Is lithium contraindicated during pregnancy for a woman of child‑bearing age with bipolar disorder?

Lithium Use in Pregnancy for Bipolar Disorder

Lithium is not absolutely contraindicated in pregnancy, but it carries a small increased risk of cardiac malformations that must be weighed against the substantial risk of bipolar relapse if treatment is discontinued. 1, 2, 3

FDA Classification and Regulatory Status

• Lithium carries a Pregnancy Category D designation from the FDA, indicating positive evidence of human fetal risk, but potential benefits may warrant use in pregnant women despite these risks. 1
• The FDA label explicitly states that lithium should be avoided during pregnancy "especially during the first trimester" unless the benefits clearly outweigh the risks. 1

Cardiac Malformation Risk: Updated Evidence

• Recent large-scale meta-analysis data (2018) show lithium exposure during the first trimester is associated with a 7.4% risk of major malformations versus 4.3% in the mood disorder reference group (pooled adjusted OR 1.71,95% CI 1.07-2.72). 3
• For major cardiac malformations specifically, the pooled prevalence was 2.1% with lithium versus 1.6% without lithium, though this difference did not reach statistical significance (pooled adjusted OR 1.54,95% CI 0.64-3.70). 3
• These contemporary risk estimates are substantially lower than historical data suggested, indicating lithium is not a major human teratogen. 4, 5
• The absolute risk of Ebstein's anomaly—the most feared cardiac defect—remains very low even with first-trimester lithium exposure. 2, 4

Clinical Decision Algorithm

When to Continue Lithium Through Pregnancy

• Continue lithium throughout pregnancy when the patient has severe, treatment-refractory bipolar disorder with high relapse risk, particularly if previous medication discontinuation led to severe manic or depressive episodes. 2, 5
• Maintain lithium when the patient has already conceived and is beyond the period of cardiac organogenesis (after 6-8 weeks post-conception), as the teratogenic risk has passed. 2, 6

When to Consider Discontinuation or Tapering

• Taper lithium during the first trimester (weeks 2-6 post-conception) if the patient has mild-to-moderate bipolar disorder with low relapse risk and can be managed with alternative mood stabilizers or close monitoring. 2, 6
• This decision must account for the very high risk of postpartum relapse (up to 50-70% in women with bipolar disorder), which may be increased by medication discontinuation during pregnancy. 2

Mandatory Monitoring and Screening Protocol

• Obtain high-resolution fetal ultrasound with detailed cardiac evaluation (fetal echocardiography) at 18-20 weeks gestation for all lithium-exposed pregnancies. 2, 4
• Monitor lithium blood levels more frequently than in non-pregnant patients—ideally every 4 weeks in the first two trimesters and weekly in the third trimester due to changing renal clearance. 2, 6
• Lithium requirements typically increase during the third trimester due to increased glomerular filtration rate, but the dose must be decreased immediately before delivery to avoid maternal and neonatal toxicity. 2, 6

Obstetric and Neonatal Outcomes

• Lithium exposure during pregnancy is not associated with increased risk of pregnancy complications, preterm birth, or adverse delivery outcomes based on the most recent meta-analysis. 3
• Neonatal readmission within 28 days of birth is increased with lithium exposure (27.5% vs 14.3%; pooled adjusted OR 1.62,95% CI 1.12-2.33), primarily due to monitoring for neonatal lithium toxicity and transient complications. 3
• Infants should be monitored immediately after birth for signs of lithium toxicity including hypotonia, poor feeding, respiratory distress, and cardiac arrhythmias. 2, 6

Delivery Planning

• Delivery should occur in a specialized hospital with both psychiatric and obstetric expertise, where neonatal intensive care is available for immediate evaluation and monitoring of the infant. 2
• Discontinue or reduce lithium dose 24-48 hours before planned delivery to minimize neonatal exposure, then restart at the pre-pregnancy dose immediately postpartum. 2, 6

Postpartum Management

• Restart lithium immediately after delivery at the pre-pregnancy therapeutic dose, as the postpartum period carries the highest risk of bipolar relapse (50-70% within the first 3 months). 2, 5
• Target a high therapeutic lithium level postpartum (0.8-1.0 mEq/L) given the very high relapse risk. 2
• Breastfeeding is generally discouraged with lithium use, as lithium is excreted in breast milk and can accumulate in the infant. 1, 2

Critical Counseling Points

• Preconception counseling is essential: women of childbearing age on lithium should be informed of pregnancy risks and encouraged to plan pregnancies to allow for optimal timing of medication adjustments. 2, 5
• The decision to continue or discontinue lithium must weigh the small absolute increase in cardiac malformation risk (approximately 3% excess risk) against the substantial risk of bipolar relapse, which can lead to suicide, impaired prenatal care, and poor maternal-fetal outcomes. 2, 3, 5
• For many women with severe bipolar disorder, the risk of untreated illness outweighs the teratogenic risk of lithium. 5

Common Pitfalls

• Do not abruptly discontinue lithium in early pregnancy without a clear plan for alternative mood stabilization, as this dramatically increases relapse risk. 2
• Do not fail to adjust lithium dosing in the third trimester and peripartum period—failure to decrease the dose before delivery can cause severe neonatal toxicity. 2, 6
• Do not rely on outdated teratogenic risk estimates; contemporary data show lithium is not a major teratogen and the absolute risk of malformations is much lower than previously believed. 4, 3, 5