New York—The largest-ever study of birth defects in babies exposed to lithium found an elevated risk of major congenital malformations in fetuses after first-trimester exposure to the mental health drug.

The report, published online by The Lancet Psychiatry, revealed that 7.4% of babies exposed to lithium during the first trimester experienced major malformations, versus 4.3% of those in the unexposed group.

A study team led by researchers from the Mount Sinai School of Medicine pointed out that, at the same time, the risk of neonatal hospital readmission was nearly doubled in lithium-exposed babies compared to the unexposed group—27.5% compared to 14.3%.

On the other hand, they reported, lithium exposure was not associated with pregnancy complications or other delivery outcomes, such as preeclampsia, preterm birth, gestational diabetes, or low birthweight. 

Not all of the news was bad, however. Researchers emphasized that the risk of birth defects in lithium-exposed infants was found to be lower than previously thought based on much smaller studies.

“Women should be informed on malformation risk in first-trimester exposed infants, but also about very high relapse risks for mental illness both during pregnancy and during the postpartum period,” suggested the study’s senior author, Veerle Bergink, MD, PhD.  “Given the well-documented effectiveness of lithium in reducing relapse in the perinatal period, some important clinical considerations are either to continue lithium in a lower dose during the first trimester or to restart lithium after the first trimester or immediately postpartum.”

In the meta-analysis, the study team gathered primary data from pregnant women and their children from six international cohorts based in the community in Denmark, Sweden, and Ontario, Canada, as well as in clinics in the Netherlands, the United Kingdom, and the United States.

Included were studies in which pregnancy resulted in a liveborn singleton between 1997 and 2015, health-related information was available for both mother and infant, and the mother had a mood disorder such as bipolar disorder or major depressive disorder or had been given lithium at least twice from 1 month before conception or until delivery or had received at least one lithium dispensation during pregnancy when there was at least one other lithium dispensation within 6 months before or after that date.

Pregnancies were grouped into a lithium-exposed group and a mood disorder reference group. The main outcome measures were pregnancy complications, delivery outcomes, neonatal readmission to hospital within 28 days of birth, and congenital malformations (major malformations and major cardiac malformations). 

While lithium exposure during the first trimester was associated with an increased risk of major malformations (pooled prevalence 7.4% [95% CI 4.0–10.7] versus 4.3% [3.7–4.8]; pooled adjusted odds ratio [aOR] 1·71, 95% CI 1.07–2.72), the difference in major cardiac malformations did not reach the level of significance (2·1% [0.5–3.7] versus 1·6% [1.0–2.1]; pooled aOR 1.54, 95% CI 0.64–3.70).

“Considering both the effect sizes and the precision of the estimates in this meta-analysis, treatment decisions for pregnant women with mood disorders must weigh the potential for increased risks of lithium during pregnancy—in particular those associated with use of lithium during the first trimester—against its effectiveness at reducing relapse,” study authors concluded.

Background information in the study noted that lithium therapy is widely recommended as a first-line treatment for bipolar disorder, which affects approximately 2% of the world’s population In the U.S., bipolar disorder is commonly treated with antipsychotic drugs instead of lithium, the article stated.

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