MedicalResearch.com Interview with:
Elisabetta Patorno, MD, DrPH
Assistant Professor of Medicine, Harvard Medical School
Division of Pharmacoepidemiology and Pharmacoeconomics,
Department of Medicine, Brigham and Women’s Hospital
MedicalResearch.com: What is the background for this study?
Response: Lithium, a widely used medicine to treat bipolar disorder, has been associated with a 400 fold increased risk of Ebstein’s anomaly, a congenital malformation of the heart, and a 5 fold increased risk of cardiac defects overall in infants when taken early in pregnancy, based on the results from the International Register of Lithium Babies in the 1970’s. Beyond this data, most of the information on the safety of lithium during pregnancy accumulated in the last 40 years is based on case reports and small studies with conflicting results. Despite these concerns and the limited information, lithium remains a first-line treatment for the 1% of women of reproductive age with bipolar disorder in the U.S. population, due to its recognized efficacy during pregnancy and the postpartum period, and due to the presence of a larger body of evidence showing increased risk of congenital malformations for other mood stabilizers, such as valproate.
MedicalResearch.com: What are the main findings?
Response: To quantify the association between maternal use of lithium early in pregnancy and the risk of cardiac malformations in their infants, we conducted a cohort study involving over 1.3 million pregnancies in women who were enrolled in Medicaid (nested in the U.S. Medicaid Analytic eXtract (MAX)) 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, which has not been associated with congenital malformations. After carefully accounting for differences between exposed pregnancies and comparator groups, we found a two-fold increase in the risk of cardiac malformations in infants exposed to lithium use in early pregnancy. Results were consistent with an increase in risk on the order of 1 additional case per 100 live births, and suggested that this association was dose-dependent. The magnitude of the association was substantially smaller than originally proposed by the International Register of Lithium Babies in the 1970’s.
MedicalResearch.com: What should readers take away from your report?
Response: Our results suggest that maternal use of lithium during the first trimester is associated with a modest increase in risk of cardiac malformations, which is substantially smaller than what has been postulated nearly four decades ago, and that lithium’s teratogenic effect might be dose-dependent.
MedicalResearch.com: What recommendations do you have for future research as a result of this study?
Response: As our study focused only on the association of lithium with congenital malformations, future research on other potential outcomes that may be relevant for treatment decisions during pregnancy would be valuable. Among these, maternal outcomes, for example placental complications, and the potential long-term effects of the exposure to lithium and other psychotropic medications during pregnancy, such as neurodevelopmental disorders including autism spectrum disorders, attention deficit/hyperactivity disorder, developmental delays, etc.
MedicalResearch.com: Is there anything else you would like to add?
Response: Our results suggest that maternal use of lithium during the first trimester is associated with a modest increase in risk of cardiac malformations, which is substantially smaller than what has been postulated nearly four decades ago, and that lithium’s teratogenic effect might be dose-dependent. The quantification of the risk associated with lithium use early in pregnancy can guide treatment decisions for women with bipolar disorder in reproductive age and in pregnancy.
MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.
N Engl J Med 2017; 376:2245-2254June 8, 2017DOI: 10.1056/NEJMoa1612222
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