Skip to main content

Prophylaxis protects infants with congenital heart disease from severe forms of RSV infection: an Italian observational retrospective study

Palivizumab prophylaxis in children with congenital heart disease



In children with congenital heart disease (CHD) respiratory syncytial virus (RSV) infection may have a severe course, with increased risk of morbidity and mortality, requiring hospital admission and intensive care. The aim of the present study was to evaluate the effect of prophylaxis with palivizumab in preventing RSV-associated hospitalization in infants with CHD.


We carried out an observational, retrospective study in a paediatric cardiology division at a secondary-care centre in Italy, extracting from the database children with CHD who, from November 2004 to March 2022, matched the criteria for palivizumab prophylaxis, to evaluate the hospitalization rate in CHD patients with and without palivizumab prophylaxis and their RSV-related hospitalization characteristics compared with a group of children without CHD and no other underlying clinical conditions (control group, CG), hospitalized for RSV infection.


One hundred twenty-eight children with CHD were enrolled in the study, mainly (71.9%) with increased pulmonary flow, and received palivizumab prophylaxis. Twenty-seven received hospital care for bronchiolitis. Almost all CHD patients hospitalized for bronchiolitis (26 out of 27) received partial prophylaxis (≤ 3 doses). CHD patients with bronchiolitis stay longer in the hospital than control (14.4 ± 21.7 days vs 6.2 ± 2.3 days) some of which require intensive care (n = 4).


Our study provides evidence of the efficacy of palivizumab in protecting patients with hemodynamically significant CHD under the age of 2 years from RSV disease and its life-threatening complications. Reducing hospitalisation rate, morbidity, and mortality in this category of patients, passive immune prophylaxis with palivizumab may impact healthcare resource availability and utilisation.


Congenital heart disease (CHD) is a leading cause of infant mortality related to birth defects, with an approximate incidence of 8 per 1,000 live births [1, 2]. Delayed CHD diagnosis and treatment may cause chronic disability and morbidity, dramatically reducing life expectancy of patients. In the last decades remarkable progress in diagnostic tools and surgical technics significantly improved survival of children with CHD, allowing them to reach adulthood [3,4,5]. Nowadays the majority of newborns with complex CHD survive, who turn one year old reach 16 years of age [6].

It has been speculated that children with CHD may present altered cellular and humoral effectors of innate immunity and have detectable circulating markers of chronic inflammation [7], which may have important clinical implications in the management of CHD and comorbidities. Children with CHD might be therefore more susceptible to common infections [8].

Respiratory syncytial virus (RSV) is the most common cause of low respiratory tract infections in children up to the age of 2 years [9]. RSV infection causes a variety of disease manifestations, such as bronchiolitis and pneumonia, with clinical presentation ranging from mild to severe. In most cases, RSV-related disease heals spontaneously; however, some newborns and infant may require hospitalization, experience severe morbidity and early mortality. Because of their clinical conditions, infants with CHD are at high-risk for RSV infection and related complications, thus at risk of RSV induced hospitalisation; several studies have targeted hospitalization rate due to RSV-infection in CHD children, reporting high rates, however difficult to compare because of differences in study populations, methods used and inclusion criteria [10]. In addition to hospitalisation, serious acute forms may need strict follow-up to monitor long-term morbidities [11].

To date, there is no specific treatment for RSV infection, and disease management is based on control of the symptoms, although the severe forms require supportive measures, such as oxygen supplementation or other type of respiratory support [12]. Therefore, the best strategy to limit the spread of RSV infection and protect patients at risk of severe complications is the adoption of preventive strategies of immunization.

RSV epidemics show different seasonal cycles, with a peak during winter months in temperate regions, such as Italy [13]. So far, the only agent available for seasonal prophylaxis of RSV infections is palivizumab, a mAb that recognizes an antigenic site of the F glycoprotein of RSV [14]. In Italy, prophylaxis with palivizumab is recommended, as indicated by regulatory authority (Regione Emilia-Romagna) and scientific societies (Italian Society of Neonatology, Italian Society of Pediatric Cardiology and Congenital heart Diseases) in children under the age of 2 years with hemodynamically significant CHD (HS-CHD), with congestive heart failure that requires medical therapy, cyanosis with systemic saturation less than 90%, or pulmonary hypertension, and in children post cardiac transplantation; prophylaxis in the 2nd year of life is recommended when there is still a need of medical therapy on an ongoing basis [15, 16].

We report on a retrospective analysis of a group of patients with HS-CHD from a single center who received palivizumab prophylaxis, to evaluate its effect in preventing RSV-associated hospitalization.


Study design and patients

This was a single center, observational, retrospective study conducted in the Paediatric Cardiology Division in a secondary-care Hospital in Italy. The study was approved by the Local Health Authority, and the Site’s Ethics Committee approved the request to use each identified patient. Specific written informed consent was obtained from each patient or their parental guardian prior to treatment start.

We searched our database for patients with CHD who underwent prophylaxis with palivizumab to assess it effect in preventing RSV-induce hospitalisation; we also evaluate their hospitalization characteristics and compare them with a group of healthy children (CG) of same age, without CHD or any other clinical condition, hospitalized for bronchiolitis during the same period. CHD patients were divided in groups and subgroups according to the type of congenital heart defect, for statistical studies:

  1. A

    Congenital heart defects with increased pulmonary flow:

    • Simple (AS): large atrial septal defect, ventricular septal defect, large arterial duct

    • Multiple (AM): association of at least two simple lesions

    • Complex (AC): anomalous pulmonary venous return, atrioventricular canal, aortopulmonary window, truncus arteriosus

  2. B

    Congenital heart defects with pulmonary hypo-afflux:

    • Complex (BC): tetralogy of Fallot, tricuspid atresia, pulmonary atresia, Ebstein anomaly, unilateral absence of a pulmonary artery, anomalous systemic venous return

  3. C

    Complex congenital heart defects (CC):

    • interrupted aortic arch

    • transposition of the Great Arteries with ventricular septal defect

    • combination of complex lesions:

      • Double outlet right ventricle plus interrupted aortic arch

      • Double outlet right ventricle plus anomalous pulmonary venous return plus Coarctation of the aorta

      • Major aortopulmonary collateral arteries plus ventricular septal defect

    • univentricular heart

    • primary pulmonary hypertension

  4. D

    Myocardial disease (DM)

Assessments and data collection

Patients’ data were collected from the database of the Paediatric Cardiology Unit of Parma General and University Hospital from November 2004 to March 2022. A post-hoc analysis was conducted to determine any possible association between palivizumab prophylaxis of CHD patients and hospitalization. Patients with bronchiolitis were hospitalized according to their need for oxygen therapy (O2 saturation, respiratory, and heart rate) and parenteral nutrition. Hospitalization for bronchiolitis was assessed in CHD and CG children.

Statistical analysis

Continuous variables were given as means with standard deviations (SD) and categorical variables as the number of subjects and percentage values.

Demographic-clinical baseline differences in patients with CHD and control group were tested using Pearson's Chi-square Test (Fisher's exact where appropriate).

Univariate penalized logistic and negative binomial regression models were performed to detect the effect of the demographic-clinical characteristics on hospitalization and high flows outcome, respectively.

Those covariates with a p-value < 0.10 were then selected for the multivariate analysis, where the hospitalization and high flows were the dependent variables. Multivariate analysis was performed using again the penalised logistic and negative binomial regression model for dichotomic and count outcomes, respectively. The model selection was done using the Akaike information criterion and the Likelihood Ratio test was used as the test of statistical significance. The estimated p-values were adjusted for multiple comparisons by the Holm correction method. A p-value < 0.05 was considered as significant and data were acquired and analysed in R v4.2.0 software environment [17].


Characteristics of the patient population

The study population included 128 infants with HS-CHD, the majority of which (72%) had congenital heart defects with increased pulmonary flow, while CHD with pulmonary, complex CHD and myocardial disease were less represented (Table 1). In about 20% of CHD patients, heart defect was part of a syndrome (Down syndrome; Noonan syndrome; Goldenhar syndrome; DiGeorge syndrome or other genetic disorders). CG consists of 50 children randomly selected who were hospitalized for bronchiolitis.

Table 1 Characteristics of the study participants

All HS-CHD patients received RSV prophylaxis, of which 26 received only partial prophylaxis (≤ 3 doses) because born at the beginning of the epidemic period, diagnosed during the epidemic period or during the hospitalization for bronchiolitis. Patients who underwent hospitalisation were assessed with a Respiratory Severity Score (RSS), Silverman score for newborns and babies under 3 months of age [18] and a clinical score for babies older than 3 months [19], score that picture, on a scale from 1 to 10, the patients’ condition on admission to the hospital, and useful tool for rapid disease severity assessment in other to decide the correct hospitalization setting (up to intensive care unit) and adequate treatment management as far as the clinical picture may vary and worsen abruptly. The higher the score is the worse are the patient’s conditions. Twenty-seven HS-CHD patients required hospitalisation for bronchiolitis, they showed a higher RSS score compared with CG children (3.2 ± 0.9 and 2.3 ± 0.9 respectively); however, the difference was not statistically significative (p-value = 0.1211); 28.6% of CHD patients analysed for access to hospital were admitted in intensive care unit against 10% in the CG group.

Impact of palivizumab prophylaxis on hospitalization

Twenty-six of the 27 CHD patients hospitalized for bronchiolitis did not receive a complete cycle of prophylaxis (≤ 3 doses). Regarding the length of hospitalization, the univariate negative binomial regression analysis (Table 2) showed a significant association between CHD diagnosis, RSS, PICU and the length of hospitalisation. The subsequent multivariate analysis confirmed a significant association between CHD diagnosis, PICU and the length of hospitalisation (p-values: < 0.0001 and 0.0036, respectively) (Table 3). CHD patients who completed a cycle of prophylaxis are less likely to be hospitalized for bronchiolitis (0,99% vs 96,30% p-value < 0.0001); CHD patients with an incomplete prophylaxis, besides being more likely to get hospitalized, in case of hospitalization have a longer stay than CG patients (Table 4) (14.4 ± 21.7 days vs 6.2 ± 2.3 days; p-value˂ 0.0001).

Table 2 Univariate analysis on days of hospitalization (n = 57)
Table 3 Multivariate analysis on the hospitalization days (n = 63)
Table 4 Analysis on the hospitalization

The univariate penalized logistic regression analysis demonstrated no significant association between high flow oxygen therapy and any of the demographic-clinical characteristics.


This study shows the shielding effect of palivizumab prophylaxis on patients with HS-CHD. and the results are consistent with other previous studies on palivizumab prophylaxis. In the present study of the 128 HS-CHD infants aged from 0 to 24 months who received palivizumab prophylaxis, 102 completed the 5-dose cycle while 26 received incomplete prophylaxis (≤ 3 doses). In this group, 27 patients needed hospitalisation for RSV-infection disease. Noteworthy, nearly all of them (26 out of 27) did not receive a complete cycle of prophylaxis (≤ 3 doses) (Fig. 1A) CHD patients are more likely to have a severe course of RSV-infection disease and thus are at higher risk of increased morbidity and mortality. HS-CHD patients have an altered hemodynamic balance which may be worsened by RSV-infection which causes a ventilation – perfusion mismatch leading to respiratory failure.

Fig. 1
figure 1

Descriptive statistics of the hospitalization (A) and the PICU (B). A Descriptive statistics of the hospitalization for bronchiolitis in the prophylaxis levels (n = 178). B Descriptive statistics of the PICU in the prophylaxis levels (n = 64). Prophylaxis levels: NO; Partial (≤ 3 doses of palivizumab); Yes (a complete cycle of immunization

In several studies CHD have been found to be an independent risk factor for hospitalisation irrespective of hemodynamic significance [20,21,22,23]. Children with HS-CHD with RSV-infection may need hospital admission for prompt supportive care and oxygen therapy. Data reported in literature show high RSV-hospitalization rate in HS-CHD patients even if data present a wide range of variation [22, 24,25,26]. The length of hospital stay in HS-CHD patients RSV-infected, in our study, was longer compared with CG (14.4 ± 21.7 days vs 6.2 ± 2.3 days; p-value˂ 0.0001), and some require admission in PICU, finding similar to that of other studies [27, 28], which may impact health care resource availability and utilisation. During hospitalisation patients may go through comorbidities (bacterial co-infection, or others hospitalisation related complications) which may worsen the course of the disease, protracting hospital stay. The fatality rate in HS-CHD children range from 0 to 3%, due to a more severe course of the RSV infection, particularly in complex CHD, compared to children without CHD; and the mortality rate increases along with the severity of the heart defect [11]. Moreover, RSV infection and consequent hospitalization may delay and complicate corrective heart surgery, increasing CHD-related morbidity in CHD patients [29]. In a study including children who underwent cardiac surgery comparing outcomes for those who acquired RSV infection with those who did not, matched for demographics and physiology of cardiac morphology it was found that RSV infection more than 6 weeks before cardiopulmonary bypass caused significant morbidity [30, 31]. In our study one HS-CHD patient who received complete prophylaxis needed hospitalisation for RSV-bronchiolitis, though the reduced dimension of our sample, this is also consistent with the findings in other studies where the RSV-associated hospitalisations rate for children < 24 months, who received complete prophylaxis is very low [31,32,33,34,35], usually HS-CHD patients with one or more underlying medical conditions (genetic and/or neurological disorders, chronic lung disease). Despite this, data confirm that up to now, palivizumab prophylaxis protects CHD from RSV infection and may be the best strategy for control of morbidity and mortality [36,37,38,39,40,41].

This retrospective study is subject to several bias and limitations. A part for its retrospective nature, it is a single center study with a relatively small sample, some results depend on documentation accuracy by healthcare providers involved. However, these data have been collected in a well define geographical region which capture a significant number of CHD patients who either received or not RSV prophylaxis, thus can be generalizable to similar center providing care to comparable population.


Our study provides evidence of the efficacy of palivizumab in protecting HS-CHD patients under the age of 2 years from RSV disease and its life-threatening complications. Our observations strikingly demonstrate the efficacy of complete cycle of palivizumab prophylaxis in preventing hospitalization, showing that even with partial prophylaxis CHD patients go through RSV-infection, need hospitalisation with longer stay than children without underlying medical conditions and may require admission in PICU. Reducing hospitalisation rate, morbidity, and mortality in this category of patients, passive immune prophylaxis with palivizumab may impact healthcare resource availability and utilisation, even if the need of more rigorous studies to address the issue persists, there are studies showing a favourable trend in the cost-utility analyses. Therefore, the current limits of prophylaxis may be questionable and the extension of palivizumab prophylaxis period considered.

Availability of data and materials

All data generated or analyzed during this study are included in this published article.



Complex congenital heart defects with increased pulmonary flow


Italian medicine agency


Multiple congenital heart defects with increased pulmonary flow


Simple congenital heart defects with increased pulmonary flow


Complex congenital heart defects with pulmonary hypo-afflux


Complex congenital heart defects


Congenital heart disease


Odd ratio


Pediatric intensive care unit


Respiratory severity score


Respiratory syncytial virus


Standard deviations


Italian society for pediatric cardiology and congenital cardiopathies


  1. van der Linde D, Konings EE, Slager MA, Witsenburg M, Helbing WA, Takkenberg JJ, Roos-Hesselink JW. Birth prevalence of congenital heart disease worldwide: a systematic review and meta-analysis. J Am Coll Cardiol. 2011;58(21):2241–7.

    Article  Google Scholar 

  2. Bernier PL, Stefanescu A, Samoukovic G, Tchervenkov CI. The challenge of congenital heart disease worldwide: epidemiologic and demographic facts. Semin Thorac Cardiovasc Surg Pediatr Card Surg Annu. 2010;13(1):26–34.

    Article  Google Scholar 

  3. Liu Y, Chen S, Zuhlke L, Black GC, Choy MK, Li N, Keavney BD. Global birth prevalence of congenital heart defects 1970–2017: updated systematic review and meta-analysis of 260 studies. Int J Epidemiol. 2019;48(2):455–63.

    Article  Google Scholar 

  4. Khairy P, Ionescu-Ittu R, Mackie AS, Abrahamowicz M, Pilote L, Marelli AJ. Changing mortality in congenital heart disease. J Am Coll Cardiol. 2010;56(14):1149–57.

    Article  Google Scholar 

  5. Hunter LE, Simpson JM. Prenatal screening for structural congenital heart disease. Nat Rev Cardiol. 2014;11(6):323–34.

    Article  Google Scholar 

  6. Wren C, O’Sullivan JJ. Survival with congenital heart disease and need for follow up in adult life. Heart. 2001;85(4):438–43.

    Article  CAS  Google Scholar 

  7. Wienecke LM, Cohen S, Bauersachs J, Mebazaa A, Chousterman BG. Immunity and inflammation: the neglected key players in congenital heart disease? Heart Fail Rev. 2022;27(5):1957–71.

  8. Ghimire LV, Chou FS, Moon-Grady AJ. Impact of congenital heart disease on outcomes among pediatric patients hospitalized for influenza infection. BMC Pediatr. 2020;20(1):450.

    Article  Google Scholar 

  9. Tabor DE, Fernandes F, Langedijk AC, Wilkins D, Lebbink RJ, Tovchigrechko A, Ruzin A, Kragten-Tabatabaie L, Jin H, Esser MT, et al. Global molecular epidemiology of respiratory syncytial virus from the 2017–2018 Inform-RSV study. J Clin Microbiol. 2020;59(1):e01828-20.

    Article  Google Scholar 

  10. Bozzola E. Respiratory syncytial virus resurgence in italy: the need to protect all neonates and young infants. Int J Environ Res Public Health. 2021;19(1):380.

    Article  Google Scholar 

  11. Checchia PA, Paes B, Bont L, Manzoni P, Simoes EA, Fauroux B, Figueras-Aloy J, Carbonell-Estrany X. Defining the risk and associated morbidity and mortality of severe respiratory syncytial virus infection among infants with congenital heart disease. Infect Dis Ther. 2017;6(1):37–56.

    Article  Google Scholar 

  12. Baraldi E, Lanari M, Manzoni P, Rossi GA, Vandini S, Rimini A, Romagnoli C, Colonna P, Biondi A, Biban P, et al. Inter-society consensus document on treatment and prevention of bronchiolitis in newborns and infants. Ital J Pediatr. 2014;40:65.

    Article  Google Scholar 

  13. Moore HC, Jacoby P, Hogan AB, Blyth CC, Mercer GN. Modelling the seasonal epidemics of respiratory syncytial virus in young children. PLoS ONE. 2014;9(6): e100422.

    Article  Google Scholar 

  14. Synagis, INN-palivizumab []

  15. Riassunto delle caratteristiche del prodotto: Synagis []

  16. Lombardi M, Carrozza M, Morelli C. Prevenzione della malattia da virus respiratorio sinciziale nei bambini con cardiopatia congenita o acquisita. 2019.

    Google Scholar 

  17. R: A language and environment for statistical computing. []

  18. Silverman WA, Andersen DH. A controlled clinical trial of effects of water mist on obstructive respiratory signs, death rate and necropsy findings among premature infants. Pediatrics. 1956;17(1):1–10.

    CAS  Google Scholar 

  19. American Academy of Pediatrics Subcommittee on D, Management of B: Diagnosis and management of bronchiolitis. Pediatrics 2006, 118(4):1774–1793.

  20. Resch B, Kurath-Koller S, Hahn J, Raith W, Kostenberger M, Gamillscheg A. Respiratory syncytial virus-associated hospitalizations over three consecutive seasons in children with congenital heart disease. Eur J Clin Microbiol Infect Dis. 2016;35(7):1165–9.

    Article  CAS  Google Scholar 

  21. Cilla G, Sarasua A, Montes M, Arostegui N, Vicente D, Perez-Yarza E, Perez-Trallero E. Risk factors for hospitalization due to respiratory syncytial virus infection among infants in the Basque Country. Spain Epidemiol Infect. 2006;134(3):506–13.

    Article  CAS  Google Scholar 

  22. Kristensen K, Stensballe LG, Bjerre J, Roth D, Fisker N, Kongstad T, Svendsen AL, Nielsen BW. Risk factors for respiratory syncytial virus hospitalisation in children with heart disease. Arch Dis Child. 2009;94(10):785–9.

    Article  CAS  Google Scholar 

  23. Stranak Z, Saliba E, Kosma P, Posfay-Barbe K, Yunis K, Farstad T, Unnebrink K, van Wyk J, Wegzyn C, Notario G, et al. Predictors of RSV LRTI hospitalization in infants born at 33 to 35 weeks gestational age: a large multinational study (PONI). PLoS ONE. 2016;11(6): e0157446.

    Article  Google Scholar 

  24. Boyce TG, Mellen BG, Mitchel EF Jr, Wright PF, Griffin MR. Rates of hospitalization for respiratory syncytial virus infection among children in medicaid. J Pediatr. 2000;137(6):865–70.

    Article  CAS  Google Scholar 

  25. Duppenthaler A, Ammann RA, Gorgievski-Hrisoho M, Pfammatter JP, Aebi C. Low incidence of respiratory syncytial virus hospitalisations in haemodynamically significant congenital heart disease. Arch Dis Child. 2004;89(10):961–5.

    Article  CAS  Google Scholar 

  26. Wang EE, Law BJ, Robinson JL, Dobson S, al Jumaah S, Stephens D, Boucher FD, McDonald J, Mitchell I, MacDonald NE: PICNIC (Pediatric Investigators Collaborative Network on Infections in Canada) study of the role of age and respiratory syncytial virus neutralizing antibody on respiratory syncytial virus illness in patients with underlying heart or lung disease. Pediatrics 1997, 99(3):E9

  27. Medrano Lopez C, Garcia-Guereta L. Group CS: Community-acquired respiratory infections in young children with congenital heart diseases in the palivizumab era: the Spanish 4-season civic epidemiologic study. Pediatr Infect Dis J. 2010;29(12):1077–82.

    Article  Google Scholar 

  28. Alexander PM, Eastaugh L, Royle J, Daley AJ, Shekerdemian LS, Penny DJ. Respiratory syncytial virus immunoprophylaxis in high-risk infants with heart disease. J Paediatr Child Health. 2012;48(5):395–401.

    Article  Google Scholar 

  29. Altman CA, Englund JA, Demmler G, Drescher KL, Alexander MA, Watrin C, Feltes TF. Respiratory syncytial virus in patients with congenital heart disease: a contemporary look at epidemiology and success of preoperative screening. Pediatr Cardiol. 2000;21(5):433–8.

    Article  CAS  Google Scholar 

  30. Tulloh RFL, Henderson J, Thompson R, Feltes T. Does RSV infection cause pulmonary hypertension in children undergoing cardiac surgery? Arch Dis Child. 2011;96:A37–8.

    Article  Google Scholar 

  31. Feltes TF, Cabalka AK, Meissner HC, Piazza FM, Carlin DA, Top FH Jr, Connor EM, Sondheimer HM. Cardiac synagis study G: palivizumab prophylaxis reduces hospitalization due to respiratory syncytial virus in young children with hemodynamically significant congenital heart disease. J Pediatr. 2003;143(4):532–40.

    Article  CAS  Google Scholar 

  32. Chang RK, Chen AY. Impact of palivizumab on RSV hospitalizations for children with hemodynamically significant congenital heart disease. Pediatr Cardiol. 2010;31(1):90–5.

    Article  Google Scholar 

  33. Medrano C, Garcia-Guereta L, Grueso J, Insa B, Ballesteros F, Casaldaliga J, Cuenca V, Escudero F, delaCalzada LG, Luis M, et al. Respiratory infection in congenital cardiac disease. hospitalizations in young children in Spain during 2004 and 2005: the CIVIC Epidemiologic Study. Cardiol Young. 2007;17(4):360–71.

    Article  Google Scholar 

  34. Cohen SA, Zanni R, Cohen A, Harrington M, VanVeldhuisen P, Boron ML. Palivizumab outcomes registry G: palivizumab use in subjects with congenital heart disease: results from the 2000–2004 palivizumab outcomes registry. Pediatr Cardiol. 2008;29(2):382–7.

    Article  Google Scholar 

  35. Mitchell I, Paes BA, Li A, Lanctot KL. investigators C: CARESS: the Canadian registry of palivizumab. Pediatr Infect Dis J. 2011;30(8):651–5.

    Article  Google Scholar 

  36. Gadomski AM, Scribani MB. Bronchodilators for bronchiolitis. Cochrane Database Syst Rev. 2014;6:CD001266.

    Google Scholar 

  37. Ralston SL, Lieberthal AS, Meissner HC, Alverson BK, Baley JE, Gadomski AM, Johnson DW, Light MJ, Maraqa NF, Mendonca EA, et al. Clinical practice guideline: the diagnosis, management, and prevention of bronchiolitis. Pediatrics. 2014;134(5):e1474-1502.

    Article  Google Scholar 

  38. Barbieri E, Cantarutti A, Cavagnis S, Cantarutti L, Baraldi E, Giaquinto C, Dona D. Impact of bronchiolitis guidelines publication on primary care prescriptions in the Italian pediatric population. NPJ Prim Care Respir Med. 2021;31(1):15.

    Article  Google Scholar 

  39. Ochoa Sangrador C. Gonzalez de Dios J, Research Group of the a BP: Overuse of bronchodilators and steroids in bronchiolitis of different severity: bronchiolitis-study of variability, appropriateness, and adequacy. Allergol Immunopathol (Madr). 2014;42(4):307–15.

    Article  CAS  Google Scholar 

  40. Azzari C, Baraldi E, Bonanni P, Bozzola E, Coscia A, Lanari M, Manzoni P, Mazzone T, Sandri F, Checcucci Lisi G, et al. Epidemiology and prevention of respiratory syncytial virus infections in children in Italy. Ital J Pediatr. 2021;47(1):198.

    Article  Google Scholar 

  41. Pongiglione G, Possidoni A, di Luzio PU, Costanzo AM, Gualberti G, Bonvicini M, Rimini A, Agnoletti G, Calabro MP, Pozzi M, et al. Incidence of respiratory disease during the first two years of life in children with hemodynamically significant congenital heart disease in Italy: a retrospective study. Pediatr Cardiol. 2016;37(8):1581–9.

    Article  Google Scholar 

Download references


Support for medical writing was provided by Maria Vittoria Verga Falzacappa, PhD (EDRA S.p.A., Milan, Italy), for statistical analysis by Fabio Gallo on behalf of EDRA S.p.A., with an unrestricted grant by AstraZeneca.


Support from AstraZeneca for development of this manuscript is acknowledged. The sponsor had no influence on the content.

Author information

Authors and Affiliations



BT contributed to study conception and design and data collection. CR, AdG, DB and MR performed data curation. All authors revised and approved the final manuscript.

Corresponding author

Correspondence to Bertrand Tchana.

Ethics declarations

Ethics approval and consent to participate

The program was approved by the Italian Local Health Authority, and the Site’s Ethics Committee approved the request to use each identified patient. Specific written informed consent was obtained from each patient or their parental guardian prior to treatment start.

The study was carried out according to the amended Declaration of Helsinki.

Consent for publication

Institutional consent form has been used to obtain the consent to publication from children’s parents or legal guardian.

Competing interests

The authors have no relevant financial or non-financial interests to disclose.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Ratti, C., Greca, A.d., Bertoncelli, D. et al. Prophylaxis protects infants with congenital heart disease from severe forms of RSV infection: an Italian observational retrospective study. Ital J Pediatr 49, 4 (2023).

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI:


  • Palivizumab
  • Congenital heart disease
  • RSV infection
  • RSV prophylaxis
  • Respiratory syncytial virus
  • Hospitalization
  • Infants with CHD