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


Ann Wairimu Mwangi
Joseph Kariuki Kweri
Cyrus Kamau Kweri
James Mangi Kanyoni
Alex Muriithi Kigundu
Elijah Githinji Mwangi
Dominic Oduor Marera

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. 


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eISSN: 1561-7645