European Journal of Epidemiology

, Volume 33, Issue 3, pp 313–321 | Cite as

Respiratory distress syndrome in preterm infants and risk of epilepsy in a Danish cohort

  • Sandra Kruchov Thygesen
  • Morten Olsen
  • Lars Pedersen
  • Victor W. Henderson
  • John Rosendahl Østergaard
  • Henrik Toft Sørensen


Infant respiratory distress syndrome (IRDS) may be complicated by intracerebral hemorrhage, a known trigger of epilepsy. However, few data exist on long term epilepsy risk following IRDS. We therefore examined the association between IRDS in preterm infants and childhood epilepsy. We conducted a population-based cohort study using individual-level data linkage among nationwide registries. All infants born at 32–36 weeks of gestation in 1978–2009 were identified in the Medical Birth Registry. We identified children with IRDS and those with epilepsy using the Danish National Patient Registry. We computed the cumulative incidence of epilepsy with follow-up from birth until epilepsy, emigration, death, age 15, or December 31, 2014. We used Cox’s regression analysis to compute hazard ratios comparing children with and without IRDS, adjusting for sex, birth year, gestational age, multiplicity, major malformations, and maternal age. We identified 95,026 infants, of whom 6426 (6.8%) had IRDS. The cumulative incidence of epilepsy was 3.4% by age 15 in children with IRDS and 2.1% in children without IRDS. The adjusted hazard ratio of epilepsy among children with IRDS compared to those without was 1.4 (95% CI 1.2–1.6). When we restricted the IRDS cohort to children with no simultaneous morbidities that had clinical symptoms overlapping with IRDS, the overall adjusted HR was 1.1 (95% CI 0.9–1.4). In children born preterm at 32–36 weeks’ gestation, IRDS was associated with increased risk of childhood epilepsy.


Epidemiology Cohort study Epilepsy Infant respiratory distress syndrome Neurodevelopmental outcome 



Confidence interval


Civil Personal Registration


Civil Registration System


Danish National Patient Registry


Hazard ratio


International Classification of Diseases, Eighth Edition


International Classification of Diseases, Tenth Edition


Intracerebral hemorrhage/intraventricular hemorrhage


Infant respiratory distress syndrome



This study was supported by grants from the Clinical Epidemiological Research Foundation (‘Klinisk Epidemiologisk Forskningsfond’), Denmark and the Program for Clinical Research Infrastructure (PROCRIN) established by the Lundbeck and the Novo Nordisk Foundations. The authors have no financial relationships relevant to this article to disclosure. The Department of Clinical Epidemiology, Aarhus University Hospital, receives funding for other studies from companies and agencies in the form of research grants to (and administered by) Aarhus University. None of these studies have any relation to the present study.

Author Contributions

Sandra Kruchov Thygesen (SKT) and Henrik Toft Sørensen (HTS) conceptualized and designed the study, acquired the data, carried out the analyses, drafted the initial manuscript (SKT), reviewed and revised the manuscript, and approved the final manuscript as submitted. Morten Olsen, John Rosendahl Østergaard, and Victor W. Henderson designed the study, supervised the data interpretation, critically reviewed and revised the manuscript for important intellectual content, and approved the final manuscript as submitted. Lars Pedersen (LP) helped to acquire the data and extract the raw data, critically supervised/reviewed the data analyses and reviewed the data interpretation, revised the manuscript, and approved the final manuscript as submitted. SKT and LP had complete access to the study data that support the publication.

Compliance with ethical standards

Conflict of interest

All authors declare no conflict of interest.


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Copyright information

© Springer Science+Business Media B.V. 2017

Authors and Affiliations

  • Sandra Kruchov Thygesen
    • 1
  • Morten Olsen
    • 1
  • Lars Pedersen
    • 1
  • Victor W. Henderson
    • 1
    • 2
  • John Rosendahl Østergaard
    • 3
  • Henrik Toft Sørensen
    • 1
    • 4
  1. 1.Department of Clinical EpidemiologyAarhus University HospitalÅrhusDenmark
  2. 2.Departments of Health Research and Policy (Epidemiology) and of Neurology and Neurological SciencesStanford UniversityStanfordUSA
  3. 3.Department of PediatricsAarhus University HospitalÅrhusDenmark
  4. 4.Departments of Health Research and Policy (Epidemiology)Stanford UniversityStanfordUSA

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