For women taking lithium to treat bipolar disorder, The choice of maintaining or discontinuing lithium during pregnancy is difficult. This is a process that requires careful and thoughtful consideration, weighing the risk of adverse effects associated with lithium exposure. the risk of recurrent disease upon discontinuation of medication. Although we have considerable data on the teratogenicity of lithium, we have much less data on other pregnancy and neonatal outcomes.
Five Linked Data Analysis Swedish National RegistersHasti and Associates examined the association between lithium use during pregnancy and adverse pregnancy and neonatal outcomes.
Of the 854,017 women included in this analysis, 434 (0.05%) used lithium during pregnancy. Women using lithium during pregnancy had an increased risk of preterm birth compared with unexposed controls (8.7% vs. 3.0%, adjusted relative risk [aRR] 2.64; 95% CI 1.82-3.82) and for large-gestational-age infants (9.0% vs. 3.5%; aRR 2.64, 95% CI 1.91-3.66). There is no association between lithium exposure and preeclampsia or the birth of a baby of gestational age.
These associations remained significant after restricting the analysis to pregnant women with a diagnosed psychiatric illness (n=9552) and comparing the results to a control group of lithium-treated women who chose to discontinue lithium before pregnancy.
Inconsistent results across studies
In the current study, including 434 lithium-exposed pregnancies, lithium use during pregnancy was associated with an increased risk of preterm birth and large-for-gestational-age birth. There was no association between lithium exposure and preeclampsia or birth of a gestational age infant.
Previous studies have raised concerns about the effects of lithium on pregnancy outcomes; however, it is difficult to distinguish drug effects from effects of the underlying disorder. Analyzing in the previous study data from Medicaid Analytic Extract and outcomes of 874 lithium-exposed pregnancies, Cohen and colleagues were able to control for a wider range of potential confounders. After adjusting for these potential confounders, they found no association between lithium exposure and the risk of several different adverse pregnancy outcomes: preeclampsia, placental abruption, growth restriction, and preterm birth.
In another study. Boden and colleagues analyzed pregnancy outcomes in women with bipolar disorder and concluded that bipolar disorder in women, whether treated with medication or not, was associated with poorer pregnancy outcomes. Research suggests that while exposure to mood stabilizers during pregnancy may pose some risk, exposure to this medication is not the only cause of adverse pregnancy outcomes in women with bipolar disorder, and it is important to note that the illness or behavior itself is involved. having an illness – can also negatively affect pregnancy outcomes.
It’s complicated
In counseling women with bipolar disorder who are pregnant or planning to become pregnant, we must focus on optimizing treatment during pregnancy, recognizing that avoiding all medications is not necessarily the safest option. Women planning pregnancy should be properly counseled about the risks of treatment and the risks associated with untreated maternal psychiatric illness, and the woman’s health care provider plays an important role in weighing these individual risks and choosing the best treatment options.
Lithium is not widely used. However, for a subset of women, it is a well-tolerated and effective treatment. There may be no effective alternatives for these women. There is a well-documented increase in the risk of heart defects associated with first-trimester lithium exposure. Based on the available data, we must consider the possibility that lithium is associated with certain adverse effects, including the risk of preterm birth and large for gestational age; however, findings are inconsistent. These potential risks must be balanced against the important benefits of treatment and should be used to guide shared decision making.
Ruta Nonacs, MD, PhD
Hastie R, Tong S, Hiscock R, et al. Maternal lithium use and risk of adverse pregnancy and neonatal outcomes. A Swedish population-based cohort study. BMC Med. in 2021 19 (1). 291.