Pregnancy outcome after use of zopiclone during first trimester

Introduction: The piperazine sedative-hypnotic zopiclone is also used to treat insomnia during the childbearing years. So far there is only limited experience on the effects of zopiclone after use in early pregnancy. Methods: In a prospective follow-up study we collected data of pregnancy outcomes after medication with zopiclone (n = 73) between 1991 and 2014. Our Teratology Information Service (TIS) was contacted by physicians and patients after exposure to zopiclone in the first trimester. We compared the results with a control group (n = 777) of our TIS in the same interval, which was not or not severely exposed. Results: The incidence of elective terminations of pregnancy was much higher (p = 0.002) after medication with zopiclone (8/73 = 11.0%) than in the control group (20/777 = 2.6%). The rate of spontaneous abortions (9/65 = 13.8%) did not differ significantly from the control group (81/757 = 10.7%, p = 0.41). Four congenital anomalies were reported after intrauterine exposure to zopiclone: atrial septal defect, hemangioma, hip dysplasia, muscular hyertonia. The overall rate of congenital anomalies was not significantly increased after application of zopiclone in early pregnancy (4/56 = 7.1% vs. 27/676 = 4.0%; relative risk 1.79; 95% confidence interval 0.54, 5.05). A consistent pattern of anomalies could not be confirmed. Conclusions: Our prospective controlled follow-up study does not support the assumption of a teratogenic effect of zopiclone.