Risk factors for respiratory syncytial virus associated with acute lower respiratory infection in children under five years: Systematic review and meta–analysis

Abstract

BackgroundRespiratory syncytial virus (RSV) is the most common pathogen identified in young children with acute lower respiratory infection (ALRI) as well as an important cause of hospital admission. The high incidence of RSV infection and its potential severe outcome make it important to identify and prioritise children who are at higher risk of developing RSV–associated ALRI. We aimed to identify risk factors for RSV–associated ALRI in young children.MethodsWe carried out a systematic literature review across 4 databases and obtained unpublished studies from RSV Global Epidemiology Network (RSV GEN) collaborators. Quality of all eligible studies was assessed according to modified GRADE criteria. We conducted meta–analyses to estimate odds ratios with 95% confidence intervals (CI) for individual risk factors.ResultsWe identified 20 studies (3 were unpublished data) with “good quality” that investigated 18 risk factors for RSV–associated ALRI in children younger than five years old. Among them, 8 risk factors were significantly associated with RSV–associated ALRI. The meta–estimates of their odds ratio (ORs) with corresponding 95% confidence intervals (CI) are prematurity 1.96 (95% CI 1.44–2.67), low birth weight 1.91 (95% CI 1.45–2.53), being male 1.23 (95% CI 1.13–1.33), having siblings 1.60 (95% CI 1.32–1.95), maternal smoking 1.36 (95% CI 1.24–1.50), history of atopy 1.47 (95% CI 1.16–1.87), no breastfeeding 2.24 (95% CI 1.56–3.20) and crowding 1.94 (95% CI 1.29–2.93). Although there were insufficient studies available to generate a meta–estimate for HIV, all articles (irrespective of quality scores) reported significant associations between HIV and RSV–associated ALRI.ConclusionsThis study presents a comprehensive report of the strength of association between various socio–demographic risk factors and RSV–associated ALRI in young children. Some of these amenable risk factors are similar to those that have been identified for (all cause) ALRI and thus, in addition to the future impact of novel RSV vaccines, national action against ALRI risk factors as part of national control programmes can be expected to reduce burden of disease from RSV. Further research which identifies, accesses and analyses additional unpublished RSV data sets could further improve the precision of these estimates.

The association between environmental tobacco smoke exposure and childhood respiratory disease: a review

“…ETS has been found to increase the risk of severe RSV disease as measured by hospitalization and hypoxia in both infants and children (adjusted OR 2.2–3.8) [46]. A recent systematic review and meta-analysis identifying risk factors for RSV-associated LRTI in children reported maternal smoking to be one of the most important risk factors (OR 1.36, 95% CI 1.24–1.50) [47] (Table 4). …”

“…A recent systematic review and meta-analysis identifying risk factors for RSV-associated LRTI in children reported maternal smoking to be one of the most important risk factors (OR 1.36, 95% CI 1.24–1.50) [47] (Table 4). …”

Tuberculosis and pneumonia in HIV-infected children: an overview

“…HIV is an important risk factor for severe RSV infections, especially in high-burden settings [86]. HIV-infected children are older and may develop RSV outside of the seasonal peaks.…”

Childhood pneumonia – the Drakenstein Child Health Study

“…[20,21] Consistent with other studies, RSV occurred in young infants with the peak incidence under 6 months. [22] Maternal immunisation against RSV during late pregnancy may therefore be an attractive novel strategy to prevent disease in young infants. [23] In addition, B. pertussis occurred in young infants, and mostly before completion of the primary series of three immunisations; in turn, immunisation of pregnant women with B. pertussis may also be an effective strategy to prevent this burden.…”