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. 2021 Jun 10:37:100945.
doi: 10.1016/j.eclinm.2021.100945. eCollection 2021 Jul.

Estimated impact of maternal vaccination on global paediatric influenza-related in-hospital mortality: A retrospective case series

Yvette N Löwensteyn  1 , Harish Nair  2   3 , Marta C Nunes  2   4 , Ichelle van Roessel  1 , Femke S Vernooij  1 , Joukje Willemsen  1 , Louis J Bont  1   2 , Natalie I Mazur  1 ; FLU GOLD study group
Collaborators, Affiliations

Estimated impact of maternal vaccination on global paediatric influenza-related in-hospital mortality: A retrospective case series

Yvette N Löwensteyn et al. EClinicalMedicine. .

Abstract

Background: Influenza virus infection is an important cause of under-five mortality. Maternal vaccination protects children younger than 3 months of age from influenza infection. However, it is unknown to what extent paediatric influenza-related mortality may be prevented by a maternal vaccine since global age-stratified mortality data are lacking.

Methods: We invited clinicians and researchers to share clinical and demographic characteristics from children younger than 5 years who died with laboratory-confirmed influenza infection between January 1, 1995 and March 31, 2020. We evaluated the potential impact of maternal vaccination by estimating the number of children younger than 3 months with in-hospital influenza-related death using published global mortality estimates.

Findings: We included 314 children from 31 countries. Comorbidities were present in 166 (53%) children and 41 (13%) children were born prematurely. Median age at death was 8·6 (IQR 4·5-16·6), 11·5 (IQR 4·3-24·0), and 15·5 (IQR 7·4-27·0) months for children from low- and lower-middle-income countries (LMICs), upper-middle-income countries (UMICs), and high-income countries (HICs), respectively. The proportion of children younger than 3 months at time of death was 17% in LMICs, 12% in UMICs, and 7% in HICs. We estimated that 3339 annual influenza-related in-hospital deaths occur in the first 3 months of life globally.

Interpretation: In our study, less than 20% of children is younger than 3 months at time of influenza-related death. Although maternal influenza vaccination may impact maternal and infant influenza disease burden, additional immunisation strategies are needed to prevent global influenza-related childhood mortality. The missing data, global coverage, and data quality in this study should be taken into consideration for further interpretation of the results.

Funding: Bill & Melinda Gates Foundation.

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Conflict of interest statement

LJB reports grants from Bill and Melinda Gates Foundation, during the conduct of the study. LJB has regular interaction with pharmaceutical and other industrial partners. He has not received personal fees or other personal benefits. The University Medical Centre Utrecht (UMCU) has received major funding obtained by LJB (>€100,000 per industrial partner) for investigator initiated studies from AbbVie, MedImmune, Janssen, the Bill and Melinda Gates Foundation, Nutricia (Danone) and MeMed Diagnostics. UMCU has received major cash or in kind funding as part of the public private partnership IMI-funded RESCEU project from GSK, Novavax, Janssen, AstraZeneca, Pfizer and Sanofi. UMCU has received major funding by Julius Clinical for participating in the INFORM study sponsored by MedImmune. UMCU has received minor funding for participation in trials by Regeneron and Janssen from 2015 to 2017 (total annual estimate less than €20,000). UMCU received minor funding for consultation and invited lectures by AbbVie, MedImmune, Ablynx, Bavaria Nordic, MabXience, Novavax, Pfizer, Janssen (total annual estimate less than €20,000). LJB is the founding chairman of the ReSViNET Foundation. HN reports grants and personal fees from the World Health Organisation, personal fees from the Bill & Melinda Gates Foundation, personal fees from Sanofi, outside the submitted work. MCN reports grants from the Bill & Melinda Gates Foundation, personal fees from Sanofi Pasteur, personal fees from Pfizer, outside the submitted work. NIM has regular interaction with pharmaceutical and other industrial partners. She has not received personal fees or other personal benefits. UMCU received minor funding for NIMs consultation and invited lectures by Abbvie and Merck. All other authors have nothing to declare.

Figures

Fig. 1.
Fig. 1.
Flowchart of included deaths. RSV=respiratory syncytial virus. GOLD=global online database. LMIC=low-income and lower-middle-income countries. UMIC=upper-middle-income countries. HIC=high-income countries. *For 1 child the collaborator had indicated in the comments that the death was not influenza-related.
Fig. 2.
Fig. 2.
Countries of children with influenza-related in-hospital death included in the analysis. Number of included deaths are given for each country (in pink) from which collaborators shared data.
Fig. 3
Fig. 3
A) Age younger than 3 months or 3 months and older at time of influenza-related in-hospital death for children younger than 5 years from low- and lower-middle-income countries (LMIC), upper-middle-income countries (UMIC), and high-income countries (HIC). B) Age distribution at time of influenza-related in-hospital death for children younger than 5 years from low- and lower-middle-income countries (LMIC), upper-middle-income countries (UMIC), and high-income countries (HIC).
See this image and copyright information in PMC

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