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Objective: The SENTINEL1 observational study characterized confirmed respiratory syncytial virus hospitalizations (RSVH) among U.S. preterm infants born at 29 to 35 weeks' gestational age (wGA) not receiving respiratory syncytial virus (RSV) immunoprophylaxis (IP) during the 2014 to 2015 and 2015 to 2016 RSV seasons., Study Design: All laboratory-confirmed RSVH at participating sites during the 2014 to 2015 and 2015 to 2016 RSV seasons (October 1-April 30) lasting ≥24 hours among preterm infants 29 to 35 wGA and aged <12 months who did not receive RSV IP within 35 days before onset of symptoms were identified and characterized., Results: Results were similar across the two seasons. Among infants with community-acquired RSVH ( N  = 1,378), 45% were admitted to the intensive care unit (ICU) and 19% required invasive mechanical ventilation (IMV). There were two deaths. Infants aged <6 months accounted for 78% of RSVH observed, 84% of ICU admissions, and 91% requiring IMV. Among infants who were discharged from their birth hospitalization during the RSV season, 82% of RSVH occurred within 60 days of birth hospitalization discharge., Conclusion: Among U.S. preterm infants 29 to 35 wGA not receiving RSV IP, RSVH are often severe with almost one-half requiring ICU admission and about one in five needing IMV., Competing Interests: E.J.A., J.P.D., E.A.F.S., L.R.K., M.L.F., P.S.P., C.M.E., R.C.W., L.I.W., R.Y., P.A.C., J.B.D., and N.H. are independent investigators who have received research support from AstraZeneca/MedImmune. J.P.D., E.A.F.S., L.R.K., and M.L.F. also received travel support from AstraZeneca/MedImmune to present the results of this or other research studies at scientific meetings. J.P.D., M.L.F., and P.S.P. have served on the speakers’ bureau for AstraZeneca/MedImmune. E.J.A., E.A.F.S., and J.P.D. have served as consultants to AbbVie; P.A.C. has received research support from AbbVie. S.J.M. is an independent statistical consultant to AstraZeneca. K.K.M. and C.S.A. are employees of AstraZeneca and hold stock. V.R.K. and C.P.R. were employees of AstraZeneca at the time this research was conducted. C.P.R. is a current employee of Sobi Inc., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Background: Palivizumab is the standard immunoprophylaxis against serious disease due to respiratory syncytial virus infection. Current evidence-based prophylaxis guidelines may not address certain children with CHD within specific high-risk groups or clinical/management settings., Methods: An international steering committee of clinicians with expertise in paediatric heart disease identified key questions concerning palivizumab administration; in collaboration with an additional international expert faculty, evidence-based recommendations were formulated using a quasi-Delphi consensus methodology., Results: Palivizumab prophylaxis was recommended for children with the following conditions: <2 years with unoperated haemodynamically significant CHD, who are cyanotic, who have pulmonary hypertension, or symptomatic airway abnormalities; <1 year with cardiomyopathies requiring treatment; in the 1st year of life with surgically operated CHD with haemodynamically significant residual problems or aged 1-2 years up to 6 months postoperatively; and on heart transplant waiting lists or in their 1st year after heart transplant. Unanimous consensus was not reached for use of immunoprophylaxis in children with asymptomatic CHD and other co-morbid factors such as arrhythmias, Down syndrome, or immunodeficiency, or during a nosocomial outbreak. Challenges to effective immunoprophylaxis included the following: multidisciplinary variations in identifying candidates with CHD and prophylaxis compliance; limited awareness of severe disease risks/burden; and limited knowledge of respiratory syncytial virus seasonal patterns in subtropical/tropical regions., Conclusion: Evidence-based immunoprophylaxis recommendations were formulated for subgroups of children with CHD, but more data are needed to guide use in tropical/subtropical countries and in children with certain co-morbidities.

Objective  SENTINEL1 characterized U.S. preterm infants 29 to 35 weeks' gestational age (wGA) < 12 months old hospitalized for laboratory-confirmed respiratory syncytial virus (RSV) disease and not receiving RSV immunoprophylaxis during the 2014 to 2015 RSV season. Study Design  This is a noninterventional, observational, cohort study. Results  A total of 702 infants were hospitalized with community-acquired RSV disease, of whom an estimated 42% were admitted to the intensive care unit (ICU) and 20% required invasive mechanical ventilation (IMV). Earlier gestational age and younger chronologic age were associated with an increased frequency of RSV-confirmed hospitalization (RSVH), ICU admission, and IMV. Among infants 29 to 32 wGA and < 3 months of age, 68% required ICU admission and 44% required IMV. One death occurred of an infant 29 wGA. Among the 212 infants enrolled for in-depth analysis of health care resource utilization, mean and median RSVH charges were $55,551 and $27,461, respectively, which varied by intensity of care required. Outpatient visits were common, with 63% and 62% of infants requiring visits before and within 1 month following the RSVH, respectively. Conclusion  Preterm infants 29 to 35 wGA are at high risk for severe RSV disease, which imposes a substantial health burden, particularly in the first months of life., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Palivizumab monthly injections throughout the RSV season prevent severe respiratory syncytial virus (RSV) disease in preterm infants ≤ 35 wGA. However, some RSV guidelines currently recommend stopping palivizumab after 3 months of age in the midst of the RSV season. This article evaluates the need for full-season dosing by reviewing the pharmacokinetic properties of palivizumab and RSV hospitalization (RSVH) risk as a function of chronologic age. Precise human palivizumab protective levels are not established. Clinical trials show significant interpatient variability in palivizumab serum trough concentrations. Partial season dosing is associated with increased risk of RSVH. For late-preterm infants, data suggest that the risk of RSVH remains elevated through at least 6 months of age. Monthly, full-season palivizumab dosing provides the only empirically proven protection from RSVH. In conclusion, late-preterm infants are at significant risk for RSVH through at least 6 months of age and would benefit from dosing throughout the RSV season.

Objectives: A systematic literature review and meta-analysis was performed to evaluate the impact of prophylaxis with palivizumab on mortality and morbidity associated with respiratory syncytial virus infection in infants at high risk (≤ 35 wks of gestational age, chronic lung disease, or congenital heart disease)., Data Sources: MEDLINE, EMBASE, and Current Contents were used. MEDLINE was searched from January 1, 1990 to May 16, 2007. The bibliographies of accepted studies and recent reviews and proceedings from the past 2 yrs were searched to identify additional relevant studies., Study Selection: Randomized controlled trials and prospective or retrospective cohort studies evaluating all-cause and respiratory syncytial virus-specific mortality, respiratory syncytial virus hospitalizations, and health care use in infants at high risk for respiratory syncytial virus infection receiving prophylaxis with palivizumab., Data Extraction: Data elements from each accepted study were extracted by one researcher and confirmed by a second researcher. Differences were resolved before data entry and analysis., Data Synthesis: A total of 2473 citations were screened and ten comparative studies of palivizumab prophylaxis evaluating >15,000 infants were included. Comparisons of mortality and hospitalization outcomes between infant groups using prophylaxis and not using prophylaxis were made using meta-analyses., Conclusions: Prophylaxis and nonprophylaxis infant groups appeared to be comparable at baseline. All-cause mortality during the respiratory syncytial virus season was 12 of 6380 (0.19%) for infants with prophylaxis vs. 33 of 8182 (0.53%) for infants without prophylaxis (Peto odds ratio, 0.30; 95% confidence interval, 0.17-0.55). Only five respiratory syncytial virus-specific deaths were reported, and the majority of the studies did not report respiratory syncytial virus-related deaths. The rate of respiratory syncytial virus hospitalization was significantly lower among preterm infants with prophylaxis compared with those without prophylaxis (4.1% vs. 10.4%; odds ratio, 0.35; 95% confidence interval, 0.25-0.47). Prophylaxis with palivizumab was associated with a reduction in all-cause mortality and respiratory syncytial virus hospitalization among preterm infants at high risk. Additional research on cause of death among infants at high risk is needed.

Objective: To review the fatalities among children hospitalized with respiratory syncytial virus (RSV) infection, and identify factors leading to a fatal outcome., Research Design and Methods: Review of literature identified from a structured search of PubMed (1966-2009) using the following Medical Subject Headings: respiratory syncytial virus infection; hospitalized; infants; and risk factors. Publications were restricted to: English language; full papers; inclusion of > or =10 subjects; children aged < or =18 years, hospitalization for RSV infection; and deaths reported. Case fatality rates were defined as number of deaths divided by number of children hospitalized for RSV and were calculated for each study., Results: Thirty-six studies met the inclusion and exclusion criteria. Case fatality rates among children hospitalized for RSV ranged from 0 to 33%. In general, studies showed that subgroups of high-risk children (chronic lung disease [CLD] 3.5-23%, congenital heart disease [CHD] 2-37%, and prematurity 0-6.1%) had higher fatality rates than older or otherwise healthy children (consistently <1%). Presence of severe underlying comorbidities such as neuromuscular disease, immunosuppression, and malignancies was associated with death among term and/or older (>1 year) children. Higher fatality rates were reported for infants receiving intensive unit care (1.1-8.6%), extracorporeal life support (33%) or for those who acquired nosocomial RSV infection (0-12.2%). The majority of studies did not report cause of death and clinical details of the fatal cases were often not provided. Other limitations of this review include our search limits, the possibility of inherent bias in our methodology that could result in an under or over estimation of case-fatality rates, and potential publication bias., Conclusions: Children at high risk for RSV (CLD, CHD and prematurity), those with severe underlying comorbidities, or those with nosocomial RSV appear to be at increased risk for death after RSV hospitalization. More data are needed on cause of death and how much is directly attributable to RSV.

Introduction: The American Academy of Pediatrics recommends palivizumab prophylaxis for children born premature or with chronic lung disease to reduce the severity of respiratory syncytial virus (RSV) infection. The purpose of the current study is to examine palivizumab administration among children hospitalized with RSV infection., Method: This is a retrospective medical record review at a tertiary care children's hospital. The study included children <2 years of age hospitalized between October 1, 2000, and April 1, 2001, with the diagnosis of RSV infection., Results: The records of 264 children meeting inclusion criteria were reviewed. Forty children qualified for administration of palivizumab using American Academy of Pediatrics recommendations. Of these, 14 (35%) received palivizumab prior to admission. Palivizumab administration rate was not affected by age, race, or insurance coverage., Discussion: Exact barriers to the administration of palivizumab remain unclear. The identification of high-risk children, prevention of RSV by use of palivizumab, and collaboration between hospital and community health care providers will help increase the use of palivizumab and decrease the incidence of RSV.

This pilot study was performed to assess the use of cardiac troponin I to predict respiratory failure in children admitted to the hospital with respiratory syncytial virus (RSV) infections. We enrolled a prospective convenience sample of children under 5 years of age who were admitted to our university-based, tertiary care children's hospital from December 1, 2000, to February 1, 2002, with RSV infections. A cardiac troponin I was drawn at admission. We assessed the test characteristics for positive cardiac troponin I (defined as >0.3 ng/mL, the manufacturer's upper limit of normal) in correctly identifying children who had respiratory failure as evidenced by the need for endotracheal intubation. Twenty-five children from 9 days to 38 months of age were included. Ten children had a positive cardiac troponin I and 3 of these children had respiratory failure. A positive cardiac troponin I demonstrated a sensitivity of 100%, specificity 68%, positive predictive value of 30%, negative predictive value of 100%, and accuracy of 72%. The area under the receiver operating characteristic curve was 0.939 (95% confidence interval, 0.820-1.0), suggesting a high degree of discriminatory power in selecting children with respiratory failure. A sample size calculation revealed that a follow-up study of 359 patients is needed before the clinical use of cardiac troponin I for this purpose.