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Risk factors for hospitalisation due to respiratory syncytial virus infection in children receiving prophylactic palivizumab

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Abstract

Respiratory syncytial virus (RSV) is a common pathogen that causes extremely severe respiratory symptoms in the first few weeks and months of life. In infants with cardiopulmonary diseases, RSV infections have a significant clinical impact. Palivizumab, a humanised monoclonal antibody for RSV, has been shown to significantly reduce the rate of hospitalisation of high-risk infants diagnosed with RSV. However, we have experienced a significant number of RSV infections in our institution that required hospitalisation or intensive care, despite the administration of palivizumab. This study aimed to analyse the risk factors associated with severe RSV despite the use of palivizumab. We retrospectively reviewed the medical records of 688 patients who visited or were admitted to our hospital and received palivizumab. Thirty-seven (5.4%) patients required hospitalisation for RSV, despite receiving palivizumab. In addition, 31 of these patients (83.8%) required hospitalisation out of season for palivizumab injection. Preterm birth (≤ 28-week gestation), bronchopulmonary dysplasia (BPD), and trisomy 21 were risk factors for RSV-related hospitalisation in infected patients, despite receiving palivizumab. Furthermore, subgroup analysis of 69 patients with RSV revealed that hemodynamically significant congenital heart disease (CHD) was also a risk factor for RSV-related hospitalisation.

Conclusion: Preterm birth (≤ 28 weeks of gestation), BPD, trisomy 21, hemodynamically significant CHD, and CHD requiring surgery or cardiac catheterisation/intervention during infancy could be considered when determining whether year-round administration of palivizumab is appropriate.

What is Known:

• Respiratory syncytial virus causes severe respiratory symptoms in infants, particularly those with cardiopulmonary diseases.

• The use of palivizumab has reduced the rate of hospitalisation of infants diagnosed with RSV. Despite this, the rate of hospitalisation is still high.

What is New:

• We identified that preterm birth (≤ 28-week gestation), bronchopulmonary dysplasia, trisomy 21, and hemodynamically significant congenital heart disease were risk factors for RSV-related hospitalisation, even after receiving palivizumab treatment.

• High-risk infants should be closely monitored and the prolonged use of palivizumab should be considered.

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Abbreviations

AVSD:

Atrioventricular septal defect

BPD:

Bronchopulmonary dysplasia

CI:

Confidence interval

CHD:

Congenital heart disease

ICR:

Intracardiac repair

MS:

Mitral stenosis

MVR:

Mitral valve replacement

PAPVC:

Partial anomalous pulmonary venous connection

PH:

Pulmonary hypertension

PS:

Pulmonary stenosis

RSV:

Respiratory syncytial virus

SD:

Standard deviation

TOF:

Tetralogy of Fallot

VSD:

Ventricular septal defect

References

  1. Hall CB, Weinberg GA, Iwane MK, Blumkin AK, Edwards KM, Staat MA, Auinger P, Griffin MR, Poehling KA, Erdman D et al (2009) The burden of respiratory syncytial virus infection in young children. N Eng J Med 36:588–598. https://doi.org/10.1056/nejmoa0804877

    Article  Google Scholar 

  2. Nair H, Nokes DJ, Gessner BD, Dherani M, Madhi SA, Singleton RJ, O’Brien KL, Roca A, Wright PF, Bruce N et al (2010) Global burden of acute lower respiratory infections due to respiratory syncytial virus in young children: a systematic review and meta-analysis. Lancet 375:1545–1555. https://doi.org/10.1016/S0140-6736(10)60206-1

    Article  PubMed  PubMed Central  Google Scholar 

  3. Krzyzaniak MA, Zumstein MT, Gerez JA, Picotti P, Helenius A (2013) Host cell entry of respiratory syncytial virus involves macropinocytosis followed by proteolytic activation of the F protein. PLoS Pathog 9:e1003309. https://doi.org/10.1371/journal.ppat.1003309

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Zhao M, Zheng ZZ, Chen M, Modjarrad K, Zhang W, Zhan LT, Cao JL, Sun YP, McLellan JS, Graham BS et al (2017) Discovery of a prefusion respiratory syncytial virus F-specific monoclonal antibody that provides greater in vivo protection than the murine precursor of palivizumab. J Virol 91:e00176-e217. https://doi.org/10.1128/JVI.00176-17

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Kusuda S, Takahashi N, Saitoh T, Terai M, Kaneda H, Kato Y, Ohashi A, Watabe S, Joh-o K, Hirai K (2011) Survey of pediatric ward hospitalization due to respiratory syncytial virus infection after the introduction of palivizumab to high-risk infants in Japan. Pediatr Int 53:368–373. https://doi.org/10.1111/j.1442-200X.2010.03249.x

    Article  PubMed  Google Scholar 

  6. Feltes TF, Cabalka AK, Meissner HC, Piazza FM, Carlin DA, Top FH, Jr, Connor EM, Sondheimer HM, Cardiac Synagis Study Group (2003) Palivizumab prophylaxis reduces hospitalization due to respiratory syncytial virus in young children with hemodynamically significant congenital heart disease. J Pediatr 143:532–540. https://doi.org/10.1067/s0022-3476(03)00454-2

    Article  Google Scholar 

  7. Beckhaus AA, Castro-Rodriguez JA (2018) Down syndrome and the risk of severe RSV infection: a meta-analysis. Pediatrics 142:e20180225. https://doi.org/10.1542/peds.2018-0225

    Article  PubMed  Google Scholar 

  8. Grut V, Soderstrom L, Naumburg E (2017) National cohort study showed that infants with Down’s syndrome faced a high risk of hospitalisation for the respiratory syncytial virus. Acta Paeditr 106:1519–1524. https://doi.org/10.1111/apa.13937

    Article  Google Scholar 

  9. Ma L, Chung WK (2014) The genetic basis of pulmonary arterial hypertension. Hum Genet 133:471–479. https://doi.org/10.1007/s00439-014-1419-3

    Article  CAS  PubMed  Google Scholar 

  10. Tahara M, Shimozono S, Nitta T, Yamaki S (2014) Medial defects of the small pulmonary arteries in fatal pulmonary hypertension in infants with trisomy 13 and trisomy 18. Am J Med Genet A 164a:319–323. https://doi.org/10.1002/ajmg.a.36282

  11. American Academy of Pediatrics Committee on Infectious Diseases, American Academy of Pediatrics Bronchiolitis Guidelines Committee (2014) Updated guidance for palivizumab prophylaxis among infants and young children at increased risk of hospitalization for respiratory syncytial virus infection. Pediatrics 134:415–420. https://doi.org/10.1542/peds.2014-1665

    Article  Google Scholar 

  12. Granbom E, Fernlund E, Sunnegardh J, Lundell B, Naumburg E (2016) Respiratory tract infection and risk of hospitalization in children with congenital heart defects during season and off-season: a Swedish national study. Pediatr Cardiol 37:1098–1105. https://doi.org/10.1007/s00246-016-1397-4

    Article  PubMed  PubMed Central  Google Scholar 

  13. Glick AF, Kjelleren S, Hofstetter AM, Subramony A (2017) RSV hospitalizations in comparison with regional RSV activity and inpatient palivizumab administration, 2010–2013. Hosp Pediatr 7:271–278. https://doi.org/10.1542/hpeds.2016-0124

    Article  PubMed  Google Scholar 

  14. Lim A, Butt ML, Dix J, Elliott L, Paes B (2019) Respiratory syncytial virus (RSV) infection in children with medical complexity. Eur J Clin Microbiol Infect Dis 38:171–176. https://doi.org/10.1007/s10096-018-3409-1

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We are deeply grateful for our patients and their families who participated in this study. We also thank the medical staff of the Hokkaido University Hospital for their assistance in the collection of data.

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Authors and Affiliations

  1. Department of Pediatrics, Hokkaido University, Kita14, Nishi5, Kita-Ku, Sapporo, Hokkaido, 060-8648, Japan

    Ayako Chida-Nagai, Itsumi Sato, Masahiro Shiraishi, Daisuke Sasaki, Gaku Izumi, Hirokuni Yamazawa, Atsushi Manabe & Atsuhito Takeda

  2. Department of Cardiology and Clinical Examination, Oita University, Oita, Japan

    Hiroki Sato

  3. Department of Preventive Medicine and Public Health, Tokyo Medical University, Shinjuku, Tokyo, Japan

    Hiroki Sato

  4. Maternity and Perinatal Care Center, Hokkaido University Hospital, Sapporo, Japan

    Kazutoshi Cho

Authors
  1. Ayako Chida-Nagai
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  2. Hiroki Sato
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  3. Itsumi Sato
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  4. Masahiro Shiraishi
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  5. Daisuke Sasaki
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  6. Gaku Izumi
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  7. Hirokuni Yamazawa
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  8. Kazutoshi Cho
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  9. Atsushi Manabe
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  10. Atsuhito Takeda
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Contributions

Collected and analysed the patient data: ACN, IS, MS, DS, GI, HY, KC, and AT. Interpreted the patient data: ACN, HS, and KC. Wrote the draft manuscript: ACN. Revised and edited the final manuscript: ACN, KC, AM, and AT. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Atsuhito Takeda.

Ethics declarations

Ethics approval

This study was performed in line with the principles of the Declaration of Helsinki. The Institutional Review Board of Hokkaido University Hospital for clinical research approved this study (approval no. 019–0452).

Consent to participate

The requirement for informed consent was waived due to the retrospective nature of the study.

Consent for publication

The requirement for informed consent was waived due to the retrospective nature of the study.

Conflict of interest

The authors declare no competing interests.

Additional information

Communicated by Nicole Ritz

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Cite this article

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 181, 539–547 (2022). https://doi.org/10.1007/s00431-021-04216-7

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  • DOI: https://doi.org/10.1007/s00431-021-04216-7

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