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Lithium reduction during pregnancy and postpartum period lowers fetal health risks

Pregnant women undergoing treatment for mood disorders should be prescribed the lowest therapeutic range of lithium, according to a study published in The American Journal of Psychiatry.

The study included a systematic review and random-effects meta-analysis assessing case-control, cohort and interventional studies reporting on the safety and efficacy of lithium treatment and exposure on pregnant women and the fetus. Researchers reviewed original studies and chose to evaluate 29 studies suitable for narrative synthesis and 13 studies for meta-analysis.

According to the findings from the review, lithium exposure during pregnancy was associated with a significantly increased risk for any congenital anomaly, cardiac malformations and spontaneous abortion, but was not associated with an increased risk for preterm birth. From the studies analyzed, lithium was more effective than no prophylaxis in preventing postpartum mood episodes in women, which shows clinical relevancy due to the risk for bipolar disorder relapse during pregnancy being almost three times higher than in nonpregnant women.

“In the analysis of exposure during the first trimester, lithium was associated with an increased risk of cardiac malformations compared with any unexposed group,” Michele Fornaro, MD, PhD, an associate research scientist at Columbia University, and colleagues wrote. “The risk was identical to that for exposure during any pregnancy period compared with the general population and was again significantly increased compared with unexposed patients with affective disorders.”

Lithium dosage, along with exposure, played a role in health outcomes of the fetus and newborn. Data from the qualitative synthesis showed the risk for cardiac malformations tripled with dosages less than 900 mg per day compared with dosages equal or greater than 600 mg per day. Lowering the lithium dosage during the first trimester of a pregnancy while keeping within therapeutic range may minimize the risk for malformations and relapse.

Pregnancies in women with bipolar disorder should ideally be planned to gradually reduce lithium dosage to the lowest extreme in the therapeutic range, especially during the first trimester to avoid health complications in the mother and fetus.

“Close monitoring of the pregnant woman’s serum lithium levels is therefore crucial to inform clinical choices on the basis of the physiological fluctuations occurring during pregnancy to avoid suboptimal therapeutic dosing for the pregnant woman, or potentially toxic doses thereafter,” the investigators wrote. “Especially for the infant, in whom the adverse neonatal effects of lithium, such as hypoglycemia, cardia arrhythmia, thyroid dysfunction and neonatal lithium toxicity are dose related.” – by Erin T. Welsh

Disclosure: Fornaro reports no relevant financial disclosures. Please see the full study for all other authors’ relevant financial disclosures.