title: Does influenza vaccination improve pregnancy outcome? Methodological issues and research needs.
abstract: Evidence that influenza vaccination during pregnancy is safe and effective at preventing influenza disease in women and their children through the first months of life is increasing. Several reports of reduced risk of adverse outcomes associated with influenza vaccination have generated interest in its potential for improving pregnancy outcome. Gavi, the Vaccine Alliance, estimates maternal influenza immunization programs in low-income countries would have a relatively modest impact on mortality compared to other new or under-utilized vaccines, however the impact would be substantially greater if reported vaccine effects on improved pregnancy outcomes were accurate. Here, we examine the available evidence and methodological issues bearing on the relationship between influenza vaccination and pregnancy outcome, particularly preterm birth and fetal growth restriction, and summarize research needs. Evidence for absence of harm associated with vaccination at a point in time is not symmetric with evidence of benefit, given the scenario in which vaccination reduces risk of influenza disease and, in turn, risk of adverse pregnancy outcome. The empirical evidence for vaccination preventing influenza in pregnant women is strong, but the evidence that influenza itself causes adverse pregnancy outcomes is inconsistent and limited in quality. Studies of vaccination and pregnancy outcome have produced mixed evidence of potential benefit but are limited in terms of influenza disease assessment and control of confounding, and their analytic methods often fail to fully address the longitudinal nature of pregnancy and influenza prevalence. We recommend making full use of results of randomized trials, re-analysis of existing observational studies to account for confounding and time-related factors, and quantitative assessment of the potential benefits of vaccination in improving pregnancy outcome, all of which should be informed by the collective engagement of experts in influenza, vaccines, and perinatal health.
authors: Department of Epidemiology, Brown University, 47 George Street, Providence, RI 02912, USA; Department of Obstetrics and Gynecology, Brown University, Providence, RI, USA. Electronic address: david_savitz@brown.edu.
authors: David A
authors: DA
authors: Savitz
authors: Better Outcomes Registry & Network (BORN), CHEO Research Institute, 401 Smyth Road, Ottawa, ON K1H 8L1, Canada. Electronic address: dfell@bornontario.ca.
authors: Deshayne B
authors: DB
authors: Fell
authors: Initiative for Vaccine Research, World Health Organization, Avenue Appia 20, 1211 Geneva 27, Switzerland. Electronic address: ortizj@who.int.
authors: Justin R
authors: JR
authors: Ortiz
authors: PATH, PO Box 900922, Seattle, WA 98109, USA. Electronic address: nbhat@path.org.
authors: Niranjan
authors: N
authors: Bhat
mesh_terms: D005260:Female; D005317:Fetal Growth Retardation / Q000453:epidemiology* / Q000517:prevention & control*; D006801:Humans; D007252:Influenza Vaccines / Q000008:administration & dosage* / Q000276:immunology; D007251:Influenza, Human / Q000150:complications* / Q000517:prevention & control*; D011247:Pregnancy; D011256:Pregnancy Outcome; D047928:Premature Birth / Q000453:epidemiology* / Q000517:prevention & control*
chemical_list: D007252:Influenza Vaccines
keywords: Fetal growth; Influenza vaccination; Pregnancy; Preterm birth