How to decide whether to continue lithium (lithium carbonate) therapy in a pregnant woman?

Decision-Making for Lithium Continuation in Pregnancy

The decision to continue lithium during pregnancy requires weighing the substantial risk of maternal psychiatric relapse (which is very high if discontinued) against the confirmed but relatively modest risk of fetal cardiac malformations, particularly Ebstein's anomaly, with first-trimester exposure being the most critical period.

Risk Assessment Framework

Maternal Psychiatric Risk

• Women with bipolar disorder face extremely high relapse rates when lithium is discontinued, particularly in the postpartum period, which poses significant risks to both maternal and fetal wellbeing 1
• Pregnancy itself is strongly associated with lithium discontinuation—only 33% of women on continuous lithium pre-pregnancy continue beyond 6 weeks gestation 2
• Psychiatric relapses during pregnancy and postpartum result from multiple factors and can severely compromise maternal functioning and safety 3

Fetal and Neonatal Risks

• The FDA warns that lithium may cause fetal harm, with data from birth registries suggesting increased cardiac and other anomalies, especially Ebstein's anomaly 4
• Recent large studies confirm the association between first-trimester lithium exposure and congenital malformations, though risk estimates are lower than historically reported 1
• First-trimester exposure (weeks 2-6 post-conception) carries the highest risk for cardiac defects 5
• Second and third trimester exposure poses risks for fetal/neonatal complications including altered renal and endocrine function 5

Clinical Decision Algorithm

Step 1: Assess Disease Severity and Relapse Risk

• Evaluate the severity of the patient's bipolar disorder and her specific history of relapses when off lithium
• Consider whether previous discontinuation attempts resulted in severe psychiatric decompensation requiring hospitalization
• Assess presence of psychotic features, suicidality, or severe functional impairment during past episodes 1

Step 2: Timing-Based Strategy

If Preconception or Very Early Pregnancy (before 6 weeks):

• Consider tapering lithium during the first trimester if the patient has mild-to-moderate disease and good prior stability 4, 1
• This approach minimizes cardiac teratogenicity risk during organogenesis
• Plan to restart immediately after the first trimester if discontinued 1

If Pregnancy Discovered After First Trimester:

• Continue lithium if already past the period of cardiac organogenesis (after 6-8 weeks), as the primary teratogenic risk has passed 5
• The risk-benefit ratio shifts toward continuation given that discontinuation poses high relapse risk

If Severe Bipolar Disorder Requiring Continuous Treatment:

• Continue lithium throughout pregnancy if discontinuation would seriously endanger the mother, as stated in FDA labeling 4
• This applies to patients with history of severe mania, psychosis, or suicide attempts when off medication 1

Step 3: Implement Enhanced Monitoring Protocol

Lithium Level Monitoring:

• Monitor lithium levels more frequently than outside pregnancy, with weekly monitoring recommended in the third trimester 1
• Lithium requirements typically increase during third trimester due to increased renal clearance 5
• Decrease lithium dose in the peripartum period to avoid maternal and neonatal toxicity 5

Fetal Monitoring:

• Obtain high-resolution ultrasound with fetal anomaly scanning at 20 weeks gestation 1
• Monitor for fetal ultrasound abnormalities including increased abdominal circumference, which occurs more frequently with lithium exposure 3

Renal Function:

• Assess baseline renal function before continuing lithium
• Monitor for acute deterioration in renal function, which can precipitate lithium toxicity (as ureteric obstruction can occur in pregnancy) 6

Step 4: Delivery Planning

• Arrange delivery at a specialized hospital with both psychiatric and obstetric expertise, plus immediate neonatal evaluation and monitoring capabilities 1
• This is critical given the high-risk nature of this population, with 88% experiencing antenatal complications and 54% having medical comorbidities 3

Alternative Strategy: Discontinue-and-Restart Approach

For patients with moderate disease severity:

• Discontinue lithium during first trimester to avoid cardiac teratogenicity
• Restart lithium immediately after delivery as a relapse prevention strategy for the postpartum period, when risk is highest 1
• Target high therapeutic lithium levels postpartum given the extremely high relapse risk 1

Critical Pitfalls to Avoid

• Failing to provide preconception counseling: Only 33% of women in one cohort received preconception counseling, but this significantly increased likelihood of informed decision-making (p=0.007) 3
• Abrupt discontinuation without psychiatric support: This dramatically increases relapse risk 1
• Inadequate frequency of lithium level monitoring: Pregnancy alters lithium pharmacokinetics, requiring more frequent monitoring than standard protocols 1
• Delivering at a non-specialized center: These patients require coordinated psychiatric, obstetric, and neonatal care 1, 3
• Ignoring the 33% smoking rate and 54% medical comorbidity rate in this population, which compounds obstetric risk 3

Documentation and Counseling

Inform the patient about:

• The confirmed but relatively modest increased risk of cardiac malformations with first-trimester exposure
• The very high risk of psychiatric relapse if lithium is discontinued, particularly postpartum
• The need for enhanced monitoring throughout pregnancy
• The requirement for specialized delivery planning 1

The final decision must weigh the specific patient's psychiatric stability off lithium against the teratogenic risks, with severe bipolar disorder generally favoring continuation and milder disease potentially allowing first-trimester discontinuation.