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产前地塞米松治疗21-羟化酶缺乏症的长期预后。

Long-term outcome of prenatal dexamethasone treatment of 21-hydroxylase deficiency.

作者信息

Lajic Svetlana, Nordenström Anna, Hirvikoski Tatja

出版信息

Endocr Dev. 2011;20:96-105. doi: 10.1159/000321228. Epub 2010 Dec 16.

Abstract

Prenatal treatment of congenital adrenal hyperplasia (CAH) with dexamethasone (DEX) has been in use since the mid- 1980s. Its effectiveness for reducing virilization of external genitalia is well established. DEX treatment has to be started in the 6th-7th postmenstrual week and continued until the results of the prenatal diagnosis are available. Hence, the dilemma is that 7 out of 8 fetuses (boys and unaffected girls) are treated unnecessarily. Girls with CAH are treated until term. Accumulating evidence from animal studies and follow-up data has raised concerns regarding the long-term consequences of this controversial treatment. We have previously reported that direct neuropsychological assessment of children exposed to DEX and controls show normal full-scale IQ, learning and longterm memory. However, the children exposed to DEX during the first trimester had an impaired verbal working memory which was significantly associated with low self-perceived scholastic competence. In addition, the children showed increased self-rated social anxiety. The same cohort of children answered questions concerning friends, activities and gender-related behaviors. The results indicate less masculine and more neutral behavior in short-term DEX-exposed boys. These findings indicate that long-term follow-ups of this group of patients are of extreme importance and that future DEX treatment of CAH may be questioned. We therefore encourage additional studies on larger cohorts in order to draw more decisive conclusions about the safety of the treatment. Until then, it is important that the parents are thoroughly informed about the potential risks and uncertainties, as well as the benefits, of this treatment.

摘要

自20世纪80年代中期以来,地塞米松(DEX)一直用于先天性肾上腺皮质增生症(CAH)的产前治疗。其在减少外生殖器男性化方面的有效性已得到充分证实。DEX治疗必须在月经周期后的第6 - 7周开始,并持续到产前诊断结果出来。因此,两难的是8个胎儿中有7个(男孩和未受影响的女孩)接受了不必要的治疗。患有CAH的女孩会接受治疗直至足月。来自动物研究和随访数据的越来越多的证据引发了人们对这种有争议治疗的长期后果的担忧。我们之前报道过,对暴露于DEX的儿童和对照组进行直接神经心理学评估显示,他们的全量表智商、学习和长期记忆正常。然而,在孕早期暴露于DEX的儿童存在言语工作记忆受损的情况,这与自我感知的学业能力较低显著相关。此外,这些儿童的自我评定社交焦虑增加。同一组儿童回答了有关朋友、活动和与性别相关行为的问题。结果表明,短期暴露于DEX的男孩表现出较少的男性化行为和更中性的行为。这些发现表明,对这组患者进行长期随访极为重要,并且未来CAH的DEX治疗可能会受到质疑。因此,我们鼓励对更大规模的队列进行更多研究,以便就该治疗的安全性得出更具决定性的结论。在此之前,重要的是要让家长充分了解这种治疗的潜在风险、不确定性以及益处。

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