Lithium carbonate is an effective drug for prophylaxis and treatment of major 
affective disorders. In-utero exposure to lithium during the first trimester of 
pregnancy might be associated with an increased risk of cardiac malformations, 
especially the rare Ebstein's anomaly. We prospectively recruited and followed 
148 women (mean age 30 years, SD 5 range 15-40) using lithium during the first 
trimester of pregnancy, who consulted four teratogen information centres in the 
USA and Canada. Pregnancy outcome was compared with that of controls matched for 
maternal age. We had complete follow-up of pregnancy outcome in 138 of 148 
patients recruited. In the other 10, fetal echocardiograms were available but 
postnatal follow-up was not done. Mean daily dose of lithium was 927 mg (SD 
340). Rates of major congenital malformations did not differ between the lithium 
(2.8%) and control (2.4%) groups. 1 patient in the lithium group chose to 
terminate pregnancy after Ebstein's anomaly was detected by a prenatal 
echocardiogram. There was 1 ventricular septal defect in the controls. 
Birthweight was significantly higher in the lithium-exposed infants than in the 
controls despite identical gestational ages (3475 [660] g vs 3383 [566] g, p = 
0.02). The true difference in birthweight might have been even larger, since 
significantly more women using lithium than controls were cigarette smokers 
(31.8% vs 15.5%, p = 0.002). These results indicate that lithium is not an 
important human teratogen. Women with major affective disorders who wish to have 
children may continue lithium therapy, provided that adequate screening tests, 
including level II ultrasound and fetal echocardiography, are done.