Pregnancy Outcome Following In Utero Exposure to Lithium: A Prospective, Comparative, Observational Study

• Published in: The American journal of psychiatry 2014-07, Vol.171 (7), p.785-794
• Main Authors: Diav-Citrin, Orna, Shechtman, Svetlana, Tahover, Esther, Finkel-Pekarsky, Victoriya, Arnon, Judy, Kennedy, Debra, Erebara, Aida, Einarson, Adrienne, Ornoy, Asher
• Format: Article
• Language: English
• Subjects: Abnormalities, Drug-Induced - diagnosis; Abnormalities, Drug-Induced - etiology; Abortion, Eugenic - statistics & numerical data; Abortion, Spontaneous - chemically induced; Abortion, Spontaneous - diagnosis; Adult; Bipolar Disorder - drug therapy; Congenital diseases; Drug therapy; Female; Humans; Infant, Newborn; Lithium; Lithium Compounds - therapeutic use; Lithium Compounds - toxicity; Male; Obstetric Labor, Premature - chemically induced; Pregnancy; Pregnancy Outcome; Pregnancy Trimester, First; Prenatal Exposure Delayed Effects; Risk Factors; Side effects; Ultrasonography, Prenatal
• ISSN: 0002-953X; 1535-7228
• DOI: 10.1176/appi.ajp.2014.12111402

Lithium taken during the first trimester of pregnancy appears to increase the risk of cardiovascular anomalies in infants, although some of these anomalies resolve spontaneously. Lithium also raises the likelihood of miscarriage. On the other hand, the risk of illness recurrence is high for women who discontinue taking medication during pregnancy, and so the decision should be made on an individual basis. It is recommended that women treated with lithium during organogenesis receive fetal echocardiography and level-2 ultrasound. ObjectiveThe authors conducted a prospective, comparative observational study to evaluate the risk of major anomalies following exposure to lithium during pregnancy.MethodA total of 183 lithium-exposed pregnancies of women who contacted the Israeli Teratology Information Service were followed up (90.2% in the first trimester) and compared with 72 disease-matched and 748 nonteratogenic-exposed pregnancies.ResultsThere were significantly more miscarriages (adjusted odds ratio=1.94, 95% CI=1.08–3.48) and elective terminations of pregnancy (17/183 [9.3%] compared with 15/748 [2.0%]) in the lithium-exposed group compared with the nonteratogenic exposure group. The rate of major congenital anomalies after exclusion of genetic or cytogenetic anomalies was not significantly different between the three groups (lithium-exposed in the first trimester: 8/123 [6.5%]; bipolar: 2/61 [3.3%]; nonteratogenic: 19/711 [2.7%]). Cardiovascular anomalies occurred more frequently in the lithium group exposed during the first trimester when compared with the nonteratogenic exposure group (5/123 [4.1%] compared with 4/711 [0.6%]) but not after excluding anomalies that spontaneously resolved (3/123 [2.4%] compared with 2/711 [0.3%]). Ebstein’s anomaly was diagnosed in one lithium-exposed fetus and in two retrospective lithium cases that were not included because contact with the information service was made after the prenatal diagnosis by ultrasound. The rate of noncardiovascular anomalies was not significantly different between the groups. The rate of preterm deliveries was higher in the lithium group compared with the nonteratogenic exposure group (18/131 [13.7%] compared with 41/683 [6.0%]).ConclusionsLithium treatment in pregnancy is associated with a higher rate of cardiovascular anomalies. Women who are treated with lithium during organogenesis should undergo fetal echocardiography and level-2 ultrasound.