Lithium Use During Pregnancy Flavio Guzmán, MD

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

Teratogenicity risk

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

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

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. 103-112). Springer International

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 379.9817 (2012): 721-728.

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

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.

Neonatal toxicity and neurodevelopmental effects

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

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. 103-112). Springer International

Monitoring and dose adjustments during pregnancy

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. 103-112). Springer International

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. 103-112). Springer International

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. 103-112). Springer International

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. 103-112). Springer International

Pharmacokinetic changes Stop 24-48 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. 103-112). Springer International

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. 103-112). Springer International

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)

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)