title: [Pregnancy outcome after preconceptional exposure to methotrexate for ectopic pregnancy].
abstract: BACKGROUND
  Methotrexate (MTX) is a known teratogenic drug used off-label in the treatment of ectopic pregnancies (EP). As MTX polyglutamated derivatives remains into the cells during several weeks, it is recommended to avoid conception during 3 to 6 months following MTX therapy. We report the follow-up of pregnancies after preconceptional exposure to MTX for EP.
  
  
  METHODS
  Prospective cases of pregnancy occurring within 3 months after MTX injection for an EP recorded in the Terappel database were analyzed.
  
  
  RESULTS
  Data were obtained on 52 pregnant women. The median age of patients was 28 (18-38), and the median gestational age at inclusion was 7 weeks after last menstrual period (3-22). The time between the last MTX injection and conception ranged from 12 days to 13 weeks and the total MTX dose was between 40 to 210mg. Out of 45 pregnancies with known outcome, there were 39 live births (87%), 3 spontaneous abortions (6.7%) occurring 63 to 94 days after MTX administration, 2 elective terminations, and 1 medical termination after premature rupture of membranes, oligohydramnios and arthrogryposis (48mg of MTX 9 and 8 weeks before conception). Two additional cases of major malformations were observed among 40 examinable babies or fetuses: tetralogy of Fallot (MTX 6 weeks before conception), and cerebral ventriculomegaly with normal karyotype (50mg of MTX 9 to 13 weeks before conception). The resulting rate of major malformations was 7.5% (95% CI: 1.6-20.4).
  
  
  CONCLUSIONS
  Although this prospective study shows a major malformation rate higher than expected in the general population, the observed malformations are not consistent with the typical pattern of methotrexate embryopathy. However, the case of tetralogy of Fallot is reminiscent of previously published cases with MTX exposure during early pregnancy. Owing to the small sample size, more powerful studies are needed to confirm or refute these findings.
authors.affiliation: Service de pharmacologie et toxicologie, centre régional de pharmacovigilance, CHU d'Angers, 4, rue Larrey, 49933 Angers cedex 9, France. Electronic address: LaLagarce@chu-angers.fr.
authors.forename: Laurence
authors.initials: L
authors.lastname: Lagarce
authors.affiliation: Centre régional de pharmacovigilance, hospices civils de Lyon, 69424 Lyon, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Bernard
authors.affiliation: Centre régional de pharmacovigilance, hôpital Fernand-Widal, 75475 Paris, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Carlier
authors.affiliation: Centre régional de pharmacovigilance, 679091 Strasbourg, France.
authors.forename: Silviana
authors.initials: S
authors.lastname: Phelipot-Lates
authors.affiliation: Centre régional de pharmacovigilance, CHU de Poitiers, 86021 Poitiers, France.
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Perault-Pochat
authors.affiliation: Service de pharmacologie et toxicologie, centre régional de pharmacovigilance, CHU d'Angers, 4, rue Larrey, 49933 Angers cedex 9, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Drablier
authors.affiliation: Service de pharmacologie et toxicologie, centre régional de pharmacovigilance, CHU d'Angers, 4, rue Larrey, 49933 Angers cedex 9, France.
authors.forename: Delphine
authors.initials: D
authors.lastname: Bourneau-Martin
authors.affiliation: Service de pharmacologie et toxicologie, centre régional de pharmacovigilance, CHU d'Angers, 4, rue Larrey, 49933 Angers cedex 9, France.
authors.forename: Pascale
authors.initials: P
authors.lastname: Lainé-Cessac
mesh_terms: D000014:Abnormalities, Drug-Induced / Q000453:epidemiology; D000293:Adolescent; D000328:Adult; D005260:Female; D005493:Folic Acid Antagonists / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005500:Follow-Up Studies; D006801:Humans; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use*; D056687:Off-Label Use; D011099:Polyglutamic Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D011247:Pregnancy; D011256:Pregnancy Outcome; D011271:Pregnancy, Ectopic / Q000188:drug therapy*; D011446:Prospective Studies; D055815:Young Adult
chemical_list: D005493:Folic Acid Antagonists; D011099:Polyglutamic Acid; C014085:methotrexate polyglutamate; D008727:Methotrexate
keywords: Birth defects; Ectopic pregnancy; Grossesse; Grossesse extra-utérine; Malformations congénitales; Methotrexate; Méthotrexate; Pregnancy