From the Journals

First trimester lithium exposure ups risk of cardiac malformations


 

FROM THE NEW ENGLAND JOURNAL OF MEDICINE

Cardiac malformations are three times more likely to occur in infants exposed to lithium during the first trimester of gestation than in unexposed infants.

The increased risk could account for one additional cardiac malformation per 100 live births, Elisabetta Patorno, MD, and her colleagues wrote in the June 8 issue of the New England Journal of Medicine (2017;376:2245-54).

Truncated photo of a pregnant woman's belly Jupiterimages/thinkstock
“Our results support previous findings … although the magnitude of increased risk appeared considerably lower than originally suggested” by a 40-year-old international registry, wrote Dr. Patorno of Brigham and Women’s Hospital, Boston. Published in the 1970s, the registry suggested a 400% increase in cardiac malformations associated with first trimester lithium exposure, particularly Ebstein’s anomaly, a right ventricular outflow tract obstruction defect.

Dr. Patorno’s study is the largest conducted since then. It comprised more than 1.3 million pregnancies included in the U.S. Medicaid Analytic eXtract database during 2000-2010. Of these, 663 had first trimester lithium exposure. These were compared with 1,945 pregnancies with first trimester exposure to lamotrigine, another mood stabilizer, and to the remaining 1.3 million pregnancies unexposed to either drug.

There were 16 cardiac malformations in the lithium group (2.41%); 27 in the lamotrigine group (1.39%); and 15,251 in the unexposed group (1.15%). Lithium conferred a 65% increased risk of cardiac defect, compared with unexposed pregnancies. It more than doubled the risk when compared with lamotrigine-exposed pregnancies (risk ratio, 2.25).

The risk was dose dependent, however, with an 11% increase associated with 600 mg/day or less and a 60% increase associated with 601-900 mg/day. Infants exposed to more than 900 mg per day in the first trimester, however, were more than 300% more likely to have a cardiac malformation (RR, 3.22).

The investigators also examined the association of lithium with cardiac defects consistent with Ebstein’s anomaly. Lithium more than doubled the risk, compared with unexposed infants (RR, 2.66). This risk was also dose dependent; all of the right ventricular outflow defects occurred in infants exposed to more than 600 mg/day.

Dr. Patorno reported grant support from National Institute of Mental Health during the study and grant support from Boehringer Ingelheim and GlaxoSmithKline outside of the study. Other authors reported receiving grants or personal fees from various pharmaceutical companies.

On Twitter @Alz_gal

Recommended Reading

Periconception smoking found to affect birth defect risk
MDedge Pediatrics
Breast milk bacteria seed infant gut microbiome
MDedge Pediatrics
Breastfeeding among factors that modify neonatal abstinence syndrome
MDedge Pediatrics
HCV pregnancy increase suggests need for broader screening
MDedge Pediatrics
Children’s asthma risk reduced with prenatal vitamin D supplementation
MDedge Pediatrics
Corticosteroids effective just hours before preterm delivery
MDedge Pediatrics
Infants’ responses to multiple vaccines affected by maternal antibodies
MDedge Pediatrics
FDA: Some blood lead tests have reported falsely low levels since 2014
MDedge Pediatrics
First trimester use of inactivated flu vaccine didn’t cause birth defects
MDedge Pediatrics
Zika-related birth defects up in recent weeks
MDedge Pediatrics