Risk factors for mechanical ventilation in respiratory syncytial virus infection

In a prospective study, risk factors for mechanical ventilation were identified in 102 patients with respiratory syncytial virus (RSV) infection admitted to the Sophia Children's Hospital, Rotterdam. Age, weight on admission and prematurity were associated with the need for mechanical ventilation. Using multivariate analysis, only low weight was an independent risk factor for mechanical ventilation. For infants weighing less than 5 kg the relative risk for mechanical ventilation was 4.4 (95% confidential interval 1.3–13.9).     

Driscoll Children's Hospital respiratory syncytial virus database: risk factors, treatment and hospital course in 3308 infants and young children, 1991 to 2002

BACKGROUND: Treatment of respiratory syncytial virus (RSV) lower respiratory tract infection has historically been one of the most frequent reasons for admission to Driscoll Children's Hospital. OBJECTIVE: The objective of this study was to examine the relationship of risk factors for a severe and complicated disease course to the treatment and hospital length of stay. METHODS: Subjects were identified through a retrospective review of the medical records of all patients discharged with a diagnosis of RSV lower respiratory tract infection during 9 of the 11 RSV seasons between July 1, 1991 and June 30, 2002. The RSV seasons from 1991-1992 to 1994-1995 were compared with the RSV seasons from 1995-1996 to 2001-2002 with regard to treatment and hospital course. RESULTS: There were a total of 3308 admissions. Compared with patients with no risk factors, higher percentages of patients with age <6 weeks, history of prematurity, congenital heart disease and neurologic disease were admitted to the pediatric intensive care unit (PICU) and required mechanical ventilation (P < 0.001). Also the hospital length of stay was longer for patients with each of these individual risk factors (P < 0.001). The hospital length of stay and the percentages of patients admitted to the PICU and requiring on mechanical ventilation increased as the number of risk factors increased from zero to 3 or more (P < 0.001). Of patients with 3 or more risk factors, the average hospital length of stay was 13.5 days; 67% were admitted to the PICU, and 47% required mechanical ventilation. Ribavirin use decreased in patients with each of the individual risk factors (P < 0.001) as well as in patients with one or more risk factors (P < 0.001). At the same time the PICU admission rate increased from 6.1% to 11.2% (P < 0.001). CONCLUSIONS: Patients with three or more risk factors were at very high risk for having a severe or complicated disease course associated with admission to the PICU, placement on mechanical ventilation and a longer hospital length of stay.     

Comparison of human metapneumovirus and respiratory syncytial virus in children admitted to a paediatric intensive care unit

Aim: To describe the clinical presentation and course of children admitted to the paediatric intensive care unit (PICU) with human metapneumovirus (hMPV) infection, and compare them with children admitted to the PICU with respiratory syncytial virus (RSV) infection. Methods: hMPV was identified by immunofluorescence in 22 children admitted to the PICU over a 16‐month period. The medical records of these children were reviewed retrospectively, and their clinical and laboratory data were compared with 66 children admitted to the PICU with positive tests for RSV over the same period. Results: Children admitted to the PICU with hMPV were significantly older than children with RSV (P= 0.003). Children with hMPV presented more commonly with pneumonia or pneumonitis (29% vs. 16%), and less commonly with bronchiolitis (43% vs. 68%) than RSV (P= 0.13). Invasive ventilation was required in 10 patients (48%) with hMPV, and non‐invasive ventilation was required in a further 5 (28%), similar to patients with RSV. Children with hMPV were more likely to have an underlying co‐morbidity (P= 0.11). Conclusions: Children admitted to the PICU with hMPV have a similar disease presentation and severity as children admitted with RSV, including some with extremely severe disease who require additional ventilatory or cardiovascular support. Children with hMPV are likely to be older than those with RSV, and more likely to present with pneumonia and less likely to present with bronchiolitis.     

Apneas en lactantes con bronquiolitis: incidencia y factores de riesgo para un modelo de predicción

Introduction

The presence of apnoea in acute bronchiolitis (AB) varies between 1.2% and 28.8%, depending on the series, and is one of its most fearsome complications. The aim of this study is to determine the incidence of apnoea in hospitalised patients diagnosed with AB, and to define their associated risk factors in order to construct a prediction model.

Variable morbidity of respiratory syncytial virus infection in patients with underlying lung disease: a review of the PICNIC RSV database. Pediatric Investigators Collaborative Network on Infections in Canada.

OBJECTIVE: We wished to compare outcomes of respiratory syncytial virus (RSV) infection in children with bronchopulmonary dysplasia (BPD) with those with other pulmonary disorders: cystic fibrosis, recurrent aspiration pneumonitis, pulmonary malformation, neurogenic disorders interfering with pulmonary toilet, and tracheoesophageal fistula. METHODS: Children with RSV infection hospitalized at seven Canadian pediatric tertiary care hospitals in 1993 through 1994 and 9 hospitals in 1994 through 1995 were enrolled and prospectively followed. This study is a secondary analysis of data from this prospective cohort. RESULTS: Of the 1516 patients enrolled the outcomes of 159 with preexisting lung disorders before RSV lower respiratory tract infection constitute this report. There were no significant differences among the 7 groups (BPD, cystic fibrosis, recurrent aspiration pneumonitis, pulmonary malformation, neurogenic disorders interfering with pulmonary toilet, tracheoesophageal fistula, other) for the morbidity measures: duration of hospitalization, intensive care unit (ICU) admission, duration of ICU stay, mechanical ventilation and duration of mechanical ventilation. Patients using home oxygen were more likely to be admitted to the ICU than those who had never or previously used home oxygen (current 57.1%, past 23.8%, never 33.3%, P = 0.03). CONCLUSIONS: Children with other underlying diseases have morbidity similar to those with BPD. Prophylactic interventions against RSV should also be studied in these groups.     

FLIP-2 Study: risk factors linked to respiratory syncytial virus infection requiring hospitalization in premature infants born in Spain at a gestational age of 32 to 35 weeks

BACKGROUND: Ex-premature infants are more predisposed to complicated primary respiratory syncytial virus (RSV) infection. The aim of the present study was to validate the risk factors found in a previous epidemiologic case-control study regarding hospitalization as a result of RSV infection in premature infants born at 32-35 weeks of gestational age (WGA) in Spain. METHODS: A prospective 2-cohort study was conducted during the 2005-2006 (October 2005 to April 2006) and 2006-2007 (October 2006 to April 2007) RSV seasons, respectively. Cases were premature infants hospitalized for RSV infection whereas controls were premature infants of the same age who did not require any hospitalization for respiratory causes. RESULTS: During the study period 5441 children from 37 Spanish hospitals were included in the risk factor analysis. Two hundred two (3.7%) were cases and the rest controls. Of the cases, 17.8% were admitted to the intensive care unit and 7.4% required mechanical ventilation. None of the patients died. Logistic regression analysis demonstrated that the risk of RSV-related respiratory infection requiring hospital admission in preterm infants (32-35 WGA) was associated with the following factors: absolute chronologic age of < or = 10 weeks at the onset of RSV season [odds ratio (OR): 2.99; 95% confidence interval (CI): 2.23-4.01]; presence of school-age siblings or day care attendance (OR: 2.04; 95% CI: 1.53-2.74); and smoking during pregnancy (OR: 1.61; 95% CI: 1.16-2.25). CONCLUSIONS: In premature infants (32-35 WGA), only 3 independent risk factors were found to significantly increase the risk of RSV-related respiratory infection and hospitalization.     

Bacteraemia and antibiotic use in respiratory syncytial virus infections

Aims: To examine the frequency of and risk factors for bacteraemia in children hospitalised with respiratory syncytial virus (RSV) infection; and to determine current use of antibiotics in hospitalised children with RSV infection. Methods: Retrospective study of all children, aged 0–14 years, admitted to a tertiary children''s hospital with proven RSV infection over a four year period. Children with concurrent bacteraemia and RSV infection were identified, and risk factors examined for bacteraemia. The case notes of a randomly selected comparison sample of 100 of these RSV infected children were examined to assess antibiotic use and population incidence of risk factors for severe RSV infection. Results: A total of 1795 children had proven RSV infection, and blood cultures were sent on 861 (48%). Eleven (0.6%) of the 1795 RSV positive children had bacteraemia. RSV positive children had a significantly higher incidence of bacteraemia if they had nosocomial RSV infection (6.5%), cyanotic congenital heart disease (6.6%), or were admitted to the paediatric intensive care unit (2.9%). Forty five (45%) of the random comparison sample of RSV infected children received antibiotics. Conclusions: Bacteraemia is rare in RSV infection. Children with RSV infection are more likely to be bacteraemic, however, if they have nosocomial RSV infection, cyanotic congenital heart disease, or require intensive care unit admission.     

Bacteraemia and antibiotic use in respiratory syncytial virus infections.

AIMS: To examine the frequency of and risk factors for bacteraemia in children hospitalised with respiratory syncytial virus (RSV) infection; and to determine current use of antibiotics in hospitalised children with RSV infection. METHODS: Retrospective study of all children, aged 0-14 years, admitted to a tertiary children's hospital with proven RSV infection over a four year period. Children with concurrent bacteraemia and RSV infection were identified, and risk factors examined for bacteraemia. The case notes of a randomly selected comparison sample of 100 of these RSV infected children were examined to assess antibiotic use and population incidence of risk factors for severe RSV infection. RESULTS: A total of 1795 children had proven RSV infection, and blood cultures were sent on 861 (48%). Eleven (0.6%) of the 1795 RSV positive children had bacteraemia. RSV positive children had a significantly higher incidence of bacteraemia if they had nosocomial RSV infection (6.5%), cyanotic congenital heart disease (6.6%), or were admitted to the paediatric intensive care unit (2.9%). Forty five (45%) of the random comparison sample of RSV infected children received antibiotics. CONCLUSIONS: Bacteraemia is rare in RSV infection. Children with RSV infection are more likely to be bacteraemic, however, if they have nosocomial RSV infection, cyanotic congenital heart disease, or require intensive care unit admission.     

Clinical characteristics of respiratory syncytial virus infection in hospitalized healthy infants and young children in Qatar

To evaluate seasonal trends, clinical profile, and outcome of disease in previously healthy infants and young children hospitalized for respiratory syncytial virus (RSV) infection at Hamad Medical Corporation in the state of Qatar, we reviewed the records of 257 children admitted between 1 January 1996 and 31 December 1998. RSV epidemics occurred yearly during the winter months with peak hospitalizations occuring between November and February. Of the 257 admissions, 160 (62.3 per cent) were male and 97 (37.7 per cent) female. The mean age of all children was 5.7 months (range, 10 days to 32 months). The most common admitting diagnoses were bronchiolitis (59.9 per cent), pneumonia (17.5 per cent), bronchiolitis with pneumonia (8.9 per cent), possible sepsis (7.8 per cent), asthma (4.7 per cent) and apnea (1.2 per cent). A family history of asthma was quite common (63.8 per cent), although no statistical significant difference was noted in complication or length of stay. Treatment was supportive, the majority of the patients received oxygen therapy in 77.8 per cent of cases, bronchodilators in 85.4 per cent, and antibiotics therapy in 49.4 per cent. The median duration of hospital stay was 6 days (range, 1 to 29 days). Of the 14 (5.4 per cent) patients requiring intensive care, four (1.6 per cent) needed mechanical ventilation. No deaths were reported, but subjects aged < or = 12 months had a significantly higher oxygen requirement, intensive care unit admission, bronchodilators and antibiotics therapy than those > 12 months old. Within 1-2 years after admission with RSV infection, 63 of the 257 patients attended for recurrent episodes of wheezy chest. These results indicate that, during the season of infection, RSV is an important pathogen in infants and young children in the state of Qatar, highlighting the need for development of effective vaccines to ameliorate the impact of annual RSV epidemics in infants and young children.     

Central apnoeas in infants with bronchiolitis admitted to the paediatric intensive care unit

Aim: To further characterize apnoea(s) complicating bronchiolitis because of respiratory syncytial virus (RSV), to describe the incidence of this complication and identify possible risk factors for apnoea(s) and its development. Methods: The files of infants admitted to the paediatric intensive care unit (PICU) for RSV bronchiolitis during three bronchiolitis seasons (2004–2007) were reviewed for demographic, clinical and laboratory parameters. Parameters were compared between patients with and without apnoeas. Results: Seventy‐nine patients met the study criteria: 43 were admitted to the PICU for central apnoeas and the remainder for respiratory distress or failure. The percentage of infants admitted for apnoea increased during the study period (28.6 to 77.1%, p = 0.004). The overall prevalence of apnoea in this population was 4.3%. Possible risk factors for apnoea(s) were younger age (1.3 vs. 4.3 months, p = 0.002), lower admission weight (3.3 vs. 5 kg, p < 0.001), lower gestational age (35.8 vs. 37.8 weeks, p = 0.01), admission from the emergency room (50% vs. 9.1%, p < 0.001) and lack of hyperthermia (p < 0.001). Respiratory acidosis was found to be a protective factor on logistic regression analysis. Conclusion: The prevalence of apnoea in infants admitted to the PICU for RSV bronchiolitis in our centre may be increasing. Preterm, younger infants with no fever are at relatively high risk of apnoea at presentation, while older infants with fever are at lower risk.     

Characteristics of respiratory syncytial virus-related apnoea in three infants

Apnoea is a common sign in respiratory syncytial virus (RSV) infections in young infants and can be the first presentation of an acquired RSV infection. We describe polysomnographic recordings of three infants revealing prolonged RSV-related apnoea before RSV infection was diagnosed. The apnoeas were of central origin. The caregivers had not noted any apparent life-threatening events (ALTE) prior to the polysomnography. Cardiorespiratory monitoring after the acute infection did not reveal any further apnoeas.
Conclusion : Central, prolonged apnoea can be the first sign of an acquired RSV infection in young infants in the absence of other respiratory symptoms and without any previous observation of apnoea by the caregivers.     

Local variability in respiratory syncytial virus disease severity

Respiratory syncytial virus (RSV) lower respiratory tract infections are considered to be a serious disease in centres such as the Sophia Children''s Hospital (Rotterdam, the Netherlands), but as more benign infections in others such as the Geneva Children''s Hospital (Switzerland). To assess the clinical severity of RSV infections at the two sites, 151 infants primarily admitted with a virologically confirmed RSV infection were studied prospectively (1994-5) and retrospectively (1993-4) (55 infants in Geneva and 96 in Rotterdam). Parameters of RSV morbidity which were more severe in Rotterdam during the two winter seasons were apnoea (1.8 v 23.9%), the rate of admission to the intensive care unit (3.6 v 28.1%), mechanical ventilation (0 v 7.3%), and length of stay in hospital (6.8 v 9.1 days). In Geneva higher respiratory rates (59.2 v 51.2), more wheezing (65.5 v 28.8%), and more retractions (81.8 v 63.3%) were recorded. Fewer infants younger than 4 months (54.9 v 68.7%), but more breast fed infants (94.1 v 38.5%), were admitted in Geneva, although the morbidity parameters remained different after correction for these two variables in multivariate analyses. Thus unidentified local factors influence the pattern and severity of RSV infection and may affect the results of multicentre prophylactic and therapeutic studies.

     

2002~2005年期间萨斯喀彻温省儿科三级医疗中心因呼吸道合胞病毒感染住院的儿童病例分析

Objective To describe the epidemiology and severity of illness of children hospitalized with respiratory syncytial virus (RSV) infection, including those who received palivizumab prophylaxis, at Royal University Hospital (RUH), Saskatoon and Regina General Hospital (RGH) from July 2002 to June 2005. Methods Children hospitalized for ≥ 24 hours with laboratory-confirmed RSV infection were enrolled, and their health records were retrospectively reviewed for patient demographics and referral patterns, use of palivizumab prophylaxis, severity of infection (length of hospitalization, need for and duration of pediatric intensive care and mechanical ventilation) and outcome of infection. Results A total of 590 children (324 males) were hospitalized over the three years. The median chronological age at admission was 5.3 months, and median hospital stay was 4.0 days. Gestational age at birth was ≥ 36 weeks in 82.4% of patients. RSV disease severity was mild to moderate in 478 patients (81.0%) and severe in 110 (18.6%). Thirty-nine patients (6.6%) required pediatric intensive care unit admission, for a median of 5.0 days. Twenty-two of these patients (56%) were mechanically ventilated for a median of 6.0 days. Two children died, not attributed to RSV infection. Twenty-two patients had received palivizumab prophylaxis before hospital admission, with 18 completing at least 2 of the monthly doses. Most of these children (17/22) had mild to moderate illness. Conclusions RSV causes significant morbidity in Saskatchewan, affecting predominantly term infants. The majority of illness is mild to moderate. Some patients who have received palivizumab may still develop significant RSV disease.

     

Factores pronósticos de evolución complicada en la bronquiolitis que requiere ingreso en cuidados intensivos pediátricos

ObjectiveTo analyse the prognostic factors for complications in children with bronchiolitis admitted to a pediatric intensive care unit (PICU).Patients and methodA retrospective study was performed on children with bronchiolitis admitted into a PICU between 2000 and 2006. Univariate and multivariate analysis were performed to study the prognostic factors of complications, mechanical ventilation requirements, mortality and PICU stays of more than 15 days.ResultsA total of 110 patients were studied, of whom 72 (65.5%) had high risk factors: prematurity (39.1%), cardiac disease (38.2%) and bronchopulmonary dysplasia (16.3%). A total of 82.7% of patients had complications; 26% need invasive mechanical ventilation and the mortality was 3.6%, and 16.4% stayed in PICU for more than 15 days. Factors associated with mechanical ventilation were the clinical Wood-Downes score and heart disease. A weight less than 5 kg was associated with complications; heart disease and invasive mechanical ventilation were associated with a longer PICU stay; prematurity and mechanical ventilation were associated with mortality.ConclusionsChildren with bronchiolitis admitted into the PICU had a high frequency of complications, often needed mechanical ventilation and had long stays in the PICU, but the mortality is low. The best prognostic factors on admission into the PICU were the acute respiratory insufficiency score, the presence of heart disease and were premature at birth.     

Predictors of Mortality in Hospitalized Children with Pandemic H1N1 Influenza 2009 in Pune, India

Objective

To analyse the factors associated with increased mortality among Indian Children with H1N1.

Methods

Data were abstracted from available hospital records of children less than 12?y of age, who were admitted to Sassoon General Hospital in Pune, India, with confirmed pandemic 2009 H1N1 influenza infection from August 2009 through January 2010. Logistic regression analysis was used to identify clinical characteristics associated with mortality.

Results

Of 775 pediatric cases admitted with Influenza Like Illness (ILI), 92 (11.8%) had confirmed H1N1 influenza infection. The median age of HIN1 cases was 2.5?y; 13 (14%) had an associated co-morbid condition. Median duration of symptoms was 4?d (interquartile range (IQR), 3?C7?d). All 92 H1N1 cases received oseltamivir and empiric antimicrobials on admission. Intensive care unit (ICU) admission was required for 88 (96%) children, and 20 (23%) required mechanical ventilation.Fifteen children (16%) died; mortality was associated with presence of diffuse alveolar infiltrate on admission chest radiography (odds ratio (OR) 45, 95%CI :5.4?C370; p?p?=?0.001), SpO₂ <80% on admission (OR 32.8, 95% CI: 5.8?C185.5; p?p?n?=?4 each, 27%) with gram positive organisms consistent with severe viral and bacterial co-infection.

Conclusions

Hypoxia, ARDS and use of corticosteroids in children with ARDS who were mechanically ventilated were the factors associated with increased odds of mortality. Necropsy also suggested bacterial co-infection as a risk factor.     

Reflex apnoea response and inflammatory mediators in infants with respiratory tract infection*

The reflex apnoea response to water stimulation was evaluated in infants with respiratory syncytial virus (RSV) infection and compared to the response in non-infected infants who had sustained an apparent life-threatening event (ALTE) or were siblings of infants who had died of sudden infant death syndrome (SIDS). RSV-infected infants had a significantly (p < 0.05) reinforced reflex apnoea response compared with non-infected infants. There was a significant negative correlation between the concentration of interleukin 1β (IL-Iβ) in pharyngeal secretions and the duration of apnoea (p < 0.01). Increased clinical severity was, however, associated with high (>5.000 pg ml^-1) concentrations of IL-l/J. There was no correlation between apnoea and interleukin 6. These findings may be relevant for the understanding of why apnoea may be the presenting symptom of RSV infection, and offer an explanation of why a proportion of SIDS cases has a history of mild respiratory tract symptoms prior to death.     

Management of apnoea and bradycardia in the newborn

Apnoea and associated bradycardia are common in preterm newborn infants. Apnoea of prematurity is a developmental disorder, which requires careful evaluation to exclude other pathological causes contributing to the apnoeas. The long-term effects of apnoea and bradycardia are unclear, but may be associated with long-term neurodevelopmental problems. Severe apnoeas may need resuscitation, mechanical ventilation or CPAP. Caffeine is currently the drug of choice for treatment of apnoea of prematurity. The effects of may other interventions, including stimulation, Kangaroo care, RBC transfusion, etc need further evaluation. Further research into the pathophysiological mechanisms underlying apnoeas, neurodevelopmental effects and long-term follow up of affected infants will help in optimizing management strategies for apnoea of prematurity.     

Clinical spectrum of neonatal apnoea in very low birthweight infants

Abstract This study quantifies apnoea and assesses the response to xanthine derivatives amongst 172 consecutively born, surviving very low birth weight (VLBW) infants, 136 appropriate weight for gestational age (AGA), 36 small for gestatfonal age (SGA). All babies had electronic monitoring of heart and respiratory rates and nursing staff recorded episodes of apnoea (> 10 s), bradycardia (<100) and cyanosis. Only 42 (24.2%) babies had no episodes recorded. (25 AGA, 17 SGA). Sixty-four (37.2%) received active resuscitation on at least one occasion with six babies ventilated by bag and mask on more than 10 occasions. Apnoea had commenced by day 10 of life in all the babies who had apnoea and persisted beyond day 50 in only six; however four of these infants were still requiring active resuscitation. Apnoea had ceased by 37 weeks post-conceptual age in 88% and by 40 weeks in all but three babies.
Risk factor analysis revealed a strong correlation (P<0.005) with lower gestational ages and birth weights, respiratory distress syndrome (RDS) and the problems associated with it, such as mechanical ventilation, patency of the ductus arteriosus (PDA) and chronic neonatal lung disease. A single, reversible cause for apnoea was rarely demonstrated. Care must be exercised with feeding, physiotherapy and suctioning the pharynx and trachea of 'at risk' infants. Xanthine derivatives were highly effective in decreasing the frequency of recurrent apnoea from a mean of 10.08 episodes one day before, to 1.83 two days after commencement of treatment.     

Recurrent wheezing in children with respiratory syncytial virus (RSV) bronchiolitis in Qatar

Records of 70 infants admitted to Hamad General Hospital with RSV bronchiolitis and a similar number of controls were retrospectively reviewed. Two years after admission, 44% of the infants with RSV bronchiolitis developed recurrent wheezing compared with only 12.9% of controls (P=0.001). A family history of atopy appeared not to be a significant predisposing factor for the occurrence of recurrent wheezing in post RSV bronchiolitis patients. These results are similar to those from similar studies in industrialized countries.     

Hospitalized children with respiratory syncytial virus infection and neuromuscular impairment face an increased risk of a complicated course

BACKGROUND: Respiratory syncytial virus (RSV) infection is an important cause of viral respiratory tract infection in children. In contrast to other confirmed risk factors that predispose to a higher morbidity and mortality, the particular risk of a preexisting neuromuscular impairment (NMI) in hospitalized children with RSV infection has not been prospectively studied in a multicenter trial. METHODS: The DMS RSV Paed database was designed for the prospective multicenter documentation and analysis of all clinically relevant aspects of the management of inpatients with RSV infection. Patients with clinically relevant NMI were identified according to the specific comments of the attending physicians and compared with those without NMI. RESULTS: This study covers 6 consecutive seasons; the surveillance took place in 14 pediatric hospitals in Germany from 1999 to 2005. In total, 1568 RSV infections were prospectively documented in 1541 pediatric patients. Of these, 73 (4.7%) patients displayed a clinically relevant NMI; 41 (56%) NMI patients had at least 1 additional risk factor for a severe course of the infection (multiple risk factors in some patients; prematurity in 30, congenital heart disease in 19, chronic lung disease 6 and immunodeficiency in 8). Median age at diagnosis was higher in NMI patients (14 vs. 5 months); NMI patients had a greater risk of seizures (15.1% vs. 1.6%), and a higher proportion in the NMI group had to be mechanically ventilated (9.6% vs. 1.9%). Eventually, the attributable mortality was significantly higher in the NMI group (5.5% vs. 0.2%; P < 0.001 for all). Multivariate logistic regression confirmed that NMI was independently associated with pediatric intensive care unit (PICU) admission (OR, 4.94; 95% CI, 2.69-8.94; P < 0.001] and mechanical ventilation (OR, 3.85; 95% CI, 1.28-10.22; P = 0.017). CONCLUSION: This is the first prospective multicenter study confirming the hypothesis that children with clinically relevant NMI face an increased risk for severe RSV-disease. It seems reasonable to include NMI as a cofactor into the decision algorithm of passive immunization.