The effect of influenza virus infection on pregnancy outcomes: A systematic review and meta-analysis of cohort studies

Background: Adverse pregnancy outcomes are risk factors for neonatal mortality and morbidity. While some studies have demonstrated notable associations between influenza and adverse pregnancy outcomes, the findings have contrasted with other studies. This meta-analysis was conducted to assess the effect of influenza infection on pregnancy outcomes. Methods: We searched PubMed, Embase, Cochrane Library and Web of Science from inception to 4 November 2020. Relative risks (RRs) with 95% confidence intervals (CIs) were pooled using random effects or fixed-effects models. Results: A total of 17 studies involving 2,351,204 participants were included. Influenza infection increased the risk of stillbirth (RR = 3.62, 95% CI: 1.60-8.20), with no significant effect on preterm birth (RR = 1.17, 95%CI: 0.95-1.45), fetal death (RR = 0.93, 95%CI: 0.73-1.18), small for gestational age (SGA) (RR = 1.10, 95% CI: 0.98-1.24) and low birth weight (LBW) (RR = 1.88, 95%CI: 0.46-7.66). In a subgroup analysis of LBW, the association was evident in studies conducted during the 2009 H1N1 pandemic (RR = 2.28, 95%CI: 1.81-2.87), with no evidence of an association in pre-pandemic or post-pandemic studies. Conclusions: Influenza virus infection was associated with an increased risk of stillbirth, but its effect on preterm birth, fetal death, SGA and LBW is still uncertain. (c) 2021 The Author(s). Published by Elsevier Ltd on behalf of International Society for Infectious Diseases. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-ncnd/4.0/).