本帖最後由 lsc0019 於 2009-5-24 21:39 編輯
作者：Caroline Cassels
出處：WebMD醫學新聞
May 7, 2009（西雅圖）－一項大型觀察性研究初期分析數據顯示，在子宮內暴露到抗癲癇藥物valproate（Depakote、Depakote ER、Depakine、Depacon，亞培藥廠）可能會增加兒童發生癲癇風險。然而，研究者提醒，這項研究結果並未達到統計上顯著差異，且在初期階段，研究的價值在於推動其他研究的進行。
這項來自抗癲癇藥物對神經發展效應（NEAD）研究的最新發現，是一項多中心、觀察性前瞻性研究，比較母體接受四種最常見的抗癲癇藥物，包括lamotrigine（Lamictal，格蘭素史克藥廠）、carbamazepine（Carbatrol，Shire藥廠；Equetro，Validus藥廠；Tegretol、Tegretol XR，諾華藥廠）、phenytoin與valproate，對神經發展的效應，這項研究結果發表在美國神經醫學會第61屆年會上。
來自喬治亞洲亞特蘭大Emory大學的主要研究者Kimford J. Meador醫師向Medscape神經學與神經外科學表示，在子宮內暴露到valproate的兒童發生癲癇的可能性似乎較高，是暴露到carbamazepine、phenytoin或是lamotrigine的2至3倍。但是我們在判讀這項研究結果時必須十分地小心，因為該樣本數目非常的少、且並未達到統計上顯著差異。
【在動物實驗中，抗癲癇藥物與神經遷移異常有關】
來自NEAD研究最近發表的數據顯示，valproate對兒童的認知功能發展有負面影響，相較於其他抗癲癇藥物，這些兒童在三歲時的IQ分數顯著較低。
眾所週知，在懷孕時喝酒會造成胎兒腦神經細胞死亡，造成認知功能受損。在動物實驗中，其他的抗癲癇藥物也有這樣的作用。進一步的，最近的動物實驗指出，在子宮中暴露到特定藥物，包括抗癲癇藥物，例如phenytoin或是valproate，也會造成發展中腦部神經遷移發生異常。當這種腦部神經遷移異常發生在人類時，可能造成神智發展遲緩或是癲癇。
Meador醫師表示，我對於暴露在特定藥物是否對癲癇發作帶來差異、或是在這方面我們是否可以觀察到一些模式感到興趣。
【母體癲癇種類之間並無差異】
研究者檢驗311位4歲兒童的癲癇發作頻率，這些兒童自罹患癲癇的母體生產而來，癲癇的種類包括局部相關、先天性全身性、或是全身性張力性收縮性癲癇發作（GTCS），以及特定抗癲癇藥物。
從整個族群來看，188位女性有局部相關癲癇發作、99位有先天性全身性癲癇、24位有GTCS。自罹患局部相關癲癇與先天性全身性癲癇母體產下的兒童癲癇發作率分別為5.3%（10）與5.1%（5）。母體罹患GTCS的兒童沒有癲癇發作的狀況。
分別有94、100、55與62位女性服用carbamazepine、lamotrigine、phenytoin與valproate。母體使用carbamazepine產下的兒童發生癲癇機率為4.3%、lamotrigine則是3.0%、phenytoin為3.6%以及valproate的9.7%。
根據Meador醫師表示，這項研究的樣本數目太小，不足以做出任何確切的結論；但研究結果值得後續研究確認。
Meador醫師表示，我要讓這些議題浮上檯面，讓其他研究者們會考慮在不同資料庫、不同族群中尋找相似的訊號。
這項研究由國家衛生研究院、國家神經疾患與中風機構贊助。Meader醫師表示擔任亞培藥廠、Cyberonics、Eisai與葛蘭素史克藥廠、Neuropace、諾華藥廠、Ortho McNeil與UCB公司的顧問，但是沒有從這些個人活動中獲取收入。
AAN 2009: In Utero Exposure to Valproate a Possible Contributor to Children's Seizure Risk?
By Caroline Cassels
Medscape Medical News
May 7, 2009 (Seattle, Washington) — A preliminary analysis from a large, observational study suggests there may be an increased risk for seizures among children with in utero exposure to the antiepileptic drug valproate (Depakote, Depakote ER, Depakene, Depacon, Abbott Laboratories). However, researchers caution, the results are not statistically significant, and at this early stage their only value is to serve as an impetus for further research.
These latest findings from the Neurodevelopmental Effects of Antiepileptic Drugs (NEAD) study, a multicenter, observational, prospective study comparing neurodevelopmental effects of maternal monotherapy with 4 of the most commonly prescribed antiepileptic drugs — lamotrigine (Lamictal, GlaxoSmithKline), carbamazepine (Carbatrol, Shire; Equetro, Validus; Tegretol, Tegretol XR, Novartis), phenytoin, and valproate — were presented here at the American Academy of Neurology 61st Annual Meeting.
"There seemed to be higher instance of seizures in children that were exposed in utero to valproate that was 2 to 3 times greater than with carbamazepine, phenytoin, or lamotrigine. But we have to be extremely cautious in the interpretation of this finding, because the numbers are very small and not statistically significant," principal investigator Kimford J. Meador, MD, from Emory University, in Atlanta, Georgia, told Medscape Neurology & Neurosurgery.
Antiepileptic Drugs Linked to Neuronal Migration Disorders in Animals
Recently published results from the NEAD study showed that valproate has an adverse effect on children's cognitive development, with significantly lower IQ scores at 3 years of age than each of the other antiepileptic drugs.
It is well-recognized that alcohol consumption during pregnancy can cause death of brain nerve cells in the fetus, resulting in impaired cognition. In animals, a similar effect has been found for some antiepileptic drugs. Further, recent animal research indicates that in utero exposure to certain medications, including antiepileptic drugs such as phenytoin and valproate, can also produce disorders of neuronal migration in the developing brain. When neuronal migration disorders occur in humans, they can result in mental retardation or epilepsy.
"I was interested in whether there might be some difference in seizures as a function of the drug exposure and to see whether we saw any pattern in that regard," said Dr. Meador.
No Difference by Maternal Seizure Type
Investigators examined seizure frequency in 311 four-year-old children born to women with epilepsy based on broad categories of seizure type, including localization-related, idiopathic generalized, or generalized tonic-clonic seizures (GTCS), as well as specific antiepileptic drug medication.
Of the total group, 188 women had localization-related epilepsy, 99 had idiopathic generalized seizures, and 24 had GTCS. The seizure rate in children whose mothers had localization-related epilepsy and idiopathic generalized seizures was 5.3% (10) and 5.1% (5), respectively. None of the children whose mothers had GTCS had seizures.
A total of 94, 100, 55, and 62 women were taking monotherapy with carbamazepine, lamotrigine, phenytoin, and valproate, respectively. Seizure frequency in the children was 4.3% for carbamazepine, 3.0% for lamotrigine, 3.6% for phenytoin, and 9.7% for valproate.
According to Dr. Meador, the sample size is far too small to be able to draw any definitive conclusions. However, he said, the findings warrant further study.
"I wanted to bring these findings to light so that other researchers would consider this and possibly look for similar signals in different data sets in different cohorts," said Dr. Meador.
The study is supported by the National Institutes of Health and the National Institute of Neurological Disorders and Stroke. Dr. Meador discloses that he has served as a consultant for Abbott, Cyberonics, Eisai, GlaxoSmithKline, Neuropace, Novartis, Ortho McNeil, and UCB but receives no personal income from these activities.
American Academy of Neurology 61st Annual Meeting: Abstract S16.005. April 28, 2009. |
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