The safety of inactivated influenza vaccines in pregnancy for birth outcomes: a systematic review

Abstract

Pregnant women are at increased risk of morbidity and mortality from influenza and are recognized as a priority group for influenza vaccination. Despite this, uptake is often poor and one reason cited for this is concerns about safety. The objective of this study was to perform a systematic review of the safety of inactivated influenza vaccination (IIV) in pregnancy. Studies were included if they were: (i) observational or experimental design; (ii) included a comparator group comprising of unvaccinated pregnant women; (iii) comprised of either seasonal IIV or monovalent H1N1 IIV (including adjuvanted vaccines); and (iv) addressed one of the following outcomes: preterm birth (PTB), small for gestational age (SGA), fetal death (including stillbirth or spontaneous abortion), low birth weight (LBW) or congenital abnormalities. Two reviewers screened abstracts and titles and selected full texts for retrieval. Crude odds ratios were calculated from reported event rates, using binomial standard errors. Adjusted odds ratios, hazard ratios and relative rates were extracted as reported in each paper. After removal of duplicates and full text eligibility assessment, 40 studies remained. The aOR for PTB was 0.87 (0.78-0.96), for LBW 0.82 (0.76-0.89), congenital abnormality 1.03 (0.99-1.07), SGA 0.99 (0.94-1.04) and stillbirth 0.84 (0.65-1.08). This study contributes to the increasing body of safety data for IIV in pregnancy and reports a protective effect on PTB and LBW.

Influenza and pertussis vaccination of women during pregnancy in Victoria, 2015–2017

“…We agree that one explanation of these results may be the potential protective effect that influenza vaccination during pregnancy has on pre‐term birth. This protective effect of influenza vaccines against a range of adverse birth outcomes has been noted in other studies . An alternative explanation, however, may be reverse causation, whereby women with longer periods of gestation (≥ 37 weeks) have an increased opportunity to be vaccinated.…”

“…This protective effect of influenza vaccines against a range of adverse birth outcomes has been noted in other studies. 2 An alternative explanation, however, may be reverse causation, whereby women with longer periods of gestation (≥ 37 weeks) have an increased opportunity to be vaccinated. In this study, data on the timing of vaccination were not available, but we are in the process of making a submission to the data custodians of the Victorian Perinatal Data Collection to enable capture and examination of these data.…”

Influenza and pertussis vaccination of women during pregnancy in Victoria, 2015–2017

“…Firstly, it may indicate a potential beneficial effect of influenza vaccine received by pregnant women in reducing pre‐term birth (< 37 weeks' gestation). This is consistent with a recent systematic review and meta‐analysis that reported inactivated influenza vaccine to have a protective effect against pre‐term birth and low birth weight …”

Influenza vaccination in pregnancy: careful assessment confirms safety concerns for the offspring

“…I have limited my assessment to the most recent of the cited references, a systematic review, published in 2018. 6 Although stating that "Publications after May 2017 were not included", the review does not include two 5,7 of the three trials already published (the fourth 4 was published in September 2017), presumably because they were not placebocontrolled but active-controlled.…”