Fetal death and preterm birth associated with maternal influenza vaccination: systematic review

Abstract

Background Before 2012, few studies had addressed pregnancy outcomes following maternal influenza vaccination; however, the number of publications on this topic has increased recently. Objectives To review comparative studies evaluating fetal death or preterm birth associated with influenza vaccination during pregnancy. Search strategy We searched bibliographic databases from inception to April 2014. Selection criteria Experimental or observational studies assessing the relationship between influenza vaccination during pregnancy and fetal death or preterm birth. Data collection and analysis Two reviewers independently abstracted data from studies meeting the inclusion criteria. Main results We included one randomised clinical trial and 26 observational studies. Meta‐analyses were not considered appropriate because of high clinical and statistical heterogeneity. Three studies of fetal death at any gestational age reported adjusted effect estimates in the range 0.56–0.79, and four of five studies of fetal death at <20 weeks reported adjusted estimates between 0.89 and 1.23, all with confidence intervals including 1.0. Adjusted effect estimates for four of five studies of fetal death at ≥20 weeks ranged from 0.44 to 0.77 (two with confidence intervals not crossing 1.0), whereas a fifth reported a non‐significant effect in the opposite direction. Among 19 studies of preterm birth, there was no strong evidence suggesting any increased risk, and meta‐regression did not explain the moderate between‐study heterogeneity (I2 = 57%). Authors' conclusions Most studies reported no association between fetal death or preterm birth and influenza vaccination during pregnancy. Although several reported risk reductions, results may be biased by methodological shortcomings of observational studies of influenza vaccine effectiveness.

The Effects of Influenza Vaccination during Pregnancy on Birth Outcomes: A Systematic Review and Meta-Analysis

“…Notwithstanding important methodological concerns regarding observational studies assessing the impact of maternal influenza vaccination on birth outcomes, which have been discussed extensively in recent reviews, 4,5,35,36 we performed meta-analyses on the effects of maternal vaccination on the rates of PTB, SGA, and LBW births reported in large studies published to date. In the meta-analyses women who received IIV during pregnancy compared with nonvaccinated women had a 13% lower risk of delivering preterm and 26% decreased risk of having an LBW baby; and women who received A/H1N1pdm09 monovalent vaccine had 8 to 10% lower risk of PTB and their babies had a 12% decreased risk of being LBW.…”

“…Two recent clinical trials and several epidemiological studies have affirmed the safety of maternal influenza vaccination 1,2 (for review [3][4][5] ). The randomized controlled trials (RCTs) reported that maternal vaccination was associated with a reduction in influenza-confirmed illness among the women (50%) and their infants (49-63%).…”

Vaccines in pregnancy: The dual benefit for pregnant women and infants

“…46 Systematic reviews on the safety of inactivated influenza virus vaccines conclude there is no association between maternal immunization and an increased risk of harm for pregnant women, 47,48 or the fetus. [47][48][49][50][51][52] The largest study investigating adverse events in pregnant women compared rates of medically attended adverse events in trivalent inactivated influenza-vaccinated and unvaccinated pregnant women. 53 Using ICD-9 coded data on inpatient, outpatient, or emergency department visits to assess medically attended visits within 3 and 42 d postvaccination, respectively there was no evidence of an increase in medical visits in the 3 d post vaccination due to adverse events, using a combined outcome measure that included allergic reactions, fever, malaise, rash, and seizures: adjusted incident rate ratio (IRR) 1.12 (95% CI: 0.81 to 1.55).…”

Hintergrundpapier der STIKO: Evaluation der bestehenden Influenzaimpfempfehlung für Indikationsgruppen und für Senioren (Standardimpfung ab 60 Jahren)

“…In der systematischen Literatursuche konnten 4 systematische Reviews identifiziert werden [71][72][73][74], die zwischen 2013 und 2014 publiziert worden waren und eine hohe methodische Qualität aufwiesen (AMSTAR-Score 9-11). Während 3 Reviews die Effektivität und Sicherheit bei schwangeren Frauen und deren Kindern untersuchten, fokussierte ein Review [73] auf das Risiko für Frühge-burtlichkeit und fetalen Tod nach Influenzaimpfung.…”

“…Während 3 Reviews die Effektivität und Sicherheit bei schwangeren Frauen und deren Kindern untersuchten, fokussierte ein Review [73] auf das Risiko für Frühge-burtlichkeit und fetalen Tod nach Influenzaimpfung. Während einer Aktualisierung der Literatursuche wurde zusätzlich 1 RCT identifiziert [75], der aufgrund seines Veröffentlichungsdatums in keinem der systematischen Reviews enthalten war.…”