Does Influenza Vaccination during Pregnancy Have Effects on Non-Influenza Infectious Morbidity? A Systematic Review and Meta-Analysis of Randomised Controlled Trials.

Katrine Pedersbæk Hansen,Sanne Marie Thysen,Christine Stabell Benn,Peter Aaby,Martin Buus,Ane Bærent Fisker,Isaquel Da Silva,Thomas Aamand

doi:10.3390/vaccines9121452

Katrine Pedersbæk Hansen, Sanne Marie Thysen + Show 6 more

Open Access

https://doi.org/10.3390/vaccines9121452

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Abstract

The recommendation to provide inactivated influenza vaccine (IIV) to pregnant women is based on observed protection against influenza-related morbidity in mother and infant. Non-live vaccines may have non-specific effects (NSEs), increasing the risk of non-targeted infections in females. We reviewed the evidence from available randomised controlled trials (RCTs) of IIV to pregnant women, to assess whether IIV may have NSEs. Four RCTs, all conducted in low- and middle-income settings, were identified. We extracted information on all-cause and infectious mortality and adverse events in women and their infants. We conducted meta-analyses providing risk ratios (RR). The meta-analysis for maternal all-cause mortality provided a RR of 1.48 (95% CI = 0.52–4.16). The estimates for miscarriage/stillbirth and infant all-cause mortality up to 6 months of age were 1.06 (0.78–1.44) and 1.11 (0.87–1.41), respectively. IIV was associated with a higher risk of non-influenza infectious adverse events, with meta-estimates of 2.01 (1.15–3.50) in women and 1.36 (1.12–1.67) in infants up to 6 months of age. Thus, following a pattern seen for other non-live vaccines, IIV was associated with a higher risk of non-influenza infectious adverse events. To ensure that scarce resources are used well, and no harm is inflicted, further RCTs are warranted.

Highlights

Influenza infection in pregnancy has been associated with increased maternal morbidity and possible adverse neonatal outcomes
The use of pneumococcal vaccines in the Bangladesh trial could have provided benefits that confounded the comparison with inactivated influenza vaccine (IIV) [29], and it has been suggested that the administration of meningococcal vaccines to mothers in the Mali trial could have conferred benefits to the offspring [23]
In spite of protecting against influenza in mother and child, there was no indication that IIV protected against all-cause mortality

Summary

Introduction

Influenza infection in pregnancy has been associated with increased maternal morbidity and possible adverse neonatal outcomes. It has been concluded that influenza vaccination of pregnant women was safe [6,7,8] and significantly reduced maternal and infant influenza risk [4,8] as well as the prevalence of stillbirth [6], preterm, and low-birth-weight infants [5]. These reviews were, to a large extent, based on observational studies; and as observational studies inherently risk healthy vaccine bias and residual confounding, potential harms could be underestimated [7]

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