Safety of the 2011-12, 2012-13, and 2013-14 seasonal influenza vaccines in pregnancy: Preterm delivery and specific malformations, a study from the case-control arm of VAMPSS.

BACKGROUND: Pregnant women have higher risks of influenza complications, but vaccine coverage is incomplete. Because concern about fetal harm limits uptake, we investigated risks for preterm delivery (PTD) and specific birth defects following vaccination in the 2011-12 through 2013-14 influenza seasons.

METHODS: We used data from the Slone Epidemiology Center's Birth Defects Study. For PTD, propensity score-adjusted time-varying hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated for exposure anytime in pregnancy and for each trimester. For 42 specific major birth defects or birth defect categories, propensity score-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated.

RESULTS: For PTD (1803 fullterm deliveries, 107 PTD for all seasons combined), an elevated adjusted risk was observed for only the 2nd trimester of the 2011-12 season (HR=2.60, 95% CI 1.21, 5.61) - a reduction in gestational length of <2days. For the 42 specific defects or categories of defects (2866 cases, 1411 controls for all seasons combined) most adjusted risks were close to 1.0; the highest was 2.38 for omphalocele and the lowest was 0.50 for atrioventricular canal defects. None had lower confidence bounds >1.0. For each season separately, only one elevated OR had a lower 95% CI >1.0: omphalocele in 2011-12 (OR=5.19, 95% CI 1.44, 18.7).

CONCLUSIONS: Our results regarding risks for PTD and birth defects are generally reassuring. The few risks that were observed are compatible with chance, but warrant testing in other data. Given that vaccine components and manufacturing processes vary, continuing studies are needed to evaluate risks and safety of each season's vaccine and specific products.