Risk of Adverse Fetal Outcomes Following Administration of a Pandemic Influenza A(H1N1) Vaccine During Pregnancy

Abstract

Pregnant women who were infected during the 2009 influenza A(H1N1) pandemic were at increased risk of morbidity, mortality, and poor pregnancy outcomes. Those without an infection were prioritized for vaccination against this virus, and it was estimated that 2.4 million pregnant women in the United States were vaccinated. Few studies have assessed the fetal safety of vaccination against influenza A(H1N1) pdm09 in pregnant women. This registry-based cohort study was designed to investigate whether vaccination of pregnant women with an adjuvanted influenza A(H1N1) pdm09 vaccine was associated with increased risk of adverse fetal outcomes. Participants were live-born singleton infants delivered between November 2009 and September 2010 in Denmark. Prevalence odds ratios (PORs) of adverse fetal outcomes were compared in unmatched cohorts and in propensity score–matched cohorts of infants who were exposed and unexposed to the vaccine during pregnancy. Logistic regression analysis was used to estimate associations between H1N1 vaccination in pregnancy and risks of adverse fetal outcomes, with adjustment for potential confounders. The primary study outcome measures were major birth defects, preterm birth, and small size for gestational age. Among a cohort of 53,432 infants, 6989 (13.1%) exposed to the influenza A(H1N1) pdm09 vaccine during pregnancy (345 in the first trimester and 6644 in the second or third trimester), 660 (330 exposed) were included in propensity score–matched analyses of adverse fetal outcomes associated with vaccination in the first trimester. Analyses of small size for gestational age and preterm birth associated with vaccination in the second or third trimester included 13,284 (6642 exposed) and 12,909 (6543 exposed) infants, respectively. There was a diagnosis of a major birth defect in 5.5% (18/330) of infants exposed to the vaccine in the first trimester compared with 4.5% unexposed infants (15/330); the POR was1.21 with a 95% confidence interval (CI) of 0.60 to 2.45. Preterm birth was diagnosed in 9.4% infants (31/330) exposed in the first trimester, compared with 7.3% unexposed infants (24/330) (POR, 1.32; 95% CI, 0.76–2.31) and in 4.6% (302/6543) of infants with second- or third-trimester exposure, compared with 4.6% (295/6366) of unexposed infants (POR, 1.00; 95% CI, 0.84–1.17). Similarly, no increased risk of small size for gestational age was associated with vaccine exposure. The risk was 7.6% (25/330) for infants with first-trimester exposure compared with 9.4% (31/330) for unexposed infants (POR, 0.79; 95% CI, 0.46–1.37) and 9.7% (641/6642) for infants with second- or third-trimester exposure compared with 9.9% (657/6642) for unexposed infants (POR, 0.97; 95% CI, 0.87–1.09). The findings of this cohort study provide no evidence for a significant association between exposure to the adjuvanted influenza A(H1N1) pdm09 vaccine in pregnancy and risk of adverse fetal outcomes including major birth defects, preterm birth, and growth restriction.