Defining the Risk and Associated Morbidity and Mortality of Severe Respiratory Syncytial Virus Infection Among Preterm Infants Without Chronic Lung Disease or Congenital Heart Disease

Abstract

IntroductionThe REGAL (RSV Evidence—a Geographical Archive of the Literature) series provide a comprehensive review of the published evidence in the field of respiratory syncytial virus (RSV) in Western countries over the last 20 years. This second publication covers the risk and burden of RSV infection in preterm infants born at <37 weeks’ gestational age (wGA) without chronic lung disease or congenital heart disease.MethodsA systematic review was undertaken for articles published between January 1, 1995 and December 31, 2015. Studies reporting data for hospital visits/admissions for RSV infection among preterm infants as well as studies reporting RSV-associated morbidity, mortality, and risk factors were included. Study quality and strength of evidence (SOE) were graded using recognized criteria.Results2469 studies were identified of which 85 were included. Preterm infants, particularly those born at lower wGA, tended to have higher RSV hospitalization (RSVH) rates compared with otherwise healthy term infants (high SOE). RSVH rates ranged from ~5 per 1000 children to >100 per 1000 children with the highest rates shown in the lowest gestational age infants (high SOE). Independent risk factors associated with RSVH include: proximity of birth to the RSV season, living with school-age siblings, smoking of mother during pregnancy or infant exposure to environmental smoking, reduced breast feeding, male sex, and familial atopy (asthma) (high SOE). Predictive models can identify 32/33–35 wGA infants at risk of RSVH (high SOE).ConclusionRSV infection remains a major burden on Western healthcare systems and is associated with significant morbidity. Further studies focusing on the prevalence and burden of RSV in different gestational age cohorts, the changing risk of RSVH during the first year of life, and on RSV-related mortality in preterm infants are needed to determine the true burden of disease.FundingAbbVie.Electronic supplementary materialThe online version of this article (doi:10.1007/s40121-016-0130-1) contains supplementary material, which is available to authorized users.

The impact of respiratory viruses on lung health after preterm birth

“…Following the neonatal hospitalisation, the overall risk of re-hospitalisation with an acute respiratory infection remains at least three times higher during the first year of life compared to infants born at term [2,3,38,39]. The frequency of re-hospitalisation during the first year of life among preterm infants ranges from 6 to 50% [5,40–42] depending on the cohort studied.…”

“…The frequency of re-hospitalisation during the first year of life among preterm infants ranges from 6 to 50% [5,40–42] depending on the cohort studied. Young chronological age is the main predictor of infection-related morbidity among preterm infants, with studies reporting increased risk of infection, healthcare utilisation and hospital readmissions during the first 6 months of life [39,43,44]. …”

“…Reduced gestational age is another well-known risk factor for respiratory infection-related re-hospitalisations during early life [39], with community-based studies reporting increasing cost, risk and severity of infection as gestational age decreases [5,40,45]. In one series, preterm infants born at less than 25 weeks’ gestation had more than twice the frequency of re-hospitalisation due to acute respiratory infections and more than twice the length of hospital admission compared to those born in the late preterm period (31% and 12 days vs. 13% and 5 days, respectively) [40].…”

“…Preterm infants with certain coexisting morbidities, including BPD, congenital heart disease or chronic oxygen dependency are particularly at risk for severe infections and infection-related hospitalisation during early life [39]. Preterm infants with BPD have an increased frequency of health care utilisation and hospital admissions due to acute respiratory infections compared to those without BPD [2,38,46].…”

Phase 1 First‐in‐Human, Single‐ and Multiple‐Ascending Dose, and Food Effect Studies to Assess the Safety, Tolerability, and Pharmacokinetics of Presatovir for the Treatment of Respiratory Syncytial Virus Infection

“…RSV is the most common viral cause of death in children under 5 years of age in the United States and is associated with approximately 10‐fold greater mortality compared with influenza in children younger than 1 year . Relative to full‐term infants, preterm infants face increased rates of hospitalization, health care resource utilization, and morbidity resulting from RSV infection . Certain adult populations also experience higher morbidity and mortality due to RSV infection.…”