RSV hospitalization in infancy increases the risk of current wheeze at age 6 in late preterm born children without atopic predisposition

  • Koos Korsten
  • Maarten O. Blanken
  • Brigitte J. M. Buiteman
  • Elisabeth E. Nibbelke
  • Christiana A. Naaktgeboren
  • Louis J. Bont
  • Joanne G. WildenbeestEmail author
Original Article


Severe respiratory syncytial virus (RSV) infection during infancy is associated with ongoing respiratory morbidity. In a large birth cohort of 2210 healthy preterm infants born at 32–35 weeks of gestation, we aimed to determine the role of atopy in the link between RSV hospitalization and current wheeze at age 6. We defined current wheeze as parent-reported wheeze or the use of respiratory medication in the past 12 months. Based on a positive family history of atopic disease, we distinguished between children with and without atopic predisposition. Six-year follow-up data was obtained in 997/1559 (64%) children of which 102 (10.2%) children had been hospitalized with RSV during infancy. Current wheeze was present in 184/997 (18.6%) children. RSV hospitalization was an independent risk factor for current wheeze in children without atopic predisposition (aOR 4.05 [95% CI 1.22–12.52]) but not in children with this atopic background (aOR 1.50 [95% CI 0.81–2.71]).

Conclusion: This is the largest published birth cohort demonstrating that in late preterm infants, atopic predisposition defines the relationship between RSV hospitalization and current wheeze. Future RSV prevention trials aiming to prevent ongoing respiratory symptoms should be analyzed separately for atopic status.

What is Known:

RSV infection is responsible for a significant burden of disease in young children worldwide.

Severe RSV infection in early life is associated with asthmatic symptoms later in life.

What is New:

This is the largest published birth cohort reporting about the role of atopic predisposition in the link between severe RSV infection and current wheeze at school age.

We show that RSV hospitalization in infancy is an independent risk factor for current wheeze in late preterm children without atopic predisposition at age 6. This was not seen in children with atopic predisposition.


RSV Respiratory syncytial virus Wheeze Atopy Preterm 



Odds ratio


Adjusted odds ratio


Confidence interval


Lower respiratory tract infection


Respiratory syncytial virus


RSV hospitalization


Weeks gestational age


Authors’ contributions

Koos Korsten designed the study, collected the data, drafted the manuscript, performed the analyses, and approved the manuscript to be published.

Maarten O. Blanken designed the study, critically reviewed the manuscript, and approved the manuscript to be published.

Brigitte J.M. Buiteman collected the data, critically reviewed the manuscript, and approved the manuscript to be published.

Elisabeth E. Nibbelke collected the data, critically reviewed the manuscript, and approved the manuscript to be published.

Christiana A. Naaktgeboren performed the analyses, critically reviewed the manuscript, and approved the manuscript to be published.

Louis J. Bont designed the study, critically reviewed the manuscript, and approved the manuscript to be published.

Joanne G. Wildenbeest drafted the manuscript, critically reviewed the manuscript, and approved the manuscript to be published.


This investigator-driven study was funded by a grant from the Netherlands Organization for Health Research and Development (NWO-AGIKO grant 920-035-89 to Dr. Blanken) and by an unrestricted grant from AbbVie. The study hypothesis, data collection, analysis, and interpretation were performed independently by the researchers. No honorarium, grant, or other form of payment was given to anyone to produce the manuscript. The funders of the study had no role in the study design, data collection, data analysis, data interpretation, or writing of the article. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication.

Compliance with ethical standards

Ethics statement

The RISK study was reviewed and approved by the Institutional Review Board of the University Medical Centre Utrecht and subsequently approved by Institutional Review Boards of all participating hospitals. All parents provided written informed consent for screening of hospital records. The study was conducted in compliance with the Declaration of Helsinki and the standards of Good Clinical Practice. This manuscript was written according to the guidelines from the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement [28].

Supplementary material

431_2018_3309_MOESM1_ESM.docx (200 kb)
Supplemental Table S1 (DOCX 199 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Koos Korsten
    • 1
  • Maarten O. Blanken
    • 1
  • Brigitte J. M. Buiteman
    • 1
  • Elisabeth E. Nibbelke
    • 1
  • Christiana A. Naaktgeboren
    • 2
  • Louis J. Bont
    • 1
    • 3
  • Joanne G. Wildenbeest
    • 1
    Email author
  1. 1.Department of Pediatric Infectious Diseases and ImmunologyWilhelmina Children’s Hospital University Medical Center UtrechtUtrechtThe Netherlands
  2. 2.Julius Centre for Health Sciences and Primary CareUniversity Medical Centre UtrechtUtrechtThe Netherlands
  3. 3.ReSVinetUtrechtThe Netherlands

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