title: Risk of Adverse Pregnancy Outcome After Paternal Exposure to Methotrexate Within 90 Days Before Pregnancy.
abstract: To study the association between paternal exposure to methotrexate within the 90-day period before pregnancy and congenital malformations and stillbirth in the offspring.
  
  
  
  We conducted a nationwide register study. Our cohort consisted of all live births in Denmark between 1997 and 2011 identified from the Medical Birth Registry. Methotrexate-exposed fathers were identified from the National Prescription Registry. From the national Hospital Registry we identified paternity, live births, and stillbirths as well as discharge diagnoses on congenital malformations.
  
  
  
  We identified 849,676 live births with known paternity. There were 127 live births of methotrexate-exposed fathers. Of these, four (3.2%) had major malformations compared with 28,814 (3.4%) of the unexposed. The odds ratio (OR) for major congenital malformation among exposed fathers compared with unexposed was 0.93 (95% confidence interval [CI] 0.34-2.51) and when adjusted for year of birth, maternal age, educational length, household income, and parity, the adjusted OR was 1.01 (95% CI 0.37-2.74). There were no stillbirths in the methotrexate-exposed group compared with 2,541 (0.3%) in the unexposed group and no increased risk of preterm birth (adjusted OR 1.31, 95% CI 0.66-2.59) among the children from exposed fathers.
  
  
  
  We found no association between paternal exposure to methotrexate within 90 days before pregnancy and congenital malformations, stillbirths, or preterm birth. Available data suggest that prepregnancy paternal methotrexate exposure should not be of major concern. Multinational recommendations should be changed accordingly.
authors.affiliation: Department of Clinical Pharmacology, Copenhagen University Hospital Bispebjerg, and the Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, the Department of Rheumatology, Copenhagen University Hospital Rigshospitalet, Glostrup, and the Department of Urology, Copenhagen University Hospital Roskilde, Roskilde, Denmark; the Department of Obstetrics and Gynecology, University of Illinois at Chicago, Chicago, Illinois.
authors.forename: Lasse Karlsen
authors.initials: LK
authors.lastname: Eck
authors.forename: Thomas Bo
authors.initials: TB
authors.lastname: Jensen
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Mastrogiannis
authors.forename: Arendse
authors.initials: A
authors.lastname: Torp-Pedersen
authors.forename: Bjarke
authors.initials: B
authors.lastname: Askaa
authors.forename: Torben Kjær
authors.initials: TK
authors.lastname: Nielsen
authors.forename: Henrik Enghusen
authors.initials: HE
authors.lastname: Poulsen
authors.forename: Espen
authors.initials: E
authors.lastname: Jimenez-Solem
authors.forename: Jon Trærup
authors.initials: JT
authors.lastname: Andersen
mesh_terms: D000328:Adult; D015331:Cohort Studies; D000013:Congenital Abnormalities / Q000453:epidemiology*; D003718:Denmark / Q000453:epidemiology; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects; D007231:Infant, Newborn; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects; D018812:Paternal Exposure / Q000009:adverse effects / Q000706:statistics & numerical data; D011247:Pregnancy; D047928:Premature Birth / Q000453:epidemiology*; D055553:Prescription Drugs / Q000008:administration & dosage / Q000009:adverse effects; D012042:Registries / Q000706:statistics & numerical data; D018570:Risk Assessment; D013223:Statistics as Topic; D050497:Stillbirth / Q000453:epidemiology*
chemical_list: D007166:Immunosuppressive Agents; D055553:Prescription Drugs; D008727:Methotrexate