Does Ketogenic Diet Used in Pregnancy Affect the Nervous System Development in Offspring?RFTIR Microspectroscopy Study

Anti-seizure medications used during pregnancy may havetransientor long-lasting impact on the nervous system of the offspring. Therefore,there is a great need to search for alternative therapies for pregnantwomen suffering from seizures. One of the solutions may be the useof the ketogenic diet (KD), which has been successfully applied asa treatment of drug-resistant epilepsy in children and adults. However,the risks associated with the use of this dietary therapy during pregnancyare unknown and more investigation in this area is needed. To shedsome light on this problem, we attempted to determine the potentialabnormalities in brain biomolecular composition that may occur inthe offspring after the prenatal exposure to KD. To achieve this,the female Wistar rats were, during pregnancy, fed with either ketogenicor standard laboratory diet, and for further studies, their male offspringat 2, 6, or 14 days of age were used. Fourier transform infrared microspectroscopywas applied for topographic and quantitative analysis of main biologicalmacromolecules (proteins, lipids, compounds containing phosphate andcarbonyl groups, and cholesterol) in brain samples. Performed chemicalmapping and further semi-quantitative and statistical analysis showedthat the use of the KD during pregnancy, in general, does not leadto the brain biochemical anomalies in 2 and 6 days old rats. The exceptionfrom this rule was increased relative (comparing to proteins) contentof compounds containing phosphate groups in white matter and cortexof 2 days old rats exposed prenatally to KD. Greater number of abnormalitieswas found in brains of the 14 days old offspring of KD-fed mothers.They included the increase of the relative level of compounds containingcarbonyl groups (in cortex as well as multiform and molecular cellsof the hippocampal formation) as well as the decrease of the relativecontent of lipids and their structural changes (in white matter).What is more, the surface of the internal capsule (structure of thewhite matter) determined for this age group was smaller in animalssubjected to prenatal KD exposure. The observed changes seem to arisefrom the elevated exposition to ketone bodies during a fetus lifeand the disturbance of lipid metabolism after prenatal exposure tothe KD. These changes may be also associated with the processes ofcompensation of mother organism, which slowly began to make up forthe deficiencies in carbohydrates postpartum.