What are the fetal risks of lamotrigine during pregnancy?

Updated: Aug 20, 2019
  • Author: Carmel Armon, MD, MSc, MHS; Chief Editor: Stephen A Berman, MD, PhD, MBA  more...
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The North American Antiepileptic Drug (NAAED) pregnancy registry reported an elevated prevalence of isolated, nonsyndromic oral clefts in infants exposed to lamotrigine monotherapy during the first trimester as compared with a reference population. [26]

A “Dear Health Professional” letter issued by the manufacturer reported 5 cases of oral clefts among 564 pregnancies exposed to lamotrigine during the first trimester, for a rate of 8.9 cases per 1000 pregnancies. The letter stated that this rate is 24 times higher than the prevalence of 0.37 cases per 1000 pregnancies in the general population of the surveillance program of Brigham and Women’s Hospital.

An FDA alert in September 2006, Information for Healthcare Professionals: Lamotrigine (marketed as Lamictal), (accessed March 30, 2011) stated the following:

“Preliminary data from the North American Antiepileptic Drug Pregnancy Registry suggest a possible association between exposure to lamotrigine monotherapy during the first trimester of pregnancy and cleft lip and/or cleft palate. The oral clefts reported were few and were not part of a syndrome that included other birth defects. Other pregnancy registries of similar size have not replicated this observation. The validity of this possible association cannot be established until further data are collected in the NAAED Pregnancy Registry, in other ongoing pregnancy registries, or through other research efforts. The clinical significance of this preliminary report is thus uncertain.”

The differences among the different series may be related to the levels of lamotrigine attained in the sera of the mothers and fetuses; presumably, teratogenicity is less with lower levels, but data confirming this hypothesis are lacking.

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