Palivizumab use in infants with Down syndrome—report from the German Synagis™ Registry 2009–2016
Infants with Down syndrome (DS) face an increased risk of respiratory tract infections. Recent studies describe DS as independent risk factor for a complicated clinical course in infants with respiratory syncytial virus (RSV) infection. The prospective observational German Synagis™ Registry comprises data from 249 children below 25 months of age with DS and palivizumab prophylaxis 2009–2016 (1191 administrations; mean 4.8 per patient and season). The median gestational age and the birth weight in patients without and with DS were 31 versus 37 weeks (P < 0.001) and 1590 versus 2750 g, respectively (P < 0.001). Patients with DS significantly more often had congenital heart disease (CHD), siblings in kindergarten or school, treatment with oxygen at home, immunodeficiency, and neuromuscular impairment. The RSV-related hospitalization rate in patients with DS was 1.20%; the hospitalization rate in patients without DS was 0.71%.
What is Known:
• Recent studies describe the Down syndrome as independent risk factor for a complicated clinical course in infants with RSV infection.
What is New:
• Compared with other infants receiving palivizumab prophylaxis, patients with Down syndrome significantly more often had congenital heart disease, siblings in kindergarten or school, treatment with oxygen at home, immunodeficiency, and neuromuscular impairment.
• In infants with palivizumab prophylaxis breakthrough, RSV-related hospitalization rates were not significantly higher in those with Down syndrome.
KeywordsDown syndrome Respiratory syncytial virus Palivizumab prophylaxis RSV-related hospitalization Bronchiolitis
congenital heart disease
chronic lung disease of prematurity
electronic case report form
lower respiratory tract infection
postmarketing observational study
respiratory syncytial virus
respiratory syncytial virus hospitalization rate
respiratory tract infection
serious adverse event
AS is the scientific advisor of the German Synagis Registry, developed the online eCRF together with SG and wrote the draft of the manuscript. SG coordinated the internal review of the manuscript. GW and SW performed the statistical data analysis. All authors contributed to the final version of the manuscript.
The German Synagis Registry is supported by an unrestricted scientific grant of AbbVie GmbH, Wiesbaden, Germany.
Compliance with ethical standards
Conflict of interest
AbbVie Deutschland GmbH & Co KG, Wiesbaden, Germany provided financial support for this Registry. AbbVie participated in the review and approval of the manuscript. Susanne Gehrmann is Medical Unit Leader in the Medical Affairs Department of AbbVie Deutschland GmbH & Co.KG, Wiesbaden and may own AbbVie stock or stock options. Arne Simon has received scientific grants from Abbott GmbH, Wiesbaden for the DSM RSV Paed Study and honoraria for the development and scientific administration of Internet-based Version of the German Synagis™ Registry from AbbVie Deutschland GmbH & Co.KG, Wiesbaden, Germany. Stefan Wagenpfeil has received scientific grants from AbbVie Deutschland GmbH & Co. KG for epidemiologic evaluation of the German Synagis™ Registry. Gudrun Wagenpfeil has no conflicts of interest to declare.
Parents/legal guardians provided written informed consent for data recording on the eCRF and anonymized data analysis and publication for scientific purposes. Before the practical implementation of the protected Internet data entry platform, the medical advisor of the study (AS) obtained approval for the POMS by the Ethics Committee of the Medical Faculty, University of Bonn, Germany (reference no. 132/08). This approval was prolonged to July 2012 on September 9, 2010. After a change of affiliation to the University Hospital Homburg/Saar, approval for the study was obtained by the Ethics Committee of the Medical Association of the Saarland on April 13, 2013 (reference no. Ha89/13).
- 1.Bloemers BL, van Furth AM, Weijerman ME, Gemke RJ, Broers CJ, van den Ende K, Kimpen JL, Strengers JL, Bont LJ (2007) Down syndrome: a novel risk factor for respiratory syncytial virus bronchiolitis—a prospective birth-cohort study. Pediatrics 120(4):e1076–e1081. https://doi.org/10.1542/peds.2007-0788 CrossRefPubMedGoogle Scholar
- 2.Boghossian NS, Hansen NI, Bell EF, Stoll BJ, Murray JC, Laptook AR, Shankaran S, Walsh MC, Das A, Higgins RD (2010) Survival and morbidity outcomes for very low birth weight infants with Down syndrome. Pediatrics 126(6):1132–1140. https://doi.org/10.1542/peds.2010-1824 CrossRefPubMedPubMedCentralGoogle Scholar
- 4.Deutsche Gesellschaft für Pädiatrische Infektiologie (DGPI), Deutsche Gesellschaft für Pädiatrische Kardiologie (DGPK), Deutsche Gesellschaft für Pädiatrische Pneumonologie (DPP), Deutsche Gesellschaft für Neonatologie und Pädiatrische Intensivmedizin (GNPI) (2008) Stellungnahme zur Prophylaxe von schweren RSV-Erkrankungen bei Risikokindern mit Palivizumab. http://wwwdgpide/pdf/Palivizumab_LL_final_30Sep2008pdf (30. September 2008)Google Scholar
- 5.Deutsche Gesellschaft für Pädiatrische Infektiologie (DGPI), Deutsche Gesellschaft für Pädiatrische Kardiologie (DGPK), Gesellschaft für Pädiatrische Pneumologie (GPP), Gesellschaft für Neonatologie und Pädiatrische Intensivmedizin (GNPI), Berufsverband der Kinder- und Jugendärzte (BVKJ), Bundesverband „Das frühgeborene Kind“ e.V. (2012) AWMF-LL 048-012 - Leitlinie zur Prophylaxe von schweren Erkrankungen durch Respiratory Syncytial Virus (RSV) bei Risikokindern 28. Oktober2012Google Scholar
- 6.Feltes TF, Cabalka AK, Meissner HC, Piazza FM, Carlin DA, Top FH Jr, Connor EM, Sondheimer HM (2003) Palivizumab prophylaxis reduces hospitalization due to respiratory syncytial virus in young children with hemodynamically significant congenital heart disease. J Pediatr 143(4):532–540CrossRefPubMedGoogle Scholar
- 7.Hall CB, Weinberg GA, Iwane MK, Blumkin AK, Edwards KM, Staat MA, Auinger P, Griffin MR, Poehling KA, Erdman D, Grijalva CG, Zhu Y, Szilagyi P (2009) The burden of respiratory syncytial virus infection in young children. N Engl J Med 360(6):588–598. https://doi.org/10.1056/NEJMoa0804877 CrossRefPubMedPubMedCentralGoogle Scholar
- 9.Kristensen K, Hjuler T, Ravn H, Simoes EA, Stensballe LG (2012) Chronic diseases, chromosomal abnormalities, and congenital malformations as risk factors for respiratory syncytial virus hospitalization: a population-based cohort study. Clin Infect Dis 54(6):810–817. https://doi.org/10.1093/cid/cir928 CrossRefPubMedGoogle Scholar
- 14.PaesB, MitchellI, LiA, HarimotoT, LanctotKL (2013) Respiratory-related hospitalizations following prophylaxis in the Canadian registry for palivizumab (2005-2012) compared to other international registries. Clin Dev Immunol2013:917068. doi: https://doi.org/10.1155/2013/917068, 1, 15
- 15.Paes B, Mitchell I, Li A, Lanctot KL (2012) A comparative study of respiratory syncytial virus (RSV) prophylaxis in premature infants within the Canadian Registry of Palivizumab (CARESS). Eur J Clin Microbiol Infect Dis 31(10):2703–2711. https://doi.org/10.1007/s10096-012-1617-7 [doi]Google Scholar
- 16.Paes B, Mitchell I, Li A, Lanctot KL (2012) Respiratory hospitalizations and respiratory syncytial virus prophylaxis in special populations. Eur J Pediatrin press. https://doi.org/10.1007/s00431-011-1654-8 [doi]Google Scholar
- 17.Paes B, Mitchell I, Li A, Lanctot KL (2012) Respiratory hospitalizations and respiratory syncytial virus prophylaxis in special populations. Eur J Pediatr 171(5):833–841. https://doi.org/10.1007/s00431-011-1654-8 [doi]Google Scholar
- 19.Perez-Padilla R, Fernandez R, Garcia-Sancho C, Franco-Marina F, Aburto O, Lopez-Gatell H, Bojorquez I (2010) Pandemic (H1N1) 2009 virus and Down syndrome patients. Emerg Infect Dis 16(8):1312–1314. https://doi.org/10.3201/eid1608.091931 [doi]Google Scholar
- 21.Simon A, Nowak H, Sterz R (2011) Use of Palivizumab in Germany: data from 2002–2007. Klin Padiatr 223(5):292–298. https://doi.org/10.1055/s-0030-1270515 [doi]Google Scholar
- 24.Sullivan C, Morgan C (2014) PC.74 The importance of testing for Respiratory Syncytial Virus (RSV) in infants presenting with bronchiolitis who are receiving palivizumab. Arch Dis Child Fetal Neonatal Ed 99(Suppl 1):A61.3–A6A61. https://doi.org/10.1136/archdischild-2014-306576.175 CrossRefGoogle Scholar
- 26.Whelan B, Musters E, Murray A, Moore E, Lievaart L, Visser S, Toxopeus E, van Veen A, Notario G, Campbell FJ (2016) Review of the home care programmes for respiratory syncytial virus (RSV) prophylaxis in Ireland and The Netherlands. Drugs Therapy Perspectives: Rational Drug Selection Use 32:119–130. https://doi.org/10.1007/s40267-015-0275-0 CrossRefGoogle Scholar
- 28.Zachariah P, Ruttenber M, Simoes EA (2011) Hospitalization due to respiratory syncytial virus in children with congenital malformations. Pediatr Infect Dis J 30(5):442–445. https://doi.org/10.1097/INF.0b013e318201813b [doi]Google Scholar