EXPOSURE TO MISOPROSTOL IN PREGNANCY

Misoprostol is a synthetic prostaglandin E1 analogue which acts as a potent uterine stimulant. It is used subsequently to mifepristone for medical termination of pregnancy (TOP). Misoprostol is also used in monotherapy for the prophylaxis and treatment of NSAID-induced gastric ulcers, and for induction of labour.

Where ongoing pregnancy has followed exposure to misoprostol in the first trimester, there are numerous case reports describing a spectrum of anomalies consistent with Möbius syndrome. Observed anomalies include cranial nerve palsies, central nervous system defects, limb defects, orofacial clefts, arthrogryposis, and talipes. Amniotic banding has also been noted. The absolute risk of malformations following misoprostol exposure is unquantified. A teratogenic risk period of between five and eight weeks’ gestation has been suggested but not fully proven.

Increased risks of intrauterine death and reduced birth weight following gestational misoprostol exposure have also been observed in some studies. Neurodevelopment has not been systematically assessed. It is uncertain whether the frequencies of autism and neurodevelopmental anomalies differ between individuals with Möbius syndrome due to misoprostol exposure compared to those with Möbius syndrome of different aetiology.

Due to its abortifacient and teratogenic effects, women of childbearing potential who are using misoprostol for the prophylaxis and treatment of NSAID-induced gastric ulcers should be counselled on the importance of effective contraception. Pregnancy should be excluded before treatment is initiated.

Additional monitoring of fetal viability, growth, and development is indicated in ongoing pregnancies with misoprostol exposure. The manufacturer recommends a careful ultrasound scan, with special attention to the limbs and head, carried out in a specialised centre. It should be noted that cranial nerve defects are unlikely to be detected by ultrasound examination but should be suspected if limb anomalies or arthrogryposis are observed. Other risk factors may also be present in individual cases which may independently increase the risk of adverse pregnancy outcome. Clinicians are reminded of the importance of consideration of such factors when performing case-specific risk assessments.