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Congenital Heart Disease and Risk of Central Nervous System Infections: A Nationwide Cohort Study

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Abstract

Congenital heart disease (CHD) is associated with risk factors of central nervous system (CNS) infections including infective endocarditis, cardiac shunt physiology, and immune deficiencies. We aimed to investigate the risk of CNS infections in the CHD population compared to the general population. In this cohort study, we used Danish nationwide medical registries to identify individuals diagnosed with CHD at any age, born between 1977 and 2012. For each CHD individual, we matched 10 individuals on sex and birth year from the general population. Subjects were followed until first-time hospital diagnosis of CNS infection, death, emigration, or end of study. We computed cumulative incidences of CNS infections with death as a competing risk, as well as hazard ratios (HRs) with corresponding 95% confidence intervals (CIs) adjusted for birth year and sex. We identified 17,550 individuals with CHD (50% male). Among subjects with CHD, the cumulative incidence of CNS infection at age 30 years was 1.0% compared to 0.6% in the general population. The overall HR of CNS infections in CHD subjects relative to the general population was 2.1 (95% CI 1.6–2.7). The HR was 1.9 (95% CI 1.4–2.7) for mild to moderate CHD, 2.1 (95% CI 1.3–3.3) for severe CHD and 3.0 (95% CI 1.1–8.2) for univentricular physiology. The HR for CHD subjects without record of infective endocarditis was 2.0 (95% CI 1.5–2.5). The risk of CNS infections was increased among individuals with CHD compared to the general population, and the risk was not limited to individuals with infective endocarditis.

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References

  1. Sun R et al (2015) Congenital heart disease: causes, diagnosis, symptoms, and treatments. Cell Biochem Biophys 72(3):857–860

    CAS  PubMed  Google Scholar 

  2. Hoffman JI, Kaplan S, Liberthson RR (2004) Prevalence of congenital heart disease. Am Heart J 147(3):425–439

    PubMed  Google Scholar 

  3. Garne E (2004) Congenital heart defects—occurrence, surgery and prognosis in a Danish County. Scand Cardiovasc J 38(6):357–362

    PubMed  Google Scholar 

  4. Marelli AJ et al (2007) Congenital heart disease in the general population: changing prevalence and age distribution. Circulation 115(2):163–172

    PubMed  Google Scholar 

  5. Silvia MT, Licht DJ (2005) Pediatric central nervous system infections and inflammatory white matter disease. Pediatr Clin North Am 52(4):1107–1126

    PubMed  Google Scholar 

  6. Riddell J, Shuman EK (2012) Epidemiology of central nervous system infection Neuroimaging. Clin N Am 22(4):543–556

    Google Scholar 

  7. Baltimore RS et al (2015) Infective endocarditis in childhood: 2015 update: a scientific statement from the American Heart Association. Circulation 132(15):1487–1515

    PubMed  Google Scholar 

  8. Elder RW, Baltimore RS (2015) The changing epidemiology of pediatric endocarditis. Infect Dis Clin N Am 29(3):513–524

    Google Scholar 

  9. Novy E et al (2013) Neurological complications of infective endocarditis: new breakthroughs in diagnosis and management. Med Mal Infect 43(11–12):443–450

    CAS  PubMed  Google Scholar 

  10. Jortveit J et al (2018) Endocarditis in children and adolescents with congenital heart defects: a Norwegian nationwide register-based cohort study. Arch Dis Child 103(7):670–674

    PubMed  Google Scholar 

  11. Owayed AF, Campbell DM, Wang EE (2000) Underlying causes of recurrent pneumonia in children. Arch Pediatr Adolesc Med 154(2):190–194

    CAS  PubMed  Google Scholar 

  12. Granbom E et al (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(6):1098–1105

    PubMed  PubMed Central  Google Scholar 

  13. Nyboe C et al (2014) Risk of pneumonia in adults with closed versus unclosed atrial septal defect (from a nationwide cohort study). Am J Cardiol 114(1):105–110

    PubMed  Google Scholar 

  14. Radford DJ, Lachman R, Thong YH (1986) The immunocompetence of children with congenital heart disease. Int Arch Allergy Appl Immunol 81(4):331–336

    CAS  PubMed  Google Scholar 

  15. Armstrong D (1984) Central nervous system infections in the immunocompromised host. Infection 12(Suppl 1):S58–64

    PubMed  Google Scholar 

  16. Elder RW, George RP, McCabe NM, Rodriguez FH III, Book WM, Mahle WT, Kirk AD (2015) Immunologic aging in adults with congenital heart disease: does infant sternotomy matter? Pediatr Cardiol 36(7):1411–1416

    PubMed  PubMed Central  Google Scholar 

  17. Kagawa M et al (1983) Brain abscess in congenital cyanotic heart disease. J Neurosurg 58(6):913–917

    CAS  PubMed  Google Scholar 

  18. Stawicki SP et al (2013) Septic embolism in the intensive care unit. Int J Crit Illn Inj Sci 3(1):58–63

    PubMed  PubMed Central  Google Scholar 

  19. Kaur C, Ling EA (2008) Blood brain barrier in hypoxic-ischemic conditions. Curr Neurovasc Res 5(1):71–81

    CAS  PubMed  Google Scholar 

  20. Limperopoulos C et al (2010) Brain volume and metabolism in fetuses with congenital heart disease: evaluation with quantitative magnetic resonance imaging and spectroscopy. Circulation 121(1):26–33

    CAS  PubMed  Google Scholar 

  21. Sun L et al (2015) Reduced fetal cerebral oxygen consumption is associated with smaller brain size in fetuses with congenital heart disease. Circulation 131(15):1313–1323

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Lanz J et al (2015) Stroke in adults with congenital heart disease: incidence, cumulative risk, and predictors. Circulation 132(25):2385–2394

    Article  Google Scholar 

  23. Bouchardy J et al (2009) Atrial arrhythmias in adults with congenital heart disease. Circulation 120(17):1679–1686

    PubMed  Google Scholar 

  24. Marino BS et al (2012) Neurodevelopmental outcomes in children with congenital heart disease: evaluation and management: a scientific statement from the American Heart Association. Circulation 126(9):1143–1172

    PubMed  Google Scholar 

  25. Barker GM et al (2010) Major infection after pediatric cardiac surgery: a risk estimation model. Ann Thorac Surg 89(3):843–850

    PubMed  PubMed Central  Google Scholar 

  26. Schmidt M, Pedersen L, Sorensen HT (2014) The Danish civil registration system as a tool in epidemiology. Eur J Epidemiol 29(8):541–549

    PubMed  Google Scholar 

  27. Olsen M et al (2017) Myocardial infarction in adults with congenital heart disease. Am J Cardiol 120(12):2272–2277

    PubMed  Google Scholar 

  28. Madsen NL et al (2016) Congenital heart disease with and without cyanotic potential and the long-term risk of diabetes mellitus: a population-based follow-up study. J Am Heart Assoc 5(7):e003076

    PubMed  PubMed Central  Google Scholar 

  29. Schwartz SS et al (2018) Incidence and mortality of adults with pulmonary hypertension and congenital heart disease. Am J Cardiol 121(12):1610–1616

    PubMed  Google Scholar 

  30. European Surveillance of Congenital Anomalies (2005) Guide 1.3: instructions for the registration and surveillance of congenital anomalies. https://www.eurocat-network.eu/content/EUROCAT-Guide-1.3.pdf. Accessed 4 July 2016

  31. Murni IK et al (2017) Perioperative infections in congenital heart disease. Cardiol Young 27(S6):S14–s21

    PubMed  Google Scholar 

  32. Moore B et al (2017) Incidence, predictors and outcomes of infective endocarditis in a contemporary adult congenital heart disease population. Int J Cardiol 249:161–165

    PubMed  Google Scholar 

  33. Knirsch W, Nadal D (2011) Infective endocarditis in congenital heart disease. Eur J Pediatr 170(9):1111–1127

    PubMed  Google Scholar 

  34. Morris NA et al (2014) Neurologic complications in infective endocarditis: identification, management, and impact on cardiac surgery. Neurohospitalist 4(4):213–222

    PubMed  PubMed Central  Google Scholar 

  35. Lucas MJ et al (2013) Endocarditis in adults with bacterial meningitis. Circulation 127(20):2056–2062

    PubMed  Google Scholar 

  36. Agergaard P et al (2011) Children diagnosed with congenital cardiac malformations at the national university departments of pediatric cardiology: positive predictive values of data in the Danish National Patient Registry. Clin Epidemiol 3:61–66

    PubMed  PubMed Central  Google Scholar 

  37. Jorgensen LK et al (2016) Validity of the coding for herpes simplex encephalitis in the Danish National Patient Registry. Clin Epidemiol 8:133–140

    PubMed  PubMed Central  Google Scholar 

  38. Bodilsen J et al (2018) Positive predictive value of ICD-10 diagnosis codes for brain abscess in the Danish National Patient Registry. Clin Epidemiol 10:1503–1508

    PubMed  PubMed Central  Google Scholar 

  39. Howitz MF, Samuelsson S, Molbak K (2008) Declining incidence of meningococcal disease in Denmark, confirmed by a capture-recapture analysis for 1994 and 2002. Epidemiol Infect 136(8):1088–1095

    CAS  PubMed  Google Scholar 

  40. Sundboll J et al (2016) Positive predictive value of cardiovascular diagnoses in the Danish National Patient Registry: a validation study. BMJ Open 6(11):e012832

    PubMed  PubMed Central  Google Scholar 

  41. Ostergaard L et al (2018) Positive predictive value of infective endocarditis in the Danish National Patient Registry: a validation study. Epidemiol Infect 146(15):1965–1967

    PubMed  PubMed Central  Google Scholar 

  42. Thomsen RW et al (2006) Rising incidence and persistently high mortality of hospitalized pneumonia: a 10-year population-based study in Denmark. J Intern Med 259(4):410–417

    CAS  PubMed  Google Scholar 

  43. Rothman KJ (2012) Epidemiology: an introduction, 2nd edn. Oxford University Press, New York, p 268

    Google Scholar 

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Acknowledgements

This work was supported by the Department of Clinical Epidemiology at Aarhus University Hospital and Cincinnati Children’s Hospital as well as a grant from the University of Copenhagen’s Foundation for medical students (A5033) and the Oticon Foundation (17-0600).

Funding

This study was funded by Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark, Heart Institute, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, USA, The University of Copenhagen’s Foundation for medical students (A5033), Copenhagen, Denmark and The Oticon Foundation (17-0600), Copenhagen, Denmark.

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Authors and Affiliations

  1. Department of Clinical Epidemiology, Aarhus University Hospital, Olof Palmes Allé 43-45, 8200, Århus, Denmark

    Carina N. Bagge & Nicolas L. Madsen

  2. Department of Infectious Diseases, Aalborg University Hospital, Ålborg, Denmark

    Jesper Smit

  3. University of Cincinnati Department of Pediatrics, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA

    Nicolas L. Madsen

  4. Department of Radiology, Aarhus University Hospital, Århus, Denmark

    Morten Olsen

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  1. Carina N. Bagge
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  2. Jesper Smit
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  3. Nicolas L. Madsen
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  4. Morten Olsen
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Correspondence to Carina N. Bagge.

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Bagge, C.N., Smit, J., Madsen, N.L. et al. Congenital Heart Disease and Risk of Central Nervous System Infections: A Nationwide Cohort Study. Pediatr Cardiol 41, 869–876 (2020). https://doi.org/10.1007/s00246-020-02324-z

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  • DOI: https://doi.org/10.1007/s00246-020-02324-z

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