BACKGROUND: There has been concern that exposure to lithium early in pregnancy 
may be associated with a marked increase in the risk of Ebstein's anomaly (a 
right ventricular outflow tract obstruction defect) in infants and overall 
congenital cardiac defects, but data are conflicting and limited.
METHODS: We conducted a cohort study involving 1,325,563 pregnancies in women 
who were enrolled in Medicaid and who delivered a live-born infant between 2000 
and 2010. We examined the risk of cardiac malformations among infants exposed to 
lithium during the first trimester as compared with unexposed infants and, in 
secondary analyses, with infants exposed to another commonly used mood 
stabilizer, lamotrigine. Risk ratios and 95% confidence intervals were estimated 
with control for psychiatric and medical conditions, medications, and other 
potential confounders.
RESULTS: Cardiac malformations were present in 16 of the 663 infants exposed to 
lithium (2.41%), 15,251 of the 1,322,955 nonexposed infants (1.15%), and 27 of 
the 1945 infants exposed to lamotrigine (1.39%). The adjusted risk ratio for 
cardiac malformations among infants exposed to lithium as compared with 
unexposed infants was 1.65 (95% confidence interval [CI], 1.02 to 2.68). The 
risk ratio was 1.11 (95% CI, 0.46 to 2.64) for a daily dose of 600 mg or less, 
1.60 (95% CI, 0.67 to 3.80) for 601 to 900 mg, and 3.22 (95% CI, 1.47 to 7.02) 
for more than 900 mg. The prevalence of right ventricular outflow tract 
obstruction defects was 0.60% among lithium-exposed infants versus 0.18% among 
unexposed infants (adjusted risk ratio, 2.66; 95% CI, 1.00 to 7.06). Results 
were similar when lamotrigine-exposed infants were used as the reference group.
CONCLUSIONS: Maternal use of lithium during the first trimester was associated 
with an increased risk of cardiac malformations, including Ebstein's anomaly; 
the magnitude of this effect was smaller than had been previously postulated. 
(Funded by the National Institute of Mental Health.).