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Risks of Pregnancy in Women with Epilepsy   总被引:3,自引:3,他引:1  
Mark S. Yerby 《Epilepsia》1992,33(S1):S23-S27
Summary: Pregnant women with epilepsy are at increased risk of seizures and complications. An increase in seizure frequency is seen in 25–30% of pregnant women with epilepsy; the offspring of mothers who experienced seizures during pregnancy are at a 2.5 times higher risk for seizures later in life. One of the main reasons for the increase in seizures during pregnancy is a decline in plasma concentrations of antiepileptic drug (AED) that occurs as pregnancy progresses, largely as a result of marked alterations in plasma protein binding. It is well known that epilepsy represents a risk for a variety of adverse pregnancy outcomes or malformations, especially in polytherapy. The adverse outcomes range from dysmorphic features to hemorrhagic disorders resulting from a deficiency of vitamin K-dependent clotting factors or to spina bifida. Folic acid supplements appear to reduce the risk of spina bifida. A strong genetic link seems to exist for many of the malformations that occur, and more research is required in this field. In the meantime, there are interventions that clinicians can already make to reduce the risk of adverse outcomes, such as seizure control without toxicity, monotherapy, and preconceptual use of vitamins with folate.  相似文献
3.
Summary: Exposure to antiepileptic drug (AED) treatment in utero occurs in 1 of every 250 newborns. The absolute risk of major malformations in these infants is about 7–10%, ˜3–5% higher than in the general population. Specific risk factors include high maternal daily dosage or serum concentrations of AED, low folate levels, polytherapy, and generalized seizures during pregnancy. Adverse pregnancy outcomes, including congenital heart malformations, facial clefts, spina bifida aperta, hypospadias, growth retardation, and psychomotor and mental retardation, are associated with, although not necessarily caused by, AED exposure. Specific cognitive defects, hypertelorism, and nail hypoplasia can be causally related to specific AED exposures. To prevent teratogenic side effects, the prospective mother should be treated with AEDs only when absolutely necessary. Monotherapy with the AED that is most effective in the lowest possible daily dose (divided into at least two or three administrations) should be prescribed. High-dose folate supplementation (4–5 mg/day) reduces the risk of a neural tube defect in a child whose sibling had such a defect, but its impact on the specific teratogenic risks of AEDs is unknown. A substantial proportion of fetal malformations may be secondarily prevented by prenatal diagnosis, consisting of a fetal structural ultrasound examination at weeks 18 and 20 of gestation and, with VPA or CBZ administration, an α1-fetoprotein analysis of amniotic fluid at week 16. Determination of a specific defect prevention strategy depends largely on parental attitudes toward prenatal diagnosis and termination of pregnancy, which should be discussed before conception. The availability of many new AEDs, many of which will be used in polytherapy, will make prospective evaluation of large numbers of pregnancy outcome on a population basis even more important in the future.  相似文献
4.
Four groups of pregnant rats were used to study the effects of dietary supplements of folic acid (FA) alone or a mixture of FA, vitamins (Vit), and amino acids (AA) on the teratogenic effects of phenytoin (PHT). Groups A, B, and C received intraperitoneal (i.p.) injections of high-dose (75 mg/kg/day) phenytoin (PHT) between 9 and 11 days of gestation, while the controls, group D, rats received distilled water. The diet was modified in groups A and B. Group A received a mixture of FA, Vit, and AA, while group B received FA supplementation alone. Groups C and D received a regular diet. We found that PHT, when administered without dietary supplementation, resulted in a decrease in weight and length of the fetuses, an increased rate of subcutaneous (s.c.) bleeding, a retardation of ossification centers, and an increased number of malformations. Supplementation of the diet with FA alone or FA with Vit and AA resulted in statistically greater fetal weight and length, decreased subcutaneous bleeding, more ossification centers, and fewer malformations. The mixture of FA and Vit and AA was superior to FA alone in reducing the incidence of internal abnormalities, ossification abnormalities of the distant phalanxes, and s.c. bleeding.  相似文献
5.
Martha J. Morrell 《Epilepsia》1996,37(S6):S34-S44
Summary: As new antiepileptic drugs (AEDs) become available, physicians will define their appropriate use in particular patient populations. For women, the issues in clude gender-specific efficacy and tolerability, including the impact of the AED on reproductive health. Women with epilepsy who are treated with established AEDs ap pear to be at risk for compromised bone health, for dis turbances in fertility, menstrual cyclicity, ovulatory func tion, and sexuality and, with some AEDs, for failure of hormonal contraception. Finally, pregnancy outcome may be adversely affected by the established AEDs, all of which are human teratogens. Felbamate (FBM), gabap-entin (GBP), lamotrigine (LTG), oxcarbazepine (OCBZ), tiagabine (TGB), topiramate (TPM), and vigabatrin (VGB) were reviewed. The preclinical development pro cess had not addressed all the issues of concern to women. Although gender-specific efficacy is routinely evaluated, impact on reproductive health is not. FBM, GBP, LTG, TGB, TPM, and VGB have similar efficacy in women and men. It is not known whether the new AEDs will affect bone health, fertility, the menstrual cycle, and sexuality. FBM, GBP, LTG, TGB, and probably VGB do not interfere with hormonal contraception. Whether these new AEDs are good choices for the pregnant woman with epilepsy awaits further experience in human pregnancy. However, animal reproductive toxicology studies appear promising. The limited number of human pregnancy ex posures do not, thus far, signal a significant number or particular type of adverse outcomes. However, only with improved postmarketing surveillance can essential infor mation about teratogenic effects be acquired in an accept ably short time.  相似文献
6.
同型半胱氨酸与高原地区急性脑梗死关系的探讨   总被引:2,自引:0,他引:2  
目的 探讨不同高海拔地区急性脑梗死(acute cerebral infarction,ACI)与血浆同型半胱氨酸(Homocysteine,Hcy)水平的关系.方法 采用发光免疫法测定高海拔地区ACI患者40例,中度海拔地区ACI患者48例及70例不同海拔健康对照组血浆Hcy、叶酸(FA)和维生素B12(VitB12)浓度.结果 不同海拔地区ACI组患者血浆Hcy水平明显升高,FA水平明显低于各对照组(P<0.01).与中度海拔ACI组相比,高海拔ACI组Hcy水平显著增高,FA的含量显著降低.健康对照组随着海拔增高Hcy的含量增高而FA的含量降低.VitB12在4组间变化不大.ACI组Hcy与FA间呈负相关(r=-0.034,P<0.05).与VitB12相关不显著.结论 高Hcy血症与高原地区急性脑梗死有密切关系.  相似文献
7.
Decrease of Serum Folates in Healthy Male Volunteers Taking Phenytoin   总被引:1,自引:1,他引:1  
The effect of phenytoin (PHT) on serum folate and the effect of additional oral folic acid (FA) on serum folate during continued treatment with PHT were studied in 13 healthy male subjects 20-35 years of age. The study was divided into two phases: Phase I determined Vmax (mg/kg/day) and Km (microgram/ml) of PHT in order to calculate the PHT doses needed for the second phase. Phase II was a four-way cross-over study to examine the effect of 1 and 5 mg FA on total serum PHT concentrations 1 microgram/ml less and 5 micrograms/ml greater than the subject's Km, Km-1 and Km+5, respectively. Both phases examined the effect of PHT on serum folate. In Phase I, serum folate decreased by a mean and standard deviation of 42.15 +/- 21.44% after an average of 24.15 +/- 5.63 days of PHT administration, with a mean steady-state total serum PHT concentration of 8.45 +/- 2.70 micrograms/ml. Mean percentage decreases in serum folate before the addition of 1 and 5 mg FA in Phase II were 12.80 +/- 31.45% and 23.24 +/- 21.24% for Km-1 and Km+5, respectively. The average numbers of days of PHT administration and total serum PHT concentrations before FA administration were 9.52 +/- 3.34 and 15.84 +/- 7.02 days, and 2.60 +/- 2.18 and 8.64 +/- 3.44 micrograms/ml, for Km-1 and Km+5, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献
8.
血清同型半胱氨酸水平与帕金森病的关系   总被引:1,自引:0,他引:1  
目的探讨帕金森病(PD)患者伴发高同型半胱氨酸血症(HHcy)情况及美多巴对其血清同型半胱氨酸(Hcy)水平的影响。方法选择2006-06-01-2009-12-31入住作者医院的PD患者53例,按入院前是否服用美多巴治疗分为非美多巴组和美多巴组,两组患者入院后均予美多巴口服治疗;另选择31名同期健康体检者为对照。采用荧光偏振免疫分析法(FPIA)检测血清Hcy水平,微粒子酶免分析法(MEIA)检测血清叶酸(FA)及维生素B12(VitB12)水平。收集患者初次就诊及初次复诊时的血清Hcy、FA、VitB12水平资料至2010-01-30,并进行分析比较。结果 (1)初次就诊时非美多巴组和美多巴组PD患者血清Hcy水平〔分别(17.28±6.79)、(18.50±6.56)μmol/L〕均高于健康对照组〔(13.49±3.21)μmol/L〕(均P<0.01),HHcy的比例〔分别为50%(14/28)和76%(19/25)〕亦高于健康对照组〔29%(9/31)〕(均P<0.01),而血清FA、VitB12的水平无统计学差异(均P>0.05)。HHcy患者的血清Hcy水平与FA、VitB12水平无相关性(分别r=0.118,P=0.455;r=0.001,P=0.995)。(2)非美多巴组患者复诊时血清Hcy水平〔(15.84±3.33)μmol/L〕较治疗前〔(12.92±3.15)μmol/L〕升高(P<0.05),血清FA、VitB12水平同治疗前比较无统计学差异(P>0.05)。美多巴组患者服用美多巴治疗后血清Hcy、FA、VitB12水平同初次就诊时比较均无统计学差异(均P>0.05)。结论服用美多巴可能使PD患者血清Hcy水平升高,但可能不是PD患者伴有HHcy的惟一原因。  相似文献
9.
叶酸、普伐他汀对急性脑梗死患者炎症因子的影响   总被引:1,自引:0,他引:1  
目的 观察急性脑梗死患者应用叶酸和瞢伐他汀对其血C反应蛋白(CRP)、纤维蛋白原(FIB)、肿瘤坏死因子-α(TNF-α)、白介素6(I-一6)的影响.方法 124例急性脑梗死患者随机分为叶酸组、普伐他汀组及叶酸+普伐他汀组.分别在给药前及给药治疗4周后测定血中C反应蛋白、纤维蛋白原、肿瘤坏死因子-α、白介素6的数值,了解其变化情况.结果 三组治疗后血CRP、FIB、TNF-a、IL-6水平均较治疗前显著降低(P<0.05),叶酸组与叶酸+普伐他汀组及普伐他汀组与叶酸+普伐他汀组CRP、FIB、TNF-α、IL-6水平比较差异均有统计学意义(P<0.05).结论 叶酸和普伐他汀联合干预对降低血炎症因子CRP、FIB、TNF-α,IL-6水平效果显著,二者具有协同作用,对于延缓和逆转颈动脉粥样硬化疗效优于单一使用叶酸或普伐他汀,对临床预防脑梗死复发具有明显作用,值得推广使用.  相似文献
10.
目的 观察叶酸和维生素B6、B12联合治疗青年脑卒中合并高同型半胱氨酸(Hcy)血症的疗效.方法 将150例青年脑卒中合并高Hcy血症患者随机分为低剂量叶酸和维生素B6、B12治疗组(低剂量组)、高剂量叶酸和维生素B6、B12治疗组(高剂量组)、对照组,每组50例.用药剂量:低剂量组给予叶酸2.5mg/d、维生素B6 10 mg/d、维生素B12 0.5 mg/d,高剂量组给予叶酸5 mg/d、维生素B6 30 ms/d、维生素B12 1.5mg/d,连续给药4周,对照组不予叶酸和维生素B6、B12治疗.治疗前后检测血浆Hcy浓度,治疗后血浆Hcy浓度<15 μmol/L为有效;并观察不良反应.结果 治疗4周后低剂量组、高剂量组临床有效率分别是70.4%、71.6%,与对照组(4.6%)相比差异有统计学意义(均P<0.01);治疗后低剂量组、高剂量组血浆Hcy浓度比治疗前明显降低(下降33.9%和36.1%)(均P<0.01);对照组治疗后的血浆Hcy浓度无明显下降.3组治疗过程中均未出现不良反应.结论 叶酸和维生素B6、B12联合治疗青年脑卒中合并的高Hcy血症有明显效果,而且高、低两种剂量均有效;无不良反应.  相似文献
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