What are the risks and considerations for using lithium in pregnant women with a history of bipolar disorder?

Lithium Use in Pregnancy for Bipolar Disorder

Direct Recommendation

Lithium should be continued during pregnancy for women with bipolar disorder who have a high risk of relapse, as the risk of untreated bipolar disorder generally outweighs the small increased risk of cardiac malformations, particularly when proper monitoring and dose adjustments are implemented. 1, 2

Risk Assessment and Counseling

Cardiac Malformation Risk

• The FDA warns that lithium may cause fetal harm, with data from birth registries suggesting an increase in cardiac anomalies, especially Ebstein's anomaly, when exposed during weeks 2-6 post-conception (first trimester). 1
• Recent evidence indicates either no increased malformation risk or only a small increase in cardiac malformations including Ebstein's anomaly, which is substantially lower than previously reported in older registry data. 2
• A prospective cohort study of 100 pregnant women with bipolar disorder found no significant differences in congenital anomalies between lithium-exposed and unexposed groups, though newborns had slightly lower Apgar scores at 1 minute (8.2 vs 8.9) and 5 minutes (9.6 vs 9.9). 3

Maternal Psychiatric Risk

• Women with bipolar disorder who discontinue mood stabilizers during pregnancy face extremely high relapse rates, with 24.4% relapsing during pregnancy despite prophylaxis use by the majority. 4
• Untreated or inadequately treated bipolar disorder results in poor prenatal care adherence, inadequate nutrition, exposure to alternative medications including illicit substances, and maternal self-harm—a leading yet underappreciated cause of maternal mortality. 5
• The postpartum relapse rate reaches 60% in women with bipolar disorder who experienced mood episodes during pregnancy. 4

Treatment Algorithm by Clinical Scenario

For Women Planning Pregnancy on Lithium Maintenance

• If the patient has bipolar disorder with frequent episodes or history of severe mania: Continue lithium throughout pregnancy with enhanced monitoring. 2, 4
• If the patient has a history of psychosis limited only to the postpartum period (not bipolar disorder): Discontinue lithium during pregnancy and reinitiate immediately postpartum, as none of these women relapsed during pregnancy when medication-free. 4
• Counsel all women of reproductive age taking lithium about pregnancy planning to allow for informed decision-making before conception. 6

For Women Who Become Pregnant While Taking Lithium

• Do not abruptly discontinue lithium without psychiatric consultation, as the relapse risk typically outweighs the teratogenic risk. 2
• Obtain baseline renal function (serum creatinine, creatinine clearance), thyroid function tests, complete blood count, urinalysis, and serum calcium levels. 5
• Arrange for fetal echocardiography at 16-20 weeks gestation to screen for cardiac anomalies, particularly Ebstein's anomaly. 6

Monitoring Throughout Pregnancy

Lithium Level Management

• Check lithium levels monthly during first and second trimesters, then weekly during the third trimester, as lithium requirements typically increase in the third trimester due to increased glomerular filtration rate. 6
• Maintain therapeutic lithium levels (0.6-1.0 mEq/L) while avoiding toxicity, as lithium toxicity is closely related to serum levels and can occur at doses close to therapeutic levels. 1
• Monitor renal function every 3-6 months, as chronic lithium therapy may be associated with diminished renal concentrating ability and morphologic changes with glomerular and interstitial fibrosis. 1

Peripartum Dose Adjustments

• Decrease lithium dose by 30-50% at the onset of labor or 24-48 hours before planned cesarean delivery to avoid neonatal and maternal toxicity, as glomerular filtration rate drops precipitously postpartum. 6, 7
• Ensure adequate hydration during labor to prevent lithium retention and toxicity, as dehydration can rapidly lead to toxic levels. 1, 7
• Resume pre-pregnancy lithium dose within 24-48 hours postpartum once fluid status stabilizes. 6

Fetal and Neonatal Monitoring

• Monitor for fetal polyhydramnios (from fetal polyuria due to nephrogenic diabetes insipidus) and altered thyroid function during second and third trimesters. 6
• Arrange for neonatal monitoring in the first 24-48 hours after delivery for signs of lithium toxicity including hypotonia, lethargy, poor feeding, cyanosis, and cardiac arrhythmias. 6

Critical Pitfalls to Avoid

• Do not withdraw lithium for the entire first trimester based solely on older teratogenicity data, as this significantly increases maternal relapse risk and the absolute risk of Ebstein's anomaly remains very low (estimated 0.05-0.1% versus 0.005% baseline). 2
• Do not fail to decrease the lithium dose peripartum, as this is when lithium toxicity most commonly occurs due to the sudden decrease in glomerular filtration rate after delivery. 7
• Do not assume all women with psychiatric histories require the same approach—women with postpartum psychosis only (not bipolar disorder) can safely discontinue lithium during pregnancy and restart postpartum. 4
• Do not overlook the need for close psychiatric follow-up, as maintenance therapy duration should be 12-24 months after mood stabilization, with some individuals requiring lifelong therapy when benefits outweigh risks. 5

Breastfeeding Considerations

• Lithium is excreted in breast milk at 40-50% of maternal serum levels, resulting in infant serum levels approximately 10-50% of maternal levels. 6
• The decision to breastfeed while taking lithium requires careful consideration of the infant's renal function, hydration status, and monitoring for signs of lithium toxicity (lethargy, poor feeding, hypotonia). 6
• If breastfeeding is chosen, monitor infant lithium levels, thyroid function, and renal function at 4-6 weeks postpartum and as clinically indicated. 6