title: Risks and safety of pandemic H1N1 influenza vaccine in pregnancy: birth defects, spontaneous abortion, preterm delivery, and small for gestational age infants.
abstract: BACKGROUND
  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.
authors.affiliation: Department of Pediatrics, University of California San Diego, La Jolla, CA, United States; Rady Children's Hospital, San Diego, CA, United States; Department of Family and Preventive Medicine, University of California San Diego, La Jolla, CA, United States; Clinical Translational Research Institute, University of California San Diego, La Jolla, CA, United States; Vaccines and Medications in Pregnancy Surveillance System, United States. Electronic address: chchambers@ucsd.edu.
authors.forename: Christina D
authors.initials: CD
authors.lastname: Chambers
authors.forename: Diana
authors.initials: D
authors.lastname: Johnson
authors.forename: Ronghui
authors.initials: R
authors.lastname: Xu
authors.forename: Yunjun
authors.initials: Y
authors.lastname: Luo
authors.forename: Carol
authors.initials: C
authors.lastname: Louik
authors.forename: Allen A
authors.initials: AA
authors.lastname: Mitchell
authors.forename: Michael
authors.initials: M
authors.lastname: Schatz
authors.forename: Kenneth L
authors.initials: KL
authors.lastname: Jones
mesh_terms: D000022:Abortion, Spontaneous / Q000453:epidemiology*; D000328:Adult; D002170:Canada; D000013:Congenital Abnormalities / Q000453:epidemiology; D062665:Epidemiological Monitoring; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D007236:Infant, Small for Gestational Age; D053118:Influenza A Virus, H1N1 Subtype; D007252:Influenza Vaccines / Q000008:administration & dosage* / Q000009:adverse effects; D007251:Influenza, Human / Q000517:prevention & control; D011247:Pregnancy; D047928:Premature Birth / Q000453:epidemiology*; D011446:Prospective Studies; D012306:Risk; D014481:United States
chemical_list: D007252:Influenza Vaccines
keywords: Birth defects; Pandemic H1N1 influenza vaccination; Pregnancy; Preterm delivery; Small for gestational age; Spontaneous abortion