title: Misoprostol exposure during the first trimester of pregnancy: Is the malformation risk varying depending on the indication?
abstract: OBJECTIVE
  To report the prospective follow-up of pregnancies exposed to misoprostol during the first trimester and analyse the teratogenic risk depending on the indication for use.
  
  
  METHODS
  Prospective observational study of 265 women exposed to misoprostol during the first 12 weeks of pregnancy and followed until the delivery. Women were included if they or their physician had contacted a French pharmacovigilance centre before 22 weeks of gestation (WG) to obtain information on the risk of misoprostol exposure, and if there had been misoprostol exposure before 13 WG. Data were collected at the time of the first contact, and the pregnancy outcome was recorded at follow-up. Women were prospectively enrolled from January 1988 to December 2013.
  
  
  RESULTS
  The main indication for misoprostol was voluntary abortion (60.9%). Ten major malformations (5.5%) (95% CI 2.65-9.82%) were reported and five of them were consistent with the pattern of malformations attributed to misoprostol: Möbius sequence, hydrocephalus, terminal transverse limb reduction associated with a clubfoot, syndactyly, and complete posterior encephalocele. The rate of malformations was higher, but not significantly, in women exposed to misoprostol for voluntary abortion (7.9%) compared with women exposed to misoprostol for other or unknown indications (3.2%).
  
  
  CONCLUSIONS
  Our results confirmed a specific pattern of malformations due to misoprostol use in early pregnancy, even with low dose of misoprostol. Despite the small number of cases, we observed a higher proportion of major malformations in fetuses born to women who continued their pregnancy after a failed voluntary abortion with misoprostol. Further studies should be conducted to evaluate other potential factors, such as combination treatment with mifepristone and the socio-environmental characteristics in this group of women.
authors.affiliation: Centre Régional de PharmacoVigilance du Nord-Pas de Calais, CHRU de Lille, France. Electronic address: marine.auffret@chru-lille.fr.
authors.forename: Marine
authors.initials: M
authors.lastname: Auffret
authors.affiliation: Centre Régional de PharmacoVigilance de Lyon, Hospices Civils de Lyon, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Bernard-Phalippon
authors.affiliation: Centre Régional de PharmacoVigilance du Nord-Pas de Calais, CHRU de Lille, France.
authors.forename: Joëlle
authors.initials: J
authors.lastname: Dekemp
authors.affiliation: Centre Régional de Pharmacovigilance Paris, Hôpital Fernand Widal, AP-HP, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Carlier
authors.affiliation: Centre Régional de PharmacoVigilance de Marseille, AP-HM, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Gervoise Boyer
authors.affiliation: Centre Régional de PharmacoVigilance de Lyon, Hospices Civils de Lyon, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Vial
authors.affiliation: Centre Régional de PharmacoVigilance du Nord-Pas de Calais, CHRU de Lille, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Gautier
mesh_terms: D000014:Abnormalities, Drug-Induced / Q000453:epidemiology / Q000209:etiology*; D000020:Abortifacient Agents, Nonsteroidal / Q000633:toxicity*; D000328:Adult; D000897:Anti-Ulcer Agents / Q000009:adverse effects; D005260:Female; D005500:Follow-Up Studies; D005602:France / Q000453:epidemiology; D006801:Humans; D006849:Hydrocephalus / Q000139:chemically induced / Q000453:epidemiology; D007231:Infant, Newborn; D008431:Maternal-Fetal Exchange; D016595:Misoprostol / Q000009:adverse effects / Q000633:toxicity*; D020331:Mobius Syndrome / Q000139:chemically induced / Q000453:epidemiology; D060735:Pharmacovigilance; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D011446:Prospective Studies; D012306:Risk; D013723:Teratogens / Q000633:toxicity*; D055815:Young Adult
chemical_list: D000020:Abortifacient Agents, Nonsteroidal; D000897:Anti-Ulcer Agents; D013723:Teratogens; D016595:Misoprostol
keywords: Congenital malformation; Misoprostol; Pregnancy; Teratogenic risk; Voluntary abortion