Source:

Håberg
SE
,
Trogstad
L
,
Gunnes
N
, et al
.
Risk of fetal death after pandemic influenza virus infection or vaccination
.
N Engl J Med.
2013
;
368
(
4
):
333
340
; doi:
https://doi.org/10.1056/NEJMoa1207210

Investigators from multiple institutions examined the risk of fetal death in pregnant Norwegian women exposed to pandemic influenza and pandemic influenza vaccination. A retrospective cohort study was performed linking information from various national health registries to national data regarding reimbursement of primary care physicians to capture comprehensive data on influenza illness and vaccination. The main wave of pandemic influenza in Norway occurred between October 1 and December 31, 2009; women who gave birth in 2009 to 2010 were eligible for inclusion in the study. The sample was restricted to women who became pregnant at least 43 weeks before December 31, 2010. Pregnancies were followed from completion of the 12th week of gestation or January 1, 2009 until delivery or fetal death. Fetal death was defined as any miscarriage or stillbirth after 12 weeks of gestation. Exposure to influenza was defined as a primary care visit resulting in that diagnosis.

The risk of fetal death in women pregnant during the pandemic was compared to that of women pregnant outside of the pandemic window, using Cox proportional-hazard models. The primary outcomes were the adjusted hazard ratios (aHR) for women who were vaccinated against pandemic influenza and the aHR for fetal death in women who were exposed to, or diagnosed with, influenza.

Among 117,347 pregnancies in Norway in 2009 to 2010, 570 fetal deaths occurred (4.9 per 1,000 births). For the study analyses, data from 113,331 singleton pregnancies were analyzed; a total of 492 fetal deaths occurred among this group (4.3 per 1,000 births). During the influenza pandemic, 54% of pregnant women analyzed were vaccinated. Among vaccinated women, the rate of fetal death was 3.0 per 1,000 births, while the rate for unvaccinated women was 4.7 per 1,000 births, and that for women infected with influenza was 7.0 per 1,000 births. Vaccination during pregnancy reduced the risk of influenza (aHR 0.30; 95% CI, 0.25–0.34). Women exposed to the pandemic had an increased risk of fetal death as compared to those who were pregnant outside of the pandemic window (aHR 1.26; 95% CI, 1.02–1.55); the risk was increased among those with influenza (aHR 1.91; 95% CI, 1.07–3.41). Unvaccinated women had a higher risk of fetal death during the pandemic (aHR 1.25; 95% CI, 1.02–1.55). Finally, women who were vaccinated had a slightly lower risk of fetal death compared to unvaccinated women that was not significant (HR 0.88; 95% CI, 0.66–1.17). Those who were vaccinated also had no increase in preterm delivery, low birth weight at term, or low Apgar score at term compared to those who were not vaccinated.

The authors conclude that pandemic influenza posed a measurable risk to the fetuses of pregnant women, as the rate of fetal death in unvaccinated women was approximately twice that of vaccinated...

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