生育大事件：准妈妈滴血可查胎儿基因

    美国每年都会迎来大约400万名新生婴儿的诞生，他们的母亲在产前都会接受同一套产检流程：验血、验尿，分析血压、体重、血糖，甚至是基因组，以测定胎儿是否有患上遗传疾病的风险。一般来说，医生总是通过母亲来测定体内胎儿的健康状况，只有超声波造影是个例外。而这种技术并不完全精确。

    但是如果现在有了新的方法让准爸爸、准妈妈们在产前了解更多关于胎儿的健康状况，他们是否会乐意呢？如果只需要准妈妈的一滴血，就可以知道关于胎儿的大量信息，甚至包括胎儿的整个基因组及其隐含的所有信息，准爸爸、准妈妈们会愿意接受这种检查吗？答案显而易见。有几家专门从事医疗诊断的公司也是这样想的。过去一两年里，他们推出的新一代非侵入式产前检查技术（NIPT）已经全然改变了医生们做孕检的方式。光是在美国，这项技术每年就为400万准妈妈们带来了福音。

    非侵入式产前检查技术来自最近的一项科研成果：一个怀孕的准妈妈的血液内存在大量胎儿的DNA片段，它们在胎盘细胞死亡和脱落之后游离进入母亲的血液中。这些DNA片段又叫游离DNA，之所以这样命名，是因为这些DNA并非存在于一个完整的胎儿细胞的原子核中，而是在母体的血液中游荡。它们可以从母亲自己的DNA中鉴定和分离出来。事实证明，在一个准妈妈的循环系统的所有游离DNA中，胎儿的游离DNA所占的比例可能高达20%。当然，目前也有其它可以获得胎儿DNA数据的技术，比如羊水穿刺，或是胎儿绒毛采样等，但是这些技术必须通过物理手段侵入到胎儿附近（通常是通过针或管子），而这会加大流产和并发感染的风险。而NIPT技术的优点就在于，只需要准妈妈的一滴血样，就可以获得胎儿的基因以及其中包含的所有染色体信息。

    虽然游离DNA早在15年前就被发现了，但是这门基因技术却没有很快获得实际应用。随着基因技术的快速发展，这种情况一直到过去10年里才有所改变。现在，非侵入性测试已经可以拼凑出胎儿的完整基因组，并通过这些基因数据测定婴儿是否有患上遗传病或畸型的风险——比如性染色体异常、唐氏综合症以及许多其它发育问题。早期实验显示，这种测试非常可靠，因此好几家公司都在争做NIPT领域的第一代领头羊，其中包括Verinata【由亿明达公司（Illumina）所有】、西格诺（Sequenom）、Natera、Ariosa Diagnostics和Ravgen等公司。他们相信，自己的测试技术将在未来两三年里成为一种标准的、常规的产前检查技术。

    国际战略投资集团（International Strategy and Investing Group）的医疗分析师兼常务副董事维杰•库玛尔说：“NIPT只需要取一滴血样。一旦用NIPT这种简单的技术取代了羊水穿刺等技术，人们无疑就会选择它。但是接下来就是成本的问题了。考虑到目前的医疗环境，这种讨论会变得更艰难。”

    事实也的确如此，目前NIPT技术的最大阻碍不是技术本身而是其成本。这种测试的价格相对比较昂贵，即使是低端测试也需要800美元，更贵的高端检查方法需要将近3,000美元。Sequenom、Natera和Ariosa Diagnostics这三家公司正因为专利打诉讼战，让人搞不清楚哪些技术到底是哪家公司的（更不用说各方的开支都有所增加）。而且这种技术对保险公司来说也太新了，虽然他们已经认识到了NIPT技术在预防方面的好处，但是他们还没决定是否要给这种测试提供报销，采用什么方式报销。

    Every year, the U.S. welcomes 4 million new babies into the world, the result of roughly 4 million pregnancies that in large part go through the same battery of prenatal health checks 4 million times: analyses of the mother's blood and urine, of the mother's blood pressure, of the mother's weight, of the mother's blood sugar -- even of the mother's genetic makeup if she's deemed a risk for certain inheritable disorders. Ultrasound imaging being the obvious exception, doctors generally measure an unborn baby's health via the mother -- a kind of science by proxy that offers only a rough approximation of the baby's developmental health.

    But if parents could know more about their child's health before birth, wouldn't they want to? And if a bounty of health information -- even the unborn child's entire genome and all the data contained therein -- could be accessed via nothing more than a simple blood draw from the mother, wouldn't parents want to have that option? A handful of medical diagnostics companies think so, and a new generation of non-invasive prenatal tests (NIPT) they have brought to market over the past couple of years have positioned them to completely transform the way clinicians perform routine prenatal care -- a full 4 million times annually in the U.S. alone.

    NIPT technology rests on the fairly recent discovery that a pregnant mother's blood is practically swimming with fragments of her baby's DNA, deposited there as cells from the placenta die and break down. This cell-free DNA -- so named because it is not contained within the nucleus of a complete fetal cell, but rather floats free in the mother's bloodstream -- can be identified and isolated from the mother's own DNA (it turns out cell-free fetal DNA can make up as much as 20% of the free-floating DNA in a pregnant mother's circulatory system). There are other ways to access fetal DNA of course -- Amniocentesis for instance, or the more accurate chorionic villus sampling (or CVS) test -- but these require a physical incursion into the neighborhood of the fetus itself (usually via a long needle or tube) which ups the risk of miscarriage and pregnancy-complicating infections. That's the beauty of NIPT: A sample of maternal blood, a simple blood draw, is all that's needed to access the fetal genome and all the chromosomal information it contains.

    When cell-free DNA was discovered about 15 years ago, the science of genetics was not yet far enough along to make much practical use of it, but with the rapid advancement of genetic science over the past decade that's changed. Non-invasive tests can now piece together entire fetal genomes and mine that genetic information for indicators of various disorders and abnormalities that can lead to health problems later on -- things like sex chromosome abnormalities, Down syndrome, and a host of other developmental disorders. Initial trials have shown the tests to be so reliable that executives at more than one company vying for the lead in the nascent NIPT space -- companies that include Verinata (owned by Illumina (ILMN)), Sequenom (SQNM), Natera, Ariosa Diagnostics, and Ravgen -- believe their tests will become a standard, routine part of prenatal care in the next two or three years.

    "When you offset something like amniocentesis against NIPT -- which is as simple as taking a blood sample -- it becomes a no-brainer," says Vijay Kumar, a health care analyst and associate managing director at International Strategy and Investing Group. "But then the question becomes cost, and given the current health care environment it becomes a much tougher discussion."

    Indeed, it's cost more so than science holding NIPT testing back at this point. The tests remain relatively expensive, around $800 at the low end, and just less than $3,000 for the more expensive screening methods. Ongoing litigation between Sequenom and two other players in the space -- Natera and Ariosa Diagnostics -- has created some confusion as to who really owns what technology (not to mention some increased expense for all parties). And the technology is so new that insurers, though cognizant of the potential preventative health benefits of NIPT, have not yet determined exactly whether or how they will reimburse for the tests.