Is lithium safe to use during pregnancy?

Lithium Use During Pregnancy

Lithium carries teratogenic risks during pregnancy, particularly for cardiac malformations including Ebstein's anomaly, but can be continued when the benefits of preventing maternal relapse outweigh fetal risks, with careful monitoring and dose adjustments throughout gestation. 1, 2

Teratogenic Risk Profile

The FDA classifies lithium as Pregnancy Category D, indicating evidence of fetal risk but potential benefits may warrant use in serious conditions 1. Recent large studies demonstrate:

• Cardiac malformations occur at increased rates, with Ebstein's anomaly being the most concerning defect when lithium exposure occurs during weeks 2-6 post-conception (the period of cardiac organogenesis) 1, 2, 3
• The absolute risk is lower than historically reported - modern data show more modest risk increases compared to earlier registry data, though the association remains clinically significant 2
• First trimester exposure poses the highest teratogenic risk, particularly for structural heart defects 1, 3

One guideline notes that Ebstein's anomaly occurs more commonly when mothers receive lithium or benzodiazepines during pregnancy 4, though this represents older data.

Clinical Decision-Making Algorithm

Preconception Planning (Ideal Scenario)

• Counsel all women of reproductive age on lithium about pregnancy risks before conception 2, 3
• Consider tapering lithium during first trimester if the patient has been stable and the risk of relapse is acceptable, then reinstitute after organogenesis 1, 2, 3
• Weigh discontinuation risks carefully - bipolar disorder relapse during pregnancy carries substantial maternal morbidity and mortality risks 2

If Pregnancy Occurs on Lithium

For women who become pregnant while taking lithium, continuation versus discontinuation depends on:

• Severity of underlying bipolar disorder - women with severe, treatment-refractory disease may require continuous lithium 2, 3
• History of rapid relapse after discontinuation - these patients are poor candidates for drug holidays 2
• Timing of presentation - if the patient presents after week 6 post-conception, cardiac organogenesis is complete and first-trimester discontinuation offers less benefit 3

The FDA label states: "If possible, lithium should be withdrawn for at least the first trimester unless it is determined that this would seriously endanger the mother." 1

Monitoring Requirements During Pregnancy

Lithium Level Monitoring

Lithium pharmacokinetics change dramatically during pregnancy, requiring intensive monitoring:

• First trimester: Levels decrease by 24% due to increased renal clearance 5
• Second trimester: Levels reach nadir with 36% reduction from baseline 5
• Third trimester: Levels increase to 21% below baseline as renal clearance normalizes 5
• Postpartum: Levels increase 9% above baseline in early postpartum period 5

Recommended monitoring schedule:

• Close monitoring until 34 weeks gestation 5
• Weekly monitoring from 34 weeks until delivery 5
• Twice weekly monitoring for first 2 weeks postpartum 5
• Measure creatinine levels concurrently to assess renal clearance 5

Fetal Monitoring

• High-resolution ultrasound with fetal anomaly scanning at 20 weeks gestation to detect cardiac malformations 2
• Monitor for altered fetal renal and endocrine function during second and third trimesters 3

Dose Adjustments

• Lithium requirements typically increase during third trimester due to changing pharmacokinetics 3, 5
• Decrease lithium dose in the peripartum period to avoid maternal and neonatal toxicity 3
• Delivery itself does not cause acute changes in lithium levels, so prophylactic dose reduction immediately before delivery is not necessary 5

Obstetric Outcomes

• Premature delivery occurs at increased rates - 36% of infants in the International Register of Lithium Babies were born prematurely, representing a 2.5-fold increase compared to untreated bipolar women 6
• Large-for-gestational-age births may occur more frequently in premature infants (37% of premature lithium-exposed infants versus 15% of term infants) 6
• Close monitoring for onset of premature labor is warranted 6
• No clear association with other pregnancy complications has been established, though more research is needed 2

Delivery Planning

• Delivery should occur in a specialized hospital with both psychiatric and obstetric expertise, plus neonatal monitoring capabilities 2
• Neonatal evaluation and monitoring should begin immediately after birth to detect lithium toxicity in the newborn 2

Postpartum Management

The postpartum period carries extremely high relapse risk for bipolar disorder:

• Restart lithium immediately after delivery if it was discontinued during pregnancy, as a relapse prevention strategy 2
• Target high therapeutic lithium levels postpartum given the very high relapse risk 2
• Intensive monitoring is critical - twice weekly lithium levels for first 2 weeks postpartum 5

Breastfeeding Considerations

• Most clinical guidelines discourage breastfeeding during lithium treatment 2
• Lithium is excreted in breast milk and detectable in infant serum 1, 7
• The FDA label states: "Nursing should not be undertaken during lithium therapy except in rare and unusual circumstances" 1
• If breastfeeding occurs, monitor infant lithium levels, renal function, and thyroid function regularly 7

Common Pitfalls to Avoid

• Failing to increase monitoring frequency during third trimester and postpartum - this is when levels change most rapidly 5
• Not reducing dose peripartum - can lead to maternal and neonatal toxicity 3
• Discontinuing lithium without considering relapse risk - bipolar relapse during pregnancy carries significant maternal risks 2
• Inadequate fetal cardiac monitoring - missing the 20-week anomaly scan opportunity 2
• Assuming delivery causes acute lithium level changes - it does not, so prophylactic dose reduction immediately before delivery is unnecessary 5