Is lithium a real teratogen? What can we conclude from the prospective versus retrospective studies? A review

Background: Lithium is a drug used mainly for the treatment of Bipolar Disorder (BD). Case reports and several retrospective studies have demonstrated possible teratogenicity, but the data in the different studies was inconclusive. Methods: We summarized all published studies in English, including case reports. Results: We found 24 case reports, of which six infants had congenital anomalies, five having cardiac anomalies, one of them being Ebsteins anomaly. In the retrospective studies there were, in the Lithium Baby Registry, 225 registered cases with 25 anomalies, 18 of them being cardiac, of which six had Ebsteins anomaly. An additional retrospective study on 59 cases found seven anomalies, four of them being cardiac. On the other hand, none of the prospective studies (296 liveborn infants) demonstrated any increase in the rate of congenital anomalies, although two had Ebsteins anomaly. All case control studies regarding Ebsteins anomaly were negative, and among 222 infants with Ebsteins anomaly and 44 with tricuspid atresia none of the mothers had taken lithium during pregnancy. Conclusions: Considering the serious limitations of the retrospective and case control studies that are also retrospective, lithium does not seem to be a significant teratogen, and hence should be given, if indicated, in pregnancy. It is, however, advisable to perform a fetal echocardiography to exclude the possibility of cardiac anomalies. Lamotrigine seems to be a possible alternative.