. Fatality rates in published reports of RSV hospitalizations among high-risk and otherwise healthy children. Curr Med Res Opin. 2010;26:2175–2181.
  • Holman RC, Shay DK, Curns AT, et al. Risk factors for bronchiolitis-associated deaths among infants in the United States. Pediatr Infect Dis J. 2003;22:483–490.
  • Simon A, Ammann RA, Wilkesmann A, et al. Respiratory syncytial virus infection in 406 hospitalized premature infants: results from a prospective German multicentre database. Eur J Pediatr. 2007;166:1273–1283.
  • Thorburn K. Pre-existing disease is associated with a significantly higher risk of death in severe respiratory syncytial virus infection. Arch Dis Child. 2009;94:99–103.
  • Szabo SM, Gooch KL, Bibby MM, et al. The risk of mortality among young children hospitalized for severe respiratory syncytial virus infection. Paediatr Respir Rev. 2013;13(Suppl 2):S1–8.

**  A thorough, updated systematic review of 34 articles reporting RSV case-fatality rates in children aged <2 years based on underlying risk factors of prematurity, bronchopulmonary dysplasia and congenital heart disease

  • Wu S. Molecular basis for normal and abnormal lung development, injury and repair. In: Bancalari E, Polin RA, editors. The newborn lung: neonatology questions and controversies. 2nd ed. Philadelphia, PA: Elsevier; 2012. p. 3–28.
  • Hislop AA, Haworth SG. Airway size and structure in the normal fetal and infant lung and the effect of premature delivery and artificial ventilation. Am Rev Respir Dis. 1989;140:1717–1726.
  • Ishii N, Kono Y, Yonemoto N, et al. Outcomes of infants born at 22 and 23 weeks’ gestation. Pediatrics. 2013;132:62–71.
  • Crowley PA. Antenatal corticosteroid therapy: a meta-analysis of the randomized trials, 1972 to 1994. Am J Obstet Gynecol. 1995;173:322–335.
  • Crowther CA, McKinlay CJ, Middleton P, et al. Repeat doses of prenatal corticosteroids for women at risk of preterm birth for improving neonatal health outcomes. Cochrane Database Syst Rev. 2011;6:CD003935.
  • Soll R, Ozek E. Multiple versus single doses of exogenous surfactant for the prevention or treatment of neonatal respiratory distress syndrome. Cochrane Database Syst Rev. 2009;1:CD000141.
  • Bahadue FL, Soll R. Early versus delayed selective surfactant treatment for neonatal respiratory distress syndrome. Cochrane Database Syst Rev. 2012;11:CD001456.
  • Ardell S, Pfister RH, Soll R. Animal derived surfactant extract versus protein free synthetic surfactant for the prevention and treatment of respiratory distress syndrome. Cochrane Database Syst Rev. 2015;5:CD000144.
  • Alallah J. Early CPAP versus surfactant in extremely preterm infants. J Clin Neonatol. 2012;1:12–13.
  • Jain D, Bancalari E. Bronchopulmonary dysplasia: clinical perspective. Birth Defects Res A Clin Mol Teratol. 2014;100:134–144.
  • Peng W, Zhu H, Shi H, et al. Volume-targeted ventilation is more suitable than pressure-limited ventilation for preterm infants: a systematic review and meta-analysis. Arch Dis Child Fetal Neonatal Ed. 2014;99:F158–F165.
  • Jensen EA, Schmidt B. Epidemiology of bronchopulmonary dysplasia. Birth Defects Res A Clin Mol Teratol. 2014;100:145–157.

*  A detailed review and excellent summary of the factors influencing the diagnosis, causation and long-term outcome of bronchopulmonary dysplasia

  • Mourani PM, Ivy DD, Gao D, et al. Pulmonary vascular effects of inhaled nitric oxide and oxygen tension in bronchopulmonary dysplasia. Am J Respir Crit Care Med. 2004;170:1006–1013.
  • Ronkainen E, Dunder T, Peltoniemi O, et al. New BPD predicts lung function at school age: follow-up study and meta-analysis. Pediatr Pulmonol 2015. doi:10.1002/ppul.23153. [Epub ahead of print]
  • Hacking DF, Gibson AM, Robertson C, et al. Respiratory function at age 8–9 after extremely low birth weight or preterm birth in Victoria in 1997. Pediatr Pulmonol. 2013;48:449–455.
  • Kotecha SJ, Edwards MO, Watkins WJ, et al. Effect of preterm birth on later FEV1: a systematic review and meta-analysis. Thorax. 2013;68:760–766.
  • Doyle LW, Faber B, Callanan C, et al. Bronchopulmonary dysplasia in very low birth weight subjects and lung function in late adolescence. Pediatrics. 2006;118:108–113.
  • Halvorsen T, Skadberg BT, Eide GE, et al. Pulmonary outcome in adolescents of extreme preterm birth: a regional cohort study. Acta Paediatr. 2004;93:1294–1300.
  • Northway WH Jr., Rosan RC, Porter DY. Pulmonary disease following respirator therapy of hyaline-membrane disease. Bronchopulmonary dysplasia. N Engl J Med. 1967;276:357–368.
  • Merritt TA, Deming DD, Boynton BR. The ‘new’ bronchopulmonary dysplasia: challenges and commentary. Semin Fetal Neonatal Med. 2009;14:345–357.
  • Kribs A, Roll C, Gopel W, et al. Nonintubated surfactant application vs conventional therapy in extremely preterm infants: a randomized clinical trial. JAMA Pediatr. 2015;169:723–730.
  • Isayama T, Chai-Adisaksopha C, McDonald SD. Noninvasive ventilation with vs without early surfactant to prevent chronic lung disease in preterm infants: a systematic review and meta-analysis. JAMA Pediatr. 2015;169:731–739.
  • Jobe AH. The new bronchopulmonary dysplasia. Curr Opin Pediatr. 2011;23:167–172.
  • Merth IT, de Winter JP, Borsboom GJ, et al. Pulmonary function during the first year of life in healthy infants born prematurely. Eur Respir J. 1995;8:1141–1147.
  • Hjalmarson O, Sandberg K. Abnormal lung function in healthy preterm infants. Am J Respir Crit Care Med. 2002;165:83–87.
  • Friedrich L, Stein RT, Pitrez PM, et al. Reduced lung function in healthy preterm infants in the first months of life. Am J Respir Crit Care Med. 2006;173:442–447.
  • Friedrich L, Pitrez PM, Stein RT, et al. Growth rate of lung function in healthy preterm infants. Am J Respir Crit Care Med. 2007;176:1269–1273.
  • McEvoy C, Venigalla S, Schilling D, et al. Respiratory function in healthy late preterm infants delivered at 33–36 weeks of gestation. J Pediatr. 2013;162:464–469.
  • Jones M. Effect of preterm birth on airway function and lung growth. Paediatr Respir Rev. 2009;10(Suppl 1):9–11.
  • Broughton S, Bhat R, Roberts A, et al. Diminished lung function, RSV infection, and respiratory morbidity in prematurely born infants. Arch Dis Child. 2006;91:26–30.
  • Greenough A, Alexander J, Boit P, et al. School age outcome of hospitalisation with respiratory syncytial virus infection of prematurely born infants. Thorax. 2009;64:490–495.
  • Yeung CY, Hobbs JR. Serum-gamma-G-globulin levels in normal premature, post-mature, and “small-for-dates” newborn babies. Lancet. 1968;1:1167–1170.
  • Hyvarinen M, Zeltzer P, Oh W, et al. Influence of gestational age on serum levels of alpha-1 fetoprotein, IgG globulin, and albumin in newborn infants. J Pediatr. 1973;82:430–437.
  • Ballow M, Cates KL, Rowe JC, et al. Development of the immune system in very low birth weight (less than 1500 g) premature infants: concentrations of plasma immunoglobulins and patterns of infections. Pediatr Res. 1986;20: 899–904.
  • Stoll BJ, Gordon T, Korones SB, et al. Early-onset sepsis in very low birth weight neonates: a report from the National Institute of Child Health and Human Development Neonatal Research Network. J Pediatr. 1996;129:72–80.
  • Stoll BJ, Gordon T, Korones SB, et al. Late-onset sepsis in very low birth weight neonates: a report from the National Institute of Child Health and Human Development Neonatal Research Network. J Pediatr. 1996;129:63–71.
  • Group IC, Brocklehurst P, Farrell B, et al. Treatment of neonatal sepsis with intravenous immune globulin. N Engl J Med. 2011;365:1201–1211.
  • Ohlsson A, Lacy JB. Intravenous immunoglobulin for suspected or proven infection in neonates. Cochrane Database Syst Rev. 2013;7:CD001239.
  • Ohlsson A, Lacy JB. Intravenous immunoglobulin for preventing infection in preterm and/or low birth weight infants. Cochrane Database Syst Rev. 2013;7:CD000361.
  • Chu HY, Steinhoff MC, Magaret A, et al. Respiratory syncytial virus transplacental antibody transfer and kinetics in mother-infant pairs in Bangladesh. J Infect Dis. 2014;210:1582–1589.
  • Sande CJ, Cane PA, Nokes DJ. The association between age and the development of respiratory syncytial virus neutralising antibody responses following natural infection in infants. Vaccine. 2014;32:4726–4729.
  • Kasel JA, Walsh EE, Frank AL, et al. Relation of serum antibody to glycoproteins of respiratory syncytial virus with immunity to infection in children. Viral Immunol. 1987;1:199–205.
  • Reduction of respiratory syncytial virus hospitalization among premature infants and infants with bronchopulmonary dysplasia using respiratory syncytial virus immune globulin prophylaxis. The PREVENT Study Group. Pediatrics. 1997;99:93–99.

**  An efficiently designed randomized trial involving preterm infants and those with bronchopulmonary dysplasia that confirmed the efficacy of RSV immune globulin in the reduction of both overall and RSV-specific respiratory-related hospitalizations and otitis media

  • Groothuis JR, Simoes EA, Levin MJ, et al. Prophylactic administration of respiratory syncytial virus immune globulin to high-risk infants and young children. The Respiratory Syncytial Virus Immune Globulin Study Group. N Engl J Med. 1993;329:1524–1530.
  • Janssen R, Bont L, Siezen CL, et al. Genetic susceptibility to respiratory syncytial virus bronchiolitis is predominantly associated with innate immune genes. J Infect Dis. 2007;196:826–834.
  • McNally JD, Sampson M, Matheson LA, et al. Vitamin D receptor (VDR) polymorphisms and severe RSV bronchiolitis: a systematic review and meta-analysis. Pediatr Pulmonol. 2014;49:790–799.
  • Schuurhof A, Bont L, Siezen CL, et al. Interleukin-9 polymorphism in infants with respiratory syncytial virus infection: an opposite effect in boys and girls. Pediatr Pulmonol. 2010;45:608–613.
  • Siezen CL, Bont L, Hodemaekers HM, et al. Genetic susceptibility to respiratory syncytial virus bronchiolitis in preterm children is associated with airway remodeling genes and innate immune genes. Pediatr Infect Dis J. 2009;28:333–335.

**  A well-conducted study confirming that innate genes involved in both innate and adaptive immunity and airway remodeling genes variably influence disease susceptibility to RSV in preterm children

  • Drysdale SB, Prendergast M, Alcazar M, et al. Genetic predisposition of RSV infection-related respiratory morbidity in preterm infants. Eur J Pediatr. 2014;173:905–912.
  • Choi EH, Lee HJ, Chanock SJ. Human genetics and respiratory syncytial virus disease: current findings and future approaches. Curr Top Microbiol Immunol. 2013;372:121–137.
  • Goutaki M, Haidopoulou K, Pappa S, et al. The role of TLR4 and CD14 polymorphisms in the pathogenesis of respiratory syncytial virus bronchiolitis in greek infants. Int J Immunopathol Pharmacol. 2014;27:563–572.
  • Ampuero S, Luchsinger V, Tapia L, et al. SP-A1, SP-A2 and SP-D gene polymorphisms in severe acute respiratory syncytial infection in Chilean infants. Infect Genet Evol. 2011;11:1368–1377.
  • Kresfelder TL, Janssen R, Bont L, et al. Confirmation of an association between single nucleotide polymorphisms in the VDR gene with respiratory syncytial virus related disease in South African children. J Med Virol. 2011;83:1834–1840.
  • Resch B. Respiratory syncytial virus infection in high-risk infants—an update on palivizumab prophylaxis. Open Microbiol J. 2014;8:71–77.
  • Carbonell-Estrany X, Fullarton JR, Rodgers-Gray BS, et al. Can we improve the targeting of respiratory syncytial virus (RSV) prophylaxis in infants born 32–35 weeks’ gestational age with more informed use of risk factors? J Matern Fetal Neonatal Med. 2014;1–9.

*  A detailed evaluation of the key risk factors for RSV-hospitalization in late preterms with a systematic nucleation of how to use existing risk factor models to target the highest risk infants for prophylaxis

  • Sommer C, Resch B, Simoes EA. Risk factors for severe respiratory syncytial virus lower respiratory tract infection. Open Microbiol J. 2011;5:144–154.
  • Kristensen K, Hjuler T, Ravn H, et al. Chronic diseases, chromosomal abnormalities, and congenital malformations as risk factors for respiratory syncytial virus hospitalization: a population-based cohort study. Clin Infect Dis. 2012;54:810–817.
  • Resch B, Michel-Behnke I. Respiratory syncytial virus infections in infants and children with congenital heart disease: update on the evidence of prevention with palivizumab. Curr Opin Cardiol. 2013;28:85–91.
  • Paes B, Mitchell I, Li A, et al. Respiratory hospitalizations and respiratory syncytial virus prophylaxis in special populations. Eur J Pediatr. 2012;171:833–841.
  • Colin AA, McEvoy C, Castile RG. Respiratory morbidity and lung function in preterm infants of 32 to 36 weeks’ gestational age. Pediatrics. 2010;126:115–128.

*  A comprehensive overview of developmental and physiologic mechanisms that govern both an increased morbidity rate and lung function deficits in late preterms, which may persist into adulthood

  • Harijan P, Boyle EM. Health outcomes in infancy and childhood of moderate and late preterm infants. Semin Fetal Neonatal Med. 2012;17:159–162.
  • Resch B, Paes B. Are late preterm infants as susceptible to RSV infection as full term infants? Early Hum Dev. 2011;87(Suppl 1):S47–S49.
  • Carbonell-Estrany X, Fullarton JR, Gooch KL, et al. Effects of parental and household smoking on the risk of respiratory syncytial virus (RSV) hospitalisation in late-preterm infants and the potential impact of RSV prophylaxis. J Matern Fetal Neonatal Med. 2013;26:926–931.
  • Figueras-Aloy J, Carbonell-Estrany X, Quero-Jimenez J, 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.
  • Carbonell-Estrany X, Figueras-Aloy J, Law BJ, et al. 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. 2004;23:S193–201.
  • Figueras-Aloy J, Carbonell-Estrany X, Quero J, et al. Case–control study of the risk factors linked to respiratory syncytial virus infection requiring hospitalization in premature infants born at a gestational age of 33–35 weeks in Spain. Pediatr Infect Dis J. 2004;23:815–820.
  • Doering G, Gusenleitner W, Belohradsky BH, et al. The risk of respiratory syncytial virus-related hospitalizations in preterm infants of 29 to 35 weeks’ gestational age. Pediatr Infect Dis J. 2006;25:1188–1190.
  • Lanari M, Prinelli F, Adorni F, et al. Risk factors for bronchiolitis hospitalization during the first year of life in a multicenter Italian birth cohort. Ital J Pediatr. 2015;41:40. doi:10.1186/s13052-015-0149-z.
  • Simoes EA, Carbonell-Estrany X, Fullarton JR, et al. 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. 2008;9:78.
  • Sampalis JS, Langley J, Carbonell-Estrany X, et al. Development and validation of a risk scoring tool to predict respiratory syncytial virus hospitalization in premature infants born at 33 through 35 completed weeks of gestation. Med Decis Making. 2008;28:471–480.
  • Blanken MO, Koffijberg H, Nibbelke EE, et al. Prospective validation of a prognostic model for respiratory syncytial virus bronchiolitis in late preterm infants: a multicenter birth cohort study. PLoS One. 2013;8:e59161.
  • Simoes EA, Carbonell-Estrany X, Fullarton JR, et al. European risk factors’ model to predict hospitalization of premature infants born 33–35 weeks’ gestational age with respiratory syncytial virus: validation with Italian data. J Matern Fetal Neonatal Med. 2011;24:152–157.
  • Carbonell-Estrany X, Simoes EA, Fullarton JR, et al. Validation of a model to predict hospitalization due to RSV of infants born at 33-35 weeks’ gestation. J Perinat Med. 2010;38:411–417.
  • Stensballe LG, Fullarton JR, Carbonell-Estrany X, et al. Population based external validation of a European predictive model for respiratory syncytial virus hospitalization of premature infants born 33 to 35 weeks of gestational age. Pediatr Infect Dis J. 2010;29:374–376.
  • Paes B, Steele S, Janes M, et al. Risk-Scoring tool for respiratory syncytial virus prophylaxis in premature infants born at 33–35 completed weeks’ gestational age in Canada. Curr Med Res Opin. 2009;25:1585–1591.
  • Paes B, Cole M, Latchman A, et al. Predictive value of the respiratory syncytial virus risk-scoring tool in the term infant in Canada. Curr Med Res Opin. 2009;25:2191–2196.
  • Mosalli R, Abdul Moez AM, Janish M, et al. Value of a risk scoring tool to predict respiratory syncytial virus disease severity and need for hospitalization in term infants. J Med Virol. 2015;87:1285–1291.
  • Stein RT, Martinez FD. Respiratory syncytial virus and asthma: still no final answer. Thorax. 2010;65:1033–1034.
  • Jafri HS, Chavez-Bueno S, Mejias A, et al. Respiratory syncytial virus induces pneumonia, cytokine response, airway obstruction, and chronic inflammatory infiltrates associated with long-term airway hyperresponsiveness in mice. J Infect Dis. 2004;189:1856–1865.
  • Sigurs N, Bjarnason R, Sigurbergsson F, et al. Respiratory syncytial virus bronchiolitis in infancy is an important risk factor for asthma and allergy at age 7. Am J Respir Crit Care Med. 2000;161:1501–1507.
  • Sigurs N, Gustafsson PM, Bjarnason R, et al. Severe respiratory syncytial virus bronchiolitis in infancy and asthma and allergy at age 13. Am J Respir Crit Care Med. 2005;171:137–141.
  • Sigurs N, Aljassim F, Kjellman B, et al. Asthma and allergy patterns over 18 years after severe RSV bronchiolitis in the first year of life. Thorax. 2010;65:1045–1052.
  • Stein RT, Sherrill D, Morgan WJ, et al. Respiratory syncytial virus in early life and risk of wheeze and allergy by age 13 years. Lancet. 1999;354:541–545.
  • Perez-Yarza EG, Moreno A, Lazaro P, et al. The association between respiratory syncytial virus infection and the development of childhood asthma: a systematic review of the literature. Pediatr Infect Dis J. 2007;26:733–739.
  • Regnier SA, Huels J. Association between respiratory syncytial virus hospitalizations in infants and respiratory sequelae: systematic review and meta-analysis. Pediatr Infect Dis J. 2013;32:820–826.

*  An excellent systematic examination of studies evaluating the gradient effect of RSV in early infancy and asthma in childhood and adolescence that diminishes over time

  • Szabo SM, Levy AR, Gooch KL, et al. Elevated risk of asthma after hospitalization for respiratory syncytial virus infection in infancy. Paediatr Respir Rev. 2013; 13(Suppl 2): S9–15.
  • Fauroux B, Gouyon JB, Roze JC, et al. Respiratory morbidity of preterm infants of less than 33 weeks gestation without bronchopulmonary dysplasia: a 12-month follow-up of the CASTOR study cohort. Epidemiol Infect. 2014;142:1362–1374.
  • Carbonell-Estrany X, Perez-Yarza EG, Garcia LS, et al. Long-term burden and respiratory effects of respiratory syncytial virus hospitalization in preterm infants—the SPRING study. PLoS One. 2015;10:e0125422.
  • Backman K, Piippo-Savolainen E, Ollikainen H, et al. Adults face increased asthma risk after infant RSV bronchiolitis and reduced respiratory health-related quality of life after RSV pneumonia. Acta Paediatr. 2014;103:850–855.
  • Bont L, Steijn M, van Aalderen WM, et al. Impact of wheezing after respiratory syncytial virus infection on health-related quality of life. Pediatr Infect Dis J. 2004;23:414–417.
  • Drysdale SB, Wilson T, Alcazar M, et al. Lung function prior to viral lower respiratory tract infections in prematurely born infants. Thorax. 2011;66:468–473.
  • Drysdale SB, Lo J, Prendergast M, et al. Lung function of preterm infants before and after viral infections. Eur J Pediatr. 2014;173:1497–1504.
  • Zomer-Kooijker K, Uiterwaal CS, van der Gugten AC, et al. Decreased lung function precedes severe respiratory syncytial virus infection and post-respiratory syncytial virus wheeze in term infants. Eur Respir J. 2014;44:666–674.
  • Mejias A, Chavez-Bueno S, Rios AM, et al. Anti-respiratory syncytial virus (RSV) neutralizing antibody decreases lung inflammation, airway obstruction, and airway hyperresponsiveness in a murine RSV model. Antimicrob Agents Chemother. 2004;48:1811–1822.
  • Simoes EA, Groothuis JR, Carbonell-Estrany X, et al. Palivizumab prophylaxis, respiratory syncytial virus, and subsequent recurrent wheezing. J Pediatr. 2007;151(34–42): e1.
  • Simoes EA, Carbonell-Estrany X, Rieger CH, et al. The effect of respiratory syncytial virus on subsequent recurrent wheezing in atopic and nonatopic children. J Allergy Clin Immunol. 2010;126:256–262.
  • Yoshihara S, Kusuda S, Mochizuki H, et al. Effect of palivizumab prophylaxis on subsequent recurrent wheezing in preterm infants. Pediatrics. 2013;132:811–818.
  • Blanken MO, Rovers MM, Molenaar JM, et al. Respiratory syncytial virus and recurrent wheeze in healthy preterm infants. N Engl J Med. 2013;368:1791–1799.

**  A pivotal trial that for the first time prove that palivizumab not only reduces the risk of RSV hospitalization in late preterm infants but can successfully interrupt the development of childhood wheeze

  • Crowe JE Jr., Williams JV. Immunology of viral respiratory tract infection in infancy. Paediatr Respir Rev. 2003;4:112–119.
  • Shinoff JJ, O’Brien KL, Thumar B, et al. Young infants can develop protective levels of neutralizing antibody after infection with respiratory syncytial virus. J Infect Dis. 2008;198:1007–1015.
  • Chin J, Magoffin RL, Shearer LA, et al. Field evaluation of a respiratory syncytial virus vaccine and a trivalent parainfluenza virus vaccine in a pediatric population. Am J Epidemiol. 1969;89:449–463.
  • Notario G, Vo PG, Gooch KL, et al. Respiratory syncytial virus-related hospitalization in premature infants without bronchopulmonary dysplasia: subgroup efficacy analysis of the IMpact-RSV trial by gestational age group. Pediatric Health Med Ther. 2014;5:43–48.
  • Subramanian KN, Weisman LE, Rhodes T, et al. Safety, tolerance and pharmacokinetics of a humanized monoclonal antibody to respiratory syncytial virus in premature infants and infants with bronchopulmonary dysplasia. MEDI-493 Study Group. Pediatr Infect Dis J. 1998;17:110–115.
  • Groothuis JR. Safety of palivizumab in preterm infants 29 to 32 weeks’ gestational age without chronic lung disease to prevent serious respiratory syncytial virus infection. Eur J Clin Microbiol Infect Dis. 2003;22:414–417.
  • Turti TV, Baibarina EN, Degtiareva EA, et al. A prospective, open-label, non-comparative study of palivizumab prophylaxis in children at high risk of serious respiratory syncytial virus disease in the Russian Federation. BMC Res Notes. 2012;5:484.
  • Tavsu I, Gursoy T, Dirman S, et al. Palivizumab prophylaxis: does it have any influence on the growth and development of the infants? Am J Perinatol. 2014;31:667–672.
  • Pedraz C, Carbonell-Estrany X, Figueras-Aloy J, et al. Effect of palivizumab prophylaxis in decreasing respiratory syncytial virus hospitalizations in premature infants. Pediatr Infect Dis J. 2003;22:823–827.
  • Simoes EA, Groothuis JR. Respiratory syncytial virus prophylaxis—the story so far. Respir Med. 2002;96(Suppl B):S15–24.
  • Frogel M, Nerwen C, Cohen A, et al. Prevention of hospitalization due to respiratory syncytial virus: results from the Palivizumab Outcomes Registry. J Perinatol. 2008;28:511–517.
  • Paes B, Mitchell I, Li A, et al. A comparative study of respiratory syncytial virus (RSV) prophylaxis in premature infants within the Canadian Registry of Palivizumab (CARESS). Eur J Clin Microbiol Infect Dis. 2012;31:2703–2711.
  • Romero JR. Palivizumab prophylaxis of respiratory syncytial virus disease from 1998 to 2002: results from four years of palivizumab usage. Pediatr Infect Dis J. 2003;22:S46–54.
  • Paes B, Mitchell I, Li A, et al. Respiratory-related hospitalizations following prophylaxis in the Canadian registry for palivizumab (2005–2012) compared to other international registries. Clin Dev Immunol. 2013;2013:917068.

*  A comprehensive overview of the data from international registries on palivizumab and RSV-hospitalization outcomes based on its universal use for the primary indications of prematurity, bronchopulmonary dysplasia and congenital heart disease

  • Homaira N, Rawlinson W, Snelling TL, et al. Effectiveness of palivizumab in preventing RSV hospitalization in high risk children: a real-world perspective. Int J Pediatr. 2014;2014:571609. doi:10.1155/2014/571609.
  • Andabaka T, Nickerson JW, Rojas-Reyes MX, et al. Monoclonal antibody for reducing the risk of respiratory syncytial virus infection in children. Cochrane Database Syst Rev. 2013;4:CD006602.
  • Wegzyn C, Toh LK, Notario G, et al. Safety and effectiveness of palivizumab in children at high risk of serious disease due to respiratory syncytial virus infection: a systematic review. Infect Dis Ther 2014. [Epub ahead of print]

*  An in-depth analysis and update on the Cochrane review establishing that solid evidence from randomized trials and real-world prospective observational studies, reconfirms the efficacy of palivizumab

  • Morris SK, Dzolganovski B, Beyene J, et al. A meta-analysis of the effect of antibody therapy for the prevention of severe respiratory syncytial virus infection. BMC Infect Dis. 2009;9:106.
  • Butt ML, Symington A, Janes M, et al. The impact of prophylaxis on paediatric intensive care unit admissions for RSV infection: a retrospective, single-centre study. Eur J Pediatr. 2011;170:907–913.
  • Zhang T, Zhu Q, Zhang X, et al. Clinical characteristics and direct medical cost of respiratory syncytial virus infection in children hospitalized in Suzhou, China. Pediatr Infect Dis J. 2014;33:337–341.
  • Paramore LC, Ciuryla V, Ciesla G, et al. Economic impact of respiratory syncytial virus-related illness in the US: an analysis of national databases. Pharmacoeconomics. 2004;22:275–284.
  • Ranmuthugala G, Brown L, Lidbury BA. Respiratory syncytial virus–the unrecognised cause of health and economic burden among young children in Australia. Commun Dis Intell Q Rep. 2011;35:177–184.
  • Hussman JM, Li A, Paes B, et al. A review of cost-effectiveness of palivizumab for respiratory syncytial virus. Expert Rev Pharmacoecon Outcomes Res. 2012;12:553–567.
  • Ofman JJ, Sullivan SD, Neumann PJ, et al. Examining the value and quality of health economic analyses: implications of utilizing the QHES. J Manag Care Pharm. 2003;9:53–61.
  • Farina D, Rodriguez SP, Bauer G, et al. Respiratory syncytial virus prophylaxis: cost-effective analysis in Argentina. Pediatr Infect Dis J. 2002;21:287–291.
  • Hampp C, Kauf TL, Saidi AS, et al. Cost-effectiveness of respiratory syncytial virus prophylaxis in various indications. Arch Pediatr Adolesc Med. 2011;165:498–505.
  • Joffe S, Ray GT, Escobar GJ, et al. Cost-effectiveness of respiratory syncytial virus prophylaxis among preterm infants. Pediatrics. 1999;104:419–427.
  • Lofland JH, O’Connor JP, Chatterton ML, et al. Palivizumab for respiratory syncytial virus prophylaxis in high-risk infants: a cost-effectiveness analysis. Clin Ther. 2000;22:1357–1369.
  • Rodriguez SP, Farina D, Bauer G. Respiratory syncytial virus prophylaxis in a high-risk population in Argentina: a cost-effectiveness analysis. Pediatr Infect Dis J. 2008;27:660–661.
  • Roeckl-Wiedmann I, Liese JG, Grill E, et al. Economic evaluation of possible prevention of RSV-related hospitalizations in premature infants in Germany. Eur J Pediatr. 2003;162:237–244.
  • Simpson S, Burls A. A systematic review of the effectiveness and cost-effectiveness of palivizumab (Synagis) in the prevention of respiratory syncytial virus (RSV) infection in infants at high risk of infection. Birmingham: West Midlands Health Technology Assessment Group, Department of Public Health and Epidemiology, University of Birmingham; 2001. p. 1–41.
  • Vogel AM, McKinlay MJ, Ashton T, et al. Cost-effectiveness of palivizumab in New Zealand. J Paediatr Child Health. 2002;38:352–357.
  • Oncel MY, Mutlu B, Kavurt S, et al. Respiratory syncytial virus prophylaxis in preterm infants: a cost-effectiveness study from Turkey. Turk J Pediatr. 2012;54:344–351.
  • Chirico G, Ravasio R, Sbarigia U. Cost-utility analysis of palivizumab in Italy: results from a simulation model in the prophylaxis of respiratory syncytial virus infection (RSV) among high-risk preterm infants. Ital J Pediatr. 2009;35:4.
  • Elhassan NO, Sorbero ME, Hall CB, et al. Cost-effectiveness analysis of palivizumab in premature infants without chronic lung disease. Arch Pediatr Adolesc Med. 2006;160:1070–1076.
  • Lanctot KL, Masoud ST, Paes BA, et al. The cost-effectiveness of palivizumab for respiratory syncytial virus prophylaxis in premature infants with a gestational age of 32–35 weeks: a Canadian-based analysis. Curr Med Res Opin. 2008;24:3223–3237.
  • Mahadevia PJ, Masaquel AS, Polak MJ, et al. Cost utility of palivizumab prophylaxis among pre-term infants in the United States: a national policy perspective. J Med Econ. 2012;15:987–996.
  • Neovius K, Buesch K, Sandstrom K, et al. Cost-effectiveness analysis of palivizumab as respiratory syncytial virus prophylaxis in preterm infants in Sweden. Acta Paediatr. 2011;100:1306–1314.
  • Nuijten MJ, Wittenberg W. Cost effectiveness of palivizumab in Spain: an analysis using observational data. Eur J Health Econ. 2010;11:105–115.
  • Nuijten MJ, Wittenberg W, Lebmeier M. Cost effectiveness of palivizumab for respiratory syncytial virus prophylaxis in high-risk children: a UK analysis. Pharmacoeconomics. 2007;25:55–71.
  • Resch B, Gusenleitner W, Nuijten MJ, et al. Cost-effectiveness of palivizumab against respiratory syncytial viral infection in high-risk children in Austria. Clin Ther. 2008;30:749–760.

*  A nation-wide study conducted over 16 RSV seasons shows that palivizumab is cost-effective in the prevention of RSV disease for all preterms <35 weeks gestation and those with bronchopulmonary dysplasia

  • Resch B, Sommer C, Nuijten MJ, et al. Cost-effectiveness of palivizumab for respiratory syncytial virus infection in high-risk children, based on long-term epidemiologic data from Austria. Pediatr Infect Dis J. 2012;31:e1–8.
  • Salinas-Escudero G, Martinez-Valverde S, Reyes-Lopez A, et al. Cost-effectiveness analysis of the use of palivizumab in the prophylaxis of preterm patients in Mexico. Salud Publica Mex. 2012;54:47–59.
  • Wang D, Cummins C, Bayliss S, et al. Immunoprophylaxis against respiratory syncytial virus (RSV) with palivizumab in children: a systematic review and economic evaluation. Health Technol Assess. 2008;12:iii, ix–x, 1–86.
  • Weiner LB, Masaquel AS, Polak MJ, et al. Cost-effectiveness analysis of palivizumab among pre-term infant populations covered by Medicaid in the United States. J Med Econ. 2012;15:997–1018.
  • Bentley A, Filipovic I, Gooch K, et al. A cost-effectiveness analysis of respiratory syncytial virus (RSV) prophylaxis in infants in the United Kingdom. Health Econ Rev. 2013;3:18.
  • Nuijten M, Lebmeier M, Wittenberg W. Cost effectiveness of palivizumab for RSV prevention in high-risk children in the Netherlands. J Med Econ. 2009;12:291–300.
  • Rietveld E, Steyerberg EW, Polder JJ, et al. Passive immunisation against respiratory syncytial virus: a cost-effectiveness analysis. Arch Dis Child. 2010;95:493–498.
  • Diez-Domingo J, Perez-Yarza EG, Melero JA, et al. Social, economic, and health impact of the respiratory syncytial virus: a systematic search. BMC Infect Dis. 2014;14:544.

**  A systematic review that uniquely summarizes the impact of RSV in children, reporting the social, economic and health impact of the disease during the acute illness and subsequent follow-up

  • Simoes EA, DeVincenzo JP, Boeckh M, et al. Challenges and opportunities in developing respiratory syncytial virus therapeutics. J Infect Dis. 2015;211(Suppl 1):S1–S20.

*  A detailed description of the numerous hurdles encountered in the development of antivirals for the treatment of RSV infections and how they can be potentially overcome in a step-wise fashion

  • Douglas JL, Panis ML, Ho E, et al. Small molecules VP-14637 and JNJ-2408068 inhibit respiratory syncytial virus fusion by similar mechanisms. Antimicrob Agents Chemother. 2005;49:2460–2466.
  • DeVincenzo J, Lambkin-Williams R, Wilkinson T, et al. A randomized, double-blind, placebo-controlled study of an RNAi-based therapy directed against respiratory syncytial virus. Proc Natl Acad Sci USA. 2010;107:8800–8805.
  • DeVincenzo J, Fathi H, Mcclure M Treatment with oral ALS-8176: a nucleoside analog, rapidly reduces RSV viral load and clinical disease severity in a healthy volunteer challenge study. Infectious Diseases Society of America Annual Meeting, 2014; Philadelphia, PA; 2014.
  • DeVincenzo JP, Whitley RJ, Mackman RL, et al. Oral GS-5806 activity in a respiratory syncytial virus challenge study. N Engl J Med. 2014;371:711–722.
  • Meissner HC, Kimberlin DW. RSV immunoprophylaxis: does the benefit justify the cost? Pediatrics. 2013;132:915–918.
  • Blackstone EA, Fuhr JP Jr. Innovation and competition: will biosimilars succeed?: the creation of an FDA approval pathway for biosimilars is complex and fraught with hazard. Yes, innovation and market competition are at stake. But so are efficacy and patient safety. Biotechnol Healthc. 2012;9:24–27.
  • Walsh EE, Peterson DR, Kalkanoglu AE, et al. Viral shedding and immune responses to respiratory syncytial virus infection in older adults. J Infect Dis. 2013;207:1424–1432.
  • Thompson WW, Shay DK, Weintraub E, et al. Mortality associated with influenza and respiratory syncytial virus in the United States. JAMA. 2003;289:179–186.
  • Graham BS, Anderson LJ. Challenges and opportunities for respiratory syncytial virus vaccines. Curr Top Microbiol Immunol. 2013;372:391–404.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Order Reprints Request Corporate Permissions

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

Request Academic Permissions

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.

Related research

People also read lists articles that other readers of this article have read.

Recommended articles lists articles that we recommend and is powered by our AI driven recommendation engine.

Cited by lists all citing articles based on Crossref citations.
Articles with the Crossref icon will open in a new tab.