Incidence of Intussusception in Early Infancy: A Capture-Recapture Estimate for Germany

Abstract

Background: Rotavirus (RV) vaccination with the first generation vaccine (Rotashield) has been associated with intussusception (IS). Reliable age specific baseline incidence data for children ≤6 months of age in particular is fundamental for further post marketing monitoring of potential effects of recently introduced new RV vaccines.

Methods: IS incidence was estimated by a 2-source capture-recapture calculation (CRC) based on ESPED (German Paediatric Surveillance Unit) reports and on hospital discharge records for 2006 and 2007. ESPED as well as hospital records were validated according to the Brighton Collaboration's Group definition for definite IS.

Patients: Children that have been treated for IS in a hospital in one of two states of Germany (North-Rhine Westphalia and Bavaria).

Results: The annual IS incidence for infants <1 year in Germany calculated with the CRC estimate in Germany was 61.7/100 000 (95% CI: 54.5–70.1). However, the incidence appeared to vary by month of age over a range of 19.2/100 000 cases (95% CI: 12.5–30.4) in the first 3 months of life to 98.5/100 000 cases (95% CI: 80.9–120.6) during the 6^th to 8^th month. The male to female ratio for infants was 1.7:1 (95%CI: 1.6–1.8).

Conclusion: The average incidence estimate for IS in infants (< 1 year) confirms previous estimates in Germany and Switzerland. However, age specific baseline incidence estimates for IS substantially vary during the first year of life. This has to be taken into account when analysing episodes of IS potentially associated with RV vaccination.

Zusammenfassung

Hintergrund: Der erste Rotavirus-Impfstoff „Rotashield“ stand im Zusammenhang mit einer erhöhten Anzahl von Invaginationen (IV). Besonders wichtig für das Monitoring der neu eingeführten zweiten Generation von Rotavirus-Impfstoffen bzgl. dieses potenziellen Zusammenhangs, sind verlässliche altersspezifische Daten zur Hintergrundinzidenz der Invagination bei Kindern ≤6 Monate.

Patienten: Kinder, die 2006 oder 2007 in einem Krankenhaus in Nordrhein-Westfalen oder Bayern aufgrund einer IV behandelt wurden.

Methoden: Die Inzidenz der IV wurde durch eine Capture-Recapture Berechnung (CRC) anhand von 2 Quellen – ESPED (Erhebungseinheit für seltene pädiatrische Erkrankungen) und Meldungen aus den Krankenhausdatenbanken – für die Jahre 2006 und 2007 geschätzt. Alle Fallmeldungen aus beiden Quellen wurden auf Basis der Definition der Brighton Collaboration Group für „definitive IV“ validiert.

Ergebnisse: Die mit der CRC-Methode berechnete Inzidenz für Kinder <1 Jahr beläuft sich auf 61,7/100 000 pro Jahr (95% Konfidenzintervall (KI): 54,5–70,1). Die Inzidenz pro Lebensmonat variiert jedoch zwischen 19,2/100 000 (95% KI: 12,5–30,4) in den ersten 3 Lebensmonaten und 98,5/100 000 (95% KI: 80,9–120,6) in den dritten 3 Lebensmonaten. Jungen sind 1,7-mal häufiger von einer IV betroffen als Mädchen (95%KI: 1,6–1,8).

Schlussfolgerung: Die berechnete durchschnittliche Inzidenz für Säuglinge (<1 Jahr) bestätigt vorherige Schätzungen aus Deutschland und der Schweiz. Die Variation der altersspezifischen Inzidenz während des ersten Lebensjahres ist jedoch beträchtlich. Bei der Überwachung einer möglichen Assoziation zwischen der Rotavirus-Impfung und dem Auftreten von Invaginationen muss dies berücksichtigt werden.

Key words

intussusception - incidence - capture-recapture method (CRC) - rotavirus vaccine - ESPED (German Paediatric Surveillance Unit) - ICD-10

Schlüsselwörter

Invagination - Inzidenz - Capture-Recapture Methode - Rotavirus-Impfung - ESPED (Erhebungseinheit für seltene pädiatrische Erkrankungen) - ICD-10

References

• 1 Bines JE. Rotavirus vaccines and intussusception risk.  Curr Opin Gastroenterol. 2005;  21 20-25
• 2 Bines JE, Ivanoff B, Justice F. et al . Clinical case definition for the diagnosis of acute intussusception.  J Pediatr Gastroenterol Nutr. 2004b;  39 511-518
• 3 Bines JE, Kohl KS, Forster J. et al . Acute intussusception in infants and children as an adverse event following immunization: case definition and guidelines of data collection, analysis, and presentation.  Vaccine. 2004a;  22 569-574
• 4 Bines JE, Liem NT, Justice FA. et al . Risk factors for intussusception in infants in Vietnam and Australia: adenovirus implicated, but not rotavirus.  J Pediatr. 2006;  149 452-460
• 5 Boudville IC, Phua KB, Quak SH. et al . The epidemiology of paediatric intussusception in Singapore: 1997 to 2004.  Ann Acad Med Singapore. 2006;  35 674-679
• 6 Buettcher M, Baer G, Bonhoeffer J. et al . Three-year surveillance of intussusception in children in Switzerland.  Pediatrics. 2007;  Sept 473-480
• 7 CDC . From the Centers for Disease Control and Prevention. Intussusception among recipients of rotavirus vaccine – United States, 1998–1999.  JAMA. 1999;  282 520-521
• 8 Chen YE, Beasley S, Grimwood K. Intussusception and rotavirus associated hospitalisation in New Zealand.  Arch Dis Child. 2005;  90 1077-1081
• 9 Eshel G, Barr J, Heyman E. et al . Intussusception: a 9-year survey (1986–1995).  J Pediatr Gastroenterol Nutr. 1997;  24 253-256
• 10 Federal Health Monitoring . Diagnosedaten der Krankenhäuser nach Wohnsitz (ICD-4-Stellen).  ab 2000 http://www.gbe-bund.de
• 11 Federal Statistical Office of Germany . Tabelle B15. A1 Bevölkerung nach Alters- und Geburtsjahren 2000–2008.
• 12 Fischer TK, Bihrmann K, Perch M. et al . Intussusception in early childhood: a cohort study of 1.7 million children.  Pediatrics. 2004;  114 782-785
• 13 Gay N, Ramsay M, Waight P. Rotavirus vaccination and intussusception.  Lancet. 1999;  354 956
• 14 Gobel U, Heinrich B, Krauth KA. et al . Process and outcome quality of the German Paediatric Surveillance Unit (ESPED).  Klin Padiatr. 2010;  222 92-97
• 15 Greenberg D, Givon-Lavi N, Newman N. et al . Intussusception in children in Southern Israel: disparity between 2 populations.  Pediatr Infect Dis J. 2008;  27 236-240
• 16 Jenke AC, Klaassen-Mielke R, Zilbauer M. et al . Intussusception: incidence and treatment-insights from the nationwide German surveillance.  J Pediatr Gastroenterol Nutr. 2011;  52 446-451
• 17 Justice F, Carlin J, Bines J. Changing epidemiology of intussusception in Australia.  J Paediatr Child Health. 2005;  41 475-478
• 18 Kohl LJ, Streng A, Grote V. et al . Intussusception-associated hospitalisations in Southern Germany.  Eur J Pediatr. 2010; 
• 19 Kramarz P, France EK, Destefano F. et al . Population-based study of rotavirus vaccination and intussusception.  Pediatr Infect Dis J. 2001;  20 410-416
• 20 LaPorte RE, McCarty DJ, Tull ES. et al . Counting birds, bees, and NCDs.  Lancet. 1992;  339 494-495
• 21 Murphy TV, Gargiullo PM, Massoudi MS. et al . Intussusception among infants given an oral rotavirus vaccine.  N Engl J Med. 2001;  344 564-572
• 22 Nakagomi T, Takahashi Y, Arisawa K. et al . A high incidence of intussusception in Japan as studied in a sentinel hospital over a 25-year period (1978–2002).  Epidemiol Infect. 2006;  134 57-61
• 23 Nelson EA, Tam JS, Glass RI. et al . Incidence of rotavirus diarrhea and intussusception in Hong Kong using standardized hospital discharge data.  Pediatr Infect Dis J. 2002;  21 701-703
• 24 O’Ryan M, Lucero Y, Pena A. et al . Two year review of intestinal intussusception in six large public hospitals of Santiago, Chile.  Pediatr Infect Dis J. 2003;  22 717-721
• 25 Parashar UD, Holman RC, Cummings KC. et al . Trends in intussusception-associated hospitalizations and deaths among US infants.  Pediatrics. 2000;  106 1413-1421
• 26 Patel MM, Clark AD, Glass RI. et al . Broadening the age restriction for initiating rotavirus vaccination in regions with high rotavirus mortality: benefits of mortality reduction versus risk of fatal intussusception.  Vaccine. 2009;  27 2916-2922
• 27 Patel MM, Haber P, Baggs J. et al . Intussusception and rotavirus vaccination: a review of the available evidence.  Expert Rev Vaccines. 2009;  8 1555-1564
• 28 Perez-Schael I, Escalona M, Salinas B. et al . Intussusception-associated hospitalization among Venezuelan infants during 1998 through 2001: anticipating rotavirus vaccines.  Pediatr Infect Dis J. 2003;  22 234-239
• 29 Ruiz-Palacios GM, Perez-Schael I, Velazquez FR. et al . Safety and efficacy of an attenuated vaccine against severe rotavirus gastroenteritis.  N Engl J Med. 2006;  354 11-22
• 30 Staatz G, Alzen G, Heimann G. Intestinal infection, the most frequent cause of invagination in childhood: results of a 10-year clinical study.  Klin Padiatr. 1998;  210 61-64
• 31 Tate JE, Simonsen L, Viboud C. et al . Trends in intussusception hospitalizations among US infants, 1993–2004: implications for monitoring the safety of the new rotavirus vaccination program.  Pediatrics. 2008;  121 e1125-e1132
• 32 Vesikari T, Matson DO, Dennehy P. et al . Safety and efficacy of a pentavalent human-bovine (WC3) reassortant rotavirus vaccine.  N Engl J Med. 2006;  354 23-33
• 33 Webby RJ, Bines JE, Barnes GL. et al . Intussusception in the Northern Territory: the incidence is low in Aboriginal and Torres Strait Islander children.  J Paediatr Child Health. 2006;  42 235-239 discussion 227–238
• 34 WHO . Acute intussusception in infants and children. Incidence, clinical presentation and management: a global perspective.  WHO/V&B/02.19.2002

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