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J Glob Health. 2017 Dec;7(2):020413. doi: 10.7189/jogh.07.020413.

The burden of respiratory syncytial virus (RSV) associated acute lower respiratory infections in children with Down syndrome: A systematic review and meta-analysis.

Author information

Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, UK.
Joint first authroship.
Harvard TH Chan School of Public Health, Harvard University, Boston, Massachusetts, USA.
Department of Public Health and Primary Care, Leiden University Medical Centre, Leiden, the Netherlands.
Translational Pediatrics and Infectious Diseases, Pediatrics Department, Hospital Clínico Universitario de Santiago de Compostela, Santiago de Compostela, Spain.
Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, Netherlands.



Acute lower respiratory tract infections (ALRIs) caused by respiratory syncytial virus (RSV) are a leading cause of hospitalization in infants. Numerous risk factors have been identified in the aetiology of severe RSV-associated ALRI necessitating hospitalisation, including prematurity and congenital heart disease. Down syndrome (DS), a common genetic disorder associated with congenital and dysmorphic features, has recently been identified as an independent risk factor for RSV-associated ALRI requiring hospitalisation; however, the disease burden of RSV-associated ALRI in this population has not yet been established. Similarly, the impact of DS as an independent risk factor has not yet been quantified. We aimed therefore to estimate the incidence of admissions in children with DS, and by comparing this with unaffected children, to quantify the risk of DS independent of other risk factors.


A systematic review of the existing literature published between 1995 and March 1, 2017 was performed to quantify the incidence of hospitalisation due to RSV-associated ALRI in children with DS. Meta-analyses were performed on extracted data using STATA statistical software, and hospitalisation rates for children with and without DS under the age of 2 were calculated.


5 articles were ultimately deemed eligible for analyses. Analyses were limited to children under the age of 2 years. We calculated the hospitalisation rate for children with DS in this age group to be 117.6 per 1000 child-years (95% CI 67.4-205.2), vs a rate of 15.2 per 1000 child-years (95% CI 8.3-27.6) in unaffected children. This indicates DS contributes to a 6.8 (95% CI 5.5-8.4) fold increase in the relative risk of hospitalisation for RSV-associated ALRI.


Though limited by a small number of articles, this review found sufficient evidence to conclude DS was a significant independent risk factor for the development of severe RSV-associated ALRI requiring hospitalisation. Further studies are needed to define the impact of DS in conjunction with other comorbidities on the risk of severe RSV infection. Determining benefits of immunoprophylaxis or future vaccines against RSV in this at-risk population is warranted.

[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

Competing interests: HN, LB and FMT are members of the Respiratory Syncytial Virus Consortium in Europe (RESCEU). RESCEU has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No. 116019. This Joint Undertaking receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA. FM–T’s institution has received both funding for investigator initiated studies from Astra, MSD and Pfizer and trials fees from Regeneron, Medimmune, Pfizer, MSD, Sanofi Pasteur, Novartis, GSK, Ablynx, Janssen and Novavax. FM–T has received speaker and/or consultancy honoraria from Pfizer, MSD, Sanofi Pasteur, Novartis and GSK. FM–T research activities have been supported by grants from Consellería de Sanidade, Xunta de Galicia (RHI07/2–intensificación actividad investigadora, PS09749 and 10PXIB918184PR), Instituto de Salud Carlos III (Intensificación de la actividad investigadora 2007–2017), Fondo de Investigación Sanitaria (FIS; PI070069/PI1000540/PI1601569) del plan nacional de I + D + I and ‘fondos FEDER’ and 2016–PG071 Consolidación e Estructuración REDES 2016GI–1344 G3VIP (Grupo Gallego de Genética Vacunas Infecciones y Pediatría, ED341D R2016/021). FM–T reports funding from Ablynx, Jansen, GSK, Regeneron, and Medimmune outside the submitted work. MC, JJP and TS have nothing to disclose. HN reports grants from Innovative Medicines Initiative, grants and personal fees from BMGF, grants from Sanofi Pasteur, personal fees and non–financial support from MedImmune, outside the submitted work.
LB has regular interaction with pharmaceutical and other industrial partners. He has not received personal fees or other personal benefits. UMCU has received major funding (>€100 000 per industrial partner) for investigator initiated studies from AbbVie, MedImmune, Janssen, the Bill and Melinda Gates Foundation and MeMed Diagnostics. UMCU has received minor funding participation in trials by Regeneron and Janssen since 2015 (total annual estimate less than €20 000). He received minor funding for consultation and invited lectures by AbbVie, MedImmune, Ablynx, Bavaria Nordic, MabXience, Novavax, Janssen (total annual estimate less than €20 000).

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