S Friedman1, M D Larsen2, B Magnussen3, L R Jølving4, P de Silva5, B M Nørgård6. 1. Center for Crohn's and Colitis, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; Center for Clinical Epidemiology, Odense University Hospital, and Research Unit of Clinical Epidemiology, University of Southern Denmark, Odense, Denmark. Electronic address: sfriedman1@partners.org. 2. Center for Clinical Epidemiology, Odense University Hospital, and Research Unit of Clinical Epidemiology, University of Southern Denmark, Odense, Denmark. Electronic address: Michael.due.larsen@rsyd.dk. 3. Center for Clinical Epidemiology, Odense University Hospital, and Research Unit of Clinical Epidemiology, University of Southern Denmark, Odense, Denmark. Electronic address: Bjarne.magnussen@rsyd.dk. 4. Center for Clinical Epidemiology, Odense University Hospital, and Research Unit of Clinical Epidemiology, University of Southern Denmark, Odense, Denmark. Electronic address: line.jolving@rsyd.dk. 5. Center for Crohn's and Colitis, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: pdesilva@bwh.harvard.edu. 6. Center for Crohn's and Colitis, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; Center for Clinical Epidemiology, Odense University Hospital, and Research Unit of Clinical Epidemiology, University of Southern Denmark, Odense, Denmark. Electronic address: bente.noergaard@rsyd.dk.
Abstract
PURPOSE: We examined the effect of preconception paternal use of azathioprine (AZA)/6-mercaptopurine (6-MP) or methotrexate (MTX) and the risk of adverse long-term outcomes in the offspring. METHODS: This study included all children born in Denmark from 1 January 1997 through 2013. Exposed cohort: children fathered by men who used AZA/6-MP (N=735) or MTX (N=209) within three months before conception; unexposed cohort: children fathered by men who did not use AZA/6-MP/MTX (N=1,056,524). OUTCOMES: malignancies, autism spectrum disorders (ASD)/schizophrenia/psychosis, and attention deficit hyperactivity disorder (ADHD). RESULTS: Outcomes: of children: AZA/6-MP exposure: one with leukemia (0.14%), one with ASD/schizophrenia (0.14%) and three with ADHD (0.41%); MTX exposure: three with ADHD (1.4%). Unexposed: 1710 with malignancies (0.16%), 2107 with ASD/schizophrenia (0.20%), 2799 with ADHD (0.26%). Median follow up times were 6.7 [IQR:3.6-11.3] and 9.9 [IQR:5.7-14.3] years respectively. CONCLUSIONS: There was no negative impact of paternal preconception use of AZA/6-MP/MTX on selected childhood health outcomes.
PURPOSE: We examined the effect of preconception paternal use of azathioprine (AZA)/6-mercaptopurine (6-MP) or methotrexate (MTX) and the risk of adverse long-term outcomes in the offspring. METHODS: This study included all children born in Denmark from 1 January 1997 through 2013. Exposed cohort: children fathered by men who used AZA/6-MP (N=735) or MTX (N=209) within three months before conception; unexposed cohort: children fathered by men who did not use AZA/6-MP/MTX (N=1,056,524). OUTCOMES: malignancies, autism spectrum disorders (ASD)/schizophrenia/psychosis, and attention deficit hyperactivity disorder (ADHD). RESULTS: Outcomes: of children: AZA/6-MP exposure: one with leukemia (0.14%), one with ASD/schizophrenia (0.14%) and three with ADHD (0.41%); MTX exposure: three with ADHD (1.4%). Unexposed: 1710 with malignancies (0.16%), 2107 with ASD/schizophrenia (0.20%), 2799 with ADHD (0.26%). Median follow up times were 6.7 [IQR:3.6-11.3] and 9.9 [IQR:5.7-14.3] years respectively. CONCLUSIONS: There was no negative impact of paternal preconception use of AZA/6-MP/MTX on selected childhood health outcomes.
Authors: L F Perez-Garcia; R J E M Dolhain; S Vorstenbosch; W Bramer; E van Puijenbroek; J M W Hazes; B Te Winkel Journal: Hum Reprod Update Date: 2020-11-01 Impact factor: 15.610