A follow-up comparative safety analysis of pandemic H1N1 vaccination during pregnancy and risk of infant birth defects among U.S. military mothers

•Pregnant women are urged to receive H1N1-containing influenza vaccine.•Ensuring the safety of influenza vaccines is paramount for vaccination acceptance.•There was no significant association between H1N1 vaccination and birth defects.•Reassuring findings provide support for influenza vaccination during pregnancy. To update a previous assessment of birth defects among infants born to active duty U.S. military mothers who received the 2009–2010 pandemic H1N1 vaccine, in comparison to the 2008–2009 seasonal influenza vaccine, during pregnancy. Here, we updated the previous comparative analyses with a more refined definition for birth defects using an additional year of follow-up data from both inpatient and outpatient medical encounters. The study population included 15,510 live born infants born to active duty mothers vaccinated during pregnancy with either the 2009–2010 pandemic H1N1 vaccine (n = 9033) or the 2008–2009 seasonal influenza vaccine (n = 6477). Birth defect cases were defined as those infants who received a birth defect diagnosis on one inpatient record or two outpatient records on different days within the first year of life. Multivariable logistic regression models were conducted to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) for the association between birth defects and maternal vaccination during pregnancy with pandemic H1N1 vaccine versus seasonal influenza vaccine. Infants born to mothers vaccinated during pregnancy with the pandemic H1N1 vaccine, versus the seasonal influenza vaccine, were not at increased odds of birth defects in univariable (OR: 1.13, 95% CI: 0.95–1.34) or multivariable (OR: 1.14, 95% CI: 0.96–1.35) models. Findings were not significant when further limited to first trimester exposure. Multivariable models were adjusted for infant sex and plurality; maternal age, race/ethnicity, marital status, service branch, military rank, and occupation; timing of vaccination; and receipt of vaccination(s) not routinely recommended during pregnancy. Comparable to our previous analyses assessing birth defects diagnosed at birth, no significant association was found between the pandemic H1N1 vaccination during pregnancy and birth defects, versus the seasonal influenza vaccine. These findings are reassuring and provide additional support for H1N1-containing seasonal influenza vaccination during pregnancy.