Prospective multicentre study of pregnancy outcome after lithium exposure during first trimester.
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.
Department of Pediatrics and Pharmacology, Hospital for Sick Children, University of Toronto, Ontario, Canada.
S J
SJ
Jacobson
K
K
Jones
K
K
Johnson
L
L
Ceolin
P
P
Kaur
D
D
Sahn
A E
AE
Donnenfeld
M
M
Rieder
R
R
Santelli
J
J
Smythe
D000014:Abnormalities, Drug-Induced / Q000209:etiology*; D000293:Adolescent; D000328:Adult; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008094:Lithium / Q000009:adverse effects* / Q000627:therapeutic use; D019964:Mood Disorders / Q000188:drug therapy; D011247:Pregnancy; D011248:Pregnancy Complications / Q000188:drug therapy; D011261:Pregnancy Trimester, First; D011446:Prospective Studies
D008094:Lithium