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Meta-Analysis
. 2022 Mar 15;225(6):1100-1111.
doi: 10.1093/infdis/jiaa752.

Respiratory Syncytial Virus-Associated Hospitalization Rates among US Infants: A Systematic Review and Meta-Analysis

John M McLaughlin  1 , Farid Khan  1 , Heinz-Josef Schmitt  1 , Yasmeen Agosti  1 , Luis Jodar  1 , Eric A F Simões  2   3 , David L Swerdlow  1
Affiliations
Meta-Analysis

Respiratory Syncytial Virus-Associated Hospitalization Rates among US Infants: A Systematic Review and Meta-Analysis

John M McLaughlin et al. J Infect Dis. .

Abstract

Background: Although global reviews of infant respiratory syncytial virus (RSV) burden exist, none have summarized data from the United States or evaluated how RSV burden estimates are influenced by variations in study design.

Methods: We performed a systematic literature review and meta-analysis of studies describing RSV-associated hospitalization rates among US infants and examined the impact of key study characteristics on these estimates.

Results: We reviewed 3328 articles through 14 August 2020 and identified 25 studies with 31 unique estimates of RSV-associated hospitalization rates. Among US infants <1 year of age, annual rates ranged from 8.4 to 40.8 per 1000 with a pooled rate of 19.4 (95% confidence interval [CI], 17.9-20.9). Study type influenced RSV-associated hospitalization rates (P = .003), with active surveillance studies having pooled rates (11.0; 95% CI, 9.8-12.2) that were half that of studies based on administrative claims (21.4; 19.5-23.3) or modeling approaches (23.2; 20.2-26.2).

Conclusions: Applying our pooled rates to the 2020 US birth cohort suggests that 79 850 (95% CI, 73 680-86 020) RSV-associated infant hospitalizations occur each year. The full range of RSV-associated hospitalization rates identified in our review can better inform future evaluations of RSV prevention strategies. More research is needed to better understand differences in estimated RSV burden across study design.

Keywords: RSV prevention; United States; burden of disease; epidemiology; incidence; study design.

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Figures

Figure 1.
Figure 1.
Flow diagram of the literature selection process. Of the 25 studies in our analysis, 5 of 25 (20%) [6, 23, 25, 31, 32] reported >1 rate based on within-study variation(s) of the definition of respiratory syncytial virus (RSV) hospitalization. Of these, 3 of 5 [6, 23, 25] were variations in which diagnosis positions were queried when identifying incident RSV cases in administrative claims data, and 2 of 5 [31, 32] were variations in how RSV was identified (ie, International Classification of Diseases, Ninth Revision codes only vs modeled RSV burden). This resulted in 31 unique estimated rates of RSV-associated hospitalization among US infants for final analyses (ie, 4 studies [23, 25, 31, 32] reported 2 estimates and 1 [6] reported 3 estimates). Abbreviations: HCUP NIS, Healthcare Cost and Utilization Projection National (Nationwide) Inpatient Sample; NHDS, National Hospital Discharge Survey.
Figure 2.
Figure 2.
Annual respiratory syncytial virus (RSV)–associated hospitalization rates per 1000 among US infants <1 year of age (n = 31). Estimates in parentheses were imputed using RSV-associated hospitalization rates reported for a different age group. Active surveillance studies were prospective and required etiologic testing and confirmation of RSV. All active prospective surveillance study estimates came from the Centers for Disease Control and Prevention New Vaccines Surveillance Network (CDC NVSN) program and identified RSV via culture and reverse-transcription polymerase-chain reaction of nasal and throat swab samples taken from children hospitalized with acute respiratory infection in 1 of the study catchment sites. Retrospective medical record review (MRR) studies were based on passive surveillance of available standard-of-care medical and laboratory records. Two retrospective MRR studies [17, 18] adjusted their estimated RSV incidence rates upward to account for the estimated number of cases that were missed based on standard-of-care diagnostic and testing practices (ie, missed case ascertainment in passive surveillance). ICD-9 code studies were retrospective analyses of administrative claims data based on RSV-specific International Classification of Diseases, Ninth Revision (ICD-9) codes (466.11, 480.1, and 079.6). Model-based estimates supplemented RSV-specific ICD-9 claims data with etiologic surveillance data. Abbreviations: HCUP NIS, Healthcare Cost and Utilization Projection National (Nationwide) Inpatient Sample; NHDS, National Hospital Discharge Survey.
Figure 3.
Figure 3.
Annual respiratory syncytial virus (RSV)–associated hospitalization rates per 1000 among US infants <6 months of age (n = 31). Estimates in parentheses were imputed using RSV-associated hospitalization rates reported for a different age group. Active surveillance studies were prospective and required etiologic testing and confirmation of RSV. All active prospective surveillance study estimates came from the Centers for Disease Control and Prevention New Vaccines Surveillance Network (CDC NVSN) program and identified RSV via culture and reverse-transcription polymerase-chain reaction of nasal and throat swab samples taken from children hospitalized with acute respiratory infection in 1 of the study catchment sites. Retrospective MRR studies were based on passive surveillance of available standard-of-care medical and laboratory records. Two retrospective medical record review (MRR) studies [17, 18] adjusted their estimated RSV incidence rates upward to account for the estimated number of cases that were missed based on standard-of-care diagnostic and testing practices (ie, missed case ascertainment in passive surveillance). International Classification of Diseases, Ninth Revision (ICD-9) code studies were retrospective analyses of administrative claims data based on RSV-specific ICD-9 codes (466.11, 480.1, and 079.6). Model-based estimates supplemented RSV-specific ICD-9 claims data with etiologic surveillance data. Abbreviations: HCUP NIS, Healthcare Cost and Utilization Projection National (Nationwide) Inpatient Sample; NHDS, National Hospital Discharge Survey.
Figure 4.
Figure 4.
Box-and-whisker plot of annual respiratory syncytial virus (RSV)–associated hospitalization rate per 1000 among US infants aged <1 year (A) or <6 months (B), by study type (n = 31). In this Tukey box-and-whisker plot, individual studies are represented by dots, medians by the line separating the 2 different color shades in the shaded box, and interquartile ranges by shaded boxes. Outlying values (ie, those outside the whiskers) are studies that were beyond 1.5× the interquartile range. P = .003 and P = .01 among infants <1 year and <6 months old, respectively (1-way analysis of variance to determine differences in RSV-associated hospitalization rates by study type; degrees of freedom, 3). Active surveillance studies were prospective and required etiologic testing and confirmation of RSV. All active prospective surveillance study estimates came from the Centers for Disease Control and Prevention New Vaccines Surveillance Network program and identified RSV by means of culture and reverse-transcription polymerase-chain reaction of nasal and throat swab samples taken from children hospitalized with acute respiratory infection in 1 of the study catchment sites. Retrospective medical record review (MRR) studies were based on passive surveillance of available standard-of-care medical and laboratory records. Two retrospective MRR studies [17, 18] adjusted their estimated RSV incidence rates upward to account for the estimated number of cases that were missed based on standard-of-care diagnostic and testing practices (ie, missed case ascertainment in passive surveillance). International Classification of Diseases, Ninth Revision (ICD-9) code studies were retrospective analyses of administrative claims data based on RSV-specific ICD-9 codes (466.11, 480.1, and 079.6). Model-based estimates supplemented RSV-specific ICD-9 claims data with etiologic surveillance data. Three of 31 estimates (10%) came from studies that did not directly report rates for infants <1 year old or where average rates for this age group could not be calculated [16, 17, 30]. In these instances, rates for infants <1 year old were estimated from other reported age groups (2 estimates were imputed using rates reported for children <2 years old [16, 30] and 1 was imputed from rates reported for children <5 years old [17]) based on Shi et al [1]. Rates for children <6 months old were imputed based on rates in infants <1 year old for 22 of 31 (71%) [6, 16, 17, 19, 21–27, 29–34], based on Shi et al [1].
Figure 5.
Figure 5.
Forest plot of annual respiratory syncytial virus (RSV)–associated hospitalization rates per 1000 among US infants by study type and age group (n = 31). The x-axis represents the annual rates of RSV-associated hospitalization per 1000. Inverse-variance weighting, which weights each study on the inverse of the variance of each study effect estimate (ie, larger weights for studies with smaller standard errors), was used to combine individual study estimates. Active surveillance studies were prospective and required etiologic testing and confirmation of RSV. All active prospective surveillance study estimates came from the Centers for Disease Control and Prevention New Vaccines Surveillance Network program and identified RSV via culture and reverse-transcription polymerase-chain reaction of nasal and throat swab samples taken from children hospitalized with acute respiratory infection in 1 of the study catchment sites. Retrospective medical record review (MRR) studies were based on passive surveillance of available standard-of-care medical and laboratory records. Two retrospective MRR studies [17, 18] adjusted their estimated RSV incidence rates upward to account for the estimated number of cases that were missed based on standard-of-care diagnostic and testing practices (ie, missed case ascertainment in passive surveillance). International Classification of Diseases, Ninth Revision (ICD-9) code studies were retrospective analyses of administrative claims data based on RSV-specific ICD-9 codes (466.11, 480.1, and 079.6). Model-based estimates supplemented RSV-specific ICD-9 claims data with etiologic surveillance data. Abbreviation: CI, confidence interval.
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