Disease Severity of Hospitalizations for RSV Lower Respiratory Tract Infections among Term Infants and Infants Born at 33 to 35 Weeks Gestational Age in Quebec

Introduction: There is a general belief that the clinical characteristics of the hospitalization for a lower respiratory tract infection (LRTI) or for an infection due to respiratory syncytial virus (RSV) of infants born at 33 to 35 weeks gestational age (wGA) are similar to those of infants born at term (≥37 wGA). While conducting a study on the impact on the lack of immunoprophylaxis for RSV disease for infants born at 33 to 35 wGA, we included a control arm of term infants hospitalized under the same conditions and are reporting the comparison of the two infant groups.

Materials and Methods: We conducted a 4-year observational study in 25 hospitals from the Province of Quebec, Canada. Births at 33 to 35 wGA and LRTI/RSV hospitalizations (H) were identified via discharge databases using International Classification of Diseases (ICD)-9 or -10 codes. A secondary end point of this study was to document disease severity and burden of illness associated with LRTI/RSV-H among preterm infants born at 33 to 35 wGA and <6 months of age at the start of or born during the RSV season compared with term infants (born at ≥37 wGA and <6 months of age at the start of or born during the RSV season). Centers were asked to retrieve information for two term infants hospitalized for each 33 to 35 wGA infant hospitalized at their center during the RSV seasons of 2015 to 2016 and 2016 to 2017. Term infant controls were matched for calendar month of hospitalization, for chronological age, and gender (ideally). Through chart review and mailed parental questionnaires, we described the clinical course and parental burden (health resource utilization; productivity; stressors) of LRTI/RSV-H in 33 to 35 wGA infants and in ≥37 wGA infants. Categorical data were summarized using counts and percentages and continuous data using mean, standard deviations, and interquartile values. Comparisons between the preterm and term infant groups were based on the chi-square test for categorical data and the t-test for the equality of means for continuous data.

Results: We identified 130 infants born at 33 to 35 wGA (preterm) who were hospitalized for LRTI/RSV during 2 RSV seasons and 234 infants born at ≥37 wGA (term) who were hospitalized during the same months. In both cohorts, the majority of infants were male (56% for preterms and 65% for terms; p = 0.0976). Birth hospitalization characteristics were statistically significantly different between the preterm and term cohorts: birth weight (2,341 vs. 3,462 g, respectively; p < 0.0001), percentage of singleton (65 vs. 97%, respectively; p < 0.0001), length of stay (LOS) (14.8 vs. 3.3 days, respectively; p < 0.0001), and need for respiratory support (36 vs. 2%, respectively; p < 0.0001). The mean chronological age at LRTI/RSV-H was 15.3 weeks for preterm infants and 14.3 weeks for term infants (p = 0.3098). The LOS for preterm infants was on average 6.0 ± 7.84 days, whereas it was 3.6 ± 2.34 days for term infants (p = 0.0009). A greater percentage of preterm infants required a stay in the pediatric intensive care unit (19.2%) than term infants (10.7%) (p = 0.0232) and the LOS in that unit was longer for preterm infants (7.0 ± 4.15 days) than for term infants (3.4 ± 2.60 days) (p = 0.0007). Similarly, mechanical ventilation was required for a larger proportion and for longer duration for preterm infants (10.0%; 6.1 days) than for term infants (1.3%; 2.3 days) (p = 0.0001 for proportion and p = 0.0798 for duration). Oxygen supplementation was used for more days for preterm infants than for term infants (4.4 vs. 2.5 days, respectively; p = 0.0002). Prior to admission for LRTI/RSV-H, 50% of parents of preterm infants reported visiting their general practitioner/pediatrician for issues related to respiratory illness, as did 38% of parents (difference not significant) of term infants for an average of 2.3 visits in both groups. Fathers of preterm infants reported a mean of 28.5 hours missed work because of the hospitalization, whereas it was 14.3 hours for fathers of term infants (p = 0.0161). Mothers and fathers of preterm infants reported, on a numeric rating scale of 0 to 10, greater impact on their ability to do their regular daily activities (8.9 and 7.8, respectively) compared with those of term infants (8.4 and 6.6, respectively), where 0 meant no effect and 10 meant completely preventing them from doing their daily activities (p = nonsignificant for mothers; p = 0.0054 for fathers).

Conclusion: In a province-wide study, we observed increased disease severity and burden of illness for LRTI/RSV-H for preterm infants when compared with term infants.

Conflict of Interest: G.C. has no conflict of interest or any ongoing financial, professional, or personal relationships with AbbVie, except an unrestricted grant for this study. M.L. received an unrestricted grant from AbbVie for this study. E.M. has no bias, affiliation with AbbVie or disclosure to declare; received an unrestricted grant for this study. J.P. has received consulting/speaker fees/honoraria from AbbVie, BD Diagnostics, Cepheid; and research grant funding and contracted research from AbbVie, MedImmune, Janssen, BD Diagnostics. I.D. is an AbbVie employee and holds stock or stock options AbbVie.

Funding: AbbVie Inc. funded this study and participated in the study design, research, analysis, data collection, interpretation of data, reviewing, and approval of the publication.

Keywords: RSV; preterm infant; term infant; hospitalization