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. Study design 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.