Resolving the Debate on RSV Prophylaxis in Late Preterm Infants

There is still active debate in the scientific literature about the importance of providing respiratory syncytial virus (RSV) prophylaxis to late preterm infants born at 33–35 weeks’ gestational age (wGA). The American Academy of Pediatrics and the Canadian Paediatric Society position statements only advocate for RSV prophylaxis for infants <30 wGA. Several publications prove the contrary, reporting substantial morbidity and even mortality in older GA infants, following RSV infection. Consequently, other Societies, such as from Spain and Italy, have different criteria, and include as candidates 30–32 wGA infants and 33–35 wGA infants with risk factors for severe RSV disease. This chapter will systematically examine the current evidence for RSV prophylaxis in both early and late preterm infants 29–35 wGA and the cost-effectiveness of this strategy with the use of risk scoring tools. The authors will attempt to reconcile the misconception that late preterm infants do not merit RSV prophylaxis and hopefully resolve the long-standing debate that currently exists in many countries worldwide

Defining the Risk and Associated Morbidity and Mortality of Severe Respiratory Syncytial Virus Infection Among Infants with Chronic Lung Disease

INTRODUCTION: The REGAL (RSV evidence-a geographical archive of the literature) series provide a comprehensive review of the published evidence in the field of respiratory syncytial virus (RSV) in Western countries over the last 20 years. This third publication covers the risk and burden of RSV infection in infants with chronic lung disease (CLD), formerly called bronchopulmonary dysplasia (BPD). METHODS: A systematic review was undertaken of publications between January 1, 1995 and December 31, 2015 across PubMed, Embase, The Cochrane Library, and Clinicaltrials.gov. Studies reporting data for hospital visits/admissions for RSV infection among infants with CLD/BPD who were not prophylaxed, as well as studies reporting RSV-associated morbidity, mortality, and healthcare costs, were included. Burdens of disease data were compared with preterm infants without CLD/BPD, other high-risk groups and term infants. Study quality and strength of evidence (SOE) were graded using recognized criteria. RESULTS: A total of 1837 studies were identified and 39 were included. CLD/BPD is a significant independent risk factor for RSV hospitalization [RSVH (odds ratio 2.2-7.2); high SOE]. Infants and young children with CLD/BPD had high RSVH rates which were generally similar in Europe, the United States, and Canada, mostly varying between 12 and 21%. Infants with CLD also had a longer length of hospital stay than other high-risk groups and term infants (high SOE). On average, infants spent 4-11 days in hospital (moderate SOE). Once hospitalized for RSV, affected children were at risk for a more severe course of disease than children with no RSVH (moderate SOE). CONCLUSION: Severe RSV infection in infants and young children with CLD/BPD poses a significant health burden in Western countries. Further studies focussing on the burden of RSV infection in this well-recognized population at high risk for severe disease are needed to help improve outcomes and plan allocation of healthcare resources. FUNDING: AbbVie

Trends in survival among extremely-low-birth-weight infants (less than 1000 g)without significant bronchopulmonary dysplasia

Objective The aim of this study was to analyze the evolution from 1997 to 2009 of survival without significant (moderate and severe) bronchopulmonary dysplasia (SWsBPD) in extremely-low-birth-weight (ELBW) infants and to determine the influence of changes in resuscitation, nutrition and mechanical ventilation on the survival rate. Study design In this study, 415 premature infants with birth weights below 1000 g (ELBW) were divided into three chronological subgroups: 1997 to 2000 (n = 65), 2001 to 2005 (n = 178) and 2006 to 2009 (n = 172). Between 1997 and 2000, respiratory resuscitation in the delivery room was performed via a bag and mask (Ambu®, Ballerup, Sweden) with 40-50% oxygen. If this procedure was not effective, oral endotracheal intubation was always performed. Pulse oximetry was never used. Starting on January 1, 2001, a change in the delivery room respiratory policy was established for ELBW infants. Oxygenation and heart rate were monitored using a pulse oximeter (Nellcor®) attached to the newborn"s right hand. If resuscitation was required, ventilation was performed using a face mask, and intermittent positive pressure was controlled via a ventilator (Babylog2, Drägger). In 2001, a policy of aggressive nutrition was also initiated with the early provision of parenteral amino acids. We used standardized parenteral nutrition to feed ELBW infants during the first 1224 hours of life. Lipids were given on the first day. The glucose concentration administered was increased by 1 mg/kg/minute each day until levels reached 8 mg/kg/minute. Enteral nutrition was started with trophic feeding of milk. In 2006, volume guarantee treatment was instituted and administered together with synchronized intermittent mandatory ventilation (SIMV + VG). The complications of prematurity were treated similarly throughout the study period. Patent ductus arteriosus was only treated when hemodynamically significant. Surgical closure of the patent ductus arteriosus was performed when two courses of indomethacin or ibuprofen were not sufficient to close it. Mild BPD were defined by a supplemental oxygen requirement at 28 days of life and moderate BPD if breathing room air or a need for <30% oxygen at 36 weeks postmenstrual age or discharge from the NICU, whichever came first. Severe BPD was defined by a supplemental oxygen requirement at 28 days of life and a need for greater than or equal to 30% oxygen use and/or positive pressure support (IPPV or nCPAP) at 36 weeks postmenstrual age or discharge, whichever came first. Moderate and severe BPD have been considered together as"significant BPD". The goal of pulse oximetry was to maintain a hemoglobin saturation of between 88% and 93%. Patients were considered to not need oxygen supplementation when it could be permanently withdrawn....

Impact of chorioamnionitis on exhaled nitric oxide and endotracheal aspirate levels of nitrites-nitrates and interleukin-8 in mechanically ventilated preterm neonates.

OBJECTIVES: To assess the influence of maternal chorioamnionitis on early exhaled nitric oxide (NO) and levels of nitrites-nitrates and interleukin (IL)-8 in endotracheal aspirate fluid in mechanically ventilated preterm neonates. STUDY DESIGN: Cross-sectional study. PATIENT-SUBJECT SELECTION: Between September 2007 and August 2009, 54 mechanically ventilated preterm neonates were included. Patients were divided into two groups according to the presence or absence of maternal chorioamnionitis, and those without chorioamnionitis (controls) were further stratified into two subgroups by birth weight < or ≥ 2,000 g. METHODOLOGY: The ventilator used was a Babylog 8000. The NO level assessed was the plateau value given by the software of the Sievers NOA apparatus. Collection of endotracheal aspirate fluid samples was performed coinciding with routine aspirations and using the dry technique. RESULTS: The two groups of control neonates showed statistically significant differences in exhaled NO expressed as nl/min and normalized exhaled NO expressed as either nl/min or nl/min/kg, so they are not homogeneous and cannot be used in clinical practice. Serum C-reactive protein and endotracheal aspirate levels of nitrites-nitrates were significantly higher in the chorioamnionitis group than in controls (3.6 vs. 1.07 µmol/L; P = 0.035). Nitrites-nitrates levels were positively correlated with exhaled NO in ppb (ρ = 0.367; P = 0.006). Minute exhaled endogenous NO was significantly higher in the chorioamnionitis group (0.48 vs. 0.27 nl/min/kg; P = 0.021). CONCLUSIONS: In mechanically ventilated preterm infants weighing <2,000 g, maternal chorioamnionitis was associated with an increase of early exhaled NO (nl/min/kg) and serum levels of C-reactive protein and levels of nitrites-nitrates in endotracheal aspirate fluid

Cost effectiveness of palivizumab in Spain: an analysis using observational data

Objectives: To assess the cost effectiveness of palivizumab for prevention of severe respiratory syncytial virus (RSV) disease in high-risk infants in Spain, incorporating country-specific observational hospitalisation data. Methods: An existing decision tree model, designed using data from a large international clinical trial of palivizumab versus no prophylaxis, was updated to include Spanish observational hospitalisation data. The analysis was performed for preterm children born at or before 32 weeks gestational age, who are at high risk of developing severe RSV disease requiring hospitalisation. Data sources included published literature, official price/tariff lists and national population statistics. The primary perspective of the study was that of the Spanish National Health Service in 2006. Results: The base-case analysis included the direct medical costs associated with palivizumab prophylaxis and hospital care for RSV infections. Use of palivizumab produces an undiscounted incremental cost-effectiveness ratio (ICER) of €6,142 per quality-adjusted life-year (QALY), and a discounted ICER of €12,814/QALY. Conclusion: Palivizumab provides a cost-effective method of prophylaxis against severe RSV disease requiring hospitalisation among preterm infants in Spain

A predictive model for respiratory syncytial virus (RSV) hospitalisation of premature infants born at 33–35 weeks of gestational age, based on data from the Spanish FLIP study

Background: The aim of this study, conducted in Europe, was to develop a validated risk factor based model to predict RSV-related hospitalisation in premature infants born 33-35 weeks' gestational age (GA). Methods: The predictive model was developed using risk factors captured in the Spanish FLIP dataset, a case-control study of 183 premature infants born between 33-35 weeks' GA who were hospitalised with RSV, and 371 age-matched controls. The model was validated internally by 100-fold bootstrapping. Discriminant function analysis was used to analyse combinations of risk factors to predict RSV hospitalisation. Successive models were chosen that had the highest probability for discriminating between hospitalised and non-hospitalised infants. Receiver operating characteristic (ROC) curves were plotted. Results: An initial 15 variable model was produced with a discriminant function of 72% and an area under the ROC curve of 0.795. A step-wise reduction exercise, alongside recalculations of some variables, produced a final model consisting of 7 variables: birth +/- 10 weeks of start of season, birth weight, breast feeding for = 2 years, family members with atopy, family members with wheeze, and gender. The discrimination of this model was 71% and the area under the ROC curve was 0.791. At the 0.75 sensitivity intercept, the false positive fraction was 0.33. The 100-fold bootstrapping resulted in a mean discriminant function of 72% (standard deviation: 2.18) and a median area under the ROC curve of 0.785 (range: 0.768-0.790), indicating a good internal validation. The calculated NNT for intervention to treat all at risk patients with a 75% level of protection was 11.7 (95% confidence interval: 9.5-13.6). Conclusion: A robust model based on seven risk factors was developed, which is able to predict which premature infants born between 33-35 weeks' GA are at highest risk of hospitalisation from RSV. The model could be used to optimise prophylaxis with palivizumab across Europe

Immunoprophylaxis of respiratory syncytial virus: global experience

Respiratory syncytial virus (RSV) infects nearly all children by age 2 years, and it causes considerable illness and death in certain high-risk pediatric populations. Historically, treatment for RSV has been symptomatic, and developing a safe and effective vaccine has been a challenge. Therefore, research efforts have turned to passive immunization as the best option to control RSV. Palivizumab, a genetically engineered humanized monoclonal antibody, has been shown to reduce RSV-related hospitalizations significantly, with few adverse effects. It was approved for use in high-risk children in the USA in 1998 and in Europe in 1999; it is now approved for use in more than 45 countries. The efficacy and safety of palivizumab continue to be supported by both clinical trial and outcomes data