title: Evaluation of safety of A/H1N1 pandemic vaccination during pregnancy: cohort study.
abstract: OBJECTIVE
  To assess the risk of maternal, fetal, and neonatal outcomes associated with the administration of an MF59 adjuvanted A/H1N1 vaccine during pregnancy.
  
  
  METHODS
  Historical cohort study.
  
  
  METHODS
  Singleton pregnancies of the resident population of the Lombardy region of Italy.
  
  
  METHODS
  All deliveries between 1 October 2009 and 30 September 2010. Data on exposure to A/H1N1 pandemic vaccine, pregnancy, and birth outcomes were retrieved from regional databases. Vaccinated and non-vaccinated women were compared in a propensity score matched analysis to estimate risks of adverse outcomes.
  
  
  METHODS
  Main maternal outcomes included type of delivery, admission to intensive care unit, eclampsia, and gestational diabetes; fetal and neonatal outcomes included perinatal deaths, small for gestational age births, and congenital malformations.
  
  
  RESULTS
  Among the 86,171 eligible pregnancies, 6246 women were vaccinated (3615 (57.9%) in the third trimester and 2557 (40.9%) in the second trimester). No difference was observed in terms of spontaneous deliveries (adjusted odds ratio 1.02, 95% confidence interval 0.96 to 1.08) or admissions to intensive care units (0.95, 0.47 to 1.88), whereas a limited increase in the prevalence of gestational diabetes (1.26, 1.04 to 1.53) and eclampsia (1.19, 1.04 to 1.39) was seen in vaccinated women. Rates of fetal and neonatal outcomes were similar in vaccinated and non-vaccinated women. A slight increase in congenital malformations, although not statistically significant, was present in the exposed cohort (1.14, 0.99 to 1.31).
  
  
  CONCLUSIONS
  Our findings add relevant information about the safety of the MF59 adjuvanted A/H1N1 vaccine in pregnancy. Residual confounding may partly explain the increased risk of some maternal outcomes. Meta-analysis of published studies should be conducted to further clarify the risk of infrequent outcomes, such as specific congenital malformations.
authors.affiliation: Pharmacoepidemiology Unit, National Centre for Epidemiology, National Institute of Health, Viale Regina Elena 299, 00161 Rome, Italy Pharmacovigilance Unit, Italian Medicines Agency (AIFA), 00187 Rome, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Trotta
authors.affiliation: Pharmacoepidemiology Unit, National Centre for Epidemiology, National Institute of Health, Viale Regina Elena 299, 00161 Rome, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Da Cas
authors.affiliation: Pharmacoepidemiology Unit, National Centre for Epidemiology, National Institute of Health, Viale Regina Elena 299, 00161 Rome, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Spila Alegiani
authors.affiliation: Unit for Preventive Medicine, General Directorate for Health, The Lombardy Region, 20124 Milan, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Gramegna
authors.affiliation: Regional Centre for Pharmacovigilance, General Directorate for Health, The Lombardy Region, 20124 Milan, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Venegoni
authors.affiliation: Unit for Local Health Service Governance, General Directorate for Health, The Lombardy Region, 20124 Milan, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Zocchetti
authors.affiliation: Pharmacoepidemiology Unit, National Centre for Epidemiology, National Institute of Health, Viale Regina Elena 299, 00161 Rome, Italy giuseppe.traversa@iss.it.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Traversa
mesh_terms: D000276:Adjuvants, Immunologic / Q000009:adverse effects; D000293:Adolescent; D000328:Adult; D015331:Cohort Studies; D000013:Congenital Abnormalities / Q000453:epidemiology*; D005260:Female; D005317:Fetal Growth Retardation / Q000453:epidemiology*; D006801:Humans; D007236:Infant, Small for Gestational Age; D053118:Influenza A Virus, H1N1 Subtype; D007252:Influenza Vaccines / Q000009:adverse effects* / Q000627:therapeutic use; D007251:Influenza, Human / Q000517:prevention & control*; D007558:Italy / Q000453:epidemiology; D008875:Middle Aged; D015999:Multivariate Analysis; D058873:Pandemics / Q000517:prevention & control; D011247:Pregnancy; D011248:Pregnancy Complications / Q000453:epidemiology; D011256:Pregnancy Outcome; D047928:Premature Birth / Q000453:epidemiology; D014611:Vaccination / Q000706:statistics & numerical data; D055815:Young Adult
chemical_list: D000276:Adjuvants, Immunologic; D007252:Influenza Vaccines