REGULAR ARTICLE

Evaluating national guidelines for the prophylactic treatment of respiratorysyncytial virus in children with congenital heart diseaseElin Granbom (elinkgranbom@gmail.com)1, Eva Fernlund2, Jan Sunneg�ardh3, Bo Lundell4, Estelle Naumburg1

1.Department of Clinical Science, Paediatrics, Ume�a University, Ume�a, Sweden2.Department of Paediatrics, University Hospital of Link€oping and Children’s Heart Centre, Lund, Sweden3.Department of Cardiology at the Queen Silvia Children0s Hospital, Sahlgrenska University Hospital, Gothenburg, Sweden4.Paediatric Cardiology, Astrid Lindgren Children’s Hospital, Stockholm, Sweden

KeywordsCongenital heart disease, Palivizumab, Prophylaxis,Respiratory syncytial virus, Swedish nationalguidelines

CorrespondenceElin Granbom, Barn-och ungdomskliniken,€Ostersunds sjukhus, S-83183 €Ostersund, Sweden.Tel: +4663153000 |Fax: +4663154505 |Email: elinkgranbom@gmail.com

Received14 September 2013; revised 30 January 2014;accepted 9 April 2014.

DOI:10.1111/apa.12658

ABSTRACTAim: This is the first study to evaluate compliance with the 2003 Swedish national

guidelines for prophylactic treatment of respiratory syncytial virus (RSV) in children with

congenital heart disease (CHD). We estimated the relative risk (RR) of children with CHD

being hospitalised with a RSV infection, studied the extent to which RSV prophylactic

treatment with palivizumab corresponded to the guidelines and determined the morbidity

of children with CHD who developed RSV infection despite prophylaxis.

Methods: This national observational study comprised prospectively registered data on

219 children with CHD treated with palivizumab, medical records on RSV cases and

information on hospitalisation rates of children with CHD and RSV infection.

Results: The calculated RR of children with CHD being hospitalised with RSV infection was

2.06 (95% CI 1.6–2.6; p < 0.0001) compared with children without CHD. Approximately

half of the patients (49%) born before the RSV season and 25% born during the RSV

season did not start treatment as recommended by the guidelines.

Conclusion: Having CHD increased the rate and estimated RR of children being

hospitalised with RSV infection. The guidelines were not followed for about half of the

children born before a RSV season and a quarter of the children born during a RSV season

and need updating.

INTRODUCTIONRespiratory syncytial virus (RSV) causes respiratory tractinfections, and 90% of children have been affected by thevirus by the time they reach 2 years of age (1,2).Underlying conditions, such as cystic fibrosis, congenitalheart disease (CHD) and prematurity – with or withoutbronchopulmonary dysplasia – increase the risk of severeRSV disease and hospitalisation in early life (3,4). Themonoclonal antibody palivizumab (15 mg/kg im) is aprophylaxis for serious RSV disease and reduces hospital-isation rates in young children with haemodynamicallysignificant CHD (5).

In 2003, the Swedish Paediatric Cardiology Associationestablished national guidelines for the prophylactic treat-ment of CHD patients with palivizumab (6,7) (Table 1).This is the first study to evaluate compliance with thoseguidelines. Our aim was to estimate the relative risk (RR)of children with CHD being hospitalised with a RSVinfection, study the extent to which RSV prophylactictreatment with palivizumab corresponded to the nationalguidelines and determine the morbidity of children withCHD who developed RSV infection despite receivingprophylaxis.

MATERIALS AND METHODSWe retrieved information on hospitalisation rates forpatients younger than 2 years of age from the SwedishNational Inpatient Registry (8) using the InternationalClassification of Diseases (ICD) applicable to diagnoses ofrespiratory tract infections and RSV infections. The infor-mation we studied covered the RSV seasons of 2010–2011and 2011–2012. The Swedish registry includes information

Key notes� This is the first study to evaluate compliance with the

Swedish national guidelines for prophylactic treatmentof respiratory syncytial virus (RSV) infection in paediatriccongenital heart disease (CHD).

� Having CHD increased the rate and estimated relativerisk of children being hospitalised with RSV infection,and treatment did not follow the recommendations in49% of children born before and 25% born during aRSV season.

� The guidelines need updating, including when treat-ment should start.

Acta Pædiatrica ISSN 0803-5253

840 ©2014 Foundation Acta Pædiatrica. Published by John Wiley & Sons Ltd 2014 103, pp. 840–845

on when patients were admitted to the country’s hospitalsand discharged, as well as their primary and secondarydiagnoses, based on ICD10 (9). We also retrieved additionalinformation on the number of patients with and withoutCHD and younger than 2 years of age who were hospita-lised with respiratory tract and RSV infections. The registrydid not contain information on prophylactic treatment withpalivizumab in either group. We estimated the number ofchildren younger than 2 years based on the number of livebirths recorded in the national Statistics Sweden database(10), which covers more than 99% of the country’s livebirths (11). In Sweden, 0.8% of children who are born alivehave CHD, so we calculated the number of children withCHD by multiplying the number of children under the ageof 2 by 0.008 (12). The RR of hospitalisation, due torespiratory tract infection or RSV infection, among childrenwith and without CHD, was calculated using MedCalc�

(www.medcalc.org, chi-square test).A questionnaire was sent to all Swedish paediatric clinics

before the RSV seasons in 2010–2011 and 2011–2012. Thisnational prospective observational study included Swedishchildren with CHD who received prophylactic treatmentwith palivizumab. In Sweden, children with CHD are given15 mg/kg of palivizumab as a monthly intramuscularinjection, prescribed by paediatric cardiologists on anindividual basis and administered by paediatric nurses ateach centre. These nurses were asked to complete thequestionnaire for each child with CHD who receivedprophylactic treatment. Informed parental consent wasprovided for all participants.

The questionnaire included the patient’s personal iden-tification number, a civic registration code assigned to allSwedish citizens that provides their date of birth and gender(13), and the type of CHD, as stated in the questionnaire orhealth record or according to the ICD-10 (9). Otherinformation included the child’s age in months at the startof treatment, the number of palivizumab injections they hadreceived and whether the RSV infection occurred afterprophylactic treatment, caused hospitalisation or delayedtheir operation. The diagnoses were classified according toeight different subgroups (Table 2).

The calendar month at the start of treatment wasestimated based on the child’s reported age at the start oftreatment. The time between the actual start of treatment

and the recommendation in the national guidelines –November or the first month of life if the child was bornduring the RSV season – was calculated. Treatment wasconsidered to be timely if it complied with the guidelines.

The medical records of all prophylactically treated RSVcases were retrieved. We noted the duration of hospitalisa-tion, delays to surgical procedures, and oxygen and venti-lation support, such as continuous positive airway pressure,mechanical ventilation or extracorporeal membrane oxy-genation. The number of prophylactic injections before andafter the RSV infection were determined, and any addi-tional diagnoses of chromosome defects were retrievedfrom the medical records.

RESULTSThe calculated RR of hospitalisation due to RSV infectionamong children with CHD younger than 2 years of age was2.06 (95% CI 1.6–2.6; p < 0.0001) compared with childrenwithout CHD of the same age (Table 5). The RR of hospi-talisation due to any type of respiratory tract infection,including RSV infection, among childrenwith CHD youngerthan 2 years of age was 2.35 (95% CI 2.1–2.6; p < 0.0001)compared with children without CHD (Table 5).

Of the 34 clinics, 22 (65%) replied during the first RSVstudy season and 27 replied (79%) during the second, with20 (59%) responding to both. A total of 219 children wereincluded in the study, with 11 included in both seasons,and 869 doses of palivizumab were given during the studyperiod, evenly split between the two seasons. Eachincluded child received a mean of 3.97 (range 1–7)injections.

The majority of patients (70%) started treatment duringtheir first 6 months of life. A further 18 patients (8%) startedtreatment later than 12 months of age, and the mostcommon diagnosis among these patients was left ventricu-lar outflow tract obstructions, which was present in one-third of the over-age treated patients (Table 3).

Treatment was provided in line with the national guide-lines in 51% of the total cohort of 219 cases. A quarter(25%) of the 93 patients born during a RSV season startedprophylactic treatment after the recommended age of1 month (range: 1–4 months) and just over a half (53%)

Table 1 Swedish national guidelines (published 2003) for the use ofpalivizumab (Synagis) in children with CHDTiming of prophylactic treatment: 1 November–30 March

<6 months of age with Down’s syndrome and atrioventricular septal

defect (AVSD)/ventricular septal defect (VSD), not operated

<6 months of age with shunt defect plus heart failure with medication

<12 months of age with univentricular heart defects

<12 months of age with heart and lung disease

<12 months of age with pulmonary hypertension

<12 months of age with severe heart failure

CHD = Congenital heart disease.

Table 2 Eight subgroups of types of CHD1. Univentricular heart defects

2. Systemic–pulmonary shunt defects (atrioventricular septal defect, atrial

septal defect, ventricular septal defect and truncus arteriosus)

3. PHT (pulmonary hypertension with no other cardiac defect)

4. Other complex CHD

5. Left side outflow obstructions (aortic stenosis, aortic coarctation and

interrupted aortic arch)

6. Right side outflow obstructions (pulmonary atresia, pulmonary stenosis)

7. Tetralogy of Fallot

8. Cardiomyopathy

CHD = Congenital heart disease.

©2014 Foundation Acta Pædiatrica. Published by John Wiley & Sons Ltd 2014 103, pp. 840–845 841

Granbom et al. Respiratory syncytial virus: evaluating guidelines

of the 122 patients born before the RSV seasons startedtreatment later than recommended (Fig. 1).

Children with systemic–pulmonary shunt defects weremore likely to receive prophylactic treatment with pali-vizumab during both seasons, especially during the secondseason, than children with any other CHD diagnosis(Fig. 2).

Ten patients (4.6%) with CHD who had receivedprophylactic treatment with palivizumab tested positivefor respiratory tract RSV infection, eight during the firstseason and two during the second, most frequently duringJanuary and February (Table 4). The information reportedfor each of these patients is displayed in Table 5. Nine of the10 were hospitalised and required supplemental oxygen.Some children needed continuous positive airway pressureor mechanical ventilation. However, extracorporeal mem-brane oxygenation was not required and there were nodeaths.

DISCUSSIONIn this study, the overall RR of hospitalisation due to RSVinfection or any type of respiratory tract infection washigher in children with CHD under the age of 2 thanchildren without CHD of the same age. The SwedishNational Inpatient Registry did not provide information on

the exact age of each hospitalised child. Such informationcould have given further information on the adherence tothe national guidelines. The inpatient registry provided noinformation on whether a child received prophylactictreatment or whether the physician’s decision to hospitalisea child was based solely on the fact that the child had aheart condition. Further studies are needed to determinethe indications for hospitalising children with CHD inSweden.

In most cases, the diagnosis and calendar month whenprophylactic treatment was started concurred with thenational guidelines. However, during the second RSVseason of the study, we observed an increase in the numberof patients with systemic–pulmonary shunt defects orcomplex defects. The reason for this is unknown, but it ispossible that Swedish paediatric cardiologists had beenmade increasingly aware of the need for prophylactictreatment as the study progressed and decided to expandthe indications for treatment. One can speculate that thisshift in criteria was beneficial to the patients, as during thesecond season, only two patients were hospitalised withRSV infection compared with eight during the first season.The fact that fewer patients were infected during the secondseason also correlates with the total amount of RSV cases inthe country, as there were more infected patients in 2010–2011 than 2011–2012.

Most patients born before a RSV season started treatmentin November as recommended by the national guidelines,but a significant number started treatment either earlier(9%) or later (40%). These included the 25% of patientswho were born during a RSV season and started thetreatment later than 1 month of age. It can be argued thatdelays in identifying patients at risk could have affected theoutcome. A monthly injection was recorded once thepatients had started treatment.

In some countries, prophylactic treatment with pali-vizumab is recommended for children with CHD up to 24

Table 3 Number of patients and age at start of palivizumab treatment

Age at first dose 2010–2011 2011–2012 Total Percentage

≤6 months 73 81 154 70

>6 to ≤12 months 25 18 43 20

>12 months 10 8 18 8

Missing information 1 3 4 2

Total 109 110 219 100

0

10

20

30

40

50

60

70

October or earlier

On time 1 month late

2 months late

≥3 months

late

Missing info

2010–2011

2011–2012

Figure 1 Number of patients starting treatment during the recommended timeof year in line with the national guidelines.

0

5

10

15

20

25

30

35

40

452010–20112011–2012

Figure 2 Distribution of congenital heart disease (CHD) diagnoses amongpatients treated with respiratory syncytial virus (RSV) prophylaxis.

842 ©2014 Foundation Acta Pædiatrica. Published by John Wiley & Sons Ltd 2014 103, pp. 840–845

Respiratory syncytial virus: evaluating guidelines Granbom et al.

months of age, whereas the Swedish national guidelinesrecommend 12 months as the upper age limit. Our studynoted that 18 children were treated over the recommendedage of 12 months. This shift in the time when treatment wasstarted, with respect to season and age, may have beeninfluenced by the epidemiological status of RSV in thecommunity, as well as by the guidelines for RSV prophylaxisin other countries.

Omitting or delaying palivizumab prophylaxis has beenlinked to increased rates of rehospitalisation (14–16),making it essential to adhere to a prophylactic programme(15,17). However, there have been no studies to investigatephysicians’ compliance with national guidelines for pro-phylactic treatment of RSV infection, which also may affectthe risk of hospitalisation of children with CHD.

Ten of the 219 patients (4.6%) who had receivedprophylactic treatment with palivizumab were infectedwith RSV and nine were hospitalised, a higher rate thanthat reported in recent studies (18). Our study showed thatRSV infection in children with CHD required intensive careand mechanical ventilation, in line with previous studies(3,19,20). The cost-effectiveness of prophylaxis with

palivizumab has been debated, but was not addressed inthis study (5,21). Further studies are needed.

The risk of hospitalisation is known to be at its highestamong children born near the start of the RSV season andlowest for those born at the end of the RSV season in all riskcategories (4). In our study, most of the RSV infections inpatients with CHD treated with palivizumab occurredduring January and February, more than 1 month beforethe peak incidence of all RSV cases in Sweden during theseseasons (22). Three of the 10 patients with RSV had theiroperation delayed because of their infection, and in each ofthese cases, the start of their prophylactic treatment hadbeen delayed by 1 or 2 months. All ten RSV-infected infantswere <1 year of age when infected by RSV and three were asyoung as 1 month. We can speculate that young age anddelayed start of treatment are risk factors for early onsetRSV infection among children with CHD. Cardiac surgeryperformed during RSV infection is associated with anincreased risk of postoperative complications (23). How-ever, delaying the procedure may also worsen the outcome.

This study indicates that factors involved in the effectiveprophylactic treatment of infants with palivizumab includemaking sure that treatment is started at the right time andthat children with CHD are identified.

There are limitations to this study. The RR calculationswere based on the information obtained from the inpatientregistry, which covers approximately 99% of all patientshospitalised in Sweden (8). Regional and seasonal varia-tions exist in routine tests for RSV, mainly because thetreatment protocol is identical for all viral infections and apositive or negative RSV test is of little practical importancefor clinicians. Therefore, RSV infections are probablyunder-reported in the registry, both among patients withand without CHD.

We estimated the number of children with CHD based onthe incidence of CHD in Sweden (12). However, this maybe an overestimation, as prenatal diagnosis has becomeincreasingly common and almost half of the pregnanciesinvolving foetuses with severe heart conditions are termi-nated (24).

Table 4 Characteristics of prophylactically treated CHD patients with RSV infection

Patient A B C D E F G H I J Mean

Total number of injections 3 4 5 4 6 5 2 4 2 3 3.8

Number of injections prior to RSV infection 1 1 1 1 4 1 2 2 1 2 1.5

Number of injections post-RSV infection 2 3 4 3 2 4 0 2 1 1 2.3

Days of hospitalisation 0 5 5 11 4 16 1 18 26 26 11.2

Age (months) at RSV infection 7 1 6 3 6 1,5 1,5 3,5 2 9 4.05

Calendar month for RSV infection 2 2 11 1 4 12 1 3 1 2

Type of CHD (subgroup) 8 1 9 3 1 2 9 3 2 6

Chromosome disorders (trisomy) No No No 21 No 21 No No No 13

Required oxygen No Yes Yes Yes Yes Yes Yes Yes Yes Yes

CPAP No No No Yes No Yes No No Yes Yes

Mechanical ventilator No No No No No No No Yes No No

Prolonged time to operation Yes No Yes No No Yes No No No No

CHD = Congenital heart disease; RSV = Respiratory syncytial virus.

Table 5 Hospitalisation rates for children with CHD and children without CHD, dueto respiratory tract infection and RSV infections

CHD Non-CHD RR p-value CI (95%)

Hospitalised with

RSV infection

66 3967 2.06 <0.0001 1.6–2.6

Not hospitalised

with RSV infection

1728 218 511

Hospitalised with

respiratory tract

infection

244 12 895 2.35 <0.0001 2.1–2.6

Not hospitalised

with respiratory

tract infection

1550 209 583

CHD = Congenital heart disease; RR = Relative risk; RSV = Respiratory

syncytial virus.

©2014 Foundation Acta Pædiatrica. Published by John Wiley & Sons Ltd 2014 103, pp. 840–845 843

Granbom et al. Respiratory syncytial virus: evaluating guidelines

The questionnaire response rate was lower than expectedfor both study seasons, but did include replies from all themajor Swedish paediatric cardiology centres, where themajority of patients with CHD in Sweden are treated. Morethan 730 infants under the age of 1 year received surgery forCHD in Sweden during the study period. Our study patientpopulation can therefore be considered representative ofthe overall paediatric CHD population.

Ten of the children with CHD who received prophylactictreatment with palivizumab were subsequently diagnosedwith RSV infection and most of them continued the RSVprophylaxis, even after the infection. Whether clinicians aregenerally aware of the benefits of prophylactic treatmentwith palivizumab after an infection is not clear and thisshould be highlighted in the national guidelines and atnational meetings (25,26).

This is the first study to evaluate compliance with the2003 Swedish national guidelines for prophylactic treat-ment of RSV infection in children with CHD. We recom-mend that the 2003 guidelines should be revised, based onthe three key findings of our study: (i) the risk of hospital-isation due to RSV infection remains high among childrenwith CHD, (ii) the number of children with CHD contract-ing RSV despite prophylactic treatment is higher than thatin recent studies, (iii) paediatric cardiologists in Sweden areinfluenced by international guidelines, while the nationalguidelines might be regarded as outdated.

We conclude that updated guidelines include recommen-dations that the prophylactic treatment should be startedaccording to the epidemiology of RSV in the local commu-nity, to provide protection before the outbreak reaches itspeak. The different types of CHD diagnosis are complex andthe treatment recommendations should therefore take intoaccount the patient’s state of health and predicted condi-tion during the RSV season, as well as the formal diagnosis.

ACKNOWLEDGEMENTSOur sincere gratitude to all the participating paediatriccardiology clinics and to the children with CHD and theirfamilies. This work was supported by a grant from Abbott(EUDRACT No.: AIF-11-0003). The study has beenapproved by the local ethical review board in Ume�a (EPNDnr 2011-82-31M).

References

1. Simoes EA. Respiratory syncytial virus infection. Lancet 1999;354: 847–52.

2. Glezen WP, Taber LH, Frank AL, Kasel JA. Risk of primaryinfection and reinfection with respiratory syncytial virus. Am JDis Child 1986; 140: 543–6.

3. Aujard Y, Fauroux B. Risk factors for severe respiratorysyncytial virus infection in infants. Respir Med 2002; 96(Suppl.B): S9–14.

4. Boyce TG, Mellen BG, Mitchel EF Jr, Wright PF, Griffin MR.Rates of hospitalization for respiratory syncytial virusinfection among children in medicaid. J Pediatr 2000; 137:865–70.

5. Feltes TF, Cabalka AK, Meissner HC, Piazza FM, Carlin DA,Top FH Jr, et al. Palivizumab prophylaxis reduceshospitalization due to respiratory syncytial virus in youngchildren with hemodynamically significant congenital heartdisease. J Pediatr 2003; 143: 532–40.

6. Sunnegardh J. Prophylaxis with palivizumab against respiratorysyncytial virus infection in infants with congenital heartdisease–who should receive it? Acta Paediatr 2006; 95: 388–90.

7. Lakemedelsverket. Behandlingsrekommendation. 2004.Available at: http://www.lakemedelsverket.se/upload/halso-och-sjukvard/behandlingsrekommendationer/rsv.pdf.(accessed on May 20, 2014).

8. Ludvigsson JF, Andersson E, Ekbom A, Feychting M, Kim JL,Reuterwall C, et al. External review and validation of theSwedish national inpatient register. BMC Public Health 2011;11: 450.

9. WHO. World Health Organization classifications. Available at:http://www.who.int/classifications/icd/en/. (accessed on May20, 2014).

10. SCB. Statistical database Sweden. [2012-02-20; population,live births]. Available at: http://www.statistikdatabasen.scb.se/pxweb/en/ssd/?rxid=20ab8d4c-98bc-435d-8f82-6805a3d70ca8. (accessed on February 20, 2012).

11. SCB. Quality declaration. 2012 [updated 2012-02-20].Available at: http://www.scb.se/Statistik/BE/BE0101/_dokument/BE0101_BS_2011.pdf. (accessed on February 20,2012).

12. Sunnegardh J. Pediatric cardiology, a review. Lund:Studentlitteratur, 2000.

13. Ludvigsson JF, Otterblad-Olausson P, Pettersson BU, EkbomA. The Swedish personal identity number: possibilities andpitfalls in healthcare and medical research. Eur J Epidemiol2009; 24: 659–67.

14. Parnes C, Guillermin J, Habersang R, Nicholes P, Chawla V,Kelly T, et al. Palivizumab prophylaxis of respiratory syncytialvirus disease in 2000–2001: results from The PalivizumabOutcomes Registry. Pediatr Pulmonol 2003; 35: 484–9.

15. Golombek SG, Berning F, Lagamma EF. Compliance withprophylaxis for respiratory syncytial virus infection in a homesetting. Pediatr Infect Dis J 2004; 23: 318–22.

16. Resch B, Gusenleitner W, Muller WD, Haas J. Observationalstudy of respiratory syncytial virus-associated hospitalizationsand use of palivizumab in premature infants aged 29–32 weeks.Eur J Clin Microbiol Infect Dis 2006; 25: 120–2.

17. Adcock PM, Sanders CL, Marshall GS. Standardizing the careof bronchiolitis. Arch Pediatr Adolesc Med 1998; 152: 739–44.

18. Alexander PM, Eastaugh L, Royle J, Daley AJ, ShekerdemianLS, Penny DJ. Respiratory syncytial virus immunoprophylaxisin high-risk infants with heart disease. J Paediatr Child Health2012; 48: 395–401.

19. Fixler DE. Respiratory syncytial virus infection in children withcongenital heart disease: a review. Pediatr Cardiol 1996; 17:163–8.

20. Kristensen K, Stensballe LG, Bjerre J, Roth D, Fisker N,Kongstad T, et al. Risk factors for respiratory syncytial virushospitalisation in children with heart disease. Arch Dis Child2009; 94: 785–9.

21. Meberg A, Bruu AL. Respiratory syncytial virus infections incongenital heart defects–hospitalizations and costs. ActaPaediatr 2006; 95: 404–6.

22. Smittskyddsinstitutet. RSV-rapporter. Available at: http://www.folkhalsomyndigheten.se/amnesomraden/statistik-och-undersokningar/sjukdomsstatistik/rsv-veckorapporter/. (accessed on November 29, 2013).

23. Khongphatthanayothin A, Wong PC, Samara Y, Newth CJ,Wells WJ, Starnes VA, et al. Impact of respiratory syncytial

844 ©2014 Foundation Acta Pædiatrica. Published by John Wiley & Sons Ltd 2014 103, pp. 840–845

Respiratory syncytial virus: evaluating guidelines Granbom et al.

virus infection on surgery for congenital heart disease:postoperative course and outcome. Crit Care Med 1999; 27:1974–81.

24. Bergman G, Borgstrom E, Lundell B, Sonesson SE. Forbattradprenatal diagnostik av medfodda hjartfel. Uppfoljningsstudieav fosterekokardiografiska undersokningar [Improved prenataldiagnosis of congenital heart defects. A follow-up study ofprenatal ultrasound screening]. Lakartidningen 2008; 105:899–903.

25. Committee on Infectious Diseases. From the AmericanAcademy of Pediatrics: policy statements – modifiedrecommendations for use of palivizumab for prevention ofrespiratory syncytial virus infections. Pediatrics 2009; 124:1694–701.

26. Bosis S, Esposito S, Niesters HG, Zuccotti GV, Marseglia G,Lanari M, et al. Role of respiratory pathogens in infantshospitalized for a first episode of wheezing and their impact onrecurrences. Clin Microbiol Infect 2008; 14: 677–84.

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Granbom et al. Respiratory syncytial virus: evaluating guidelines