DELAYED TERATOGENIC EXPRESSION OF ANTICONVULSANTS

虽然怀孕期间给药的目标是母亲，但 胎儿通常会成为不受欢迎的接受者。毒品的巨大危险 在怀孕期间服用与以下事实有关：什么是无毒的 对母亲的治疗可能是胎儿的一种强大的致畸因素。它 研究表明，怀孕期间服用的药物可能会起到致畸作用 在胎儿中产生结构畸形。许多药物也可以 产生更多微妙的生化和生理致畸缺陷 胎儿。虽然这些可能是“延迟的”缺陷，但在 出生，甚至在儿童时期出生，都是长期的和永久的。 缺陷。几乎按照定义，致畸导致的生殖缺陷 功能缺陷可定义为延迟或“潜伏性”出生缺陷。而当 繁殖能力直到成年才会表现出来，他们是 在下丘脑-垂体-性腺轴的控制下 危重期对药物致畸作用的敏感性 性别分化。0.3%到0.5%的孕妇 患有癫痫，因此可能是抗惊厥药物的接受者 对该疗法可能产生的畸形学影响的重要关注。 由于它们的中枢神经系统作用，我们提出了抗惊厥药物可以 破坏神经内分泌轴的正常分化，从而成为 可能的致畸候选者能够产生长期生殖 异常现象。我们已经提出了检验通常使用的假设 在器官发生期后给予的抗惊厥药物可产生 性别分化中的潜在性和永久性生化出生缺陷 和繁衍。通过暴露胎儿在最后几天的 妊娠期最常开出的治疗性剂量 孕妇、新生儿、婴幼儿的抗惊厥药， 即安定、苯妥英钠、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暴露于 发育中的哺乳动物对性和生殖出生缺陷的风险。 此外，通过描述生殖和荷尔蒙的影响， 药物，我们可能会获得一些关于长期致畸的生化见解 产前接触抗惊厥药物的后果。

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.