Safety of the 2010-11, 2011-12, 2012-13, and 2013-14 seasonal influenza vaccines in pregnancy: Birth defects, spontaneous abortion, preterm delivery, and small for gestational age infants, a study from the cohort arm of VAMPSS.

INTRODUCTION: There is a need for pregnancy safety information overall and for each seasonal formulation of the influenza vaccine.

METHODS: As part of the cohort arm of the Vaccines and Medications in Pregnancy Surveillance System, vaccine-exposed and unexposed women in the U.S. or Canada were recruited during pregnancy in the 2010-2014 vaccine seasons and followed to pregnancy outcome. For the four seasons combined, crude and adjusted relative risks (RRs) were estimated with 95% confidence intervals (CIs) for major birth defects overall and infants small for gestational age. Crude and adjusted hazard ratios (HRs) were estimated with 95% CIs for spontaneous abortion and preterm delivery. Specific influenza season subanalyses were also conducted.

RESULTS: Of 1730 women, 1263 were exposed to an influenza vaccine and 467 were unexposed to any influenza vaccine. Among pregnancies with first-trimester exposure excluding lost-to-follow-up, 26/457 (5.7%) resulted in an infant with a major birth defect compared to 13/427 (3.0%) in the unexposed (RR 1.87, 95% CI 0.97, 3.59). No specific pattern of defects was evident in the vaccine-exposed cohort. The overall risk of spontaneous abortion was not elevated (HR 1.09, 95% CI 0.49, 2.40). Adjusted HRs for preterm delivery approximated 1.0 (adjusted HR 1.23, 95% CI 0.75, 2.02). RRs for small for gestational age infants on weight, length and head circumference ranged from 1.19 to 1.49 with all CIs including 1. Season-by-season analyses resulted in variation by season; however, estimates were based on small numbers.

CONCLUSIONS: Combining the 2010-2014 influenza seasons, we found a moderately elevated RR for major birth defects overall, but no evidence of a specific pattern; 95% CIs included 1, and this finding could be due to chance. In the combined seasons, we found no meaningful evidence of an increased risk for spontaneous abortion or preterm delivery following exposure to the seasonal influenza vaccine.