REVIEW OF: Fornaro M et al, Am J Psychiatry 2020;177(1):76–92

STUDY TYPE: Literature review

Most of us are wary of prescribing lithium to pregnant patients, but is prenatal lithium exposure as risky as we think? A meta-analysis of 13 case-control, cohort, and interventional studies (n = 1,349,563 pregnancies) compared congenital anomalies among lithium-exposed and unexposed mothers with and without bipolar disorder (BD).

Lithium use at any time in pregnancy, compared with unexposed women (either with BD or general population controls), was associated with a significantly elevated risk of congenital and cardiac anomalies (odds ratio [OR] 1.75, p < 0.01 and OR 1.9, p < 0.01, respectively)—and the risk was even higher if lithium was used in the first trimester. However, in their discussion, the authors point out that the absolute risks are low: 4.2% for any malformations and 1.2% for cardiac malformations. First-trimester lithium exposure was also linked with a higher risk of spontaneous abortion (OR 3.8, p = 0.03)—but this risk was about the same in pregnant patients with mood disorders not on lithium. This suggests that the underlying mood disorder contributes to the risk of spontaneous abortion.

Compared to no lithium use, lithium use was significantly more effective in preventing a mood relapse in the postpartum (OR 0.16, p = 0.12). The rate of cardiac malformations tripled with dosages above 900 mg/day when compared with dosages under 600 mg/day and maternal lithium levels < 0.64 mEq/L. At these lower doses, the risk of cardiac malformations was comparable to that of unexposed newborns. Also, infants exposed to lower lithium doses were more reactive. The authors point out several limitations in their data, including a lack of information on other prescribed medications besides lithium.

CARLAT TAKE

Lithium use during pregnancy, especially in the first trimester, elevates the risks of congenital and cardiac anomalies, but it also helps prevent postpartum mood relapses. The absolute risk for congenital issues remains low—and you can reduce this risk further by keeping the lithium dose below 600 mg/day and the maternal lithium levels below 0.64 mEq/L. However, some patients, especially those with severe illness, may require higher lithium concentrations to remain stable. While this study has methodologic limitations typically inherent in research on prenatal psychotropic medication exposures, it provides helpful guidelines for the use of lithium in pregnant patients.