Adverse macroscopic changes in developing mice treated with lamotrigine on early and late phase of gestation

Lamotrigine(LTG) is an anti epileptic drug(AED) and also used as a neuromodulator, in mood disorders. Recently, malformations have been reported in human foetuses, whose mothers were treated with LTG. However, it is not been possible to establish a recognizable pattern of malformations in the human fetuses treated with LTG, therefore the lower animal has been used as experimental model for the present study. The objective of this study is to find out the macroscopic changes in the growing embryo of mice treated with LTG in both early amnd late phase of gestation.The pregnant mice were divided into two experimental group’s i.e. early and late, each with two subgroups i.e. control group (treated with intra peritoneal injection of normal saline on Day 4 and Day 9 of gestation) and treated group (treated with intraperitoneal injection of LTG ,150mg/kg body weight on 4th day and 9th Day of gestation. Fetuses were collected on day 18th of gestation and then observed for the various macroscopic abnormalities i.e. number of live and dead fetuses, growth retardation, external hemorrhagic areas and limb malformations.The results of this study indicate that LTG administered intra peritoneally at high doses on day 9 of gestation induces intrauterine growth retardation (p value<.05), embryonic resorption (16.7%), external hemorrhage (39%), malformations of limb (34.9%). In the present study resorption and growth retardation was observed in both the treated groups however, growth retardation was statistically significant only in late treated group.