Global disease burden of and risk factors for acute lower respiratory infections caused by respiratory syncytial virus in preterm infants and young children in 2019: a systematic review and meta-analysis of aggregated and individual participant data

Xin Wang, You Li, Ting Shi, Louis Bont, Helen Y Chu, Heather J Zar, Bhanu Wahi-Singh, Yiming Ma, Bingbing Cong, Emma Sharland, Richard D Riley, Jikui Deng, Joseph Figueras-Aloy, Terho Heikkinen, Marcus H Jones, Johannes G Liese, Joško Markić, Asuncion Mejias, Marta C Nunes, Bernhard ReschAshish Satav, Kee Thai Yeo, Eric Af Simões, Harish Nair

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Background
Infants and children born prematurely are a high-risk group for severe respiratory syncytial virus (RSV) acute lower respiratory infection (ALRI). Here, we assess the global disease burden of and risk factors for RSV-associated ALRI in preterm-born [<37 weeks gestational age (wGA)] young children.

Methods
We conducted a systematic analysis of aggregated data from published studies (between 1 Jan 1995 and 31 Dec 2021, identified from MEDLINE, Embase, and Global Health) and individual participant data shared by an investigator group on respiratory infectious diseases. We estimated RSV-associated ALRI incidence in community, hospital admission, in-hospital mortality, and overall mortality among children under two years of age born preterm. We conducted two-stage random-effects meta-regression analyses accounting for chronologic age groups, gestational age bands (early preterm: <32 wGA; late preterm: 32–<37 wGA), and time trend. Using individual participant data, we assessed perinatal, sociodemographic and household factors, and underlying medical conditions for RSV-associated ALRI incidence, hospital admission, and three severity outcome groups (longer hospital stay [>4 days], use of oxygen and mechanical ventilation or intensive care unit admission) by estimating pooled odds ratios (OR) through a two-stage meta-analysis (multivariate logistic regression and random-effects meta-analysis).

Findings
We included 47 studies from the literature and 17 studies with individual-participant-level data. We estimated that globally in 2019, there were 1·64 million (95% uncertainty range: 1·35–1·99) RSV-associated ALRI episodes, 533,000 (385,000–730,000) hospital admissions, 3,050 (1,080–8,620) in-hospital deaths, and 26,760 (11,190–46,240) overall deaths in preterm infants. Among early preterm infants, RSV-associated ALRI incidence rate and hospitalisation rate were significantly higher (rate ratio [RR] ranging from 1·69 to 3·87 across different age groups and outcomes) than all infants (of any gestational age). In the second year of life, early preterm children had a comparable incidence rate but still significantly higher hospitalisation rate (RR=2·26, 1·27–3·98) compared to all children. Although late preterm children had RSV-associated ALRI incidence rate comparable to all children, they had higher RSV-associated ALRI hospitalisation rate in the first six months (RR= 1·93, 1·11–3·26). Overall, preterm infants accounted for 25% [16–37] of RSV-associated ALRI hospitalisations in all infants of any gestational age. RSV-associated ALRI in-hospital case fatality ratio in preterm infants was similar to all infants. While most factors identified to be associated with RSV-associated ALRI incidence were perinatal and sociodemographic characteristics, factors associated with severe outcomes were mainly underlying medical conditions including congenital heart disease, tracheostomy, broncho-pulmonary dysplasia, chronic lung disease, or Down syndrome (range of ORs: 1·40 to 4·23).

Interpretation
Preterm infants carry a disproportionately high RSV disease burden, with 10% of population accounting for 25% of RSV hospitalisation burden. Early preterm children have noteworthy RSV hospitalisation burden persisting into the second year of life. Preventive products for RSV will likely have a significant public health impact for preventing RSV-associated ALRI and severe outcomes in preterm children.

Funding
EU Innovative Medicines Initiative Respiratory Syncytial Virus Consortium in Europe (RESCEU)



Original languageEnglish
Number of pages13
JournalThe Lancet
Early online date14 Feb 2024
DOIs
Publication statusE-pub ahead of print - 14 Feb 2024

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