title: No evidence for an increased risk of adverse pregnancy outcome after paternal low-dose methotrexate: an observational cohort study.
abstract: OBJECTIVE
  There is increasing awareness of the potential impact of paternal exposures on pregnancy outcome. In particular this applies to MTX, which is used in low doses for the treatment of RA and other inflammatory diseases. MTX is associated with a specific pattern of malformations in fetuses of exposed women, but there is uncertainty concerning the risk of paternal low-dose MTX. The aim of this study was to investigate whether paternal low-dose MTX therapy around conception has an unfavourable effect on pregnancy outcome.
  
  
  METHODS
  We performed a prospective observational cohort study involving pregnancies fathered by men who were treated with low-dose MTX around conception. Pregnancies were identified through our Teratology Information Service. Pregnancy outcomes were compared with a cohort neither exposed to MTX nor to other teratogens. Outcomes evaluated were major birth defects, spontaneous abortion (SAB), elective termination of pregnancy, gestational age at delivery, and birth weight.
  
  
  RESULTS
  A total of 113 pregnancies with paternal low-dose MTX treatment were compared with 412 non-exposed pregnancies. Neither the rate of major birth defects [odds ratio (OR) 1.02, 95% CI 0.05, 7.0) nor the risk of SAB (hazard ratio 1.19, 95% CI 0.65, 2.17) was increased. Gestational age at delivery and birth weights did not differ significantly between groups. The rate of electively terminated pregnancies was increased in the MTX-exposed patients compared with controls.
  
  
  CONCLUSIONS
  Our study does not confirm an increased risk of adverse pregnancy outcome after paternal low-dose MTX therapy. The reassuring findings do not support the necessity of a 3-month MTX-free interval until conception. In the case of unavoidable paternal MTX therapy, it seems reasonable not to postpone family planning.
authors.affiliation: Pharmakovigilanz- und Beratungszentrum für Embryonaltoxikologie, Charité Universitätsmedizin Berlin, Spandauer Damm 130, Haus 10, 14050 Berlin, Germany. corinna.weber-schoendorfer@charite.de.
authors.forename: Corinna
authors.initials: C
authors.lastname: Weber-Schoendorfer
authors.forename: Maria
authors.initials: M
authors.lastname: Hoeltzenbein
authors.forename: Evelin
authors.initials: E
authors.lastname: Wacker
authors.forename: Reinhard
authors.initials: R
authors.lastname: Meister
authors.forename: Christof
authors.initials: C
authors.lastname: Schaefer
mesh_terms: D000022:Abortion, Spontaneous / Q000209:etiology*; D000328:Adult; D018501:Antirheumatic Agents / Q000009:adverse effects*; D016022:Case-Control Studies; D015331:Cohort Studies; D000013:Congenital Abnormalities / Q000209:etiology*; D005220:Fathers; D005260:Female; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000009:adverse effects*; D011247:Pregnancy; D011256:Pregnancy Outcome; D011446:Prospective Studies
chemical_list: D018501:Antirheumatic Agents; D008727:Methotrexate
keywords: cohort study; human; low-dose methotrexate; malformation; paternal; pregnancy outcome; rheumatoid arthritis; spontaneous abortion; teratogen