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

[Image: see text] Anti-seizure medications used during pregnancy may have transient or long-lasting impact on the nervous system of the offspring. Therefore, there is a great need to search for alternative therapies for pregnant women suffering from seizures. One of the solutions may be the use of the ketogenic diet (KD), which has been successfully applied as a treatment of drug-resistant epilepsy in children and adults. However, the risks associated with the use of this dietary therapy during pregnancy are unknown and more investigation in this area is needed. To shed some light on this problem, we attempted to determine the potential abnormalities in brain biomolecular composition that may occur in the offspring after the prenatal exposure to KD. To achieve this, the female Wistar rats were, during pregnancy, fed with either ketogenic or standard laboratory diet, and for further studies, their male offspring at 2, 6, or 14 days of age were used. Fourier transform infrared microspectroscopy was applied for topographic and quantitative analysis of main biological macromolecules (proteins, lipids, compounds containing phosphate and carbonyl groups, and cholesterol) in brain samples. Performed chemical mapping and further semi-quantitative and statistical analysis showed that the use of the KD during pregnancy, in general, does not lead to the brain biochemical anomalies in 2 and 6 days old rats. The exception from this rule was increased relative (comparing to proteins) content of compounds containing phosphate groups in white matter and cortex of 2 days old rats exposed prenatally to KD. Greater number of abnormalities was found in brains of the 14 days old offspring of KD-fed mothers. They included the increase of the relative level of compounds containing carbonyl groups (in cortex as well as multiform and molecular cells of the hippocampal formation) as well as the decrease of the relative content of lipids and their structural changes (in white matter). What is more, the surface of the internal capsule (structure of the white matter) determined for this age group was smaller in animals subjected to prenatal KD exposure. The observed changes seem to arise from the elevated exposition to ketone bodies during a fetus life and the disturbance of lipid metabolism after prenatal exposure to the KD. These changes may be also associated with the processes of compensation of mother organism, which slowly began to make up for the deficiencies in carbohydrates postpartum.