The histostereological teratogenic effects of in-utero exposure to varied doses of lamotrigine on the developing fetal brain in albino rats (Rattus Norvegicus)

Abstract

The histoqualitative teratogenic effects of lamotrigine, a second-line anticonvulsant medicine, on the developing fetal brain structures when exposed in utero in a time- and dose-dependent manner remain unclear. On the other hand, lamotrigine is currently being widely prescribed as a first-line medicine in the management of maternal conditions like epileptic seizures and bipolar disorders, among others. The preferential use of lamotrigine is attributed to the considerations of its efficacy, tolerability, and minimal teratogenic effects on fetal organs like the brain, among others, though with insufficient supportive data. The aim of this study was therefore to evaluate the histo-quantitative effects of lamotrigine on the developing fetal brain structures when exposed in utero at varying dosages during different trimesters. The study adopted a post-test only experimental study design where a sample size of 30 sexually mature albino rat dams of the species (Rattus norvegicus) weighing between 250 + 30 grams was used. The rats were divided into two broad groups: 3 control rats and 27 dosage rats. The data collected was coded in Excel spreadsheets and analyzed in SPSS. Results were expressed as the mean + standard error of the mean (SEM), and values with a P < 0.05 were considered to be significant. Study findings depicted a reduction in brain weights, length, width, volumes, and volume densities of cortical and subcortical layers in a dose- and time-dependent manner. High lamotrigine dosages, especially during the first and second trimesters, were observed to be associated with significant mean reductions in the brain weights, length, width, volumes, and volume densities of the developing fetal brain structures. Therefore, further studies with higher primates closer to the human species as well as clinical trials are recommended to rule out the safety index of lamotrigine during pregnancy.