1. Lithium Use During Pregnancy
Flavio Guzmán, MD

2. Overview Risks of teratogenicity
Risks of neonatal toxicity and developmental abnormalities
Monitoring and dose adjustment

3. Teratogenicity risk

4. Ebstein's anomaly Image credit: CardioCongenital.com
Modified with permission

5. Ebstein's anomaly
Downward displacement of the tricuspid valve into the right ventricle
Right ventricular hypoplasia
Image credit: CardioCongenital.com
Modified with permission

6. Ebstein's anomaly 1/20,000 Incidence in the general population
Elevated risk
Initial retrospective reports
Risk may be overestimated possibly due to overreporting bias
Recent studies
Bauer, M., & Gitlin, M. (2016). Lithium During Pregnancy and in the Postpartum Period. In The Essential Guide to Lithium Treatment (pp ). Springer International

7. Review and meta-analysis:
Ebstein's anomaly
1/2,000
10x increase over the general population
Recent estimate :
No increased risk of congenital malformations
Review and meta-analysis:
McKnight, Rebecca F., et al. "Lithium toxicity profile: a systematic review and meta-analysis." The Lancet  (2012):

8. Ebstein's anomaly
“Concerns about lithium and cardiac malformations appear to have been disproportionate”
Goodwin, G. O., & Consensus Group of the British Association for Psychopharmacology. (2016). Evidence-based guidelines for treating bipolar disorder: revised second edition—recommendations from the British Association for Psychopharmacology. Journal of Psychopharmacology

9. Recommended monitoring
Fetal echocardiography
Level 2 ultrasound
Monitoring (first trimester)
Diav-Citrin, O.. (2014). Pregnancy outcome following in utero exposure to lithium: a prospective, comparative, observational study. American Journal of Psychiatry.

10. Neonatal toxicity and neurodevelopmental effects

11. Neonatal toxicity Neonatal effects
Occasional cases of floppy baby syndrome
Cyanosis and hypotonic muscle tone
Neonatal hypothyroidism

12. Neurodevelopmental effects
No evidence of developmental abnormalities
No long-term studies
Yonkers, K. A.,at al (2004). Management of bipolar disorder during pregnancy and the postpartum period. American Journal of Psychiatry.
Bauer, M., & Gitlin, M. (2016). Lithium During Pregnancy and in the Postpartum Period. In The Essential Guide to Lithium Treatment (pp ). Springer International

13. Monitoring and dose adjustments during pregnancy

14. Discontinuing and restarting lithium
Lithium discontinuation
1st trimester
2nd trimester
Bauer, M., & Gitlin, M. (2016). Lithium During Pregnancy and in the Postpartum Period. In The Essential Guide to Lithium Treatment (pp ). Springer International

15. Discontinuing and restarting lithium
Lithium discontinuation
At the beginning of 2nd trimester
If symptoms occur
1st trimester
2nd trimester
Bauer, M., & Gitlin, M. (2016). Lithium During Pregnancy and in the Postpartum Period. In The Essential Guide to Lithium Treatment (pp ). Springer International

16. Monitoring during pregnancy
Increase monitoring:
Every 1-2 weeks
Last month of pregnancy
Bauer, M., & Gitlin, M. (2016). Lithium During Pregnancy and in the Postpartum Period. In The Essential Guide to Lithium Treatment (pp ). Springer International

17. Pharmacokinetic changes
Decreases in:
Vascular volume
Lithium clearance
Increases in:
Lithium serum levels
Delivery
Bauer, M., & Gitlin, M. (2016). Lithium During Pregnancy and in the Postpartum Period. In The Essential Guide to Lithium Treatment (pp ). Springer International

18. Pharmacokinetic changes
Stop hours before delivery
Restart at normal dose
Delivery
Bauer, M., & Gitlin, M. (2016). Lithium During Pregnancy and in the Postpartum Period. In The Essential Guide to Lithium Treatment (pp ). Springer International

19. Pharmacokinetic changes
Restart at normal dose
Reduce dose by 25%-50%
Week before delivery
Delivery
Bauer, M., & Gitlin, M. (2016). Lithium During Pregnancy and in the Postpartum Period. In The Essential Guide to Lithium Treatment (pp ). Springer International

20. Summary Increased risk of Ebstein’s anomaly
Lower than initially thought
Monitor with fetal echocardiography and level 2 ultrasound during organogenesis
No evidence of developmental abnormalities
Monitor maternal lithium levels to preserve efficacy and avoid toxicity
Before delivery:
Discontinue (24-48 hours before)
Decrease dose (a week before)

21. Summary Increased risk of Ebstein’s anomaly
Lower than initially thought
Monitor with fetal echocardiography and level 2 ultrasound during organogenesis
No evidence of developmental abnormalities
Monitor maternal lithium levels to preserve efficacy and avoid toxicity
Before delivery:
Discontinue (24-48 hours before)
Decrease dose (a week before)