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BIOL PSYCHIAT :胎盘异常或可预测自闭症风险

2013-05-15 Biological Psychiatry 生物360

婴儿生下来后,完成了养育和支持胎儿发育作用的胎盘通常就被扔掉了。然而一项新研究表明,分析产后胎盘也许能为推测儿童将来是否患自闭症提供线索。在观察了217个胎盘后,研究者发现:那些出生在自闭症遗传风险较高的家庭中的新生儿,其胎盘上特别有可能出现异常折痕与皱褶。研究发表在《生物精神病学》(Biological Psychiatry)杂志上。“这一点特别明显,”该研究的合作者、加州大学戴维斯分校(Uni

胎盘异常或可预测自闭症风险

婴儿生下来后,完成了养育和支持胎儿发育作用的胎盘通常就被扔掉了。

然而一项新研究表明,分析产后胎盘也许能为推测儿童将来是否患自闭症提供线索。在观察了217个胎盘后,研究者发现:那些出生在自闭症遗传风险较高的家庭中的新生儿,其胎盘上特别有可能出现异常折痕与皱褶。研究发表在《生物精神病学》(Biological Psychiatry)杂志上。

“这一点特别明显,”该研究的合作者、加州大学戴维斯分校(University of California, Davis)神经发育障碍研究所(MIND institute)妇产科医生谢莉尔· K·沃克尔(Cheryl K. Walker)说:“自闭风险高的新生儿,他们的胎盘明显不寻常。”

至少在明年之前,研究者还无法知道在这些胎盘被分析过的2-5岁儿童中,有多少会患上自闭症。不过专家说,研究者如果发现自闭症儿童出生时,胎盘上可见很多皱折——滋养层夹杂物,那么这种情况就可视为自闭高危儿童的早期指标或生物标记。

“有一个真正的生物标记,特别是在出生时就能获得,实在是令人兴奋,”费城儿童医院(Children’s Hospital of Philadelphia)自闭症研究中心研究员塔拉·温格(Tara Wenger)博士说道。(她没有参与该实验。)

这项新研究很可能不只为自闭症研究,也为胎盘——长期被当做产后附带品——的重要性开拓了一片新的领域。现在,仅仅10%-15%的胎盘被分析过,还往往是由于妊娠并发症或新生儿死亡的缘故。

研究的首席作者、耶鲁医学院(Yale School of Medicine)研究员哈维·J·克里曼(Harvey J. Kliman)博士说,在医学界,胎盘通常是很不被重视的,想研究胎盘就像海军士兵想用牙刷洗战舰上的马桶一样。但是,克里曼对胎盘有很大兴趣,他发现夹杂物总是与有问题的生育相关,而且经常是遗传病。

他还注意到“滋养层夹杂物越多,问题越严重”。2006年,克里曼博士和同事发表了一项以13名自闭症儿童为对象的研究。他们发现,这些儿童的胎盘含有夹杂物的可能性是普通胎盘的三倍。这次的新研究是从克里曼博士联系神经发育障碍研究所开始。研究所正进行着一项名为“Marbles”(全名Markers of Autism Risk in Babies:婴儿自闭症风险标记——译注)的广泛研究,考察可能引发自闭症的因素。克里曼想要寻找更多的胎盘。

“不知道从哪儿冒出来这么个人,说‘我要研究滋养层夹杂物’,”沃克尔医生回忆道,“我算是挺聪明的,当产科医生也很多年了,可从来没听说过这个东西。”

沃克尔医生说,她当时下的结论是:“尽管听起来像是个很有脑子的人提了一个很吸引人的假说,可我不了解他,也不知道该信他多少。”所以她给了他217个巧克力棒大小的胎盘,并告诉他这些胎盘都来自于高自闭风险婴儿(他们的哥哥或姐姐患有自闭症)。就在克里曼博士清点完每个胎盘的夹杂物后,沃克尔告诉他:只有117个胎盘来自高危婴儿;另外100个来自低自闭风险婴儿。

她的解释是:如果克里曼发现“所有胎盘都有很多夹杂物,那么他恐怕只是热心过头”,想在夹杂物和自闭症之间建立联系。然而,她说结果“令人震惊”。三分之二以上的低风险胎盘无任何夹杂物,且没有一个是含有两个以上夹杂物的。但是,77个高危胎盘都有夹杂物,其中48个含有两个以上,还有16个胎盘有五到15个夹杂物。

沃克尔称,通常2%-7%的高自闭症风险婴儿会最终发展成自闭症;20%-25%或自闭、或出现其他发育迟滞。她说她认为,那117个高危婴儿在未来,将会有些被诊断为自闭症,而有些则没有,但仍不清楚这些诊断与胎盘夹杂物之间的关系。

哈佛医学院(Harvard Medical School)病理学副教授乔纳森·L·赫克特(Jonathan L. Hecht)博士说,这个研究是很有意思的,并且“它找出的滋养层夹杂物与自闭症的关系有可能是正确的”。不过他又说,夹杂物是胎盘的应激方式,所以它们在预测自闭症方面也许特异性不足。

克里曼博士称夹杂物为“发动机警示灯”,“标志着:有点儿不对劲,但不知是什么。”

这也是克里斯·曼·沙利文(Chris Mann Sullivan)的看法。沙利文博士是北卡罗来纳州摩力斯维尔的一名行为分析师,他没有参加上述研究,但他把三岁女儿达尼亚(Dania)出生时的胎盘寄给了克里曼博士。克里曼找出了五个夹杂物。沙利文开始对达尼亚实行一对一强化治疗。达尼亚未被诊断为自闭,但已显露出一些相对轻微的发育障碍。

“假如我什么都不做,那会发生什么?我不清楚,”沙利文博士说:“我觉得对于家长而言最好是‘好吧,我们知道存在一定风险因素,我们不能坐视不理’。”

胎盘相关的拓展阅读:


Background
Gestation is a critical window for neurodevelopmental vulnerability. This study examined whether the presence of trophoblast inclusions (TIs) in the placenta could serve as a predictor for children at elevated risk for autism spectrum disorder (ASD).
Methods
Placentas were obtained from 117 births in the MARBLES (Markers of Autism Risk in Babies—Learning Early Signs) cohort of families who have one or more previous biological children with ASD, placing their newborn at elevated risk for neurodevelopmental compromise. Control samples were obtained from 100 uncomplicated term pregnancies of multiparous women with one or more typically developing biological children. Frequency of TIs was compared across the two groups.
Results
Placentas from at-risk pregnancies had an eightfold increased odds of having two or more TIs compared with control samples (odds ratio: 8.0, 95% confidence interval: 3.6–18.0). The presence of≥2 TIs yielded a sensitivity of 41% and a specificity of 92% for predicting ASD risk status, whereas≥4 TIs yielded a sensitivity of 19%, a specificity of 99.9%, and a positive likelihood ratio of 242 and conservatively predicted an infant with a 74% probability of being at risk for ASD.
Conclusions
Our findings suggest that the placentas from women whose fetuses are at elevated risk for autism are markedly different from control placentas. These differences are manifested histologically as TIs. Their identification has the possibility of identifying newborns at risk for ASD who might benefit from targeted early interventions aimed at preventing or ameliorating behavioral symptoms and optimizing developmental outcomes.

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    2013-05-29 sunylz
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    2013-05-17 xiongke014
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