Risk of Fetal Death After Pandemic Influenza Virus Infection or Vaccination

and the London School of Hygiene and Tropical Medicine, London (A.S.).
New England Journal of Medicine (Impact Factor: 55.87). 01/2013; 368(4). DOI: 10.1056/NEJMoa1207210
Source: PubMed


During the 2009 influenza A (H1N1) pandemic, pregnant women were at risk for severe influenza illness. This concern was complicated by questions about vaccine safety in pregnant women that were raised by anecdotal reports of fetal deaths after vaccination.

We explored the safety of influenza vaccination of pregnant women by linking Norwegian national registries and medical consultation data to determine influenza diagnosis, vaccination status, birth outcomes, and background information for pregnant women before, during, and after the pandemic. We used Cox regression models to estimate hazard ratios for fetal death, with the gestational day as the time metric and vaccination and pandemic exposure as time-dependent exposure variables.

There were 117,347 eligible pregnancies in Norway from 2009 through 2010. Fetal mortality was 4.9 deaths per 1000 births. During the pandemic, 54% of pregnant women in their second or third trimester were vaccinated. Vaccination during pregnancy substantially reduced the risk of an influenza diagnosis (adjusted hazard ratio, 0.30; 95% confidence interval [CI], 0.25 to 0.34). Among pregnant women with a clinical diagnosis of influenza, the risk of fetal death was increased (adjusted hazard ratio, 1.91; 95% CI, 1.07 to 3.41). The risk of fetal death was reduced with vaccination during pregnancy, although this reduction was not significant (adjusted hazard ratio, 0.88; 95% CI, 0.66 to 1.17).

Pandemic influenza virus infection in pregnancy was associated with an increased risk of fetal death. Vaccination during pregnancy reduced the risk of an influenza diagnosis. Vaccination itself was not associated with increased fetal mortality and may have reduced the risk of influenza-related fetal death during the pandemic. (Funded by the Norwegian Institute of Public Health.).

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    • "However, influenza has also been associated with adverse fetal outcomes including a higher risk of perinatal death, intrauterine growth restriction, and being born preterm [12]. In a recent Norwegian study of 117 347 pregnancies [13] "
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    • "The effectiveness ofAS03-adjuvanted split-virion H1N1 vaccine was demonstrated in pregnant women during the second and third trimesters in a cohort study in Norway. A total of 46 491 pregnant women were followed up during the pandemic wave, of which 54% were vaccinated [16]. In a small study in the United Kingdom, 77 pregnant women received AS03 adjuvant end vaccine in the second or third trimester; three-quarters of the newborn infants were found to have passive immunity at hemagglutination inhibition titers of 1:40 or greater consistent with clinical protection, as a result of transplacental transfer [43]. "
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    • "In pregnancies not affected by early loss, there has been an excess of adverse outcomes in women with influenza. In a Norwegian national registry study, there was an increased rate of fetal death among pregnancies complicated by 2009 H1N1 influenza.23 In a United Kingdom series of 256 women with 2009 H1N1 influenza, there was an increased perinatal mortality rate (39 per 1000 births compared to 7 per 1000 in women without influenza), stillbirth rate, and a fourfold increased likelihood of preterm birth.24 "
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