PRENATAL PREDICTION OF RISK OF THE FETAL HYDANTOIN SYNDROME
PRENATAL PREDICTION OF RISK OF THE FETAL HYDANTOIN SYNDROME
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DOI：
10.1056/nejm199005313222204
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发表时间：
1990-05-31
影响因子：
158.5
通讯作者：
FINNELL, RH
中科院分区：
文献类型：
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作者：
BUEHLER, BA;DELIMONT, D;FINNELL, RH
众所周知，几种抗惊厥药物的致畸性与氧化代谢物水平升高有关，这些代谢物通常由环氧化物水解酶消除。在这项研究中，我们试图确定是否可以通过测量环氧化物水解酶的活性来确定有先天性畸形风险的婴儿。在确定胎儿处于危险中之前，有必要在随机选择的样本人群中测量环氧化物水解酶的活性，该样本人群具有明显的三峰分布，表明酶受具有两种等位基因形式的单个基因调节。隐性等位基因纯合子的胎儿环氧化物水解酶活性较低，因此在妊娠期间暴露于抗惊厥药物会有风险。在一项前瞻性研究中，对19例妊娠进行了氨基穿刺监测，根据低酶活性（<标准的30%），预测了4例胎儿的不良结局。在所有4例病例中，母亲接受苯妥英单药治疗，婴儿出生后的临床表现与胎儿乙内酰脲综合征一致。酶活性高于标准30%的15个胎儿被认为没有风险，所有15个新生儿都没有任何胎儿乙内酰脲综合征的特征。这些初步结果表明，这种酶生物标志物可能有助于确定哪些婴儿因抗惊厥药物引起的先天性畸形风险增加。
The well-known teratogenicity of several anticonvulsant medications is associated with an elevated level of oxidative metabolites that are normally eliminated bythe enzyme epoxide hydrolase. In this study, we attempted to determine whether infants who are at risk for congenital malformations could be identified prenatally by the measurement of epoxide hydrolase activity. Before fetuses at risk could be identified, it was necessary to measure epoxide hydrolase activity in a randomly selected sample population had an apparently trimodal distribution, suggestive of an enzyme regulated by a single gene with two allelic forms. Fetuses homozygous for the recessive allele would have low epoxide hydrolase activity and would therefore be at risk if exposed to anticonvulsant drugs during gestation. In a prospective study of 19 pregnancies monitored by aminocentesis, an adverse outcome was predicted for four fetuses on the basis of low enzyme activity (< 30 percent of the standard). In all four cases, the mother was receiving phenytoin monotherapy, and after birth the infants had clinical findings compatible with the fetal hydantoin syndrome. The 15 fetuses with enzyme activity above 30 percent of the standard were not considered to be at risk, and all 15 neonates lacked any characteristic features of the feal hydantoin syndrome. These preliminary results suggest that this enzymatic biomarker may prove useful in determining which infants are at increased risk for congenital malformations induced by anticonvulsant drugs.