Abstract:
Lamotrigine and levetiracetam are second-generation antiepileptic medicines that are
currently being used widely in the management of maternal epilepsy and other
neuralgic disorders during pregnancy. However, their comparative histo-
morphological and histo-stereological teratogenic risks on the developing fetal
kidneys remains unclear. The broad objective of this study therefore was to
comparatively evaluate their histo-morphological and histo-stereological nephron-
teratogenic effects on the developing fetal kidney when exposed in varied doses and
at different gestational periods. In carrying out this study, a posttest experimental
study design with a control group was adopted. All animal experimentation
procedures that included breeding of the animals, feeding, drug administration up to
harvesting of fetuses was done in Nairobi university (UON) while tissue processing
for histology and stereological analysis was done in the department of Human
anatomy in JKUAT. A sample size of 30 albino rat dams was used for each of
lamotrigine and the levetiracetam treatment groups. These 30 albino rat dams for
each of the two study categories were first randomly assigned into two broad study
groups of 3 rats control and 27 rats experimental. The 27 rats in each of the
experimental category were further randomly assigned into three subgroups of 9 rats
each according to the three dose groups of low, medium and high dose as follows, 9
rats low dose lamotrigine/ levetiracetam treatment group, 9 rats for the medium dose
lamotrigine/ levetiracetam treatment group and 9 rats for the high dose lamotrigine/
levetiracetam treatment groups. To further evaluate the effects of the time of
exposure, the 9 rats in each of the three dose categories were further randomly sub-
divided into three sub-groups of 3 rats each as follows; 3 rats for trimester I, the next
3rats for trimester II; and the last 3 rats for Trimester III. The study findings showed
that in both lamotrigine and levetiracetam treatment groups, there was a statistical
significance increase (p<0.05) in medullary thickness while the cortical thickness
reduced in a proportionate manner. Stereologically there was marked reduction in
glomerular numbers per field of view as well as in their volume densities resulting to
their observed sparse distribution. There was an observed remarkable condensation
of glomerular tufts capillaries with significantly hypertrophied bowman spaces. The
critical nephron-teratogenic period was noted to be when both the drugs were
administered in trimester one and trimester two with critical teratogenic doses being
both the high dose of the two medicines. Lamotrigine was established to be more
teratogenic compared to levetiracetam across all dose groups and across all the
trimesters of exposure. In conclusion, both lamotrigine and levetiracetam are
teratogenic to the developing fetal kidney and their teratogenic effects depicted
patterns of both time-dose dependency. The study recommends caution when using
high doses of both drugs by pregnant mothers particularly during trimester one and
trimester two. It also recommends further studies on higher primates with close
relations to humans.
