Pregnancy as a risk factor for severe outcomes from influenza virus infection: A systematic review and meta-analysis of observational studies

Abstract

Background: Pregnancy is considered to be an important risk factor for severe complications following influenza virus infection. As a consequence, WHO recommendations prioritize pregnant women over other risk groups for influenza vaccination. However, the risk associated with pregnancy has not been systematically quantified.

Purpose: Systematic review and meta-analysis of observational studies that reported on pregnancy as a risk factor for severe outcomes from influenza virus infection.

Data source: MEDLINE, EMBASE, CINAHL, and CENTRAL up to April 2014.

Data selection: Studies reporting on outcomes in pregnant women with influenza in comparison to non-pregnant patients with influenza. Outcomes included community-acquired pneumonia, hospitalization, admission to intensive care units (ICU), ventilatory support, and death.

Data extraction: Two reviewers conducted independent screening and data extraction. A random effects model was used to obtain risk estimates. Ecological studies were summarized descriptively.

Data synthesis: A total of 142 non-ecological and 10 ecological studies were included. The majority of studies (n=136, 95.8%) were conducted during the 2009 influenza A (pH1N1) pandemic. There was a higher risk for hospitalization in pregnant versus non-pregnant patients infected with influenza (odds ratio [OR] 2.44, 95% CI 1.22-4.87), but no significant difference in mortality (OR 1.04, 95% CI 0.81-1.33) or other outcomes. Ecologic studies confirmed the association between hospitalization risk and pregnancy and 4 of 7 studies reported higher mortality rates in pregnant women.

Limitations: No studies were identified in which follow-up began prior to contact with the healthcare system and lack of adjustment for confounding factors.

Conclusions: We found that influenza during pregnancy resulted in a higher risk of hospital admission than influenza infection in non-pregnant individuals, but that the risk of mortality following influenza was similar in both pregnant and non-pregnant individuals.

Keywords: Influenza; Pregnancy; Risk; Systematic review; Vaccination.

Fig. 1

Flow sheet of studies included and excluded (search update). Legend: ^* “Original search” refers to the search for the systematic review conducted in 2011 ; ^† One article reported on two study populations; ^‡ One article reported ecological as well as individual-level data.

Fig. 2

Forest plot for pregancy as a risk factor for mortality following influenza. Legend: Subgroups: source of population (community-based, hospital-based, ICU-based patient population). Not estimable: each study was only included once in the forest plot with data on the largest patient population available. E.g. the study for Buda et al. was only included in the community subgroup but deemed not estimable in the hospitalized group.

Fig. 3

Forest plot for pregancy as a risk factor for hospitalization following influenza.