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JAMA:产前服用抗癫痫药物丙戊酸钠增加儿童自闭症风险

2013-04-30 JAMA dxy

丙戊酸钠常用于癫痫及其他神经心理学障碍的治疗,而且可能是妊娠期女性的唯一治疗选择。然而,产前服用丙戊酸钠可能会增加后代患自闭症的风险。来自丹麦Aarhus 大学附属医院的Jakob Christensen博士及其同事对母亲在妊娠期间服用丙戊酸钠与其后代发生自闭症谱系疾病及儿童自闭症之间的关系进行了评估。日前,他们的研究结果发表于国际权威杂志《美国医学会杂志》2013年4月24日在线版上。研究显示,

丙戊酸钠常用于癫痫及其他神经心理学障碍的治疗,而且可能是妊娠期女性的唯一治疗选择。然而,产前服用丙戊酸钠可能会增加后代患自闭症的风险。来自丹麦Aarhus 大学附属医院的Jakob Christensen博士及其同事对母亲在妊娠期间服用丙戊酸钠与其后代发生自闭症谱系疾病及儿童自闭症之间的关系进行了评估。日前,他们的研究结果发表于国际权威杂志《美国医学会杂志》2013年4月24日在线版上。研究显示,在妊娠时母亲使用丙戊酸钠(治疗癫痫和其它神经精神疾病的药物)与其后代中自闭症风险的明显增加有关。对于使用抗癫痫药物治疗的孕期女性来说,这些发现必须要与需要用丙戊酸钠对癫痫进行控制的妇女的治疗裨益进行平衡。

这一基于人口的研究包括了从1996-2006年期间在丹麦的所有活产的孩子。全国性的登记资料被用来确认那些其母亲在怀孕期间接触过丙戊酸钠并且被诊断患有的孩子(自闭症谱系疾病包括儿童自闭症[自闭性疾病]、阿斯伯格综合症、非典型自闭症及其它的或未具体说明的广泛性发育障碍)。研究人员对数据进行了分析并用诸如父母的精神病史、胎龄、出生时体重、性别、先天畸形及产次等可能的混淆因子(即可能会影响结果的因子)对其进行了校正。研究人员从这些孩子出生时就开始对其进行追踪直到这些孩子得到自闭症谱系疾病的诊断之日、或死亡的日期、或移居外国的日期,或时间为2010年12月31日(以其中最先出现的日期为准)。试验主要结局为母亲产前服用丙戊酸钠造成儿童自闭症谱系障碍及儿童自闭症的绝对风险(累积发生率)和风险比(HR)。

这一研究分析了包括了从1996年直至2006年中出生的65. 5615万名儿童。在研究期间,有5437名儿童被诊断患有自闭症谱系疾病,其中包括2067人患有儿童自闭症。这些孩子在随访结束时的平均年龄为8.84岁(阈值, 4-14; 均值, 8.85)。估计在结束14年随访后,这些儿童患有自闭症谱系疾病的绝对风险约为1.53% (95% CI, 1.47%-1.58%),患有儿童自闭症的绝对风险为0.48% (95% CI, 0.46%-0.51%)。研究人员发现了2644个孩子在其母亲妊娠期间接触过抗癫痫药物,其中有508个孩子接触过丙戊酸钠。文章的作者发现,在妊娠期间服用丙戊酸钠与发生自闭症谱系疾病的4.42% (95% CI, 2.59%-7.46%)的绝对风险及发生儿童自闭症的2.50% (95% CI, 1.30%-4.81%)的绝对风险有关(校正后HR, 5.2 [95% CI, 2.7-10.0])。

如果仅对母亲患有癫痫症的6584例儿童进行分析,则发现其中432例暴露于丙戊酸钠的儿童患有自闭症谱系疾病的绝对风险为4.15% (95% CI, 2.20%-7.81%) (校正后HR, 1.7 [95% CI, 0.9-3.2]),患有儿童自闭症的绝对风险为2.95% (95% CI, 1.42%-6.11%) (校正后HR, 2.9 [95% CI, 1.4-6.0]),与之相比,其他未暴露于丙戊酸钠的儿童患有自闭症谱系疾病的绝对风险为2.44% (95% CI, 1.88%-3.16%),患有儿童自闭症的绝对风险为1.02% (95% CI, 0.70%-1.49%)。

妊娠期间接触抗癫痫药物与后代的先天性畸形及认知发育延迟有关,但人们对它是否会造成严重的神经精神疾病的风险则知之甚少。由于自闭症谱系疾病是对患儿及其家人具有终身影响的严重疾病,因此即使是该风险的适度增加都可能会对健康产生极大的意义。不过,发生自闭症谱系疾病的绝对风险低于5%,这是在向怀孕期妇女提供有关服用丙戊酸钠的咨询服务时需要考虑到的重要内容。”

文章的作者从这一基于人口的群组研究中得出结论,与那些怀孕期间没有服用丙戊酸钠的妇女的孩子相比,那些母亲在怀孕期间服用过丙戊酸钠的孩子具有较高的发生自闭症谱系疾病及儿童自闭症的风险,他们的风险也比那些先前服用过丙戊酸钠但在怀孕前停止服用丙戊酸钠的妇女的孩子要高。甚至在校正母亲是否患有癫痫症因素后仍显示这一趋势。对于使用抗癫痫药物治疗的孕期女性来说,这些发现必须要与需要用丙戊酸钠对癫痫进行控制的妇女的治疗裨益进行平衡。

随刊述评:

丙戊酸钠是一种用于控制癫痫发作的药物,也可用于治疗偏头痛和双向情感障碍,但这种药物可能会导致出生缺陷和智力发育延迟。亚特兰大埃默里大学神经病学教授Kimford Meador博士说,发生出生缺陷风险与怀孕早期使用丙戊酸钠有关,而发生智力发育延迟和自闭症谱系障碍的风险则更有可能源于孕晚期使用丙戊酸钠。

他补充说,在任何情况下,只有对这种药物具有遗传易感性的高危女性才会由于服药发生问题,这就解释了为什么不是所有服用丙戊酸钠孕妇的孩子都出现了出生缺陷或其他问题。

Meador说,服用丙戊酸钠的妇女还是太多了。据估计,全国每年大约有926000张开给育龄妇女的处方中包含有丙戊酸钠。Meador解释说,尽管依靠丙戊酸钠控制癫痫发作的女性只占很少一部分,但开给她们的药物剂量应当尽可能低,因为药物剂量越高,发生问题的风险越大。

Meador说,最重要的是应该让女性们懂得权衡她们所服用的任何药物的利弊。“这个并非无足轻重,医生应该告诉女性这些风险。而且,这些风险应当不只是当你计划怀孕时才考虑的,因为在美国,大约一半的怀孕属于意外怀孕。进行关于药物的谈话是在怀孕前,使用药物的原则是在控制癫痫发作的前提下,尽可能降低药物剂量,”Meador补充说,“我的方法是,首先尝试服用其他药物。”

然而,Christensen说:“一些育龄女性只有通过丙戊酸钠治疗才能控制癫痫发作。而孕期癫痫发作对于母亲和未出生的婴儿都会产生严重的影响。因此,医生和孕妇将有可能既要面对停药所导致的孕期癫痫发作的风险,又要面对胎儿药物暴露所导致的先天畸形和其他潜在不良后果的风险,他们必须在二者之间找到平衡点。此外,并非所有的怀孕都是计划好的,因此,有些孩子可能在无意中已经暴露于丙戊酸钠了。”

他注意到,近年来育龄女性服用丙戊酸钠的比例呈现下降趋势,但由于上述原因,总会有一些育龄女性不得不服用这种药物。Christensen和Meador都认为丙戊酸钠很可能是通过改变大脑神经细胞的发育来增加自闭症和自闭症谱系障碍的发病风险的。这种药物并不一定是破坏了发育中的细胞,但它一定通过某种方式使细胞间的相互作用变得困难。

虽然此项研究对孕期服用丙戊酸钠与儿童自闭症发病风险进行了关联,但并不足以确立它们之间的因果关系。
自闭相关的拓展阅读:


Prenatal Valproate Exposure and Risk of Autism Spectrum Disorders and Childhood Autism
Importance 
Valproate is used for the treatment of epilepsy and other neuropsychological disorders and may be the only treatment option for women of childbearing potential. However, prenatal exposure to valproate may increase the risk of autism.
Objective 
To determine whether prenatal exposure to valproate is associated with an increased risk of autism in offspring.
Design, Setting, and Participants 
Population-based study of all children born alive in Denmark from 1996 to 2006. National registers were used to identify children exposed to valproate during pregnancy and diagnosed with autism spectrum disorders (childhood autism [autistic disorder], Asperger syndrome, atypical autism, and other or unspecified pervasive developmental disorders). We analyzed the risks associated with all autism spectrum disorders as well as childhood autism. Data were analyzed by Cox regression adjusting for potential confounders (maternal age at conception, paternal age at conception, parental psychiatric history, gestational age, birth weight, sex, congenital malformations, and parity). Children were followed up from birth until the day of autism spectrum disorder diagnosis, death, emigration, or December 31, 2010, whichever came first.
Main Outcomes and Measures 
Absolute risk (cumulative incidence) and the hazard ratio (HR) of autism spectrum disorder and childhood autism in children after exposure to valproate in pregnancy.
Results 
Of 655 615 children born from 1996 through 2006, 5437 were identified with autism spectrum disorder, including 2067 with childhood autism. The mean age of the children at end of follow-up was 8.84 years (range, 4-14; median, 8.85). The estimated absolute risk after 14 years of follow-up was 1.53% (95% CI, 1.47%-1.58%) for autism spectrum disorder and 0.48% (95% CI, 0.46%-0.51%) for childhood autism. Overall, the 508 children exposed to valproate had an absolute risk of 4.42% (95% CI, 2.59%-7.46%) for autism spectrum disorder (adjusted HR, 2.9 [95% CI, 1.7-4.9]) and an absolute risk of 2.50% (95% CI, 1.30%-4.81%) for childhood autism (adjusted HR, 5.2 [95% CI, 2.7-10.0]). When restricting the cohort to the 6584 children born to women with epilepsy, the absolute risk of autism spectrum disorder among 432 children exposed to valproate was 4.15% (95% CI, 2.20%-7.81%) (adjusted HR, 1.7 [95% CI, 0.9-3.2]), and the absolute risk of childhood autism was 2.95% (95% CI, 1.42%-6.11%) (adjusted HR, 2.9 [95% CI, 1.4-6.0]) vs 2.44% (95% CI, 1.88%-3.16%) for autism spectrum disorder and 1.02% (95% CI, 0.70%-1.49%) for childhood autism among 6152 children not exposed to valproate.
Conclusions and Relevance 
Maternal use of valproate during pregnancy was associated with a significantly increased risk of autism spectrum disorder and childhood autism in the offspring, even after adjusting for maternal epilepsy. For women of childbearing potential who use antiepileptic medications, these findings must be balanced against the treatment benefits for women who require valproate for epilepsy control.

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    2013-05-04 XiaoSHuang1126

    准备要小孩的应该看看 为了自己和家人的健康 还是要慎重使用药物

    0

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  5. [GetPortalCommentsPageByObjectIdResponse(id=2009361, encodeId=2e8b2009361b6, content=<a href='/topic/show?id=df47284508e' target=_blank style='color:#2F92EE;'>#儿童自闭症#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=90, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=28450, encryptionId=df47284508e, topicName=儿童自闭症)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4c37265, createdName=hb2008ye, createdTime=Thu Nov 28 02:30:00 CST 2013, time=2013-11-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1716006, encodeId=9a161e16006c7, content=<a href='/topic/show?id=a4175555e85' target=_blank style='color:#2F92EE;'>#抗癫痫#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=107, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=55557, encryptionId=a4175555e85, topicName=抗癫痫)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=695a32117432, createdName=shuangle, createdTime=Thu Apr 03 18:30:00 CST 2014, time=2014-04-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=5685, encodeId=cc6b568524, content=准备要小孩的应该看看 为了自己和家人的健康 还是要慎重使用药物 <br> , beContent=null, objectType=article, channel=null, level=null, likeNumber=161, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=bc1580659, createdName=XiaoSHuang1126, createdTime=Sat May 04 14:32:00 CST 2013, time=2013-05-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1414688, encodeId=0cd81414688b9, content=<a href='/topic/show?id=94a85555919' target=_blank style='color:#2F92EE;'>#抗癫痫药物#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=91, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=55559, encryptionId=94a85555919, topicName=抗癫痫药物)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=05ca3082114, createdName=mgqwxj, createdTime=Thu May 02 04:30:00 CST 2013, time=2013-05-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1502440, encodeId=d7ec150244067, content=<a href='/topic/show?id=ef4b2441971' target=_blank style='color:#2F92EE;'>#产前#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=79, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=24419, encryptionId=ef4b2441971, topicName=产前)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=b49a9545081, createdName=qilu_qi, createdTime=Thu May 02 04:30:00 CST 2013, time=2013-05-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1507572, encodeId=5e55150e57226, content=<a href='/topic/show?id=adee2090e8b' target=_blank style='color:#2F92EE;'>#丙戊酸#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=72, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=20907, encryptionId=adee2090e8b, topicName=丙戊酸)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=46789929366, createdName=steven_u5, createdTime=Thu May 02 04:30:00 CST 2013, time=2013-05-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1527531, encodeId=c1f1152e531a7, content=<a href='/topic/show?id=68b5863e5d2' target=_blank style='color:#2F92EE;'>#自闭#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=71, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=86375, encryptionId=68b5863e5d2, topicName=自闭)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=159511872623, createdName=xiongke014, createdTime=Thu May 02 04:30:00 CST 2013, time=2013-05-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1548218, encodeId=51ca15482182f, content=<a href='/topic/show?id=2222209098f' target=_blank style='color:#2F92EE;'>#丙戊酸钠#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=72, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=20909, encryptionId=2222209098f, topicName=丙戊酸钠)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=41c714051691, createdName=12498f17m70暂无昵称, createdTime=Thu May 02 04:30:00 CST 2013, time=2013-05-02, status=1, ipAttribution=)]
    2013-05-02 qilu_qi
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  7. [GetPortalCommentsPageByObjectIdResponse(id=2009361, encodeId=2e8b2009361b6, content=<a href='/topic/show?id=df47284508e' target=_blank style='color:#2F92EE;'>#儿童自闭症#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=90, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=28450, encryptionId=df47284508e, topicName=儿童自闭症)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4c37265, createdName=hb2008ye, createdTime=Thu Nov 28 02:30:00 CST 2013, time=2013-11-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1716006, encodeId=9a161e16006c7, content=<a href='/topic/show?id=a4175555e85' target=_blank style='color:#2F92EE;'>#抗癫痫#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=107, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=55557, encryptionId=a4175555e85, topicName=抗癫痫)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=695a32117432, createdName=shuangle, createdTime=Thu Apr 03 18:30:00 CST 2014, time=2014-04-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=5685, encodeId=cc6b568524, content=准备要小孩的应该看看 为了自己和家人的健康 还是要慎重使用药物 <br> , beContent=null, objectType=article, channel=null, level=null, likeNumber=161, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=bc1580659, createdName=XiaoSHuang1126, createdTime=Sat May 04 14:32:00 CST 2013, time=2013-05-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1414688, encodeId=0cd81414688b9, content=<a href='/topic/show?id=94a85555919' target=_blank style='color:#2F92EE;'>#抗癫痫药物#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=91, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=55559, encryptionId=94a85555919, topicName=抗癫痫药物)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=05ca3082114, createdName=mgqwxj, createdTime=Thu May 02 04:30:00 CST 2013, time=2013-05-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1502440, encodeId=d7ec150244067, content=<a href='/topic/show?id=ef4b2441971' target=_blank style='color:#2F92EE;'>#产前#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=79, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=24419, encryptionId=ef4b2441971, topicName=产前)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=b49a9545081, createdName=qilu_qi, createdTime=Thu May 02 04:30:00 CST 2013, time=2013-05-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1507572, encodeId=5e55150e57226, content=<a href='/topic/show?id=adee2090e8b' target=_blank style='color:#2F92EE;'>#丙戊酸#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=72, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=20907, encryptionId=adee2090e8b, topicName=丙戊酸)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=46789929366, createdName=steven_u5, createdTime=Thu May 02 04:30:00 CST 2013, time=2013-05-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1527531, encodeId=c1f1152e531a7, content=<a href='/topic/show?id=68b5863e5d2' target=_blank style='color:#2F92EE;'>#自闭#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=71, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=86375, encryptionId=68b5863e5d2, topicName=自闭)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=159511872623, createdName=xiongke014, createdTime=Thu May 02 04:30:00 CST 2013, time=2013-05-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1548218, encodeId=51ca15482182f, content=<a href='/topic/show?id=2222209098f' target=_blank style='color:#2F92EE;'>#丙戊酸钠#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=72, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=20909, encryptionId=2222209098f, topicName=丙戊酸钠)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=41c714051691, createdName=12498f17m70暂无昵称, createdTime=Thu May 02 04:30:00 CST 2013, time=2013-05-02, status=1, ipAttribution=)]
    2013-05-02 xiongke014
  8. [GetPortalCommentsPageByObjectIdResponse(id=2009361, encodeId=2e8b2009361b6, content=<a href='/topic/show?id=df47284508e' target=_blank style='color:#2F92EE;'>#儿童自闭症#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=90, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=28450, encryptionId=df47284508e, topicName=儿童自闭症)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4c37265, createdName=hb2008ye, createdTime=Thu Nov 28 02:30:00 CST 2013, time=2013-11-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1716006, encodeId=9a161e16006c7, content=<a href='/topic/show?id=a4175555e85' target=_blank style='color:#2F92EE;'>#抗癫痫#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=107, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=55557, encryptionId=a4175555e85, topicName=抗癫痫)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=695a32117432, createdName=shuangle, createdTime=Thu Apr 03 18:30:00 CST 2014, time=2014-04-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=5685, encodeId=cc6b568524, content=准备要小孩的应该看看 为了自己和家人的健康 还是要慎重使用药物 <br> , beContent=null, objectType=article, channel=null, level=null, likeNumber=161, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=bc1580659, createdName=XiaoSHuang1126, createdTime=Sat May 04 14:32:00 CST 2013, time=2013-05-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1414688, encodeId=0cd81414688b9, content=<a href='/topic/show?id=94a85555919' target=_blank style='color:#2F92EE;'>#抗癫痫药物#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=91, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=55559, encryptionId=94a85555919, topicName=抗癫痫药物)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=05ca3082114, createdName=mgqwxj, createdTime=Thu May 02 04:30:00 CST 2013, time=2013-05-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1502440, encodeId=d7ec150244067, content=<a href='/topic/show?id=ef4b2441971' target=_blank style='color:#2F92EE;'>#产前#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=79, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=24419, encryptionId=ef4b2441971, topicName=产前)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=b49a9545081, createdName=qilu_qi, createdTime=Thu May 02 04:30:00 CST 2013, time=2013-05-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1507572, encodeId=5e55150e57226, content=<a href='/topic/show?id=adee2090e8b' target=_blank style='color:#2F92EE;'>#丙戊酸#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=72, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=20907, encryptionId=adee2090e8b, topicName=丙戊酸)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=46789929366, createdName=steven_u5, createdTime=Thu May 02 04:30:00 CST 2013, time=2013-05-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1527531, encodeId=c1f1152e531a7, content=<a href='/topic/show?id=68b5863e5d2' target=_blank style='color:#2F92EE;'>#自闭#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=71, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=86375, encryptionId=68b5863e5d2, topicName=自闭)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=159511872623, createdName=xiongke014, createdTime=Thu May 02 04:30:00 CST 2013, time=2013-05-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1548218, encodeId=51ca15482182f, content=<a href='/topic/show?id=2222209098f' target=_blank style='color:#2F92EE;'>#丙戊酸钠#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=72, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=20909, encryptionId=2222209098f, topicName=丙戊酸钠)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=41c714051691, createdName=12498f17m70暂无昵称, createdTime=Thu May 02 04:30:00 CST 2013, time=2013-05-02, status=1, ipAttribution=)]
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