Treating mood disorders with lithium in the first trimester of pregnancy may increase infant malformation risks, according to a study published in Lancet.

An international team of investigators conducted a meta-analysis to determine the impact of lithium-containing mood disorder treatments on prenatal development and neonatal morbidities.

Using 6 international community and clinic groups, primary data were collected and analyzed for pregnant women and their offspring. Eligibility criteria included availability of health-related information; live-born singleton delivery (from 1997 to 2015); and maternal bipolar or major depressive disorder, or treatment with lithium during pregnancy. Women who were prescribed known teratogenic drugs during pregnancy were excluded from the study.

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Primary outcomes included complications during pregnancy, delivery outcomes, neonatal hospital readmission within 28 days of birth, and congenital malformations. 

Of the 22,124 pregnancies, 727 were included in the lithium-exposed cohort, which was not linked to any prespecified pregnancy or delivery complications. The researchers reported an increase in neonatal hospital readmission within 28 days of birth in the lithium-exposed cohort compared with the control group (pooled prevalence, 27.5% vs 14.3%; pooled adjusted odds ratio [aOR], 1.62).

In addition, results suggested an increased risk for major malformation with lithium exposure within the first trimester compared with no exposure (pooled prevalence, 7.4% vs 4.3%; pooled aOR, 1.71).

No significant differences were reported for major cardiac malformations between lithium exposed and unexposed infants (pooled prevalence, 2.1% vs 1.6%; pooled aOR, 1.54).

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“Considering both the effect sizes and the precision of the estimates in this meta-analysis, treatment decisions for pregnant women with mood disorders must weigh the potential for increased risks of lithium during pregnancy — in particular those associated with use of lithium during the first trimester — against its effectiveness at reducing relapse,” the authors concluded.


Munk-Olsen T, Liu X, Viktorin A, et al. Maternal and infant outcomes associated with lithium use in pregnancy: an international collaborative meta-analysis of six cohort studies [published online June 18, 2018]. Lancet. doi: 10.1016/S2215-0366(18)30180-9