Key Takeaways

• Lithium is not commonly used during pregnancy, but for some women with bipolar disorder, it remains one of the most effective treatments available.
• First-trimester lithium exposure has been associated with about a 65% relative increase in the risk of cardiac malformations (aRR 1.65, 95% CI 1.02–2.68); the absolute risk remains low.
• A recent cohort study from Victoria, Australia, observed that lithium use during pregnancy was associated with a two-fold increased risk of spontaneous preterm birth, as well as an increased risk of a large for gestational age (LGA) infant.
• The same study also found an increased risk of cardiac malformations among lithium-exposed pregnancies.
• These findings closely mirror those of an earlier Swedish cohort study from the same research group, but contrast with a multinational meta-analysis that found no increased risk of preterm birth.
• Residual confounding by illness severity remains a challenge in this literature; when lithium continuers were compared with women who had recently discontinued lithium, the associations were no longer statistically significant.

Lithium is not commonly used during pregnancy, but for a subset of women with bipolar disorder, it is one of the most effective mood stabilizers available. Women taking lithium who are planning to become pregnant must weigh the benefits of continued treatment against the potential risks of fetal lithium exposure. There is an established, roughly 65% relative increase in the risk of congenital cardiac malformations associated with first-trimester lithium use, though the absolute risk remains low (aRR 1.65, 95% CI 1.02–2.68) (Patorno et al, 2017). 

Other studies have examined the association between lithium and additional pregnancy outcomes, but findings have been inconsistent — likely because many of these studies have relied on smaller, underpowered cohorts or have not adequately adjusted for confounding factors. A recent statewide cohort study from Australia adds valuable new data to this literature (Roddy Mitchell et al, 2026).

Study Design

Using data collected in Victoria, Australia, researchers analyzed outcomes from 867,454 births occurring between 2009 and 2020, including 234 (0.03%) pregnancies exposed to lithium. The study focused on the following outcomes:

• Spontaneous preterm birth (delivery before 37 weeks’ gestation)
• Large for gestational age (LGA) infant (birthweight above the 90th percentile)
• Macrosomia (birthweight greater than 4,000 g)
• Major congenital malformations, including congenital cardiac malformations

The analysis adjusted for several potential confounders, including maternal age, parity, body mass index, smoking during pregnancy, and conception assisted by artificial reproductive technology. To reduce the potential for confounding by indication, the researchers also performed subgroup analyses restricting the cohort to women with a diagnosis of bipolar disorder and/or schizophrenia. In addition, they compared women who used lithium during pregnancy with women who had used lithium in the 12 months prior to pregnancy but discontinued it before conception.

Outcomes in Lithium-Exposed Pregnancies

Compared with unexposed women, those exposed to lithium during pregnancy were older, more likely to smoke during pregnancy, and more likely to have conceived using reproductive technology. They were also more likely to have been prescribed other psychotropic medications — antidepressants, antipsychotics, and antiepileptics — during pregnancy, and more likely to have pre-existing hypertension, pre-existing diabetes, or gestational diabetes.

• Spontaneous preterm birth: Lithium use was associated with a two-fold increased risk (8.1% vs. 2.4%; aRR 2.18, 95% CI 1.45–3.30).
• Large for gestational age: Lithium use was associated with an increased risk of an LGA infant (13.7% vs. 6.4%; aRR 1.94, 95% CI 1.36–2.76).
• Cardiac malformations: Lithium use was associated with an increased risk of congenital cardiac malformations (3.0% vs. 0.8%; aRR 2.64, 95% CI 1.26–5.53).
• Major congenital malformations overall: Lithium exposure was not associated with an increased risk (aRR 1.51, 95% CI 0.92–2.50), suggesting that the increased risk may be specific to cardiac anomalies rather than reflecting a broader teratogenic effect.

When the cohort was restricted to women with a diagnosis of bipolar disorder or schizophrenia, the increased risks of preterm birth (aRR 1.88, 95% CI 1.06–3.32) and LGA (aRR 1.68, 95% CI 1.07–2.65) remained statistically significant, suggesting these associations are not simply explained by underlying psychiatric illness. 

However, when the researchers compared outcomes in women who continued lithium during pregnancy with women who had used lithium in the year before pregnancy but discontinued it, none of the associations reached statistical significance.

How Do These Findings Compare With Previous Studies?

The results of this Victorian cohort study closely mirror those of a previous study by the same research group, using a Swedish population-based cohort (Hastie et al, 2021). Both studies found that lithium exposure during pregnancy was associated with a two-fold increased risk of spontaneous preterm birth (Victorian cohort: aRR 2.18, 95% CI 1.45–3.30; Swedish cohort: aRR 2.64, 95% CI 1.82–3.82). Both studies also reported an increased risk of having an LGA infant and of congenital cardiac malformations.

Other studies, however, have reported different results. Most notably, a 2018 meta-analysis pooling primary data from 727 lithium-exposed pregnancies across six cohorts in Canada, Denmark, the Netherlands, Sweden, the UK, and the US found that lithium use during pregnancy was not associated with an increased risk of preterm birth (717 lithium-exposed vs. 21,397 unexposed with a mood disorder; aOR 1.24, 95% CI 0.83–1.84) or with most other pregnancy complications, when women exposed to lithium were compared with women who had a mood disorder but were not exposed to lithium (Munk-Olsen et al, 2018).

The findings of the current study are, however, consistent with previous research demonstrating an increased risk of cardiac malformations among lithium-exposed pregnancies. A 2017 study by Patorno and colleagues (N = 1,325,563) reported an increased risk of cardiac malformations in women exposed to lithium during the first trimester, compared with women without lithium exposure (aRR 1.65, 95% CI 1.02–2.68) (Patorno et al, 2017). Similarly, a 2020 meta-analysis found that lithium exposure was associated with increased odds of cardiac malformations compared with unexposed pregnancies (pooled OR 1.86, 95% CI 1.16–2.96) (Fornaro et al, 2020). While these studies have consistently documented an increase in the relative risk of cardiac malformations, the absolute risk remains relatively low.

This study has many strengths, but it remains difficult to fully account for residual confounding by characteristics not captured in the dataset. Women who elect to continue lithium during pregnancy differ in important ways from women who do not use lithium — notably, when the comparison group was restricted to women who had recently discontinued lithium, the associations no longer reached statistical significance.

Clinical Takeaway

Lithium is not commonly prescribed during pregnancy, but for a subset of women with bipolar disorder, it remains one of the most effective and best-studied mood stabilizers available.  Decisions regarding the use of lithium during pregnancy are complicated and involve weighing the risks of discontinuation — illness relapse and the effects of untreated illness on the mother and pregnancy — against the risks associated with continued medication exposure.

• Lithium exposure has been consistently associated with a small but statistically significant increase in the relative risk of cardiac malformations; the absolute risk remains low.
• Some — though not all — studies have found an association between lithium use during pregnancy and spontaneous preterm birth or LGA. 
• Untreated bipolar illness and abrupt medication discontinuation are themselves associated with a substantially increased risk of relapse and with adverse pregnancy outcomes. 
• Any decision regarding lithium use in pregnancy must weigh the risks of treatment against the risks of undertreated or untreated illness in the mother.
• For women who continue lithium during pregnancy, enhanced monitoring is recommended, including fetal echocardiography and a level 2 ultrasound to screen for cardiac malformations, along with increased surveillance later in pregnancy for signs of preterm labor or excessive fetal growth.

—Ruta Nonacs, MD PhD