Respiratory Syncytial Virus Hospitalizations among U.S. Preterm Infants Compared with Term Infants Before and After the 2014 American Academy of Pediatrics Guidance on Immunoprophylaxis: 2012–2016

Abstract

Objective The objective of this study was to compare risk for respiratory syncytial virus (RSV) hospitalizations (RSVH) for preterm infants 29 to 34 weeks gestational age (wGA) versus term infants before and after 2014 guidance changes for immunoprophylaxis (IP), using data from the 2012 to 2016 RSV seasons.

Study Design Using commercial and Medicaid claims databases, infants born between July 1, 2011 and June 30, 2016 were categorized as preterm or term. RSVH during the RSV season (November–March) were identified for infants aged <6 months and rate ratios (RRs) for hospitalization comparing preterm and term infants were calculated. Difference-in-difference models were fit to evaluate the changes in hospitalization risks in preterm versus term infants from 2012 to 2014 seasons to 2014 to 2016 seasons.

Results In all seasons, preterm infants had higher RSVH rates than term infants. Seasonal RRs prior to the guidance change for preterm wGA categories versus term infants ranged from 1.6 to 3.4. After the guidance change, the seasonal RRs ranged from 2.6 to 5.6. In 2014 to 2016, the risk associated with prematurity of 29 to 34 wGA versus term was significantly higher than in 2012 to 2014 (P<0.0001 for commercial and Medicaid samples).

Conclusion In infants aged <6 months, the risk for RSVH for infants 29 to 34 wGA compared with term infants increased significantly after the RSV IP recommendations became more restrictive.

Keywords

respiratory syncytial virus - immunoprophylaxis - hospitalization rates - palivizumab

Note

This work was presented as a poster titled “Respiratory syncytial virus hospitalization rates and costs among full-term and preterm infants before and after implementation of the 2014 American Academy of Pediatrics guidance on immunoprophylaxis” at AMCP Nexus 2017, Dallas, TX, October 16–19, 2017, and was presented as a poster titled “RSV Hospitalizations Before and Two Seasons After the 2014 American Academy of Pediatrics Guidance on RSV Immunoprophylaxis” at the 2018 Pediatric Academic Societies Annual Meeting, Toronto, Canada, May 5–8, 2018.

• References

• 1 Stockman LJ, Curns AT, Anderson LJ, Fischer-Langley G. Respiratory syncytial virus-associated hospitalizations among infants and young children in the United States, 1997-2006. Pediatr Infect Dis J 2012; 31 (01) 5-9
• 2 Centers for Disease Control and Prevention. RSV in infants and young children. Available at: https://www.cdc.gov/rsv/high-risk/infants-young-children.html . Accessed February 20, 2018
• 3 Boyce TG, Mellen BG, Mitchel Jr EF, Wright PF, Griffin MR. Rates of hospitalization for respiratory syncytial virus infection among children in Medicaid. J Pediatr 2000; 137 (06) 865-870
• 4 Stevens TP, Sinkin RA, Hall CB, Maniscalco WM, McConnochie KM. Respiratory syncytial virus and premature infants born at 32 weeks' gestation or earlier: hospitalization and economic implications of prophylaxis. Arch Pediatr Adolesc Med 2000; 154 (01) 55-61
• 5 Ambrose CS, Anderson EJ, Simões EA. , et al. Respiratory syncytial virus disease in preterm infants in the U.S. born at 32-35 weeks gestation not receiving immunoprophylaxis. Pediatr Infect Dis J 2014; 33 (06) 576-582
• 6 Winterstein AG, Knox CA, Kubilis P, Hampp C. Appropriateness of age thresholds for respiratory syncytial virus immunoprophylaxis in moderate-preterm infants: a cohort study. JAMA Pediatr 2013; 167 (12) 1118-1124
• 7 Mauskopf J, Margulis AV, Samuel M, Lohr KN. Respiratory syncytial virus hospitalizations in healthy preterm infants: systemic review. Pediatr Infect Dis J 2016; 35 (07) e229-e238
• 8 Colin AA, McEvoy C, Castile RG. Respiratory morbidity and lung function in preterm infants of 32 to 36 weeks' gestational age. Pediatrics 2010; 126 (01) 115-128
• 9 Langston C, Kida K, Reed M, Thurlbeck WM. Human lung growth in late gestation and in the neonate. Am Rev Respir Dis 1984; 129 (04) 607-613
• 10 Collins PL, Graham BS. Viral and host factors in human respiratory syncytial virus pathogenesis. J Virol 2008; 82 (05) 2040-2055
• 11 Yeung CY, Hobbs JR. Serum-gamma-G-globulin levels in normal premature, post-mature, and “small-for-dates” newborn babies. Lancet 1968; 1 (7553): 1167-1170
• 12 Synagis® (palivizumab) [prescribing information]. Gaithersburg, MD: AstraZeneca; 2014
• 13 American Academy of Pediatrics. Respiratory syncytial virus. In: Pickering LK, Baker CJ, Kimberlin DW, Long SS. , eds. Red Book: 2012 Report of the Committee on Infectious Diseases, 29th ed. Elk Grove Village: American Academy of Pediatrics; 2012: 609-617
• 14 American Academy of Pediatrics Committee on Infectious Diseases; American Academy of Pediatrics Bronchiolitis Guidelines Committee. Updated guidance for palivizumab prophylaxis among infants and young children at increased risk of hospitalization for respiratory syncytial virus infection. Pediatrics 2014; 134 (02) 415-420
• 15 Anderson EJ, Krilov LR, DeVincenzo JP. , et al. SENTINEL1: an observational study of respiratory syncytial virus hospitalizations among U.S. infants born at 29 to 35 weeks' gestational age not receiving immunoprophylaxis. Am J Perinatol 2017; 34 (01) 51-61
• 16 Rajah B, Sánchez PJ, Garcia-Maurino C, Leber A, Ramilo O, Mejias A. Impact of the updated guidance for palivizumab prophylaxis against respiratory syncytial virus infection: a single center experience. J Pediatr 2017; 181: 183-188
• 17 Blake SM, Tanaka D, Bendz LM, Staebler S, Brandon D. Evaluation of the financial and health burden of infants at risk for respiratory syncytial virus. Adv Neonatal Care 2017; 17 (04) 292-298
• 18 Grindeland CJ, Mauriello CT, Leedahl DD, Richter LM, Meyer AC. Association between updated guideline-based palivizumab administration and hospitalizations for respiratory syncytial virus infections. Pediatr Infect Dis J 2016; 35 (07) 728-732
• 19 Farber HJ. Impact of the 2014 American Academy of Pediatrics guidance on respiratory syncytial virus and bronchiolitis hospitalizations rates for infants born prematurely. J Pediatr 2017; 185: 250
• 20 Kong AM, Krilov LR, Fergie J. , et al. The 2014–2015 national impact of the 2014 American Academy of Pediatrics guidance for respiratory syncytial virus immunoprophylaxis on preterm infants born in the United States. Am J Perinatol 2018; 35 (02) 192-200
• 21 Palmer L, Hall CB, Katkin JP. , et al. Respiratory outcomes, utilization and costs 12 months following a respiratory syncytial virus diagnosis among commercially insured late-preterm infants. Curr Med Res Opin 2011; 27 (02) 403-412
• 22 Palmer L, Hall CB, Katkin JP. , et al. Healthcare costs within a year of respiratory syncytial virus among Medicaid infants. Pediatr Pulmonol 2010; 45 (08) 772-781
• 23 Krilov LR, Masaquel AS, Weiner LB, Smith DM, Wade SW, Mahadevia PJ. Partial palivizumab prophylaxis and increased risk of hospitalization due to respiratory syncytial virus in a Medicaid population: a retrospective cohort analysis. BMC Pediatr 2014; 14: 261
• 24 McLaurin KK, Farr AM, Wade SW, Diakun DR, Stewart DL. Respiratory syncytial virus hospitalization outcomes and costs of full-term and preterm infants. J Perinatol 2016; 36 (11) 990-996
• 25 Pavilack M, Clifford RA, Gonzales T, Kong AM, Wade S, McLaurin KK. Trends in utilization of outpatient respiratory syncytial virus prophylaxis with palivizumab among Medicaid- and commercially insured infants. Infect Dis Ther 2018; 7 (01) 121-134
• 26 Blanken MO, Rovers MM, Molenaar JM. , et al; Dutch RSV Neonatal Network. Respiratory syncytial virus and recurrent wheeze in healthy preterm infants. N Engl J Med 2013; 368 (19) 1791-1799
• 27 Palivizumab, a humanized respiratory syncytial virus monoclonal antibody, reduces hospitalization from respiratory syncytial virus infection in high-risk infants. The IMpact-RSV Study Group. Pediatrics 1998; 102 (3 Pt 1): 531-537
• 28 Feltes TF, Cabalka AK, Meissner HC. , et al; Cardiac Synagis Study Group. Palivizumab prophylaxis reduces hospitalization due to respiratory syncytial virus in young children with hemodynamically significant congenital heart disease. J Pediatr 2003; 143 (04) 532-540
• 29 Anderson EJ, Carosone-Link P, Yogev R, Yi J, Simões EAF. Effectiveness of palivizumab in high-risk infants and children: a propensity score weighted regression analysis. Pediatr Infect Dis J 2017; 36 (08) 699-704
• 30 Hall CB, Weinberg GA, Blumkin AK. , et al. Respiratory syncytial virus-associated hospitalizations among children less than 24 months of age. Pediatrics 2013; 132 (02) e341-e348
• 31 Simões EA, Anderson EJ, Wu X, Ambrose CS. Effects of chronologic age and young child exposure on respiratory syncytial virus disease among US preterm infants born at 32 to 35 weeks gestation. PLoS One 2016; 11 (11) e0166226
• 32 Tregoning JS, Schwarze J. Respiratory viral infections in infants: causes, clinical symptoms, virology, and immunology. Clin Microbiol Rev 2010; 23 (01) 74-98
• 33 AAP Updates Recommendations for Use of Palivizumab Against RSV [news release]. American Academy of Pediatrics; July 28, 2014. Available at: https://www.aap.org/en-us/about-the-aap/aap-press-room/pages/AAP-Updates-Recommendations-for-Use-of-Palivizumab-Against-RSV.aspx . Accessed February 20, 2018
• 34 American Academy of Pediatrics Committee on Infectious Diseases; American Academy of Pediatrics Bronchiolitis Guidelines Committee. Updated guidance for palivizumab prophylaxis among infants and young children at increased risk of hospitalization for respiratory syncytial virus infection. Pediatrics 2014; 134 (02) e620-e638
• 35 Ambrose CS. Statistical power to detect an association between guideline-based palivizumab administration and hospitalizations for respiratory syncytial virus infections. Pediatr Infect Dis J 2017; 36 (03) 348
• 36 Texas Medicaid/CHIP Vendor Drug Program Fee-For-Service Medicaid Synagis® Request Form, 2014–15 Season. Available at: http://www.maxor.com/forms/IVSolutions/pdfs/lubbock/synagis/SMN-Tx%20Medicaid%20Vendor%20Drug%20091614-IVSL.pdf . Accessed February 20, 2018
• 37 Makari D, Staat MA, Henrickson KJ, Wu X, Ambrose CS. The underrecognized burden of respiratory syncytial virus among infants presenting to US emergency departments. Clin Pediatr (Phila) 2015; 54 (06) 594-597
• 38 Ralston SL, Lieberthal AS, Meissner HC. , et al; American Academy of Pediatrics. Clinical practice guideline: the diagnosis, management, and prevention of bronchiolitis. Pediatrics 2014; 134 (05) e1474-e1502