DELAYED TERATOGENIC EXPRESSION OF ANTICONVULSANTS

虽然怀孕期间给药的目标是母亲， 胎儿常常成为不想要的受体。 毒品的巨大危险 在怀孕期间服用的药物与无毒的事实有关， 对母亲有治疗作用的药物可能是胎儿的强力致畸剂。 它 研究表明，怀孕期间服用的药物可能是致畸剂。 导致胎儿结构畸形 许多药物也可以 产生更微妙的生化和生理致畸缺陷， 胎儿 虽然这些可能是“延迟”缺陷， 出生时，甚至在儿童时期，它们都是长期和永久的， 缺陷 几乎根据定义，致畸性导致生殖缺陷， 功能障碍可以被定义为延迟或“潜伏”出生缺陷。 而 生殖能力直到成年才表现出来，它们是 在下丘脑-垂体-性腺轴的控制下， 对药物的致畸作用敏感， 性别分化。 0.3%到0.5%的孕妇 癫痫患者，因此可能接受抗惊厥药物治疗， 对治疗可能的致畸作用的重要关注。 由于它们的中枢神经系统作用，我们提出抗惊厥药可以 破坏神经内分泌轴的正常分化， 可能的致畸候选人能够产生长期的生殖 异常 我们已经提出了测试的假设， 在器官形成期后施用的抗惊厥药可以产生 性别分化中潜在和永久性生化出生缺陷 和繁殖。 通过在最后几天暴露胎儿 妊娠期最常用的治疗剂量 用于孕妇、新生儿、婴儿和幼儿的抗惊厥药， 也就是说，地西泮、苯妥英、卡马西平、丙戊酸等，我们将 确定早期使用部分或全部这些药物治疗是否会暴露 发育中的哺乳动物面临性和生殖出生缺陷的风险。 此外，通过描述生殖和激素的影响， 药物，我们可能会获得一些生化见解的长期致畸 产前暴露于抗惊厥药的后果。

While the target for drugs administered during pregnancy is the mother, the fetus often becomes an unwanted recipient. The great danger with drugs administered during pregnancy relates to the fact that what is non-toxic and therapeutic to the mother may be a powerful teratogen in the fetus. It has been shown that drugs taken during pregnancy may act as teratogens producing structural malformations in the fetus. Many drugs also can produce more subtle biochemical and physiological teratogenic defects in the fetus. While these may be "delayed" defects that are not apparent at birth or even during childhood, they are both longterm and permanent defects. Almost by definition, teratogenic induced defects in reproductive function can be defined as delayed or "latent" birth defects. While reprodductive capabilities are not exhibited until adulthood, they are under the control of the hypothalamic-pituitery-gonadal axis which is sensitive to the teratogenic effects of drugs during the critical period of sexual differentiation. The fact that 0.3 to 0.5 percent of pregnant women are epileptic and are therefore likely recipients of anticonvulsants raises important concerns about possible teratological effects of the therapy. Because of their CNS actions, we have proposed that anticonvulsants can disrupt normal differentiation of the neuroendocrine axis and thus become likely teratogenic candidates capable of producing longterm reproductive abnormalities. We have proposed to test the hypothesis that commonly used anticonvulsants administered after the period of organogenesis can produce latent and permanent biochemical birth defects in sexual differentiation and reproduction. By exposing fetuses during the last few days of gestation to therapeutic-like doses of the most often prescribed anticonvulsants for pregnant women, neonates, infants and young children, i.e., diazepam, phenytoin, carbamazepine, valproic acid, etc., we shall determine whether early treatment with some or all of these agents exposes developing mammals to the risks of sexual and reproductive birth defects. Furthermore, by describing the reproductive and hormonal effects of the drugs, we may gain some biochemical insights into the longterm teratogenic consequences of prenatal exposure to anticonvulsants.