Pregestational neurological disorders among women of childbearing age-Nationwide data from a 13-year period in Hungary.

OBJECTIVES: Comprehensive statistics evaluating pregnancies complicated by various medical conditions are desirable for the optimization of prenatal care and for improving maternal and fetal outcomes. The main objective of our study was to assess pregnancies during a 13-year study period with accompanying pregestational neurological disorders in medical history on a nationwide level. METHODS: In the framework of the NEUROHUN 2004-2017 project utilizing medical reports submitted for reimbursement purposes to the National Health Insurance Fund, we included women with at least one labor during 2004-2016 who had at least one pregestational diagnosis of a neurological disorder received within this time frame prior to their first pregnancy during the studied period. Three-digit codes from the 10th International Classification of Diseases (ICD) were used for the identification and classification of neurological and obstetrical conditions. RESULTS: Specific inclusion and exclusion criteria were employed during the study process. A total of 744 226 women have been identified with at least one delivery during the study period with 98 792 of them (13.3%) having at least one neurological diagnosis received during 2004-2016 before their first gestation in the time frame of the study. The vast majority of diagnosis codes were related to different types of headaches affecting 69 149 (9.3%) individuals. The most prevalent diagnoses following headaches were dizziness and giddiness (15 589 patients [2.1%]; nerve, nerve root and plexus disorders (10 375 patients [1.4%]); epileptic disorders (7028 patients [0.9%]); neurological diseases of vascular origin (6091 patients [0.8%]); other disorders of the nervous system (5358 patients [0.7%]); and demyelinating diseases of the central nervous system (2129 patients [0.3%]). The present findings of our study show high prevalence of pregestational neurological disorders, the dominance of headaches followed by the rather nonspecific diagnosis of dizziness and giddiness, the relevance of nerve, nerve root and plexus disorders and epilepsy, and the importance of cerebrovascular disorders among women of childbearing age. CONCLUSION: The present research findings can help healthcare professionals, researchers and decision makers in adopting specific health policy measures based on nationwide data and further aid the development of new diagnostic and therapeutic algorithms of various neurological manifestations concerning women of childbearing age.

Pharmacokinetic interaction of diosmetin and silibinin with other drugs: Inhibition of CYP2C9-mediated biotransformation and displacement from serum albumin.

Diosmin and silibinin (SIL) are polyphenolic compounds which are the active components of several drugs and dietary supplements. After the oral administration of diosmin (flavonoid glycoside), only its aglycone diosmetin (DIO) reaches the systemic circulation. Both DIO and SIL form complexes with serum albumin and are able to inhibit several cytochrome P450 enzymes. Therefore, it is reasonable to hypothesize that these polyphenols may displace some drugs from serum albumin and inhibit their biotransformation, potentially leading to the disruption of drug therapy. In this study, the inhibitory action of DIO and SIL on CYP2C9-catalyzed metabolism of diclofenac to 4'-hydroxydiclofenac was examined, using warfarin as a positive control. Furthermore, interaction of DIO and SIL with human and bovine serum albumins as well as the displacement of warfarin from albumin by DIO and SIL were tested, employing steady-state fluorescence spectroscopy, fluorescence anisotropy, ultrafiltration, and molecular modeling. It is demonstrated that DIO and SIL are potent inhibitors of CYP2C9 enzyme and are able to displace the Site I ligand warfarin from human serum albumin. Because DIO and SIL may interfere with the pharmacokinetics of several drugs through both ways, we need to consider the potentially hazardous consequences of the consumption of diosmin or SIL together with other drugs.