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

Goldstein, Mitchell; Fergie, Jaime; Krilov, Leonard R
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.
PMID: 33656649
ISSN: 2193-8229
CID: 4801522

Severity and Cost of RSV Hospitalization Among US Preterm Infants Following the 2014 American Academy of Pediatrics Policy Change

Krilov, Leonard R; Forbes, Michael L; Goldstein, Mitchell; Wadhawan, Rajan; Stewart, Dan L
The American Academy of Pediatrics (AAP) Committee on Infectious Diseases (COID) periodically publishes recommendations for respiratory syncytial virus (RSV) immunoprophylaxis (IP) use in pediatric patients considered to be at highest risk for severe RSV infection. In 2014, for the first time, the AAP COID stopped recommending the use of RSV IP for otherwise healthy infants born at 29 weeks' gestational age (wGA) or later, stating that RSV hospitalization (RSVH) rates in this population are similar to those of term infants. Subsequently, epidemiological studies in the US at national and regional levels provided evidence of the impact of the policy change in 29-34 wGA infants. The results of these studies demonstrated a significant decrease in IP use after 2014 that was associated with an increased rate of RSVH in 29-34 wGA infants and an increase in morbidities. RSVH-related morbidities included pediatric intensive care unit (ICU) admissions, an increased need for mechanical ventilation, and an increase in the length of stay. After the change in recommendations, the costs of RSVH also rose among 29-34 wGA infants. The severity of the illness and expenses associated with RSVH were generally higher among 29-34 wGA infants of younger chronologic age compared with older preterm infants. Overall, these studies underscore that 29-34 wGA infants continue to be a high-risk pediatric population that could benefit from the protection provided by RSV IP. On the basis of these data, in 2018, the National Perinatal Association developed guidelines that recommended RSV IP for all ≤ 32 wGA infants and 32-35 wGA infants with additional risk factors. Re-evaluation of the AAP COID policy is warranted in light of these observations.
PMID: 33656650
ISSN: 2193-8229
CID: 4801532

Current State of Respiratory Syncytial Virus Disease and Management

Chatterjee, Archana; Mavunda, Kunjana; Krilov, Leonard R
Respiratory syncytial virus (RSV) is a major cause of hospitalizations due to pneumonia and bronchiolitis. Substantial morbidity and socioeconomic burden are associated with RSV infection worldwide. Populations with higher susceptibility to developing severe RSV include premature infants, children with chronic lung disease of prematurity (CLDP) or congenital heart disease (CHD), elderly individuals aged > 65 years, and immunocompromised individuals. In the pediatric population, RSV can lead to long-term sequelae such as wheezing and asthma, which are associated with increased health care costs and reduced quality of life. Treatment for RSV is mainly supportive, and general preventive measures such as good hygiene and isolation are highly recommended. Although vaccine development for RSV has been a global priority, attempts to date have failed to yield a safe and effective product for clinical use. Currently, palivizumab is the only immunoprophylaxis (IP) available to prevent severe RSV in specific high-risk pediatric populations. Well-controlled, randomized clinical trials have established the efficacy of palivizumab in reducing RSV hospitalization (RSVH) in high-risk infants including moderate- to late-preterm infants. However, the American Academy of Pediatrics (AAP), in its 2014 policy, stopped recommending RSV IP use for ≥ 29 weeks' gestational age infants. Revisions to the AAP policy for RSV IP have largely narrowed the proportion of pediatric patients eligible to receive RSV IP and have been associated with an increase in RSVH and morbidity. On the other hand, after reviewing the recent evidence on RSV burden, the National Perinatal Association, in its 2018 clinical practice guidelines, recommended RSV IP use for a wider pediatric population. As the AAP recommendations drive insurance reimbursements for RSV IP, they should be revised to help further mitigate RSV disease burden.
PMCID:7928170
PMID: 33660239
ISSN: 2193-8229
CID: 4801692

RSV Disease: Current Management and the Future of Treatment and Prevention

Krilov, Leonard R; Domachowske, Joseph B; Anderson, Evan J
PMID: 33660240
ISSN: 2193-8229
CID: 4801702

An Overview of the Ongoing Clinical Issues of COVID-19

Noor, Asif; Krilov, Leonard R
Childhood cases of coronavirus disease 2019 (COVID-19) are on the rise as the pandemic continues to rage across the globe. Most children acquire infection from an adult household member. Children may stay asymptomatic, have a pre-symptomatic stage, or present with symptoms (fever, cough, and difficulty breathing being the most common). Nearly one-third of the pediatric cases (32%) in the United States occurred in children age 15 to 17 years. Children are also at risk of a postinfectious hyperinflammatory syndrome called multisystem inflammatory syndrome in children (MIS-C). The risk of vertical transmission is low (2%) in newborns of mothers with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Nucleic acid amplification testing (NAAT) is the gold standard for (SARS-CoV-2). Serology should be considered in a child with high clinical suspicion for COVID-19 when NAAT is negative and at least 2 weeks have passed since symptom onset and for assessment of MIS-C. Easy fatigability after COVID-19 infection is reported in adults; however, data in children are lacking. Implementation of early and robust containment strategies coupled with universal COVID-19 vaccination are vital to halt the spread. [Pediatr Ann. 2021;50(2):e84-e89.].
PMID: 33576834
ISSN: 1938-2359
CID: 4780192

Impact of Maternal SARS-CoV-2 Detection on Breastfeeding Due to Infant Separation at Birth

Popofsky, Stephanie; Noor, Asif; Leavens-Maurer, Jill; Quintos-Alagheband, Maria Lyn; Mock, Ann; Vinci, Alexandra; Magri, Eileen; Akerman, Meredith; Noyola, Estela; Rigaud, Mona; Pak, Billy; Lighter, Jennifer; Ratner, Adam J; Hanna, Nazeeh; Krilov, Leonard
OBJECTIVE:To assess the impact of separation of SARS-CoV-2 PCR-positive mother-newborn dyads on breastfeeding outcomes. STUDY DESIGN/METHODS:This is an observational longitudinal cohort study of SARS-CoV-2 PCR-positive mothers and their infants at three NYU Langone Health hospitals from March 25, 2020 through May 30, 2020. Mothers were surveyed by telephone regarding pre-delivery feeding plans, in-hospital feeding, and home feeding of their neonates. Any change prompted an additional question to determine whether this change was due to COVID-19. RESULTS:Of the 160 mother-newborn dyads, 103 mothers were reached by telephone, and 85 consented to participate. No significant difference was observed in pre-delivery feeding plan between the separated and unseparated dyads (P = .268). Higher rates of breastfeeding were observed in the unseparated dyads compared with the separated dyads in the hospital (p<0.001), and at home (p=0.012). Only two mothers in each group reported expressed breast milk as the hospital feeding source (5.6% of unseparated vs 4.1% of separated). COVID-19 was more commonly cited as the reason for change among the separated compared with the unseparated group (49.0% vs 16.7%, p<0.001). When dyads were further stratified by symptom status into four groups (asymptomatic separated, asymptomatic unseparated, symptomatic separated, and symptomatic unseparated), results remained unchanged. CONCLUSION/CONCLUSIONS:In the setting of COVID-19, separation of mother-newborn dyads impacts breastfeeding outcomes, with lower rates of breastfeeding both during hospitalization and at home following discharge compared with unseparated mothers and infants. No evidence of vertical transmission was observed; one case of postnatal transmission occurred from an unmasked symptomatic mother who held her infant at birth.
PMID: 32791077
ISSN: 1097-6833
CID: 4556622

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

Fergie, Jaime; Goldstein, Mitchell; Krilov, Leonard R; Wade, Sally W; Kong, Amanda M; Brannman, Lance
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.
PMID: 33090914
ISSN: 2164-554x
CID: 4646192

Respiratory syncytial virus hospitalizations in US preterm infants after the 2014 change in immunoprophylaxis guidance by the American Academy of Pediatrics

Krilov, Leonard R; Anderson, Evan J
Palivizumab is the only licensed and effective immunoprophylaxis (IP) available to prevent respiratory syncytial virus (RSV) infection in high-risk infants including infants born at ≤35 weeks' gestational age (wGA). In 2014, the American Academy of Pediatrics stopped recommending IP for otherwise healthy 29-34 wGA infants, stating that their risk of RSV hospitalization (RSVH) was similar to term infants. Recent studies have demonstrated a significant decline in IP use after 2014 that was accompanied by an increased risk of RSVH in 29-34 wGA infants vs term infants. Severity and healthcare utilization of RSVH were high among 29-34 wGA infants. In 2018, the National Perinatal Association developed guidelines advocating IP use in all ≤32 wGA infants and 32-35 wGA infants with additional risk factors. Risk factor predictive models can identify infants who are at risk for RSVH and promote cost-effective use of palivizumab until new methods of RSV prevention become available.
PMID: 32499597
ISSN: 1476-5543
CID: 4469382

Young Children Presenting With Fever and Rash in the Midst of SARS-CoV-2 Outbreak in New York

Wolfe, Danielle Marissa; Nassar, George Noble; Divya, Kanneganti; Krilov, Leonard R; Noor, Asif
PMID: 32633553
ISSN: 1938-2707
CID: 4518312

RSV and non-RSV illness hospitalization in RSV immunoprophylaxis recipients: A systematic literature review

Bloomfield, Adam; DeVincenzo, John P; Ambrose, Christopher S; Krilov, Leonard R
Respiratory syncytial virus (RSV) immunoprophylaxis (IP) has been shown to reduce RSV hospitalization rates in high-risk infants; however, it is unclear whether RSV IP is associated with increased risk of non-RSV disease, particularly non-RSV hospitalizations. We conducted a systematic literature review to understand the occurrences of non-RSV disease and/or non-RSV hospitalizations in published studies of RSV IP. Cochrane, Embase, and PubMed databases were searched and reviewed to summarize data regarding the incidence of RSV and non-RSV respiratory disease among RSV IP recipients and controls in randomized and non-randomized studies. Independent investigators screened and selected studies for inclusion. Risk-of-bias assessment was conducted to assess strength/validity of the data using the Jadad scoring system and Downs and Black quality assessment tool, where appropriate. Twenty studies were included for review (5 randomized controlled trials [RCTs]; 15 non-randomized studies). RCTs of RSV IP demonstrated reductions in RSV hospitalizations and all-cause hospitalizations, with no increase in hospitalizations for non-RSV disease. Non-randomized studies also demonstrated reduced RSV hospitalizations in RSV IP recipients but had mixed results in assessments of hospitalizations for non-RSV disease. When RSV IP recipients and controls were more similar in disease severity risk, results of non-randomized studies aligned more closely with RCTs. Observations of increased non-RSV hospitalization rates among RSV IP recipients in some non-randomized studies could be primarily explained by differences in the clinical characteristics between RSV IP recipients and controls.
PMID: 32512375
ISSN: 1873-5967
CID: 4477982