Polycystic ovary syndrome in patients with epilepsy: A study in 102 Chinese women

PurposeThe incidence of polycystic ovary syndrome (PCOS) increases in women with epilepsy (WWE), which appears to vary with ethnicity. This study was conducted to determine the incidence and risk factors of PCOS in Chinese WWE.MethodsThe study was carried out in 102 of 139 Chinese WWE at reproductive ages, with 32 receiving valproic acid (VPA), 40 receiving other antiepileptic drugs (AEDs), and 30 without AEDs therapy. PCOS was defined as having 2 or more of the following components: polycystic ovaries, hyperandrogenism, and amenorrhoea or oligomenorrhoea (a/oligomenorrhoea).ResultsOne or more isolated components of PCOS were found in 56 (54.9%) patients, with 29 (28.4%) having polycystic ovaries, 20 (19.6%) with a/oligomenorrhea, 7 (6.9%) with hyperandrogenism, and 13 (12.7%) with defined PCOS. Their average age at the start of seizure was 13.8 ± 6.5 years, younger than that of patients without these disorders (16.9 ± 8.6 years, p < 0.05). VPA therapy increased the incidence of PCOS (11/32, 34.4%), in addition to increased blood levels of testosterone and luteinizing hormone (LH) as well as LH to FSH (follicle-stimulating hormone) ratio. No significant relationship was found between the incidence of PCOS and the type, duration, or frequency of seizures in these WWE.ConclusionThere is an increased incidence of PCOS in Chinese WWE at reproductive ages, by more than 2 times of that in the general population. Risk factors include seizures starting at a young age and VPA therapy.     

Seizure type, antiepileptic drugs, and reproductive endocrine dysfunction in Indian women with epilepsy: a cross-sectional study

Background: There is paucity of data regarding occurrence of reproductive endocrine disorders in Asian women with epilepsy (WWE) on antiepileptic drug (AED) therapy. Purpose: To determine the occurrence of reproductive endocrine disorders in Indian WWE, by seizure type and the AED use. Methods: Consecutive 427 reproductive age WWE receiving various AEDs were screened for the occurrence of menstrual abnormalities, weight change, and hirsutism. Of these, 53 WWE with menstrual disturbances and/or hirsutism were further evaluated for ovarian morphology and reproductive hormonal profile. Results: Menstrual abnormalities and/or hirsutism were observed in 83 of 427 (19.4%) WWE irrespective of epileptic seizure type; of these, 50 (60.2%) received valproate, 21 (25.3%) received carbamazepine, 11 (13.3%) received phenytoin, and one (1.2%) received phenobarbitone as the primary AED. Almost half of valproate‐treated women had significant weight gain and obesity. Among 53 of 83 women evaluated further, 23.5% and 63.6% of valproate‐treated women, 25% and 58.3% of carbamazepine‐treated women, and none and 20% of phenytoin‐treated women had polycystic ovaries (PCO) and hyperandrogenemia (HA), respectively. Valproate‐treated women had significantly higher frequency of polycystic ovarian syndrome (PCOS) (11.8% vs. 2.5%, p < 0.0001) and mean serum testrosterone levels (1.78 vs. 1.36 ng/ml, p = 0.03), compared with women treated with other AEDs. Limitations: Limitations include small number of women in antiepileptic subgroups and a high drop out rate in women who underwent ultrasound and endocrinological investigations. Conclusion: Menstrual abnormalities, weight gain, obesity, and PCOS are frequent and significantly higher in WWE receiving valproate, independent of seizure type.     

Hyperandrogenism, postprandial hyperinsulinism and the risk of PCOS in a cross sectional study of women with epilepsy treated with valproate

Among a sample of 43 women with epilepsy treated for at least 2 years with valproate (n=22) or other antiepileptic drugs (AEDs) (n=21), polycystic ovary syndrome (PCOS) was diagnosed in three women, two of them were treated with valproate. Although the rate of PCOS and of menstrual disturbances, weight body mass index (BMI) and waist to hip ratio as well as fasting blood glucose levels, fasting insulin, proinsulin and C-peptide values was similar in this small sample of women treated with valproate and other AEDs, valproate exposure was associated with higher androgen levels, higher postprandial (pp) insulin and proinsulin levels, as well as lower cholesterol and low density lipoprotein (LDL) cholesterol levels. The pronounced increase in pp insulin levels during VPA treatment may indicate an effect of the fatty acid derivate VPA on pancreatic islet cells.     

Risk perception and medicines information needs in pregnant women with epilepsy - A qualitative study

PurposeTo explore risk perception and medicines information needs in pregnant women with epilepsy (WWE).MethodIn-depth interviews with pregnant WWE treated with antiepileptic drugs (AEDs).ResultsTen women aged 22–39 years in 20–34 weeks’ gestation were interviewed. Avoiding seizures by taking AEDs in pregnancy outweighed perceived risks, but dose adjustments during and after pregnancy increased perceived risks of teratogenicity or seizures. The women had restrictive attitudes towards taking medicines for other indications than epilepsy. They appreciated their neurologist as a source for medicines information, though their needs for medicines information were reduced by long-term use of AEDs.ConclusionsPregnant WWE were confident in using AEDs through communication with their neurologist, but dose adjustments caused concern. Medicines information to pregnant WWE should focus on empowering the women to control the disease, supporting realistic risk perceptions of AEDs and other necessary medicines. In this article, we outline some medicines information strategies to pregnant WWE.     

Impact of sleep-disordered breathing on metabolic dysfunctions in patients with polycystic ovary syndrome

BackgroundPolycystic ovary syndrome (PCOS) is the most common endocrinological disorder among women in the reproductive age group. These women are prone to develop sleep-disordered breathing (SDB) and metabolic disorders. SDB is also associated with metabolic dysfunctions. We hypothesized that SDB is an independent risk factor contributing to metabolic dysfunctions in women with PCOS.MethodsProspective cross-sectional study in which 50 women with PCOS and not on any treatment were selected. They were divided into two groups: Group 1 - PCOS with SDB and Group 2 - PCOS without SDB.ResultsThirty-three (66%) women with PCOS had SDB. Women in Group 1 had significantly higher systolic blood pressure (SBP) (P = 0.002); diastolic blood pressure (DBP) (P = 0.044); fasting blood sugar (P = 0.006), triglyceride levels (P = 0.014) and mean Ferriman-Gallwey score (P = 0.028). The HDL was significantly lower in group 1 (P = 0.006). In group 1, 42.4% of women had metabolic syndrome (P < 0.001). Excessive daytime sleepiness (EDS) was significantly higher in Group 1 (P = 0.04). Respiratory distress index significantly correlated positively with waist circumference (r = 0.551, P < 0.001), SBP (r = 0.455, P = 0.001), DBP (r = 0.387, P = 0.006), FBS (r = 0.524, P = 0.000), homeostatic model assessment (r = 0.512, P = 0.000), triglycerides (r = 0.384, P = 0.006), free testosterone (r = 0.390, P = 0.005), and negatively with HDL (r = –0.555, P < 0.001).ConclusionWomen with PCOS and SDB had significantly increased metabolic abnormalities as well as more severe hyperandrogenism. Women with PCOS who have metabolic abnormalities or severe hyperandrogenism should undergo an overnight PSG.     

On the Association Between Valproate and Polycystic Ovary Syndrome

Summary: Recent studies by Isojärvi et al. have raised the issue of an increased incidence of polycystic ovary syndrome (PCOS) in women with epilepsy treated with valproate (VPA) and have proposed replacement with lamotrigine (LTG). Polycystic ovaries (PCO) are a common finding, with a prevalence >20% in the general population, and are easily detected by pelvic or vaginal ultrasonography, whereas PCOS is comparatively rare: few women with PCO have fully developed PCOS, which includes hirsutism, acne, obesity, hypofertility, hyperandrogenemia, and menstrual disorders. From an extensive review of the current literature, it appears that there are no reliable data on the actual prevalence of PCOS in normal women and in women with epilepsy. The pathogenesis of PCO is multifactorial, including genetic predisposition and the intervention of environmental factors, among which weight gain and hyperinsulinism with insulin resistance may play a part. The roles of central (hypothalamic/pituitary), peripheral, and local ovarian factors are still debated. PCO and PCOS appear to be more frequent in women with epilepsy, but there are no reliable data showing a greater prevalence after VPA. The recent studies by Isojärvi et al. may have been biased by the retrospective selection of patients. To date, there is no reason to contraindicate the use of VPA in women with epilepsy. However, patients should be informed about the risk of weight gain and its consequences.     

Identifying risk factors for polycystic ovary syndrome in women with epilepsy: A comprehensive analysis of 248 patients

To assess the risk factors for polycystic ovary syndrome (PCOS) in women with epilepsy (WWE) and develop a practical approach for PCOS screening based on clinical characteristic, blood indicator, and anti-seizure medication (ASM) profiles. This cross-sectional study was conducted with 248 WWE who were consecutively enrolled from the Epilepsy Center of West China Hospital between April 2021 and March 2022. The epilepsy characteristics, blood indicators, and use of ASMs were compared between WWE with and without PCOS. Multivariate logistic regression was used to identify the factors independently associated with PCOS. The differential analysis showed that younger age at onset of epilepsy (<13 years), a history of birth hypoxia, obesity (BMI ≥25 kg/m²), use of levetiracetam (LEV) (≥1 year), higher levels of cholesterol, luteinizing hormone (LH) and anti-Müllerian hormone (AMH), and lower levels of sex hormone-binding globulin were associated with PCOS (p < .05). Multivariate logistic regression identified that obesity (BMI ≥25 kg/m²), use of LEV (≥1 year), and higher levels of AMH and LH were independently associated with PCOS in WWE (p < .05). Obesity (BMI ≥25 kg/m²), LEV use (≥1 year), and elevated AMH and LH levels suggest an increased in the probability of occurrence of PCOS in WWE. The combination of these profiles provides a practical approach for screening PCOS in WWE.     

Differential effects of antiepileptic drugs on neonatal outcomes

Offspring of women with epilepsy (WWE) on AEDs are at increased risks for major congenital malformations and reduced cognition. They may be at risk for other adverse neonatal outcomes. Women with epilepsy on carbamazepine (CBZ), lamotrigine (LTG), phenytoin (PHT), or valproate (VPA) monotherapy were enrolled in a prospective, observational, multicenter study of the neurodevelopmental effects of AEDs. The odds ratio for small for gestational age (SGA) was higher for VPA vs. PHT, VPA vs. LTG, and CBZ vs. PHT. Microcephaly rates were elevated to 12% for all newborns and at 12 months old, but normalized by age 24 months. Reduced Apgar scores occurred more frequently in the VPA and PHT groups at 1 min, but scores were near normal in all groups at 5 min. This study demonstrates increased risks for being born SGA in the VPA and CBZ groups, and transiently reduced Apgar scores in the VPA and PHT groups. Differential risks among the AEDs can help inform decisions about AED selection for women during childbearing years.     

Pharmacokinetic changes for newer antiepileptic drugs and seizure control during pregnancy

ObjectiveTo investigate pharmacokinetic changes in newer antiepileptic drugs (AEDs) and assess seizure frequencies and risk factors of increased seizures during pregnancy in women with epilepsy (WWE).MethodsA total of 56 pregnancies in 53 WWE who received newer antiepileptic drugs (AEDs) were enrolled. Data on seizure activity and types, daily dose, and AEDs blood levels were derived from routine clinical follow‐up. Changes in AEDs clearance were compared between each trimester and nonpregnant baseline. The ratio of AED levels of each trimester to their targets (nonpregnant baseline) concentrations (RTC) was compared between patients with and without an increased seizure. A binary logistic regression was used to investigate the risk factors contributing to seizure worsening during pregnancy.ResultsIncreased clearances of LTG, LEV, and OXC were observed in all trimesters versus nonpregnant baseline. The peak changes in the clearance of LTG (3.42‐fold baseline clearance) (p < 0.001) and LEV (2.78‐fold) (p < 0.001) occurred in the second trimester during pregnancy, followed by oxcarbazepine (2.11‐fold) in the third trimester (p < 0.03). Plasma concentrations of LTG and LEV during pregnancy were significantly decreased compared to baseline levels, except for OXC. However, no significant differences in RTC values were observed between patients with and without seizure worsening. Some risk factors as seizures for the prior nine months could significantly affect seizure frequency during pregnancy.ConclusionWe found substantial changes in the pharmacokinetics of multiple newer AEDs in WWE, reinforcing the need for therapeutic drug monitoring (TDM) during pregnancy. We would encourage at least one monitoring every trimester and probably more frequently for women with poorly seizure control before pregnancy, and AEDs dose adjustment should keep up with clearance changes. In addition, a well‐controlled seizure nine months before pregnancy could lower the risks of seizure during pregnancy, highlighting the importance of pre‐pregnancy counseling and seizure management before pregnancy.     

Pharmacogenetic evaluation of ABCB1, Cyp2C9, Cyp2C19 and methylene tetrahydrofolate reductase polymorphisms in teratogenicity of anti-epileptic drugs in women with epilepsy

Aim:

Pregnancy in women with epilepsy (WWE) who are on anti-epileptic drugs (AEDs) has two- to three-fold increased risk of fetal malformations. AEDs are mostly metabolized by Cyp2C9, Cyp2C19 and Cyp3A4 and transported by ABCB1. Patients on AED therapy can have folate deficiency. We hypothesize that the polymorphisms in ABCB1, Cyp2C9, Cyp2C19 and methylene tetrahydrofolate reductase (MTHFR) might result in differential expression resulting in differential drug transport, drug metabolism and folate metabolism, which in turn may contribute to the teratogenic impact of AEDs.

Materials and Methods:

The ABCB1, Cyp2C9, Cyp2C19 and MTHFR polymorphisms were genotyped for their role in teratogenic potential and the nature of teratogenecity in response to AED treatment in WWE. The allelic, genotypic associations were tested in 266 WWE comprising of 143 WWE who had given birth to babies with WWE-malformation (WWE-M) and 123 WWE who had normal offsprings (WWE-N).

Results:

In WWE-M, CC genotype of Ex07 + 139C/T was overrepresented (P = 0.0032) whereas the poor metabolizer allele *2 and *2 *2 genotype of CYP2C219 was significantly higher in comparison to WWE-N group (P = 0.007 and P = 0.005, respectively). All these observations were independent of the nature of malformation (cardiac vs. non cardiac malformations).

Conclusion:

Our study indicates the possibility that ABCB1 and Cyp2C19 may play a pivotal role in the AED induced teratogenesis, which is independent of nature of malformation. This is one of the first reports indicating the pharmacogenetic role of Cyp2C19 and ABCB1 in teratogenesis of AED in pregnant WWE.     

Physical growth and endocrinal disorders during pubertal maturation in girls with epilepsy

PURPOSE: This study investigated the effect of epilepsy and/or antiepileptic drugs (AEDs) on the physical growth, pubertal development, and androgenic status of girls with epilepsy between ages 8 and 18 years. METHODS: Sixty-six female patients with epilepsy, their mean ages 13.47 +/- 3.5 years, were included. Anthropometric measurements, staging of pubertal maturation, and clinical manifestations of hyperandrogenism were assessed, as well as measurement of serum levels of testosterone, dehydroepiandrosterone sulfate (DHEAS), sex hormone-binding globulin (SHBG), and free androgen index (FAI). Of the included patients, 44 had transabdominal ultrasonic examination of the ovaries and fasting serum insulin levels were measured. Forty healthy age-matched females served as a control group. RESULTS: Patients showed reduced mean height percentile compared with controls (z = 2.07; p = 0.04), which was negatively correlated with the duration of their epilepsy. Patients showed increased frequency of obesity, especially postpubertal girls taking valproate (VPA; 67%), who also showed higher insulin levels (t = 8.01; p = 0.0003). Patients showed increased frequency of clinical hyperandrogenemia in the different stages of puberty. High levels of testosterone and DHEAS were found in female patients with epilepsy, especially pubertal and postpubertal girls. Hyperandrogenism (clinical and/or laboratory) was most affected by the types of AEDs, with higher incidence in patients taking VPA compared with those taking enzyme-inducing AEDs (chi2= 9.16; p = 0.01). Eighteen percent of the patients were diagnosed as having polycystic ovary syndrome (PCOS). No difference was found in the types of seizures, degree of seizure control, type of AEDs, or insulin levels between patients with and those without PCOS. CONCLUSIONS: Longer duration of the disease has a negative impact on the stature of female patients with epilepsy. Postpubertal girls taking VPA are more liable to obesity, which is associated with increased incidence of hyperinsulinemia. Clinical and/or laboratory evidence of hyperandrogenism is seen at a high frequency in patients, especially with the use of VPA. Furthermore, female patients with epilepsy especially in the postpubertal stage of sexual maturation, have a high prevalence of PCOS, independent of the type of AED or the characteristics of the epilepsy disorder.     

Obesity, polycystic ovarian syndrome and thyroid dysfunction in women with epilepsy

Introduction:

Women with epilepsy (WWE) have an increased risk for several endocrine disorders. Obesity and Polycystic Ovarian Syndrome (PCOS) are common side-effects of anticonvulsant drugs.

Aim:

To study the prevalence of Obesity, PCOS, Thyroid dysfunction in WWE on monotherapy with Carbamazepine (CBZ), Sodium Valproate (VAL) and Phenytoin (DPH)

Material and Methods:

Sixty WWE in the reproductive age group (13 – 45 yr) who are on atleast 6 months of monotherapy with either CBZ (20) or VAL (20) or DPH (20) are subjects of the study. Their Anthropometric data is recorded. They are interviewed and investigated for PCOS and thyroid dysfunction. Twenty healthy women in the reproductive age group served as controls. BMI>25 is taken as cut-off for Obesity. PCOS is defined as menstrual irregularity and/or clinical /biochemical hyperandrogenism with ultrasound evidence of PCO as per the Rotterdam criteria. TSH <0.1 and >4 is taken as evidence of thyroid dysfunction. Women are grouped according to the anticonvulsant drug received and the data analyzed in each group.

Results:

The mean BMI among VAL and CBZ users is significantly higher than among DPH users (23.3 & 23.4 vs 20.4). There is no significant difference in incidence of PCOS among WWE using either DPH or VAL or CBZ. Elevated TSH>4 is seen more often in WWE on VAL (9/20) compared to CBZ (6/20) and DPH (3/20). WWE on CBZ, VAL and DPH did not differ in mean BMI, Obesity, PCOS compared to healthy controls. As compared to healthy controls, more WWE on drug therapy had significantly elevated TSH (1/20 vs20/60).

Conclusions:

WWE on VAL and CBZ had significant weight gain compared to DPH users. Despite weight gain, there was no difference in the incidence of PCOS between the users of VAL, CBZ and DPH. As compared to healthy controls, more WWE on drug therapy had significantly elevated TSH, more so in the VAL group.     

Cross-sensitivity of patient-perceived adverse cognitive effects with antiepileptic drug use

ObjectiveThe extent to which adverse cognitive effects (ACEs) to a specific antiepileptic drug (AED) affect the chance of developing ACEs to other AEDs (i.e., cross-sensitivity) is unknown. We investigated the rates of cross-sensitivity of ACEs among AEDs and examined the association between clinical characteristics and occurrence of having ACEs to multiple AEDs in adults with epilepsy.MethodsThe rates of cross-sensitivity of intolerable ACEs (IACEs; i.e., ACEs leading to dosage reduction or discontinuation) and the non-AED predictors of IACEs were investigated in 2269 patients who had taken at least two AEDs at a single center. We accounted for AED load and looked for specific cross-sensitivities between AEDs as well as cross-sensitivity based on the AED mechanism of action.ResultsAmong the 2269 patients, the highest rates of IACEs were seen with TPM (26.3%), ZNS (9.8%), PHT (8.8%), and VPA (8.5%). Intolerable ACEs to two or more AEDs occurred in 100 patients (4.4%). History of psychiatric condition(s) and absence seizure type were independent predictors of IACEs to two or more AEDs. High rates of cross-sensitivity of IACEs were seen between phenytoin (PHT) and lamotrigine (LTG), valproate (VPA) and phenytoin, and valproate and zonisamide (ZNS). For example, of patients who had IACEs to VPA and were also prescribed ZNS, 46.2% had IACEs to ZNS (abbreviated as VPA → ZNS: 46.2%); of patients who had IACEs to ZNS and were also prescribed VPA, 37.5% had IACEs to VPA (abbreviated as ZNS → VPA: 37.5%). Other results are as follows: LTG → PHT: 28.6%, PHT → LTG: 20.0%, PHT → VPA: 42.9%, and VPA → PHT: 27.3%. No specific cross-sensitivities were found among AEDs sharing a similar mechanism of action.SignificanceThe probability of ACE intolerability to an AED can increase if a patient developed ACE intolerability to another AED. The cross-sensitivity rates for ACE intolerability between LTG and PHT, PHT and VPA, and VPA and ZNS were found to be particularly high. The cross-sensitivity rates provided here may be clinically useful for predicting ACE intolerability in patients taking certain AEDs and for AED selection in individual patients.     

Effects of anticonvulsants on human p450c17 (17alpha-hydroxylase/17,20 lyase) and 3beta-hydroxysteroid dehydrogenase type 2

PURPOSE: Women with epilepsy apparently have a higher incidence of polycystic ovary syndrome (PCOS) than do women without epilepsy. Whether the underlying disease or the antiepileptic drug (AED) treatment is responsible for this increased risk is unknown, although clinical reports implicate valproic acid (VPA) as a potential cause. The steroidogenic enzymes 3beta HSDII (3beta-hydroxysteroid dehydrogenase) and P450c17 (17alpha-hydroxylase/17,20 lyase) are essential for C19 steroid biosynthesis, which is enhanced during adrenarche and in PCOS. METHODS: To determine whether the AEDs VPA, carbamazepine (CBZ), topiramate (TPM), or lamotrigine (LYG) directly affect the activities of human 3beta HSDII and P450c17, we added them to yeast expressing human P450c17 or 3beta HSDII and assayed enzymatic activities in the microsomal fraction. RESULTS: Concentrations of VPA < or = 10 mM had no effect on activities of P450c17; however, VPA inhibited 3beta HSDII activity starting at 0.3 mM (reference serum unbound concentration, 0.035-0.1 mM) with an IC50 of 10.1 mM. CBZ, TPM, and LTG did not influence 3beta HSDII or P450c17 activities at typical reference serum unbound concentrations, but did inhibit 3beta HSDII and P450c17 at concentrations >10-fold higher. CONCLUSIONS: None of the tested AEDs influenced 3beta HSDII or P450c17 activities at concentrations normally used in AED therapy. However, VPA started to inhibit 3beta HSDII activity at concentrations 3 times above the typical reference serum unbound concentration. Because inhibition of 3beta HSDII activity will shift steroidogenesis toward C19 steroid production when P450c17 activities are unchanged, very high doses of VPA may promote C19 steroid biosynthesis, thus resembling PCOS. CBZ, TPM, and LTG influenced 3beta HSDII and P450c17 only at toxic concentrations.     

Is lamotrigine a significant human teratogen? Observations from the Australian Pregnancy Register

Lamotrigine (LTG) is increasingly being prescribed in pregnancy for women with epilepsy in place of valproate (VPA), because of the teratogenic risks associated with the latter. It is therefore important to know the teratogenic hazard associated with LTG, relative to VPA and to other commonly used antiepileptic drugs (AEDs). Data from the Australian Register of Antiepileptic Drugs in Pregnancy was examined to determine the incidence of teratogenicity determined 1 year from completion of pregnancy in women who took AEDs in monotherapy during pregnancy. Compared with a 3.4% malformation incidence in women who took no AEDs (N = 118), the incidences for LTG (N = 243), carbamazepine (CBZ) (N = 302) and VPA (N = 224) were, respectively, 4.9%, 5.3% and 15.2%, the latter statistically significantly greater than the risk for no AED therapy in pregnant women with epilepsy. Logistic regression analysis showed no tendency for foetal hazard to increase with increasing LTG dose in pregnancy, unlike the situation for VPA. However, seizure control in pregnancy tended to be not as good in the women taking LTG compared with those taking VPA, though the data examined were not adequate to permit definite conclusions regarding this matter. We conclude that LTG monotherapy in pregnancy is safer than valproate monotherapy from the point of view of foetal malformations, and no more hazardous in this regard than therapy with other commonly used AEDs.     

Reproductive endocrine function in women with epilepsy: the role of epilepsy type and medication

The purpose of the analysis described here was to assess reproductive endocrine disorders in 148 women with epilepsy (WWE) by epilepsy type and antiepileptic drug use. Women with idiopathic generalized epilepsy had a higher prevalence of reproductive endocrine disorders than control subjects. In addition, hyperandrogenism, polycystic ovaries, and polycystic ovary syndrome were more prevalent in WWE on valproate than in WWE taking other drugs or control women. The use of VPA was a predictor of the development of polycystic ovaries and polycystic ovary syndrome, and the use of valproate and younger age predicted the development of hyperandrogenism. In conclusion, both idiopathic generalized epilepsy and valproate were associated with an increased risk of reproductive endocrine disorders in WWE in this post hoc reanalysis of data on a large number of WWE. This was especially evident if the epilepsy was active and required treatment early in life.     

Foetal malformations and seizure control: 52 months data of the Australian Pregnancy Registry

The Australian Pregnancy Registry, affiliated European Register of Antiepileptic drugs in Pregnancy (EURAP), recruits informed consenting women with epilepsy on treatment with antiepileptic drugs (AEDs), those untreated, and women on AEDs for other indications. Enrolment is considered prospective if it has occurred before presence or absence of major foetal malformations (FMs) are known, or retrospective, if they had occurred after the birth of infant or detection of major FM. Telephone Interviews are conducted to ascertain pregnancy outcome and collect data about seizures. To date 630 women have been enrolled, with 565 known pregnancy outcomes. Valproate (VPA) above 1100 mg/day was associated with a significantly higher incidence of FMs than other AEDs (P < 0.05). This was independent of other AED use or potentially confounding factors on multivariate analysis (OR = 7.3, P < 0.0001). Lamotrigine (LTG) monotherapy (n = 65), has so far been free of malformations. Although seizure control was not a primary outcome, we noted that more patients on LTG than on VPA required dose adjustments to control seizures. Data indicate an increased risk of FM in women taking VPA in doses >1100 mg/day compared with other AEDs. The choice of AED for pregnant women with epilepsy requires assessment of balance of risks between teratogenicity and seizure control.     

Obesity may be the common pathway for sleep-disordered breathing in women with polycystic ovary syndrome

ObjectivePolycystic ovary syndrome (PCOS) is one of the most common endocrinological disorders in women of reproductive age, and is characterized by hyperandrogenism. It is associated with long-term metabolic dysfunctions including sleep-disordered breathing (SDB). We hypothesized that the increased prevalence of SDB in PCOS results from raised testosterone levels.MethodsThis was a prospective, cross-sectional, case–control study in which 50 case patients with untreated PCOS and 100 control subjects were included. All the case patients and control subjects went through a detailed clinical, biochemical, and hormonal evaluation. Overnight polysomnography was performed in all case patients and the snorers (16 of 100) in the control group.ResultsSDB was seen in 66% of the case patients and in 4% of control group with (odds ratio [OR] = 46.5, 95% confidence interval [CI] = 14.6–148.4; p <0.001). After adjustment for body mass index (BMI) and waist circumference (WC), the difference was not significant (p = 0.993 and p = 0.931, respectively). The SDB patients with PCOS showed significantly higher respiratory distress index (RDI) values than SDB patients in the control group (22.5 ± 21.5 vs 9.0 ± 5.6, p = 0.01). On the Epworth Sleepiness Scale the PCOS case patients reported feeling more sleepy than did the control subjects (12.5 ± 3.2 vs 9.32 ± 1.7, p <0.001). Free testosterone levels were also significantly higher in the PCOS group than in the control subjects (2.95 ± 3.44 vs 1.5 ± 1.0, p <0.001). There was a significant correlation between free testosterone level and RDI values (r = 0.377; p = 0.007), WC (r = 0.315; p = 0.026), and BMI (r = 0.398; p = 0.004). A significant correlation of WC (r = 0.551; p <0.001) and BMI (r = 0.572; p <0.001) was observed with RDI.ConclusionTestosterone-induced obesity is probably the common pathway for the development of SDB in PCOS.     

Epileptiform activity in the electroencephalogram of 6-year-old children of women with epilepsy

Purpose:To study the epileptiform discharges (EDs) in the electroencephalogram (EEG) of 6-8-year-old children of women with epilepsy (WWE).Results:Of the 185 children examined, 37 (20%) children (19 males, 18 females) had ED in their EEG. The EDs were generalized in 7 children, and focal in 30 children. The EDs were present in the sleep record only of 16 (43%) children and in the awake record only of 6 (16%) children. Out of the 94 children for whom seizure history was available, 7 children (7.4%) had seizures (neonatal seizures: 4, febrile seizure: 1, and single nonfebrile seizure: 2) and none had history of epilepsy or recurrent nonfebrile seizures. The odds ratio (OR) for occurrence of ED in the EEG was significantly higher for children of WWE [OR = 3.5, 95% confidence interval (CI) 2.3-6.0] when compared to the published data for age-matched children of mothers without epilepsy. There was no association between the occurrence of ED and the children''s maternal characteristics [epilepsy syndrome, seizures during pregnancy, maternal intelligence quotient (IQ)] or the children''s characteristics [antenatal exposure to specific antiepileptic drugs (AEDs), birth weight, malformations, IQ].Conclusion:Children of WWE have a higher risk of epileptiform activity in their EEG when compared to healthy children in the community though none had recurrent seizures.     

Pregnancy outcome in women with epilepsy in Western China: A prospective hospital based study

ObjectiveGaps exist in the diagnosis and treatment of women with epilepsy (WWE) between China and Euro-American countries. We aim to find out and share our experience of the multidisciplinary integrated treatment for WWE.MethodsWe prospectively registered WWE who were diagnosed by both epileptologists and obstetrician in our green way system for the past 5 years (2009–2015). Registration information include years of education, epilepsy history, seizure type and frequency, pregnancy and delivery complications, delivery mode, and Apgar score of newborn. All data were analyzed by SAS 9.3 version.ResultsWe included 137 cases of maternal epilepsy (155 pregnancies with average maternal age of 26 years old). 18 cases underwent epilepsy surgery before pregnancy. 103 pregnancies (66.45%) were cesarean section, 52 (33.55%) were natural childbirth, only 10 pregnancies have pregnancy complications, 2 have delivery complication, and 15 have seizures during delivery process. Most offspring were healthy when they were born (only 11 newborn got Apgar score < 7). For drug treatment, patients never took AEDs or withdrew AEDs in 55 (35.48%) pregnancies. For folic acid supplementation, only 9 (5.81%) achieved the dose recommended by ILAE guideline (5 mg/day). For the seizure frequency, 108 pregnancies (69.68%) did not changed, 3 (1.94%) reduced, 44(28.39%) increased and mainly increased in the first and last trimesters. For feeding way, 90 (58.06%) chose artificial feeding, followed by 39 (16.77%) of mixed feeding and 26 of breastfeeding.ConclusionClinical features and perinatal outcome of Chinese WWE are similar to western WWE. For mode of delivery, even suggested by our epileptologists and obstetrician to deliver naturally, more patients selected cesarean section. Moreover, withdrawal of AEDs during pregnancy is common. Therefore, it is necessary to pay more attention to standard management of WWE and establish a more practical green way for WWE in China, to keep up with developed countries and improve the health level of birth in China.