Risk Of Respiratory Syncytial Virus Hospitalization Research Articles

Birth characteristics as predictors of respiratory syncytial virus hospitalisation in newborns to optimise immunisation schedule.

To examine birth characteristics that influence infant respiratory syncytial virus (RSV) hospitalisation risk in order to identify risk factors for severe RSV infections. Retrospective cohort study of 460 771 Sicilian children under 6 months old from January 2007 to December 2017. Hospital discharge records were consulted to identify cases and hospitalisations with International Classification of Diseases, Ninth Revision, Clinical Modification codes 466.11 (RSV bronchiolitis), 480.1 (RSV pneumonia) and 079.6 (RSV). RSV hospitalisation risk was estimated using adjusted odds ratios (aOR) and 95% confidence intervals (95% CI). Overall, 2420 (5.25 per 1000 infants) RSV-related hospitalisations were identified during the study, with girls accounting for 52.8%. RSV hospitalisation risk increased for full-term, transferred, extreme immature, and preterm neonates with serious issues (aOR 3.25, 95% CI 2.90-3.64; aOR 1.86, 95% CI 1.47-2.32; aOR 1.54, 95% CI 1.11-2.07; and aOR 1.48, 95% CI 1.14-1.90). Compared to children born in June, the risk of RSV hospitalisation was significantly higher in children born in January (aOR 28.09, 95% CI 17.68-48.24) and December (aOR 27.36, 95% CI 17.21-46.99). This study identified birth month and diagnosis-related groups as key predictors of RSV hospitalisations. This could help manage monoclonal antibody appropriateness criteria.

Respiratory Syncytial Virus-Associated Hospitalization in Adults With Comorbidities in 2 European Countries: A Modeling Study.

Individuals with comorbidities are at increased risk of severe respiratory syncytial virus (RSV) infection. We estimated RSV-associated respiratory hospitalization among adults aged ≥45 years with comorbidities in Denmark and Scotland. By analyzing national hospital and virologic data, we estimated annual RSV-associated hospitalizations by 7 selected comorbidities and ages between 2010 and 2018. We estimated rate ratios of RSV-associated hospitalization for adults with comorbidity than the overall population. In Denmark, annual RSV-associated hospitalization rates per 1000 adults ranged from 3.1 for asthma to 19.4 for chronic kidney disease (CKD). In Scotland, rates ranged from 2.4 for chronic liver disease to 9.0 for chronic obstructive pulmonary disease (COPD). In both countries, we found a 2- to 4-fold increased risk of RSV hospitalization for adults with COPD, ischemic heart disease, stroke, and diabetes; a 1.5- to 3-fold increased risk for asthma; and a 3- to 7-fold increased risk for CKD. RSV hospitalization rates among adults aged 45 to 64 years with COPD, asthma, ischemic heart disease, or CKD were higher than the overall population. This study provides important evidence for identifying risk groups and assisting health authorities in RSV vaccination policy making.

50 New Analysis on the Cost-effectiveness of Palivizumab (PVZ) for the Prevention of Severe Respiratory Syncytial Virus (RSV) Infection in Canadian Infants Born 29-31 and 32-35 weeks’ Gestational Age (wGA)

Abstract Background PVZ remains the only licensed intervention to prevent severe RSV infection. The last formal cost-utility analysis (CUA) of its use in Canadian premature infants was published in 2010 (Smart J Med Econ 2010). Since then, the 3-variable International Risk Scoring tool (IRST) has been published (Blanken Pediatr Pulmonol 2018), which can guide prophylaxis for infants born 32-35 wGA at greatest risk of RSV hospitalization (RSVH). Objectives The objective of this study was to incorporate the IRST and non-hospitalized, medically-attended (emergency room/outpatient) RSV infections (MARI) into a CUA for the first time to provide an up-to-date economic evaluation of palivizumab versus no prophylaxis in Canadian 29-31 wGA and 32-35 wGA infants. Design/Methods Infants followed a semi-Markov process, having an RSVH, MARI, or being uninfected/non-medically attended. Hospitalized infants could be admitted to the intensive care unit (ICU; 17.9%) and ICU-admitted infants could die (0.43%). All surviving infants could experience respiratory morbidity up to 18 years, according to RSV infection and PVZ status. The RSVH rate in non-prophylaxed 29-31 wGA and moderate to high (MH) risk 32-35 wGA infants was 5.9% and 6.3%, respectively. PVZ reduced RSVH by 63.3% and 82.2% in 29-31 wGA and 32-35 wGA infants, respectively. PVZ costs (assuming 50 mg: CAN$752; 100 mg: $1,505) were calculated using Canadian birth statistics. The base case assumed all 29-31 wGA infants and MH-risk 32-35 wGA infants received PVZ, inclusion of indirect costs, no vial sharing, and a lifetime time horizon with 1.5% discounting. A cost per quality-adjusted life-year (QALY) of ≤$50,000 was considered cost-effective. Results PVZ prophylaxis resulted in a cost/QALY of $29,579 in 29-31 wGA infants and $27,951 in MH-risk 32-35 wGA infants versus no prophylaxis. In deterministic sensitivity analyses (±20% on main variables) the model was most sensitive to utility scores, PVZ cost, non-prophylaxed RSVH rate, and PVZ efficacy. Probabilistic sensitivity analyses (10,000 iterations) resulted in incremental costs of $30,857/QALY, with a 76.0% probability of cost-effectiveness at a $50,000 willingness-to-pay threshold for 29-31 wGA infants, and $28,167/QALY and 79.1% for MH-risk 32-35 wGA infants. Conclusion This new CUA, the first to incorporate the IRST and MARI, found that PVZ is highly cost-effective in Canadian 29-35 wGA infants (vs no prophylaxis) and has implications for prophylaxis policies in Canada. Potential competing interests Xavier Carbonell-Estrany and Bosco Paes have received research funding and/or compensation as advisor/lecturer from AbbVie and AstraZeneca. Jean-Eric Tarride has nothing to disclose. Barry Rodgers-Gray, Ian Keary and John Fullarton employers have received payment from AbbVie and AstraZeneca for work on various projects.

Comparison of the Canadian vs. the international risk scoring tool for respiratory syncytial virus prophylaxis in moderate-to-late preterm infants.

The study objective was to compare the Pediatric Investigators Collaborative Network on Infections in Canada risk scoring tool (CRST) that determines need for respiratory syncytial virus (RSV) prophylaxis in infants 33-35 weeks gestational age during the RSV season, with the newly developed international risk scoring tool (IRST). Children 33-35 weeks gestational age born during the 2018-2021 RSV seasons were prospectively identified following birth and scored with the validated CRST and IRST, that comprises seven and three variables respectively, into low- moderate- and high-risk groups that predict RSV-related hospitalization. Correlations between total scores on the two tools, and cut-off scores for the low-, moderate- and high-risk categories were conducted using the Spearman rank correlation. Over a period of 3 RSV seasons, 556 infants were scored. Total risk scores on the CRST and the IRST were moderately correlated (rs = 0.64, p < 0.001). A significant relationship between the risk category rank on the CRST and the risk category rank on the IRST (rs = 0.53; p < 0.001) was found. The proportion of infants categorized as moderate risk for RSV hospitalization by the CRST and IRST were 19.6% (n = 109) and 28.1% (n = 156), respectively. The IRST may provide a time-efficient scoring alternative to the CRST with three vs. seven variables, and it selects a larger number of infants who are at moderate risk for RSV hospitalization for prophylaxis. A cost-utility analysis is necessary to justify country-specific use of the IRST, while in Canada a cost comparison is necessary between the IRST vs. the currently approved CRST prior to adoption.

Summary of the National Advisory Committee on Immunization (NACI) statement update on the recommended use of palivizumab to reduce complications of respiratory syncytial virus infection in infants.

Respiratory syncytial virus (RSV) is the most common cause of lower respiratory tract infection in young children worldwide. Underlying health conditions, especially premature birth, chronic lung disease and congenital heart disease, predispose to severe RSV illness. The only means of prophylaxis against RSV disease is passive prophylaxis with the monoclonal antibody, palivizumab (PVZ) (SynagisTM). The National Advisory Committee on Immunization (NACI) published a statement for PVZ use in 2003. The purpose of this article is to update previous NACI recommendations for the use of PVZ, taking into consideration recent data on RSV burden of illness, effectiveness of PVZ in infants at risk of more severe RSV disease and economic implications of PVZ use. The NACI Working Group and external experts performed systematic literature reviews on three topics to support updated NACI guidance: 1) RSV burden of disease; 2) PVZ effectiveness; and 3) cost effectiveness of PVZ prophylaxis. Full details and results are presented in the statement and supporting documents. Respiratory syncytial virus hospitalization (RSVH) rates are highest in children younger than one year of age and especially in the first two months of life. In various populations of infants at risk of severe RSV infection, PVZ prophylaxis is associated with reductions of 38%-86% in the risk of RSVH. Only rare cases of anaphylaxis have been reported after decades of use. Palivizumab is expensive and only cost-saving in rare scenarios. Updated NACI recommendations on use of PVZ for the prevention of complications of RSV in infants are now available.

Prevalence of respiratory viruses among paediatric patients in acute respiratory illnesses in Malaysia.

ObjectivesAcute respiratory infections (ARIs) are one of the leading causes of childhood morbidity and mortality worldwide. However, there is limited surveillance data on the epidemiological burden of respiratory pathogens in tropical countries like Malaysia. This study aims to estimate the prevalence of respiratory pathogens causing ARIs among children aged <18 years old in Malaysia and their epidemiological characteristics.MethodsNasopharyngeal swab specimens received at 12 laboratories located in different states of Malaysia from 2015–2019 were studied. Detection of 18 respiratory pathogens were performed using multiplex PCR.ResultsData from a total of 23,306 paediatric patients who presented with ARI over a five-year period was studied. Of these, 18538 (79.5%) were tested positive. The most prevalent respiratory pathogens detected in this study were enterovirus/ rhinovirus (6837/ 23000; 29.7%), influenza virus (5176/ 23000; 22.5%) and respiratory syncytial virus (RSV) (3652/ 23000; 15.9%). Throughout the study period, RSV demonstrated the most pronounce seasonality; peak infection occurred during July to September. Whereas the influenza virus was detected year-round in Malaysia. No seasonal variation was noted in other respiratory pathogens. The risk of RSV hospitalisation was found to be significantly higher in children aged less than two years old, whereas hospitalisation rates for the influenza virus peaked at children aged between 3–6 years old.ConclusionThis study provides insight into the epidemiology and the seasonality of the causative pathogens of ARI among the paediatric population in Malaysia. Knowledge of seasonal respiratory pathogens epidemiological dynamics will facilitate the identification of a target window for vaccination.

Respiratory Syncytial Virus-Associated Hospitalizations in Children With Neurological Disorders, 2006-2015.

We quantified the risk of respiratory syncytial virus (RSV) hospitalizations and severe outcomes among children with neurological disorders. We estimated RSV-specific and RSV-associated hospitalization rates using International Classification of Diseases, Ninth Revision (ICD-9) codes from 2 insurance claims IBM MarketScan Research Databases (Commercial and Multi-State Medicaid) from July 2006 through June 2015. For comparison, a simple random sample of 10% of all eligible children was selected to represent the general population. Relative rates (RRs) of RSV hospitalization were calculated by dividing rates for children with neurological disorders by rates for children in the general population by age group and season. The RSV-specific hospitalization rate for children with any neurological condition was 4.2 (95% confidence interval [CI]: 4.1, 4.4) per 1000 person-years, and the RSV-associated hospitalization rate was 7.0 (95% CI: 6.9, 7.2) per 1000 person-years among children <19 years of age. Among privately insured children, the overall RR of RSV hospitalization in children with neurological disorders compared with the general population was 10.7 (95% CI: 10.0, 11.4) for RSV-specific hospitalization and 11.1 (95% CI: 10.5, 11.7) for RSV-associated hospitalizations. Among children in Medicaid, the RSV-specific hospitalization RR was 6.1 (95% CI: 5.8, 6.5) and the RSV-associated hospitalization RR was 6.4 (95% CI: 6.2, 6.7) compared with the general population. Our population-based study of children with neurological disorders found that the risk of RSV hospitalization was 6 to 12 times higher among children with neurological disorders than among the general pediatric population. These findings should be considered when determining who should be targeted for current and future RSV interventions.

Respiratory Syncytial Virus (RSV)-Specific Antibodies in Pregnant Women and Subsequent Risk of RSV Hospitalization in Young Infants.

BackgroundThe fusion (F) glycoprotein of respiratory syncytial virus (RSV) represents the major neutralizing antigen, and antibodies against the pre-F conformation have the most potent neutralizing activity. This study aimed to assess the correlation between maternal antibody titers against the pre-F, post-F, and G glycoproteins and the child’s risk of developing severe RSV bronchiolitis early in infancy.MethodsWe identified previously healthy term infants <3 months of age hospitalized with RSV bronchiolitis from December 2015 to March 2016. We measured IgG antibody titers to pre-F, post-F, and G proteins in maternal sera obtained at 9–12 weeks of pregnancy of these hospitalized infants’ mothers (n = 94) and compared them with serum antibody titers of control pregnant mothers (n = 130) whose children were not hospitalized.ResultsAll maternal samples (n = 224) had detectable pre-F antibodies. Pre-F antibody titers were significantly lower in mothers whose infants were hospitalized with RSV bronchiolitis compared with those mothers whose infants were not hospitalized (23.9 [range (or antibody titer range), 1.4–273.7] µg/L vs 30.6 [XXX, 3.4–220.0] µg/L; P = .0026). There were no significant differences in maternal post-F and G antibody titers between hospitalized and nonhospitalized infants.ConclusionsOur findings indicate that maternal pre-F antibodies are fundamental for providing immune protection to the infant.

Early Life RSV: Can Vaccines Help Fix Societal Ills?

* Abbreviations: LRI — : lower respiratory infection RSV — : respiratory syncytial virus SDOH — : social determinants of health During this pandemic, the impact of health disparities on mortality due to COVID-19 has been high among our concerns about this illness.1–4 Unfortunately, disparities related to respiratory infections are not limited to COVID-19. There are decades of research revealing that morbidity and mortality are strongly influenced by the social determinants of health (SDOH). Respiratory syncytial virus (RSV) is the leading cause of lower respiratory infection (LRI) in infants and a major cause of hospitalization in the first 2 years of life.5–7 In this issue of Pediatrics , Fitzpatrick et al8 report on the impact of sociodemographic and psychosocial factors on the risk for RSV hospitalization in children <3 years of age in Ontario, Canada. The authors used linked sociodemographic and health administrative data sets covering the period from 2012 to 2018 to identify factors associated with hospitalization. Their findings reveal the increased risk of hospitalization associated with maternal characteristics consistent with social vulnerability, including younger age, involvement with the criminal justice system, and mental health problems or addiction. The use of low-income drug benefits, a measure of socioeconomic status, was also associated with RSV hospitalization, as was an area level measure of income showing an increased risk of hospitalization with the lowest two quartiles of income. In their study, Fitzpatrick et al8 reinforce the important, enduring, and widespread influence of SDOH on our youngest patients. These … Address correspondence to Mary T. Caserta, MD, Department of Pediatrics, University of Rochester Medical Center, Golisano Children’s Hospital at Strong, 601 Elmwood Ave, Box 690, Rochester, NY 14642. E-mail: mary_caserta{at}urmc.rochester.edu

Impact of the 2014 American Academy of Pediatrics Policy on RSV Hospitalization in Preterm Infants in the United States.

Despite being a leading cause of hospitalization due to lower respiratory tract infections, the treatment of respiratory syncytial virus (RSV) infection is primarily supportive. Palivizumab is the only licensed immunoprophylaxis (IP) available for preventing severe RSV infection in high-risk populations including ≤ 35 weeks’ gestational age (wGA) infants and children with chronic lung disease of prematurity or congenital heart disease. The American Academy of Pediatrics (AAP) has published its IP recommendations since the approval of palivizumab. In 2014, the AAP stopped recommending RSV IP in 29–34 wGA infants without comorbidities and stated that RSV hospitalization (RSVH) risk in otherwise healthy ≥ 29 wGA infants and term infants was similar. Since then, experts in the field have debated the appropriateness of the 2014 policy change, and several real-world evidence studies at the national and regional levels in the US have examined the impact of the AAP policy on 29–34 wGA infants. Overall, these studies showed a significant decline in RSV IP use and a concurrent increase in RSVH risk among 29–34 wGA infants relative to term infants in the seasons after the 2014 policy change. A similar decrease in IP use and increase in RSVH risk was also observed among < 29 wGA infants relative to term infants after the 2014 policy change. This decrease could be an unintended consequence as < 29 wGA infants are an in-policy population recommended to receive RSV IP. According to the National Perinatal Association, strong evidence exists to support the use of RSV IP in all ≤ 32 wGA and 32–35 wGA infants with risk factors such as attending day care, having ≥ 1 school-aged siblings, twin or greater multiple gestation, younger age, and exposure to parental smoking. Until new preventive and treatment options become available, palivizumab can help prevent and mitigate RSV disease burden among high-risk preterm infants.

Update on respiratory syncytial virus hospitalizations among U.S. preterm and term infants before and after the 2014 American Academy of Pediatrics policy on immunoprophylaxis: 2011-2017

ABSTRACT Palivizumab is the only licensed respiratory syncytial virus (RSV) immunoprophylaxis (IP) available to prevent severe RSV disease in high-risk pediatric populations, including infants born at 29–34 weeks’ gestational age (wGA). In 2014, the American Academy of Pediatrics (AAP) stopped recommending RSV IP use for otherwise healthy 29–34 wGA infants and stated that 29–34 wGA infants and term infants have similar RSV hospitalization (RSVH) rates. This study aimed to compare RSV IP use and RSVH rates in 29–34 wGA infants and term infants during the 3 RSV seasons before and after the 2014 AAP policy change. RSV IP use in otherwise healthy infants 29–30, 31–32, and 33–34 wGA was estimated from pharmacy or outpatient medical claims for palivizumab. RSVH rates in the first 6 months of life were calculated per 100 infant-seasons. RSVH rate ratios were used to compare preterm infants and term infants before and after the policy change. Across infant cohorts (29–34 wGA) and chronologic age groups (<3 months and 3-<6 months), absolute decreases in RSV IP use between the combined 2011–2014 seasons and 2014–2017 seasons ranged from 7% to 38% and from 68% to 97%, respectively. Compared with 2011–2014, the RSVH risk increased 2.09-fold (P< .001) and 1.76-fold (P< .001) in 2014–2017 for infants born at 29–34 wGA and aged <6 months with commercial and Medicaid insurance, respectively. Overall, RSV IP use declined in the RSV seasons following the 2014 RSV IP policy change, and RSVH increased among 29–34 wGA infants aged <6 months.

Calibration of Chronic Lung Disease Severity as a Risk Factor for Respiratory Syncytial Virus Hospitalization

Guidelines assume children with chronic lung disease (CLD) who require medical support within 6 months before the second respiratory syncytial virus (RSV) season remains at high risk of severe RSV disease. We determined the number of days since the last treatment (DSL) when the risk of RSV hospitalization among children with CLD becomes equivalent to the risk for those not qualified for immunoprophylaxis. The study cohort was assembled using Medicaid billing records from 1999 to 2010 linked to Florida and Texas birth certificate records. We developed DSL-trend discrete time logistic regression models within a survival analysis framework, adjusting for use of immunoprophylaxis, to compare the hospitalization risk of CLD infants at 4 age points to that of term infants at 1 month of age with siblings. The study cohort included 858 830 healthy term and 5562 preterm infants with CLD. Among 1-month-old term infants, the RSV hospitalization risk averaged across all covariate strata was 14.8 (95% confidence interval [CI], 13.5-16.1) per 1000 patient season-months. Risk for preterm CLD children reached the threshold derived from term infants when DSL was 76 (95% CI, 22-198.5), 52 (95% CI, 6.5-123), 35 (95% CI, 0-93.5), and 12 (95% CI, 0-61.5) at the respective ages of 12, 15, 17.2, and 21 months. The 180-day threshold used to define CLD severity at season start can be shortened to 120 days, 90 days, and 60 days for children with CLD at age 15, 17.2, and 21 months, respectively.

Respiratory Syncytial Virus-Associated Hospitalizations Among Adults With Chronic Medical Conditions.

In contrast with respiratory disease caused by influenza, information on the risk of respiratory syncytial virus (RSV) disease among adults with chronic medical conditions (CMCs) is limited. We linked population-based surveillance of acute respiratory illness hospitalizations to national administrative data to estimate seasonal RSV hospitalization rates among adults aged 18-80 years with the following preexisting CMCs: chronic obstructive pulmonary disease (COPD), asthma, congestive heart failure (CHF), coronary artery disease (CAD), cerebrovascular accidents (CVA), diabetes mellitus (DM), and end-stage renal disease (ESRD). Age- and ethnicity-adjusted rates stratified by age group were estimated. Among 883 999 adult residents aged 18-80 years, 281 RSV-positive hospitalizations were detected during 2012-2015 winter seasons. Across all ages, RSV hospitalization rates were significantly higher among adults with COPD, asthma, CHF, and CAD compared with those without each corresponding condition. RSV hospitalization rates were significantly higher among adults with ESRD aged 50-64 years and adults with DM aged 18-49 years and 65-80 years compared with adults in each age group without these conditions. No increased risk was seen for adults with CVA. The CMC with the highest risk of RSV hospitalization was CHF (incidence rate ratio [IRR] range, 4.6-36.5 across age strata) and COPD (IRR range, 9.6-9.7). Among RSV-positive adults, CHF and COPD were independently associated with increased length of hospital stay. Adults with specific CMCs are at increased risk of RSV hospitalizations. Age affects this relationship for some CMCs. Such populations maybe relevant for future RSV prevention strategies.

Transient Tachypnea of the Newborn Is Associated With an Increased Risk of Hospitalization Due to Respiratory Syncytial Virus Bronchiolitis.

Transient tachypnea of the newborn (TTN) is a self-limiting respiratory disorder, resulting from a failure to clear the lungs of perinatal fluid. As similar pathophysiologic features are present in children with respiratory syncytial virus (RSV) bronchiolitis, we hypothesized that these two conditions may be connected. This was a population-based cohort study that included all children born in term (≥37 weeks of gestation) without congenital malformations in Finland between 1996 and 2015. Children diagnosed with TTN (International Statistical Classification of Diseases and Related Health Problems, 10th Revision [ICD-10] code P22.1) after birth and children hospitalized because of RSV bronchiolitis (ICD-10 code J21.0) during first year of life were identified from the Medical Birth Register and National Hospital Discharge Register, respectively, and the data were linked. Logistic regression was used to analyze the association between these two conditions. Of the 1,042,045 children included in the study cohort, 16,327 (1.57%) were diagnosed with TTN at birth and 12,345 (1.18%) were hospitalized because of RSV bronchiolitis during the first year of life. The rate of RSV hospitalization was higher in children with a history of TTN compared with children without TTN diagnosis [260/16,327 (1.59%) vs. 12,085/1,025,718 (1.18%), respectively; P value <0.0001]. After adjusting for gestational age at birth, mode of delivery, gender, birth weight, multiple births, older siblings and maternal smoking, TTN was associated with increased risk for RSV hospitalization (odds ratio: 1.31, 95% confidence interval: 1.16-1.48). TTN diagnosis after birth was associated with increased risk for RSV hospitalization during the first year of life.

National cohort study showed that infants with Down's syndrome faced a high risk of hospitalisation for the respiratory syncytial virus.

The respiratory syncytial virus (RSV) is a leading cause of hospitalisation in infants. We investigated this risk in children with Down's syndrome under two years of age, adjusted for other known risk factors. This national, retrospective 1:2 matched cohort study comprised all Swedish children born with Down's from 2006 to 2011, who were each randomly matched to two controls without Down's. Data on RSV hospitalisation and risk factors for RSV were obtained from national registers. The risk of RSV hospitalisation was assessed using multivariable Cox regression with pairwise stratification. The study comprised 814 children with Down's and 1628 controls. We found that 82 children with Down's (10.1%) and 22 controls (1.4%) were hospitalised for RSV. The hazard ratio for children with Down's was 4.00 (95% confidence interval 1.58-10.13) for up to one year of age and 6.60 (95% CI: 2.83-15.38) for up to two years of age, adjusted for other risk factors. During the second year of life, RSV hospitalisation continued for children with Down's, while it was minimal for the controls. Children with Down's faced a high risk of RSV hospitalisation, which continued beyond the first year of age.

Defining the Incidence and Associated Morbidity and Mortality of Severe Respiratory Syncytial Virus Infection Among Children with Chronic Diseases.

IntroductionREGAL (RSV Evidence—a Geographical Archive of the Literature) has provided a comprehensive review of the published evidence in the field of respiratory syncytial virus (RSV) in Western countries over the last 20 years. This review covers the risk and burden of RSV infection in children with underlying medical conditions or chronic diseases (excluding prematurity and congenital heart disease).MethodsA systematic review of publications between January 1, 1995 and December 31, 2015 across PubMed, Embase, The Cochrane Library, and Clinicaltrials.gov was supplemented by papers identified by the authors through March 2017. Studies reporting data for hospital visits/admissions for RSV infection as well as studies reporting RSV-associated morbidity and mortality were included. Study quality and strength of evidence (SOE) were graded.ResultsA total of 2703 studies were identified and 58 were included. Down syndrome, irrespective of prematurity and congenital heart disease (moderate SOE), immunocompromised children (low SOE), cystic fibrosis (low SOE), and neurologic conditions (low SOE) were associated with a significantly increased risk of RSV hospitalization. A number of other congenital malformations and chronic conditions were also associated with severe RSV disease (low SOE). In general, pre-existing disease was also a predisposing factor for RSV-related mortality (low SOE).ConclusionSevere RSV infection in infants and young children with underlying medical conditions or chronic diseases poses a significant health burden. Further studies are needed to fully quantify the epidemiology, burden and outcomes in these populations, in particular RSV-attributable mortality.Electronic supplementary materialThe online version of this article (doi:10.1007/s40121-017-0160-3) contains supplementary material, which is available to authorized users.

Respiratory syncytial virus hospitalization risk in the second year of life by specific congenital heart disease diagnoses.

Children with hemodynamically significant congenital heart disease (CHD) are at elevated risk of morbidity and mortality due to respiratory syncytial virus (RSV) disease compared to their healthy peers. Previous studies have demonstrated lower RSV hospitalization risk among all children with CHD at 12–23 months of age versus 0–11 months of age. However, RSV hospitalization risk at 12–23 months of age by specific CHD diagnosis has not been characterized. Both case-control and cohort studies were conducted using data from the US National Inpatient Sample from 1997 to 2013 to characterize relative risk of RSV hospitalization among children 12–23 months of age with CHD. Related CHD diagnoses were combined for analysis. Hospitalizations for RSV and unspecified bronchiolitis were described by length of stay, mechanical ventilation use, mortality, and total charges. Over the 17-year period, 1,168,886 live birth hospitalizations with CHD were identified. Multiple specific CHD conditions had an elevated odds ratio or relative risk of RSV hospitalization. Mean total RSV hospitalization charges were significantly higher among children with CHD relative to those without CHD ($19,650 vs $7,939 in 2015 dollars) for this period. Compared to children without CHD, children with Ebstein’s anomaly, transposition of the great arteries, aortic stenosis, heterotaxia, and aortic arch anomalies had 367-, 344-, 203-, 117- and 47-fold increased risk of inpatient RSV mortality, respectively. Unspecified bronchiolitis hospitalization odds and relative risk across CHD diagnoses were similar to those observed with RSV hospitalization; however, unspecified bronchiolitis hospitalizations were associated with shorter mean days of stay and less frequently associated with mechanical ventilation or mortality. Among children with more severe CHD diagnoses, RSV disease remains an important health risk through the second year of life. These data can help inform decisions regarding interventions to protect children with CHD from severe RSV disease during their second year of life.

Defining the Risk and Associated Morbidity and Mortality of Severe Respiratory Syncytial Virus Infection Among Infants with Congenital Heart Disease.

IntroductionThe 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 fourth publication covers the risk and burden of RSV infection in infants with congenital heart disease (CHD).MethodsA systematic review was undertaken for articles published 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 children with CHD as well as studies reporting RSV-associated morbidity, mortality, and healthcare costs were included. The focus was on children not receiving RSV prophylaxis. Study quality and strength of evidence (SOE) were graded using recognized criteria.ResultsA total of 1325 studies were identified of which 38 were included. CHD, in particular hemodynamically significant CHD, is an independent predictor for RSV hospitalization (RSVH) (high SOE). RSVH rates were generally high in young children (<4 years) with CHD (various classifications), varying between 14 and 357/1000 (high SOE). Children (<6 years) with RSV infection spent 4.4–14 days in hospital, with up to 53% requiring intensive care (high SOE). Infants (<2 years) with CHD had a more severe course of RSVH than those without CHD (high SOE). Case fatality rates of up to 3% were associated with RSV infection in children with CHD (high SOE). RSV infection in the perioperative period of corrective surgery and nosocomial RSV infection in intensive care units also represent important causes of morbidity (moderate SOE).ConclusionCHD poses a significant risk for RSVH and subsequent morbidity and mortality. RSV infection often complicates corrective heart surgery. To reduce the burden and improve outcomes, further research and specific studies are needed to determine the longer-term effects of severe RSV infection in young children with CHD.Electronic supplementary materialThe online version of this article (doi:10.1007/s40121-016-0142-x) contains supplementary material, which is available to authorized users.

Defining the Risk and Associated Morbidity and Mortality of Severe Respiratory Syncytial Virus Infection Among Preterm Infants Without Chronic Lung Disease or Congenital Heart Disease

IntroductionThe 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 second publication covers the risk and burden of RSV infection in preterm infants born at <37 weeks’ gestational age (wGA) without chronic lung disease or congenital heart disease.MethodsA systematic review was undertaken for articles published between January 1, 1995 and December 31, 2015. Studies reporting data for hospital visits/admissions for RSV infection among preterm infants as well as studies reporting RSV-associated morbidity, mortality, and risk factors were included. Study quality and strength of evidence (SOE) were graded using recognized criteria.Results2469 studies were identified of which 85 were included. Preterm infants, particularly those born at lower wGA, tended to have higher RSV hospitalization (RSVH) rates compared with otherwise healthy term infants (high SOE). RSVH rates ranged from ~5 per 1000 children to >100 per 1000 children with the highest rates shown in the lowest gestational age infants (high SOE). Independent risk factors associated with RSVH include: proximity of birth to the RSV season, living with school-age siblings, smoking of mother during pregnancy or infant exposure to environmental smoking, reduced breast feeding, male sex, and familial atopy (asthma) (high SOE). Predictive models can identify 32/33–35 wGA infants at risk of RSVH (high SOE).ConclusionRSV infection remains a major burden on Western healthcare systems and is associated with significant morbidity. Further studies focusing on the prevalence and burden of RSV in different gestational age cohorts, the changing risk of RSVH during the first year of life, and on RSV-related mortality in preterm infants are needed to determine the true burden of disease.FundingAbbVie.Electronic supplementary materialThe online version of this article (doi:10.1007/s40121-016-0130-1) contains supplementary material, which is available to authorized users.

Palivizumab Prophylaxis for Healthy Preterm Infants: More Data Supporting American Academy of Pediatrics Guidelines.

* Abbreviations: AAP — : American Academy of Pediatrics RSV — : respiratory syncytial virus As licensed by the US Food and Drug Administration, “palivizumab is indicated for the prevention of serious lower respiratory tract disease caused by respiratory syncytial virus (RSV) in pediatric patients at high risk of RSV disease”.1 The American Academy of Pediatrics (AAP) Committee on Infectious Diseases has endeavored to provide pediatricians and other health care providers with guidance for determining who is at high risk for RSV disease since palivizumab was first licensed in 1998.2 Over the years, evidence has accumulated regarding the risk of RSV hospitalization and the AAP guidance for palivizumab use has become more restrictive. The most recent recommendations,3 published in 2014, removed otherwise healthy preterm infants born at or after 29 weeks of gestation from the high-risk groups recommended to receive palivizumab prophylaxis. In this issue of Pediatrics , Farber et al4 provide data from nine Medicaid managed care health programs in Texas supporting the 2014 recommendation. The investigators evaluated the effect of palivizumab administration on hospitalization for bronchiolitis with or without an RSV diagnosis among healthy preterm infants born at 29 to 36 weeks of gestation during their first RSV season occurring in 2012, 2013, or 2014.4 These infants did not have conditions known to increase hospitalization rates for RSV, specifically, chronic lung disease of prematurity or congenital heart disease. Although the recommendations to limit use of palivizumab in healthy preterm infants were released in July 2014, the Texas Medicaid program did not fully adopt them until 2015. Interestingly, even though they would have qualified under previous guidelines, the majority of the infants in the Farber study4 evaluated from 2012 to 2014, did not have paid claims for palivizumab. Overall, … Address correspondence to Carrie L. Byington, MD, HA and Edna Benning Presidential Professor of Pediatrics, Associate Vice President for Faculty and Academic Affairs, University of Utah Health Sciences Center, 26 2000 East HSEB, Suite 5515, Salt Lake City, UT. E-mail: carrie.byington{at}hsc.utah.edu