Efficacy, duration of protection, birth outcomes, and infant growth associated with influenza vaccination in pregnancy: a pooled analysis of three randomised controlled trials

• Type of Material: Article
• Authors: Saad Omer, Emory University; Dayna R. Clark, Emory University; Shabir A. Madhi, University of Witwatersrand; Milagritos D. Tapia, University of Maryland; Marta C. Nunes, University of Witwatersrand; Clare L. Cutland, University of Witwatersrand; Eric A. F. Simoes, University of Witwatersrand; Anushka R. Aqil, Johns Hopkins University; Joanne Katz, Johns Hopkins University; James M. Tielsch, George Washington University; Mark C. Steinhoff, Cincinnati Childrens Hospital Medical Center; Niteen Wairagkar, Bill & Melinda Gates Foundation
• Language: English
• Date: 2020-06-01
• Publisher: Elsevier Science Ltd.
• Publication Version: Final Published Version
• Copyright Statement: © 2020 The Author(s). Published by Elsevier Ltd.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/S2213-2600(19)30479-5
• Title of Journal or Parent Work: The Lancet: Respiratory Medicine
• Volume: 8
• Issue: 6
• Start Page: 597
• End Page: 608
• Grant/Funding Information: The three trials in Mali, South Africa, and Nepal as well as this pooled analysis were funded by the Gates Foundation.; This pooled analysis received research funding from the Gates Foundation.; SBO and DRC serve as consultants to the Gates Foundation and received compensation for these services. The terms of this arrangement have been reviewed and approved by Emory University in accordance with its conflict of interest policies.
• Keywords: Maternal immunization; Mali; Life Sciences & Biomedicine; Virus infection; Mothers; Rates; General & Internal Medicine; Women; Nepal; Critical Care Medicine; Respiratory System; Phase 4; Science & Technology; Antibodies
• Research Categories: Health Sciences, Obstetrics and Gynecology; Health Sciences, Health Care Management; Biology, Virology; Health Sciences, Public Health; Health Sciences, Immunology

Abstract

Background Maternal influenza immunisation can reduce morbidity and mortality associated with influenza infection in pregnant women and young infants. We aimed to determine the vaccine efficacy of maternal influenza immunisation against maternal and infant PCR-confirmed influenza, duration of protection, and the effect of gestational age at vaccination on vaccine efficacy, birth outcomes, and infant growth up to 6 months of age. Methods We did a pooled analysis of three randomised controlled trials done in Nepal (2011–2014), Mali (2011–2014), and South Africa (2011–2013). Pregnant women, gestational age 17–34 weeks in Nepal, 28 weeks or more in Mali, and 20–36 weeks in South Africa, were enrolled. Women were randomly assigned 1:1 to a study group, in which they received trivalent inactivated influenza vaccine (IIV) in all three trials, or a control group, in which they received saline placebo in Nepal and South Africa or quadrivalent meningococcal conjugate vaccine in Mali. Enrolment at all sites was complete by April 24, 2013. Infants and women were assessed for respiratory illness, and samples from those that met the case definition were tested for influenza by PCR testing. Growth measurements, including length and weight, were obtained at birth at all sites, at 24 weeks in South Africa, and at 6 months in Nepal and Mali. The three trials are registered with ClinicalTrials.gov, numbers NCT01430689, NCT01034254, and NCT02465190. Findings 10 002 women and 9800 liveborn infants were included. Pooled efficacy of maternal vaccination to prevent infant PCR-confirmed influenza up to 6 months of age was 35% (95% CI 19 to 47). The pooled estimate was 56% (28 to 73) within the first 2 months of life, 39% (11 to 58) between 2 and 4 months, and 19% (–9 to 40) between 4 and 6 months. In women, from enrolment during pregnancy to the end of follow-up at 6 months postpartum, the vaccine was 50% (95% CI 32–63) efficacious against PCR-confirmed influenza. Efficacy was 42% (12 to 61) during pregnancy and 60% (36 to 75) postpartum. In women vaccinated before 29 weeks gestational age, the estimated efficacy was 30% (–2 to 52), and in women vaccinated at or after 29 weeks, efficacy was 71% (50 to 83). Efficacy was similar in infants born to mothers vaccinated before or after 29 weeks gestation (34% [95% CI 12 to 51] vs 35% [11 to 52]). There was no overall association between maternal vaccination and low birthweight, stillbirth, preterm birth, and small for gestational age. At 6 months of age, the intervention and control groups were similar in terms of underweight (weight-for-age), stunted (length-for-age), and wasted (weight-for-length). Median centile change from birth to 6 months of age was similar between the intervention and the control groups for both weight and length. Interpretation The assessment of efficacy for women vaccinated before 29 weeks gestational age might have been underpowered, because the point estimate suggests that there might be efficacy despite wide CIs. Estimates of efficacy against PCR-confirmed influenza and safety in terms of adverse birth outcomes should be incorporated into any further consideration of maternal influenza immunisation recommendations.