title: Reassuring results on birth outcomes in children fathered by men treated with azathioprine/6-mercaptopurine within 3 months before conception: a nationwide cohort study.
abstract: Information on the safety of paternal use of azathioprine (AZA) and 6-mercaptopurine (6-MP) prior to conception is limited. Based on nationwide data from the Danish health registries, we examined the association between paternal use of AZA/6-MP within 3 months before conception and adverse birth outcomes.
  
  
  
  This nationwide cohort study is based on data from all singletons born in Denmark from 1 January 1997 through 2013. Children fathered by men who used AZA/6-MP within 3 months before conception constituted the exposed cohort (N=699), and children fathered by men who did not use AZA/6-MP 3 months prior to conception constituted the unexposed cohort (N=1 012 624). The outcomes were congenital abnormalities (CAs), preterm birth and small for gestational age (SGA). We adjusted for multiple covariates and performed a restricted analysis of men with IBD.
  
  
  
  There were no significantly increased risks of CAs, preterm birth or SGA in exposed versus unexposed cohorts of children. The adjusted ORs were 0.82 (95% CI 0.53 to 1.28) for CAs, 1.17 (95% CI 0.72 to 1.92) for preterm birth and 1.38 (95% CI 0.76 to 2.51) for SGA. Restricting our analysis to fathers with IBD showed similar results with no significantly increased risk of adverse birth outcomes.
  
  
  
  This nationwide study is the largest to date, examining the effect of preconceptual paternal use of AZA/6-MP on birth outcomes in live born singletons. The results of no significantly increased risks of adverse birth outcomes are reassuring and support the continuation of paternal AZA/6-MP treatment during conception.
authors.affiliation: Center for Clinical Epidemiology, Odense University Hospital, and Research Unit of Clinical Epidemiology, University of Southern Denmark, Odense, Denmark.|Center for Crohn's and Colitis, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: B M
authors.initials: BM
authors.lastname: Nørgård
authors.affiliation: Center for Clinical Epidemiology, Odense University Hospital, and Research Unit of Clinical Epidemiology, University of Southern Denmark, Odense, Denmark.
authors.forename: B
authors.initials: B
authors.lastname: Magnussen
authors.affiliation: Center for Clinical Epidemiology, Odense University Hospital, and Research Unit of Clinical Epidemiology, University of Southern Denmark, Odense, Denmark.
authors.forename: M D
authors.identifier: 0000-0002-0623-2481
authors.initials: MD
authors.lastname: Larsen
authors.affiliation: Center for Clinical Epidemiology, Odense University Hospital, and Research Unit of Clinical Epidemiology, University of Southern Denmark, Odense, Denmark.|Center for Crohn's and Colitis, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: S
authors.initials: S
authors.lastname: Friedman
mesh_terms: D000328:Adult; D001379:Azathioprine / Q000627:therapeutic use*; D016022:Case-Control Studies; D015331:Cohort Studies; D000013:Congenital Abnormalities / Q000453:epidemiology*; D003718:Denmark / Q000453:epidemiology; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007236:Infant, Small for Gestational Age; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy / Q000453:epidemiology; D008297:Male; D015122:Mercaptopurine / Q000627:therapeutic use*; D018812:Paternal Exposure; D011247:Pregnancy; D011256:Pregnancy Outcome / Q000453:epidemiology; D047928:Premature Birth / Q000453:epidemiology*; D055815:Young Adult
chemical_list: D007166:Immunosuppressive Agents; D015122:Mercaptopurine; D001379:Azathioprine
keywords: 6-MERCAPTOPURINE; AZATHIOPRINE; EPIDEMIOLOGY; INFLAMMATORY BOWEL DISEASE