Non-invasive first trimester testing for Down syndrome

By Razib Khan | June 9, 2013 9:45 pm

Fetus at ~12 weeks

I am going to get back to the eugenics debate at some point, but it is hard to motivate myself. This is due to a combination of complacency and sanguinity. Many of those who use eugenics as a “scare word” or are “very concerned about it” don’t really seem to get past generalities when it comes to the present situation (i.e., there is detailed exploration of past atrocities, and some exploration of rather unrealistic scenarios, such as occurred with the “Chinese eugenic” story, but little concrete engagement with realities such as the high abortion rates for positive tests for Down syndrome). In more crass and intellectually vapid discussions liberals and conservatives tend to use eugenics as a term of selectively useful instrumental rhetoric, a bludgeoning instrument only in the mindless screaming discourse.

Meanwhile, we have advances like the whole genome sequencing of second trimester fetuses. This is still basic science, but in genomics basic science is translated really fast to the consumer market. I’m ~90 percent sure my daughter will have a 10 x whole genome sequence by the end of 2014 (I might even get her parents in on the game for a trio). So, submitted for your interest are two papers on first trimester noninvasive screens for Down syndrome due to aneuploidies (and other syndromes). Non-Invasive First Trimester Blood Test Reliably Detects Down’s Syndrome and Other Genetic Fetal Abnormalities:

An Ultrasound in Obstetrics & Gynecology study by Kypros Nicolaides, MD, of the Harris Birthright Research Centre for Fetal Medicine at King’s College London in England, and his colleagues is the first to prospectively demonstrate the feasibility of routine screening for trisomies 21, 18, and 13 by cfDNA testing. Testing done in 1005 pregnancies at 10 weeks had a lower false positive rate and higher sensitivity for fetal trisomy than the combined test done at 12 weeks. Both cfDNA and combined testing detected all trisomies, but the estimated false-positive rates were 0.1% and 3.4%, respectively.

A second Ultrasound in Obstetrics & Gynecology study by the group, which included pregnancies undergoing screening at three UK hospitals between March 2006 and May 2012, found that effective first-trimester screening for Down’s syndrome could be achieved by cfDNA testing contingent on the results of the combined test done at 11 to 13 weeks. The strategy detected 98% of cases, and invasive testing was needed for confirmation in less than 0.5% of cases.

We did CVS. We’d rather not have to in the future. The key is to move positive tests into the first trimester. No matter the reality that most couples who receive a positive result in early second trimester choose to terminate, when it comes to killing a fetus every week counts. You can see what I mean when you look at how abortions are performed as a function of fetal development. Not only that, if you read the source papers you see that the typical woman who receives these sorts of screens is 35-40 years of age, and in that case with the fertility clock ticking every week is of the essence.


  1. Implementation of maternal blood cell-free DNA testing in early screening for aneuploidies.Ultrasound in Obstetrics & Gynecology, 2013; DOI:10.1002/uog.12504
  2. First-trimester contingent screening for trisomy 21 by biomarkers and maternal blood cell-free DNA testingUltrasound in Obstetrics & Gynecology, 2013; DOI:10.1002/uog.12511
  • A Foolish Inconsistency

    “Individuals with Down’s syndrome display a lower incidence of many
    types of cancer, and the candidate genes on chromosome 21 that confer
    this protection from cancer are actively sought. In Nature, Sandra Ryeom and colleagues now report that two chromosome-21 genes, Dscr1 (Down’s syndrome candidate region-1) and Dyrk1a (dual-specificity tyrosine phosphorylation-regulated kinase 1A), block tumor cell expansion by inhibiting angiogenesis.”

    I wonder what other potentially species-wide adaptive advantages are associated with this phenotype.

    Oh well. If I don’t understand something, I’d better just cut it out (I call this “The Cochran Method”).

    • Randy McDonald

      It’s not obvious to me why someone should be forced to remain pregnant for reasons of eventual medical research. In fact, I can think of many reasons why that is a terrible thing to do.

      • razibkhan

        well, the # of DS children isn’t declining that fast, because of later childbearing. more and more women are having positive tests, and even if 90% abort, you can maintain the # of DS children because the # of positive results keeps going up. at least this is happening in some european countries (also, when i visited italy a few years back i saw many more DS children than i’m use to seeing here in the states; combination of catholicism + late childbearing i assume).

  • Kevin Bonham

    I suspect that this debate, and the related one that will come with our increasing ability to genetically engineer people, are going to be the major moral debates of the 21st century.

    Considering the debates swirling around genetically engineered crops, I have no confidence that the debate will be rational or well thought out.

    • razibkhan

      Considering the debates swirling around genetically engineered crops, I have no confidence that the debate will be rational or well thought out.

      but GMO crops are kind of fait accompli. european (and japanese) reticence is developed nation luxury.

      • Kevin Bonham

        It is, but that luxury is spilling over into the developing world (see: resistance to golden rice). Still, considering the conversation about genetically modifying food is as shrill as it is, the conversation around genetically modifying people is going to be out of control.

        • razibkhan


          my personal experience is the left-liberal objections to *contemporary* changes are often not too coherent (e.g. one of the people responding positively to kevin mitchell’s thorough post actually made the case against selective screens on offspring because adversity makes you stronger, which i think is an extremely superficial, shallow, and frankly dangerous, argument to make). the right-conservative objection mainly has to do with abortion, and that’s obviously going to be a hot potato since i expect 1st trimester abortions are going to be a major part of the ‘portfolio’ of options (some more sophisticated catholic thinkers go beyond abortion, and converge with the left-liberal objections of anti-GMO types, about the sanctity of nature/god’s work, etc.).

          • Kevin Bonham

            Yeah, that naturalistic fallacy is quite vexing among liberals, but I wish, just once, we could have a discussion about science and morals that’s not about politics.

            Yes, it’s clear that liberally minded vs conservative minded people might have different objections based on their philosophy, and that’s appropriate, but it would be nice to come to a consensus on the facts first, and then discuss the moral arguments from there.

          • razibkhan

            well, and yet to my extent my frustration *is* about facts. the facts being the nazis, which come up over and over. this makes it almost impossible to have a deep discussion about our *present* trajectory, because the nazi referent just clouds and muddies everything.

          • Kevin Bonham

            Yeah, there are always people trying to have the thoughtful conversations, but those comment threads get filled with so much inane crap that it’s hard to hold on to the thread.

            I’m looking forward to seeing you delve into the fray on this one – I’m not sure if we’ll agree or disagree, but it should be a fun conversation.

          • omarali50

            One could still take the optimistic view that in the proverbial “long run”, evidence and rational thinking are very powerful. The first hysterical reactions and counter-reactions may echo for decades, but the echo does fade with time..eppur si muove and all that

  • Neuroconservative

    I’m fully with you on this, but I am unclear what you think about patentability of these screening tests. Would you oppose patents, as in the previous discussion of BRCA1 screening, and if so, do you think this would impede the advancement and commercialization of the technology?

    • razibkhan

      yes, and no. raw data is not value add. analysis is. the specific screens are short term stop gap. we’ll have reasonable whole genome sequencing in the next 10 years of 1st trimester fetuses i assume.


Discover's Newsletter

Sign up to get the latest science news delivered weekly right to your inbox!

Gene Expression

This blog is about evolution, genetics, genomics and their interstices. Please beware that comments are aggressively moderated. Uncivil or churlish comments will likely get you banned immediately, so make any contribution count!

About Razib Khan

I have degrees in biology and biochemistry, a passion for genetics, history, and philosophy, and shrimp is my favorite food. In relation to nationality I'm a American Northwesterner, in politics I'm a reactionary, and as for religion I have none (I'm an atheist). If you want to know more, see the links at


See More


RSS Razib’s Pinboard

Edifying books

Collapse bottom bar