Risk of fetal death after pandemic influenza virus infection or vaccination

Abstract

Background: 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.

Methods: 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.

Results: 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).

Conclusions: 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.).

Figure 1

Live births in Norway occurring in 2009 and 2010 were eligible for study if the date of last menstrual period occurred in or before the first 9 weeks of 2010 (43 weeks before 31 December 2009). Eligible pregnancies were defined as exposed to the influenza pandemic if any days between the date of the last menstrual period and birth occurred between 1 October and 31 December 2009. For a given pregnancy, days at risk are pregnancy days after week 12 occurring after 1 January 2009, and exposure days are defined as all pregnancy days from first day of exposure to delivery. For simplicity, the figure shows all pregnancies as lasting 9 months; study includes all registered pregnancies lasting at least 12 weeks. The period of the main wave of the influenza pandemic is shaded.

Figure 2

Number of pregnant women in Norway with laboratory confirmed cases of pandemic influenza (dashed line) and number of vaccinations between 19 October, 2009 through February 2010 (solid line).