Lithium Use in Pregnancy and Cardiac Malformations

Study Questions:

What is the risk of Ebstein’s anomaly and other congenital cardiac defects in infants exposed to lithium in utero?

Methods:

Medicaid data from 1,325,563 pregnancies between 2000 and 2010 were analyzed. Women exposed to lithium were compared with two control groups: one involving women exposed to another mood stabilizer, lamotrigine, and the other involving women not exposed to either.

Results:

In the first trimester, 663 women were exposed to lithium, 1,945 women were exposed to lamotrigine, and 1,322,955 women were not exposed. Cardiac malformations were present in 2.4% of infants exposed to lithium, 1.4% of infants exposed to lamotrigine, and 1.15% of infants who were not exposed. The adjusted risk ratio for infants exposed to lithium compared with unexposed infants was 1.65 (95% confidence interval [CI], 1.47-7.02). The risk ratio was dose dependent (1.11 for daily dose of ≤600 mg vs. 3.22 for >900 mg). The prevalence of right ventricular obstruction defects in infants exposed to lithium was 0.60% compared with 0.18% among unexposed infants (adjusted risk ratio, 2.66; 95% CI, 1.0-7.1).

Conclusions:

The use of lithium during the first trimester is associated with an increased risk of fetal cardiac malformations, including Ebstein’s, on the order of 1 additional case per 100 live births.

Perspective:

Lithium is an important and effective mood stabilizer for bipolar disorder, and its use during pregnancy may be necessary. Although lithium was previously postulated to cause a 400-fold increase in the risk of Ebstein’s anomaly, this was based on small retrospective data from the 1970s. This study shows that the risk is actually substantially lower. Doses <900 mg are associated with lower risk as well. These data are reassuring for pregnant women with bipolar disorder since treatment with lithium may prevent a mood-episode recurrence during pregnancy and the postpartum period. Although certain medications may be teratogenic, the level of risk can be overstated. Misperceptions can prevent pregnant women from receiving proper medical treatment, even when the fetal risks may be low.

Clinical Topics: Congenital Heart Disease and Pediatric Cardiology, Prevention, Congenital Heart Disease, CHD & Pediatrics and Arrhythmias, CHD & Pediatrics and Quality Improvement

Keywords: Bipolar Disorder, Ebstein Anomaly, Heart Defects, Congenital, Infant, Lithium, Medicaid, Mood Disorders, Pregnancy, Pregnancy Trimester, First, Risk, Secondary Prevention


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