BACKGROUND AND PURPOSE:

• Perinatal risks related to lithium exposure remains unclear
• Fornaro et al. (American Journal of Psychiatry, 2019) sought to determine the efficacy and the safety of lithium use during pregnancy

METHODS:

• Systematic review and random effects meta-analysis
• Inclusion criteria
  • Case-control, cohort, and interventional studies
  • Studies that reported quantitative data on the safety or efficacy of lithium treatment during pregnancy and the postpartum period
  • Review articles and series <10 subjects were excluded
• Primary outcomes
  • Safety: any congenital anomaly
  • Efficacy: mood relapse prevention
• Secondary outcomes
  • Other safety outcomes during pregnancy and postpartum
  • Major cardiac malformations: were defined VSD and Ebstein’s anomaly, but excluded ASD

RESULTS:

• 13 studies | 1,349,563 pregnancies
• Lithium prescribed during pregnancy was associated with higher odds of
  • Any congenital anomaly
    • Prevalence: 4.1%
    • Odds ratio (OR): 1.81 (95% CI, 1.35 to 2.41)
    • Number needed to harm (NNH): 33 (95% CI, 22 to 77)
  • Cardiac anomalies
    • Prevalence: 1.2%
    • OR: 1.86 (95% CI, 1.16 to 2.96)
    • NNH: 71 (95% CI, 48 to 167)
• Lithium exposure during the first trimester was associated with higher odds of spontaneous abortion
  • Prevalence: 8.1%
  • OR: 3.77 (95% CI, 1.15 to 12.39)
  • NNH: 15 (95% CI. 8 to 111)
• Comparing lithium-exposed with unexposed patients with affective disorders
  • There was still a significant increase in risk of
    • Any malformation (exposure during any pregnancy period or the first trimester)
    • Cardiac malformations (exposure during the first trimester)
  • There was no increase in risk for
    • Spontaneous abortion (exposure during the first trimester)
    • Cardiac malformations (exposure during any pregnancy period)
  • When cardiac anomalies were restricted to the first trimester, risk was significantly increased
    • OR: 1.75 (95% CI, 1.08 to 2.84)
• Lithium was more effective than no lithium in preventing postpartum relapse
  • OR: 0.16 (95% CI, 0.03 to 0.89)
  • Number needed to treat: 3 (95% CI, 1 to 12)
• Mothers with serum lithium levels <0.64 mEq/L and dosages <600 mg/day had more reactive newborns without an increased risk of cardiac malformations

CONCLUSION:

• Neonatal risks associated with lithium exposure in pregnancy are low
  • Risk is higher for the first trimester or with higher-doses of lithium
  • Risk needs to be balanced against benefit of medication and potential for other confounding factors including behavioral factors
• The authors suggest that
  • Preconception counseling would be of value
  • Maintain lowest therapeutic range throughout pregnancy (especially during the first trimester)

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Learn More – Primary Sources:

Lithium Exposure During Pregnancy and the Postpartum Period: A Systematic Review and Meta-Analysis of Safety and Efficacy Outcomes

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