title: Risk of spontaneous abortion and other pregnancy outcomes in 15-25 year old women exposed to human papillomavirus-16/18 AS04-adjuvanted vaccine in the United Kingdom.
abstract: BACKGROUND
  We assessed the risk of spontaneous abortion (SA) after inadvertent exposure to HPV-16/18-vaccine during pregnancy using an observational cohort design.
  
  
  METHODS
  The study population included women aged 15-25 years registered with the Clinical Practice Research Datalink General Practice OnLine Database in the United Kingdom (UK), who received at least one HPV-16/18-vaccine dose between 1st September 2008 and 30th June 2011. Exposed women had the first day of gestation between 30 days before and 45 days (90 days for the extended exposure period) after any HPV-16/18-vaccine dose. Non-exposed women had the first day of gestation 120 days-18 months after the last dose. SA defined as foetal loss between weeks 1 and 23 of gestation (UK definition).
  
  
  RESULTS
  The frequency of SA was 11.6% (among 207 exposed) and 9.0% (632 non-exposed), women: hazard ratio (HR) adjusted for age at first day of gestation 1.30 (95% confidence interval: 0.79-2.12). Sensitivity analysis per number of doses administered (-30 to +45-day risk period) showed a HR for SA of 1.11 (0.64-1.91) for 18/178 women with one dose during the risk period versus 2.55 (1.09-5.93) in 6/29 women with two doses within a 4-5 weeks period. The proportion of pre-term/full-term/postterm deliveries, small/large for gestational age infants, and birth defects was not significantly different between exposed and non-exposed women. Results were consistent using a (United States) SA definition of foetal loss between weeks 1-19 and/or the extended risk period.
  
  
  CONCLUSIONS
  There was no evidence of an increased risk of SA and other adverse pregnancy outcomes in young women inadvertently HPV-16/18-vaccinated around gestation. Nevertheless, women who are pregnant or trying to become pregnant are advised to postpone vaccination until completion of pregnancy.
authors.affiliation: GSK Vaccines, 20, Avenue Fleming, B-1300 Wavre, Belgium. Electronic address: laurence.x.baril@gsk.com.
authors.forename: Laurence
authors.initials: L
authors.lastname: Baril
authors.affiliation: GSK Vaccines, 20, Avenue Fleming, B-1300 Wavre, Belgium.
authors.forename: Dominique
authors.initials: D
authors.lastname: Rosillon
authors.affiliation: GSK Vaccines, 20, Avenue Fleming, B-1300 Wavre, Belgium.
authors.forename: Corinne
authors.initials: C
authors.lastname: Willame
authors.affiliation: GSK Vaccines, 20, Avenue Fleming, B-1300 Wavre, Belgium.
authors.forename: Maria Genalin
authors.initials: MG
authors.lastname: Angelo
authors.affiliation: GSK Vaccines, 20, Avenue Fleming, B-1300 Wavre, Belgium.
authors.forename: Julia
authors.initials: J
authors.lastname: Zima
authors.affiliation: Pallas, Health Research and Consultancy, Rotterdam, The Netherlands.
authors.forename: Judith H
authors.initials: JH
authors.lastname: van den Bosch
authors.affiliation: CPRD Research Group, London, United Kingdom.
authors.forename: Tjeerd
authors.initials: T
authors.lastname: Van Staa
authors.affiliation: CPRD Research Group, London, United Kingdom.
authors.forename: Rachael
authors.initials: R
authors.lastname: Boggon
authors.affiliation: Pallas, Health Research and Consultancy, Rotterdam, The Netherlands.
authors.forename: Eveline M
authors.initials: EM
authors.lastname: Bunge
authors.affiliation: Harvard School of Public Health, Cambridge, USA.
authors.forename: Sonia
authors.initials: S
authors.lastname: Hernandez-Diaz
authors.affiliation: University of California San Diego School of Medicine, USA.
authors.forename: Christina D
authors.initials: CD
authors.lastname: Chambers
mesh_terms: D000022:Abortion, Spontaneous / Q000139:chemically induced* / Q000453:epidemiology*; D000293:Adolescent; D000328:Adult; D000536:Aluminum Hydroxide / Q000008:administration & dosage* / Q000009:adverse effects*; D005260:Female; D006801:Humans; D008050:Lipid A / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D053918:Papillomavirus Vaccines / Q000008:administration & dosage* / Q000009:adverse effects*; D011247:Pregnancy; D011256:Pregnancy Outcome; D018570:Risk Assessment; D006113:United Kingdom / Q000453:epidemiology; D055815:Young Adult
chemical_list: C532963:ASO4 mixture; D008050:Lipid A; D053918:Papillomavirus Vaccines; D000536:Aluminum Hydroxide
keywords: Human papillomavirus vaccine; Mathematical model; Pregnancy; Safety; Spontaneous abortion; Vaccine