Risks and safety of pandemic H1N1 influenza vaccine in pregnancy: birth defects, spontaneous abortion, preterm delivery, and small for gestational age infants.

INTRODUCTION There is a need for additional information on the fetal risks and relative safety of the pandemic H1N1 monovalent or trivalent influenza (pH1N1)-containing vaccines in women exposed during pregnancy. METHODS To assess risks and relative safety of the pH1N1-containing vaccines, we conducted a prospective cohort study of pH1N1-vaccine-exposed and unexposed comparison women residing in the U.S. or Canada who were recruited during pregnancy and followed to outcome between October 2009 and August 2012. For exposure to the pH1N1 vaccine, adjusted relative risks (RRs) and 95% confidence intervals (CIs) were estimated for major birth defects and infants small for gestational age. Adjusted hazard ratios (HRs) and 95% CIs were estimated for spontaneous abortion and preterm delivery for time-varying exposure. RESULTS There were 1032 subjects available for analysis; 841 women were exposed to a pH1N1-containing vaccine in pregnancy, and 191 women were unexposed to any influenza vaccine in pregnancy. Nine of 328 (2.7%) first-trimester-exposed pregnancies resulted in an infant with a major birth defect compared to 6/188 (3.2%) in the unexposed (adjusted RR 0.79, 95% CI 0.26-2.42). The HR for spontaneous abortion was not elevated (adjusted HR 0.92, 95% CI 0.31-2.72). Adjusted HRs for preterm delivery were elevated for exposure anytime in pregnancy (3.28, 95% CI 1.25-8.63), specifically with exposure in the 1st or 2nd trimester. However, the mean decrease in gestational age in the exposed pregnancies was approximately three days. Adjusted RRs for small for gestational age infants on weight and length approximated 1.0. CONCLUSIONS For the 2009-12 influenza seasons combined, we found no meaningful evidence of increased RR or HR for major birth defects, spontaneous abortion, or small for gestational age infants. There was some evidence of an increased HR for preterm delivery following pH1N1-influenza vaccine exposure; however the decrease in gestational age on average was approximately three days.