Final results from 18 years of the International Lamotrigine Pregnancy Registry

Abstract

The Registry did not detect an appreciable increase in MCM frequency following first-trimester lamotrigine monotherapy exposure. With over 1,500 first-trimester monotherapy exposures, the Registry was powered to detect major teratogenicity. The proportion of infants with MCMs following lamotrigine/valproate polytherapy exposure was high, but similar to that previously reported with valproate monotherapy. The Registry failed to observe an increased MCM frequency with increasing lamotrigine dose. Monitoring of specific malformations among lamotrigine-exposed pregnancies will continue through case-control surveillance in the European Congenital Anomalies and Twins Registers network.

Managing epilepsy in pregnancy

“…The International Lamotrigine Pregnancy Registry has published 414 first trimester monotherapy exposures to lamotrigine, 12 MCMs (2.9%; 95% CI: 1.6-5.1%) were observed. No pattern of malformation was observed in any group [14]. The UK Epilepsy and Pregnancy Register has reported very similar results with MCMs in 3.2% (95% CI: 2.1-4.9%) of 647 children [10].…”

“…Data reported from the International Lamotrigine Pregnancy Registry showed that, among 150 pregnancies exposed to polytherapy including sodium valproate in the first trimester, 16 MCMs (10.7%; 95% CI: 6.4-17.0%) were observed. In comparison, among 430 pregnancies exposed to polytherapy including lamotrigine but not sodium valproate, only 12 MCMs (2.8%; 95% CI: 1.5-5.0%) were recorded [14].…”

“…Although there have been studies from as early as the 1960s suggesting links between major congenital malformations (MCMs) and the use of AEDs during pregnancy [6][7][8][9], the advent of the large prospective, albeit observational, epilepsy and pregnancy registries have recently added much information on the relative risks associated with the individual AEDs [5,[10][11][12][13][14][15][16][17]. The key to a successful outcome in this respect is knowledge of the individual risks and imparting these risks through preconceptual counseling, enabling women to make informed choices and allowing any alteration in therapy to be made prior to pregnancy.…”

“…As the older AEDs, which may be more teratogenic [10,12,13,29], are replaced with newer agents, which may be safer to the fetus [10,14,[30][31][32], it is possible if not probable that increased difficulty will be encountered in maintaining seizure freedom and/or control throughout pregnancy [67,68,[70][71][72][73]75].…”

Psychotropic Medications in Pregnancy and the Postpartum Period

“…In most studies to date, it has been reported to be less hazardous than other AEDs. [64][65][66] Women of reproductive age who use lamotrigine have been shown to be less likely to have an unplanned pregnancy, and, if pregnant, appear to have an increased protection against bipolar depression. 67 Use of the drug is associated with congenital malformations, with a most common rate of 2%-3% reported.…”