典型先天性腎上腺皮質增生及產前Dexamethasone治療之臨床效益與風險

Clinical Benefits and Risks of Prenatal Treatment by Dexamethasone in Individuals with Typical Congenital Adrenal Hyperplasia

吳雅惠(Ya-Hui Wu) ； 蕭如君(Ju-Chun Shiao) ； 許凱倫(Kai-Lun Sheu) ； 李建瑩(Chien-Ying Lee)

《臺灣臨床藥學雜誌》 22卷3期 (2014/09) Pp. 167-173

https://doi.org/10.6168/FJCP.2014.2203.05

摘要

先天性腎上腺皮質增生（Congenital Adrenal Hyperplasia, CAH）是新生兒很常見的遺傳疾病，典型CAH ＞ 95%乃因人體腎上腺皮質生合成路徑中缺乏酵素21-hydroxylase，造成生合成cortisol的功能不良，路徑改往雄性素方向進行。CAH會導致新生女嬰外部生殖器男性化，若能在懷孕初期給予dexamethasone治療可有效預防或降低女嬰外部生殖器男性化的表現。根據目前有限的研究指出，懷孕初期即給予dexamethasone治療，確實減低了CAH對女嬰所造成的外生殖器雄性化的影響，對於母親可能會造成食慾、紋路增加、水腫等副作用，長期重大的副作用目前研究尚無發現。統合分析文獻中並未發現產前治療有增加死產、母親自發性流產、胎兒畸形、神經心理性疾病或影響發育等結果。在評估孩童行為問題的檢視表中，投予dexamethasone相較於未投予者並無統計學上差異。至於暴露於dexamethasone下長期追蹤對孩童物理性及代謝性方面的影響則仍無相關資料。目前研究證據看來dexamethasone對減低女胎性徵不明是有顯著相關的，對母體與胎兒似乎也未帶來顯著重大副作用，至於一開始的醫療決策仍首要尊重胎兒雙親的價值觀及喜好，提供全面評估的相關資訊，以決定個別化的醫療決策。

關鍵字

先天性腎上腺皮質增生 ； 性器官不明 ； 產前治療

並列摘要

Congenital adrenal hyperplasia (CAH) is a very common hereditary disease in neonate. Typical CAH ＞ 95% is due to lack of the enzyme 21-hydroxylase during biosynthesis of adrenal androgen, which leads to an increase in androgenic hormones. CAH will result in virilization of a female fetus. It has been well documented that if prenatal dexamethasone treatment is performed at early stage of gestation, preferably before 9-week of gestation, external ambiguous genitalia can effectively be reduced or even prevented. Furthermore, there is no study clearly indicating severe side effects such as increased appetite, presence of edema and apparent striae on pregnant women undergoing dexamethasone treatment. The results of meta-analysis found that there is no increased risk in stillbirths, and that spontaneous abortions, fetal malformations, neuropsychological problems and impaired postnatal growth are negligible in pregnancies associated with exposure to dexamethasone. The conduction of Emotion-allity-Activity- Sociability-Shyness (EAS) temperament survey for children showed no statistical differences between internalized and externalized behavioral problems in dexamethasone-exposed pregnancies. There is currently no information regarding the long-term effects of children's physical and metabolic outcomes following dexamethasone -exposed pregnancies. To date the use of dexamethasone in the treatment of CAH by suppressing adrenal androgen production in female fetuses seems effective and safe in reducing or even preventing the development of ambiguous genitalia. This therapy has also been proven to be safe for most pregnant women. Nevertheless, due to limited data currently available, additional studies are needed to make more decisive conclusions on the safety of this treatment. It is also necessary that medical ethics and possible adverse effects related to prenatal use of dexamethasone for CAH should be thoroughly reviewed and discussed between the parents and physician before any final decision is made.

並列關鍵字

Congenital Adrenal Hyperplasia ； Ambiguous Genitalia ； Dexamethasone ； Prenatal Treatment