Respiratory syncytial virus disease in preterm infants in the U.S. born at 32-35 weeks gestation not receiving immunoprophylaxis

Abstract

Background: The Respiratory Syncytial Virus (RSV) Respiratory Events Among Preterm Infants Outcomes and Risk Tracking (REPORT) study evaluated RSV disease burden in U.S. preterm infants 32-35 weeks gestational age (wGA) not receiving RSV prophylaxis.

Methods: Preterm infants <6 months of age as of November 1st were followed prospectively at 188 clinics from September to May 2009-2010 or 2010-2011. Nasal and pharyngeal swabs were collected for medically attended acute respiratory illnesses (MAARI) and tested for RSV by qRT-polymerase chain reaction. Risk factors were assessed using multivariate Cox proportional hazard model adjusted for seasonality.

Results: Of 1642 evaluable infants, 287 experienced RSV MAARI. Rates of RSV-related MAARI, outpatient lower respiratory tract illness, emergency department visits and hospitalization (RSVH) during November to March were 25.4, 13.7, 5.9 and 4.9 per 100 infant-seasons, respectively. Preschool-aged, nonmultiple-birth siblings and daycare attendance were consistently associated with increased risk of RSV. RSVH rates were highest in infants 32-34 and 35 wGA who were <6 months of age during November to March with daycare attendance or nonmultiple-birth, preschool-aged siblings (8.9 and 9.3 per 100 infant-seasons, respectively, versus 3.5 for all other infants, P<0.001). Chronologic age <3 months was associated with a higher RSVH rate for infants 35 wGA but not for infants 32-34 wGA.

Conclusions: In US preterm infants who were 32-35 wGA, <6 months on November 1st and not receiving RSV prophylaxis, the burden of RSV MAARI was 25 per 100 infant-seasons. The highest RSVH rates occurred among those with daycare attendance or nonmultiple-birth, preschool-aged siblings while they were <6 months of age during the RSV season.

Trial registration: ClinicalTrials.gov NCT00983606.

FIGURE 1.

Study subject disposition and care patterns among infants with RSV-related MAARI. *Of the 32 patients with an ED and hospital visit, 9 were discharged home but hospitalized 0–8 days later, and 23 were admitted immediately to the hospital. No RSV hospitalization was recorded for 2 subjects with RSV whose ED discharge disposition was hospital admission (1 with ICU admission), because hospitalization records could not be obtained.

FIGURE 2.

Multivariate risk factor analysis. HR, hazard ratio; wGA, weeks gestational age. Variables that were not statistically significant predictors for the specific outcome evaluated and thus were not retained in the multivariate model were not presented.

FIGURE 3.

Risk of RSV disease during November to March by GA, chronologic age on November 1st, chronologic age during November to March and 2012 AAP environmental risk factors (A) RSV-related MAARI; (B) RSV Hospitalizations. GA, gestational age. Rates are per 100 infant-seasons. For chronologic age during November to March, subjects contributed events and exposure time only while they were within specific age ranges. Overall incidence rates are for November to March regardless of chronologic age during November to March. The plus (+) and minus (−) symbols represent the presence or absence of 2012 AAP environmental risk factors, respectively. AAP risk factors were associated with increased rates of RSV-related events (P < 0.02 for all event types). Older chronologic age was associated with an increased risk of RSV-related MAARI (P < 0.01 for both <3 vs. ≥3 months and <6 vs. ≥6 months). There was no evidence of a decrease in RSV hospitalization rates in infants 32–34 wGA at 3 to <6 months versus <3 months of age (P = 0.9).