Increasing Rates of RSV Hospitalization among Preterm Infants: A Decade of Data

Abstract

Objective In 2014, the American Academy of Pediatrics (AAP) changed its policy on the use of respiratory syncytial virus immunoprophylaxis (RSV-IP) so that RSV-IP was no longer recommended for use among infants without other medical conditions born >29 weeks gestational age (wGA). This study examines 10-year trends in RSV-IP and RSV hospitalizations among term infants and preterm infants born at 29 to 34 wGA, including the 5 RSV seasons before and 5 RSV seasons after the AAP guidance change. Study Design A retrospective observational cohort study of a convenience sample of infants less than 6 months of age during RSV season (November–March) born between July 1, 2008, and June 30, 2019, who were born at 29 to 34 wGA (preterm) or >37 wGA (term) in the IBM MarketScan Commercial and Multi-State Medicaid databases. We excluded infants with medical conditions that would independently qualify them for RSV-IP. We identified RSV-IP utilization along with RSV and all-cause bronchiolitis hospitalizations during each RSV season. A difference-in-difference model was used to determine if there was a significant change in the relative rate of RSV hospitalizations following the 2014 policy change. Results There were 53,535 commercially insured and 85,099 Medicaid-insured qualifying preterm infants and 1,111,670 commercially insured and 1,492,943 Medicaid-insured qualifying term infants. Following the 2014 policy change, RSV-IP utilization decreased for all infants, while hospitalization rates tended to increase for preterm infants. Rate ratios comparing preterm to term infants also increased. The relative rate for RSV hospitalization for infants born at 29 to 34 wGA increased significantly for both commercially and Medicaid-insured infants (1.95, 95% CI: 1.67–2.27, p <0.001; 1.70, 95% CI: 1.55–1.86, p <0.001, respectively). Findings were similar for all-cause bronchiolitis hospitalizations. Conclusion We found that the previously identified increase in RSV hospitalization rates among infants born at 29 to 34 wGA persisted for at least 5 years following the policy change. Key Points

RSV-related hospitalization and outpatient palivizumab use in very preterm (born at <29 wGA) infants: 2003-2020

“… 23 Higher rates of RSVH and lower rates of palivizumab use have also been reported in preterm infants aged 29–34 wGA at birth following the policy change, 16 , 21 , 24 , 29 and these changes persisted for five years after the change in guidance. 6 Higher rates of ICU admission, mechanical ventilation, and longer hospitalization duration in infants born at 29–34 wGA with RSVH have also been observed following this change in policy. 30 Despite consistent evidence of these unintended consequences in very preterm infants, for whom the AAP has consistently recommended palivizumab prophylaxis, AAP policy was renewed without revision in 2019.…”

“…Previous research has described trends in palivizumab use and RSVH among term and preterm infants, 6–27 but limited data are available for very preterm infants. 10–12 The primary objective of the current study is to characterize palivizumab prophylaxis and risk of RSVH among very preterm (<29 wGA) infants and to compare the RSVH course among very preterm infants.…”

Real-World Studies of Respiratory Syncytial Virus Hospitalizations among Moderate/Late Preterm Infants Exposed to Passive Immunoprophylaxis with Palivizumab

“…28 Kong et al found significant increases in relative rates of RSVH following the policy change among infants born at 29 to 34 wGA for both commercially insured infants (1.95; 95% confidence interval [CI]: 1.67–2.27, p < 0.001) and Medicaid-insured infants (1.70; 95% CI: 1.55–1.86, p < 0.001). 35 In the retrospective database study by Fergie et al, 37 RSVH among infants born at 29 to 34 wGA nearly doubled, from 8.7% before to 14.2% after the policy change ( p < 0.0001). Using a similar strategy with a different claims database, Krilov et al also reported an increase in RSVH (relative risk: 1.55, 95% CI: 1.10–2.17, p = 0.011).…”

“…This difference is comparable to the effect seen in infants with the same characteristics enrolled in controlled trials, where the weighted mean rate ratio was 4.9. 19,46,47 Several studies have used data from administrative databases to assess the effectiveness of palivizumab for preventing RSVH in moderate/late premature infants in the realworld setting, revealing a significant increase in RSVH among otherwise healthy infants born after 29 to 34 wGA, [32][33][34][35] that correlates with the loss of eligibility for prophylaxis in this population after implementation of the 2014 AAP guidelines. 28 Kong et al found significant increases in relative rates of RSVH following the policy change among infants born at 29 to 34 wGA for both commercially insured infants (1.95; 95% confidence interval [CI]: 1.67-2.27, p < 0.001) and Medicaid-insured infants (1.70; 95% CI: 1.55-1.86, p < 0.001).…”

“…Several strategies have been used to assess the real-world effectiveness of palivizumab. Retrospective studies have been conducted on administrative and/or hospital databases to estimate the impact of eligibility on RSVH rates in preterm infants born after 29 wGA, including the IBM MarketScan and Medicaid databases, [32][33][34][35] the Optum research database, 36 or the Pediatric Health Information System database. 37 To adjust for seasonal differences in RSV infection pressure, these studies assessed RSVH rate ratios between preterm and term infants, consistently revealing a reduction of RSVH in infant populations that were eligible for prophylaxis.…”