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Am J Perinatol 2022; 39(S 01): S7-S13
DOI: 10.1055/s-0042-1757279
Review Article

Real-World Studies of Respiratory Syncytial Virus Hospitalizations among Moderate/Late Preterm Infants Exposed to Passive Immunoprophylaxis with Palivizumab

Paolo Manzoni
1   Department of Maternal Infant Medicine, Degli Infermi Hospital, Biella, Italy
2   University of Torino, Turin, Italy
,
Eugenio Baraldi
3   Neonatal Intensive Care Unit, Department of Women's and Children's Health, University Hospital of Padova, Padova, Italy
,
Manuel Sánchez Luna
4   Neonatology Division and NICU, University Hospital Gregorio Marañón, Complutense University of Madrid, Madrid, Spain
,
Chryssoula Tzialla
5   Neonatal and Pediatric Unit, Polo Ospedaliero Oltrepò, ASST Pavia, Italy
› Author Affiliations Funding This work was supported by an unrestricted grant from AstraZeneca SpA.
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Abstract

This article aims to assess the real-world effectiveness of palivizumab immunoprophylaxis against respiratory syncytial virus (RSV)-associated hospitalization (RSVH) rates in otherwise healthy moderate/late preterm infants and discuss the role of palivizumab in preventing acute and long-term outcomes. We identified studies in the PubMed and Embase databases that reported patient-level data on (1) exposure to palivizumab in preterm infants born between 29 and 35 weeks of gestational age (or subsets within this range) ≤ 2 years of chronological age, and (2) the outcome of RSVH. Six studies assessed RSVH in infants this gestational age who had been exposed or not to palivizumab and reported patient-level data. Exposure was associated with a reduction in RSVH rates that was comparable to the reduction seen in controlled clinical trials (weighed mean 4.0-fold reduction). RSV immunoprophylaxis in preterm infants within 29 to 35 weeks of gestational age is associated with a considerably lower burden of RSVH.

Key Points

  • RSV is the leading cause of lower respiratory tract infection hospitalization in infants.

  • Palivizumab prevents RSVH in a real-world scenario.

  • Immunoprophylaxis should be used in high-risk infants.

Keywords

respiratory syncytial virus - palivizumab - immunoprophylaxis - preterm infant - hospitalization


Publication History

Received: 28 July 2022

Accepted: 04 August 2022

Article published online:
28 October 2022

© 2022. Thieme. All rights reserved.

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  • References

  • 1 Hall CB, Weinberg GA, Iwane MK. et al. The burden of respiratory syncytial virus infection in young children. N Engl J Med 2009; 360 (06) 588-598
    Search in Google Scholar
  • 2 Stockman LJ, Curns AT, Anderson LJ, Fischer-Langley G. Respiratory syncytial virus-associated hospitalizations among infants and young children in the United States, 1997-2006. Pediatr Infect Dis J 2012; 31 (01) 5-9
    Search in Google Scholar
  • 3 Li Y, Johnson EK, Shi T. et al. National burden estimates of hospitalisations for acute lower respiratory infections due to respiratory syncytial virus in young children in 2019 among 58 countries: a modelling study. Lancet Respir Med 2021; 9 (02) 175-185
    CrossrefPubMedSearch in Google Scholar
  • 4 Figueras-Aloy J, Manzoni P, Paes B. et al. Defining the risk and associated morbidity and mortality of severe respiratory syncytial virus infection among preterm infants without chronic lung disease or congenital heart disease. Infect Dis Ther 2016; 5 (04) 417-452
    CrossrefPubMedSearch in Google Scholar
  • 5 Melville JM, Moss TJ. The immune consequences of preterm birth. Front Neurosci 2013; 7: 79
    CrossrefPubMedSearch in Google Scholar
  • 6 Bozzola E, Ciarlitto C, Guolo S. et al. Respiratory syncytial virus bronchiolitis in infancy: the acute hospitalization cost. Front Pediatr 2021; 8: 594898
    CrossrefPubMedSearch in Google Scholar
  • 7 Brusco NK, Alafaci A, Tuckerman J. et al. The 2018 annual cost burden for children under five years of age hospitalised with respiratory syncytial virus in Australia. Commun Dis Intell 2018; 2022: 46
    PubMedSearch in Google Scholar
  • 8 Thampi N, Knight BD, Thavorn K. et al. Health care costs of hospitalization of young children for respiratory syncytial virus infections: a population-based matched cohort study. CMAJ Open 2021; 9 (04) E948-E956
    CrossrefPubMedSearch in Google Scholar
  • 9 Falsey AR, Hennessey PA, Formica MA, Cox C, Walsh EE. Respiratory syncytial virus infection in elderly and high-risk adults. N Engl J Med 2005; 352 (17) 1749-1759
    CrossrefPubMedSearch in Google Scholar
  • 10 Balasubramani GK, Nowalk MP, Eng H, Zimmerman RK. Estimating the burden of adult hospitalized RSV infection using local and state data - methodology. Hum Vaccin Immunother 2022; 18 (01) 1958610
    CrossrefPubMedSearch in Google Scholar
  • 11 Colosia AD, Yang J, Hillson E. et al. The epidemiology of medically attended respiratory syncytial virus in older adults in the United States: a systematic review. PLoS One 2017; 12 (08) e0182321
    CrossrefPubMedSearch in Google Scholar
  • 12 Haber N. Respiratory syncytial virus infection in elderly adults. Med Mal Infect 2018; 48 (06) 377-382
    CrossrefPubMedSearch in Google Scholar
  • 13 Kujawski SA, Whitaker M, Ritchey MD. et al. Rates of respiratory syncytial virus (RSV)-associated hospitalization among adults with congestive heart failure-United States, 2015-2017. PLoS One 2022; 17 (03) e0264890
    CrossrefPubMedSearch in Google Scholar
  • 14 Shi T, Arnott A, Semogas I. et al; RESCEU Investigators. The etiological role of common respiratory viruses in acute respiratory infections in older adults: a systematic review and meta-analysis. J Infect Dis 2020; 222 (supplement_7): S563-S569
    CrossrefPubMedSearch in Google Scholar
  • 15 Baraldi E, Lanari M, Manzoni P. et al. Inter-society consensus document on treatment and prevention of bronchiolitis in newborns and infants. Ital J Pediatr 2014; 40: 65
    CrossrefPubMedSearch in Google Scholar
  • 16 Blanken MO, Paes B, Anderson EJ. et al. Risk scoring tool to predict respiratory syncytial virus hospitalisation in premature infants. Pediatr Pulmonol 2018; 53 (05) 605-612
    CrossrefPubMedSearch in Google Scholar
  • 17 Straňák Z, Saliba E, Kosma P. et al. Predictors of RSV LRTI hospitalization in infants born at 33 to 35 weeks gestational age: a large multinational study (PONI). PLoS One 2016; 11 (06) e0157446
    CrossrefPubMedSearch in Google Scholar
  • 18 Resch B. Product review on the monoclonal antibody palivizumab for prevention of respiratory syncytial virus infection. Hum Vaccin Immunother 2017; 13 (09) 2138-2149
    CrossrefPubMedSearch in Google Scholar
  • 19 Palivizumab, a humanized respiratory syncytial virus monoclonal antibody, reduces hospitalization from respiratory syncytial virus infection in high-risk infants. Pediatrics 1998; 102 (03) 531-537
    Search in Google Scholar
  • 20 US Food and Drug Administration. Palivizumab – Summary of Product Characteristics. Accessed July 25, 2022 at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2002/palimed102302LB.pdf
    PubMed
  • 21 European Medicines Agency. Palivizumab - Summary of Product Characteristics. Accessed July 25, 2022 at: https://www.ema.europa.eu/en/documents/product-information/synagis-epar-product-information_en.pdf
    PubMed
  • 22 Sanchez-Luna M, Elola FJ, Fernandez-Perez C, Bernal JL, Lopez-Pineda A. Trends in respiratory syncytial virus bronchiolitis hospitalizations in children less than 1 year: 2004-2012. Curr Med Res Opin 2016; 32 (04) 693-698
    CrossrefPubMedSearch in Google Scholar
  • 23 Thwaites R, Buchan S, Fullarton J. et al. Clinical burden of severe respiratory syncytial virus infection during the first 2 years of life in children born between 2000 and 2011 in Scotland. Eur J Pediatr 2020; 179 (05) 791-799
    CrossrefPubMedSearch in Google Scholar
  • 24 Andabaka T, Nickerson JW, Rojas-Reyes MX, Rueda JD, Bacic Vrca V, Barsic B. Monoclonal antibody for reducing the risk of respiratory syncytial virus infection in children. Cochrane Database Syst Rev 2013; (04) CD006602
    PubMedSearch in Google Scholar
  • 25 Garegnani L, Styrmisdóttir L, Roson Rodriguez P, Escobar Liquitay CM, Esteban I, Franco JV. Palivizumab for preventing severe respiratory syncytial virus (RSV) infection in children. Cochrane Database Syst Rev 2021; 11: CD013757
    PubMedSearch in Google Scholar
  • 26 Luna MS, Manzoni P, Paes B. et al. Expert consensus on palivizumab use for respiratory syncytial virus in developed countries. Paediatr Respir Rev 2020; 33: 35-44
    PubMedSearch in Google Scholar
  • 27 Chawanpaiboon S, Vogel JP, Moller AB. et al. Global, regional, and national estimates of levels of preterm birth in 2014: a systematic review and modelling analysis. Lancet Glob Health 2019; 7 (01) e37-e46
    CrossrefPubMedSearch in Google Scholar
  • 28 American Academy of Pediatrics Committee on Infectious Diseases, American Academy of Pediatrics Bronchiolitis Guidelines Committee. Updated guidance for palivizumab prophylaxis among infants and young children at increased risk of hospitalization for respiratory syncytial virus infection. Pediatrics 2014; 134 (02) 415-420
    Search in Google Scholar
  • 29 Goldstein M, Phillips R, DeVincenzo JP. et al. National Perinatal Association 2018 respiratory syncytial virus (RSV) prevention clinical practice guideline: an evidence-based interdisciplinary collaboration. Neonatol Today 2017; 12 (10) 1-12
    CrossrefPubMedSearch in Google Scholar
  • 30 Reeves RM, van Wijhe M, Lehtonen T. et al; RESCEU Investigators. A systematic review of European Clinical Practice guidelines for respiratory syncytial virus prophylaxis. J Infect Dis 2022; 226 (supplement_1): S110-S116
    CrossrefPubMedSearch in Google Scholar
  • 31 Eichler HG, Pignatti F, Schwarzer-Daum B. et al. Randomized controlled trials versus real world evidence: neither magic nor myth. Clin Pharmacol Ther 2021; 109 (05) 1212-1218
    CrossrefPubMedSearch in Google Scholar
  • 32 Fergie J, Goldstein M, Krilov LR, Wade SW, Kong AM, Brannman L. Update on respiratory syncytial virus hospitalizations among U.S. preterm and term infants before and after the 2014 American Academy of Pediatrics policy on immunoprophylaxis: 2011-2017. Hum Vaccin Immunother 2021; 17 (05) 1536-1545
    Search in Google Scholar
  • 33 Goldstein M, Krilov LR, Fergie J. et al. Respiratory syncytial virus hospitalizations among U.S. preterm infants compared with term infants before and after the 2014 American Academy of Pediatrics guidance on immunoprophylaxis: 2012-2016. Am J Perinatol 2018; 35 (14) 1433-1442
    Search in Google Scholar
  • 34 Kong AM, Krilov LR, Fergie J. et al. The 2014-2015 national impact of the 2014 American Academy of Pediatrics guidance for respiratory syncytial virus immunoprophylaxis on preterm infants born in the United States. Am J Perinatol 2018; 35 (02) 192-200
    Search in Google Scholar
  • 35 Kong AM, Winer IH, Zimmerman NM. et al. Increasing rates of RSV hospitalization among preterm infants: a decade of data. Am J Perinatol 2021; (e-pub ahead of print). Doi:
    Thieme ConnectPubMedSearch in Google Scholar
  • 36 Krilov LR, Fergie J, Goldstein M, Brannman L. Impact of the 2014 American Academy of Pediatrics immunoprophylaxis policy on the rate, severity, and cost of respiratory syncytial virus hospitalizations among preterm infants. Am J Perinatol 2020; 37 (02) 174-183
    Thieme ConnectPubMedSearch in Google Scholar
  • 37 Fergie J, Suh M, Jiang X, Fryzek JP, Gonzales T. Respiratory syncytial virus and all-cause bronchiolitis hospitalizations among preterm infants using the Pediatric Health Information System (PHIS). J Infect Dis 2022; 225 (07) 1197-1204
    Search in Google Scholar
  • 38 Pedraz C, Carbonell-Estrany X, Figueras-Aloy J, Quero J, Group IS. IRIS Study Group. Effect of palivizumab prophylaxis in decreasing respiratory syncytial virus hospitalizations in premature infants. Pediatr Infect Dis J 2003; 22 (09) 823-827
    CrossrefPubMedSearch in Google Scholar
  • 39 Priante E, Tavella E, Girardi E. et al. Restricted palivizumab recommendations and the impact on RSV hospitalizations among infants born at > 29 weeks of gestational age: an Italian multicenter study. Am J Perinatol 2019; 36 (S 02): S77-S82
    Thieme ConnectPubMedSearch in Google Scholar
  • 40 Rajah B, Sánchez PJ, Garcia-Maurino C, Leber A, Ramilo O, Mejias A. Impact of the updated guidance for palivizumab prophylaxis against respiratory syncytial virus infection: a single center experience. J Pediatr 2017; 181: 183-188.e1
    Search in Google Scholar
  • 41 Banerji A, Panzov V, Young M. et al. The real-life effectiveness of palivizumab for reducing hospital admissions for respiratory syncytial virus in infants residing in Nunavut. Can Respir J 2014; 21 (03) 185-189
    CrossrefPubMedSearch in Google Scholar
  • 42 Creery D, Lyer P, Samson L, Coyle D, Osborne G, MacDonald A. Costs associated with infant bronchiolitis in the Baffin region of Nunavut. Int J Circumpolar Health 2005; 64 (01) 38-45
    CrossrefPubMedSearch in Google Scholar
  • 43 Banerji A, Lanctôt KL, Paes BA. et al. Comparison of the cost of hospitalization for respiratory syncytial virus disease versus palivizumab prophylaxis in Canadian Inuit infants. Pediatr Infect Dis J 2009; 28 (08) 702-706
    CrossrefPubMedSearch in Google Scholar
  • 44 Newby B, Sorokan T. Respiratory syncytial virus infection rates with limited use of palivizumab for infants born at 29 to 31+6/7 weeks gestational age. Can J Hosp Pharm 2017; 70 (01) 13-18
    PubMedSearch in Google Scholar
  • 45 Cetinkaya M, Oral TK, Karatekin S, Cebeci B, Babayigit A, Yesil Y. Efficacy of palivizumab prophylaxis on the frequency of RSV-associated lower respiratory tract infections in preterm infants: determination of the ideal target population for prophylaxis. Eur J Clin Microbiol Infect Dis 2017; 36 (09) 1629-1634
    CrossrefPubMedSearch in Google Scholar
  • 46 Blanken MO, Rovers MM, Molenaar JM. et al; Dutch RSV Neonatal Network. Respiratory syncytial virus and recurrent wheeze in healthy preterm infants. N Engl J Med 2013; 368 (19) 1791-1799
    CrossrefPubMedSearch in Google Scholar
  • 47 Notario G, Vo P, Gooch K. et al. National Perinatal Association 2018 respiratory syncytial virus (RSV) prevention clinical practice guideline: an evidence-based interdisciplinary collaboration: peer reviewed new guidelines. Pediatric Health Med Ther 2014; 5: 43
    PubMedSearch in Google Scholar
  • 48 Papenburg J, Defoy I, Massé E, Caouette G, Lebel MH. Impact of the withdrawal of palivizumab immunoprophylaxis on the incidence of respiratory syncytial virus (RSV) hospitalizations among infants born at 33 to 35 weeks' gestational age in the province of Quebec, Canada: the RSV-Quebec study. J Pediatric Infect Dis Soc 2021; 10 (03) 237-244
    CrossrefPubMedSearch in Google Scholar
  • 49 Frogel MP, Stewart DL, Hoopes M, Fernandes AW, Mahadevia PJ. A systematic review of compliance with palivizumab administration for RSV immunoprophylaxis. J Manag Care Pharm 2010; 16 (01) 46-58
    CrossrefPubMedSearch in Google Scholar
  • 50 Wong SK, Li A, Lanctôt KL, Paes B. Adherence and outcomes: a systematic review of palivizumab utilization. Expert Rev Respir Med 2018; 12 (01) 27-42
    CrossrefPubMedSearch in Google Scholar
  • 51 Kamori A, Morooka Y, Yamamura K. et al. Effect of delayed palivizumab administration on respiratory syncytial virus infection-related hospitalisation: a retrospective, observational study. Medicine (Baltimore) 2021; 100 (47) e27952
    CrossrefPubMedSearch in Google Scholar
  • 52 Chida-Nagai A, Sato H, Sato I. et al. Risk factors for hospitalisation due to respiratory syncytial virus infection in children receiving prophylactic palivizumab. Eur J Pediatr 2022; 181 (02) 539-547
    CrossrefPubMedSearch in Google Scholar
  • 53 Elhalik M, El-Atawi K, Dash SK. et al. Palivizumab prophylaxis among infants at increased risk of hospitalization due to respiratory syncytial virus infection in UAE: a hospital-based study. Can Respir J 2019; 2019: 2986286
    PubMedSearch in Google Scholar
  • 54 Committee on Infectious Diseases. From the American Academy of Pediatrics: policy statements–modified recommendations for use of palivizumab for prevention of respiratory syncytial virus infections. Pediatrics 2009; 124 (06) 1694-1701
    Search in Google Scholar
  • 55 Woods J, Schittny J. Lung structure at preterm and term birth. In: Jobe A, Whitsett J, Abman S. eds. Fetal and Neonatal Lung Development: Clinical Correlates and Technologies for the Future. Cambridge, United KIngdom: Cambridge University Press; 2016: 126-140
    Search in Google Scholar
  • 56 Kallapur SG, Jobe AH. Perinatal events and their influence on lung development and injury. In: Bancalari E. ed. The Newborn Lung: Neonatology Questions and Controversies. Philadelphia, PA: Elsevier; 2019: 115-129
    Search in Google Scholar
  • 57 Baraldi E, Bonadies L, Manzoni P. Evidence on the link between respiratory syncytial virus infection in early life and chronic obstructive lung diseases. Am J Perinatol 2020; 37 (S 02): S26-S30
    Thieme ConnectPubMedSearch in Google Scholar
  • 58 Fauroux B, Simões EAF, Checchia PA. et al. The burden and long-term respiratory morbidity associated with respiratory syncytial virus infection in early childhood. Infect Dis Ther 2017; 6 (02) 173-197
    CrossrefPubMedSearch in Google Scholar
  • 59 Makrinioti H, Hasegawa K, Lakoumentas J. et al. The role of respiratory syncytial virus- and rhinovirus-induced bronchiolitis in recurrent wheeze and asthma-A systematic review and meta-analysis. Pediatr Allergy Immunol 2022; 33 (03) e13741
    CrossrefPubMedSearch in Google Scholar
  • 60 Mochizuki H, Kusuda S, Okada K, Yoshihara S, Furuya H, Simões EAF. Scientific Committee for Elucidation of Infantile Asthma. Palivizumab prophylaxis in preterm infants and subsequent recurrent wheezing. Six-year follow-up study. Am J Respir Crit Care Med 2017; 196 (01) 29-38
    CrossrefPubMedSearch in Google Scholar
  • 61 Martinez FD. Early-life origins of chronic obstructive pulmonary disease. N Engl J Med 2016; 375 (09) 871-878
    CrossrefPubMedSearch in Google Scholar
  • 62 Bont L, Steijn M, van Aalderen WM, Kimpen JL. Impact of wheezing after respiratory syncytial virus infection on health-related quality of life. Pediatr Infect Dis J 2004; 23 (05) 414-417
    CrossrefPubMedSearch in Google Scholar
  • 63 Carbonell-Estrany X, Pérez-Yarza EG, García LS, Guzmán Cabañas JM, Bòria EV, Atienza BB. IRIS (Infección Respiratoria Infantil por Virus Respiratorio Sincitial) Study Group. Long-term burden and respiratory effects of respiratory syncytial virus hospitalization in preterm infants-the SPRING study. PLoS One 2015; 10 (05) e0125422
    CrossrefPubMedSearch in Google Scholar
  • 64 Domachowske J, Madhi SA, Simões EAF. et al; MEDLEY Study Group. Safety of nirsevimab for RSV in infants with heart or lung disease or prematurity. N Engl J Med 2022; 386 (09) 892-894
    CrossrefPubMedSearch in Google Scholar
  • 65 Griffin MP, Yuan Y, Takas T. et al; Nirsevimab Study Group. Single-dose nirsevimab for prevention of RSV in preterm infants. N Engl J Med 2020; 383 (05) 415-425
    CrossrefPubMedSearch in Google Scholar
  • 66 Hammitt LL, Dagan R, Yuan Y. et al; MELODY Study Group. Nirsevimab for prevention of RSV in healthy late-preterm and term infants. N Engl J Med 2022; 386 (09) 837-846
    CrossrefPubMedSearch in Google Scholar
  • 67 Thornhill EM, Salpor J, Verhoeven D. Respiratory syntycial virus: current treatment strategies and vaccine approaches. Antivir Chem Chemother 2020; 28: 2040206620947303
    CrossrefPubMedSearch in Google Scholar