Table 2 Findings from clinical cohort investigations on the association between in utero exposure to lithium and congenital malformations
Study | Design | Sample size | Findings |
|---|---|---|---|
Schou et al. (1973) | Cohort study | Exposed = 118 | Nine children with congenital malformations, of which six with cardiovascular malformations |
Nora et al. (1974) | Retrospective cohort study | Teratogenic history obtained in 733 women | Two lithium exposed pregnancies and both children were born with Ebstein anomaly |
Weinstein and Goldfield (1975) | Cohort study | Exposed = 143 | Cardiovascular abnormalities found in 9.1% of cases of exposure to lithium in 1st trimester |
Kallen and Tandberg (1983) | Registry-based study | Exposed = 59 Other drugs = 38 Disease matched non-exposed = 80 Controls = 110 | Four children with heart defects after lithium exposure. No cases of Ebstein anomaly |
Jacobson et al. (1992) | Prospective cohort study | Exposed = 138 Controls = 148 | No difference in the rate of major malformations |
Reis and Kallen (2008) | Registry-based study | Exposed = 79 | Eight children with congenital malformations, of which four with cardiac malformations |
Diav-citrin et al. (2014) | Prospective cohort study | Exposed = 183 Disease matched non-exposed = 72 Controls = 748 | Single center comparison: no difference in major malformations, increased risk of cardiovascular malformations (RR 7.23, 95% CI 1.97–26.53), not after excluding cases that spontaneously resolved (RR 5.78, 95% CI 0.82–40.65) |
Patorno et al. (2017) | Registry-based study | Exposed = 663 Lamotrigine = 1945 Controls = 1,322,955 | Increased risk of cardiac malformations after first trimester lithium exposure compared to controls (RR 1.65, 95% CI 1.02–2.68) and lamotrigine-exposed (RR 2.25, 95% CI 1.17–4.34) |
Munk-Olsen et al. (2018) | Meta-analysis (six study sites) | Exposed = 727 Disease matched controls = 21,397 | First trimester lithium exposure was statistically significant associated with congenital malformations (OR 1.62, 95% CI 1.12–2.33) but not with cardiac malformations in specific (OR 1.54, 95% CI 0.64–3.70) |