Pre-natal Down Syndrome screening - meaningless?

Not looking for medical advice, just trying to understand this screening.

My wife is currently around 18 weeks pregnant, last week she had the “triple test” for trisomy 21, or Down Syndrome. The doc informed her yesterday that the child is “at risk for Down Syndrome”. I assume that equates to a positive result on the screening.

So naturally I started looking for information. One of the first things I read is that “The likelihood of a fetus having trisomy 21 in a patient with a positive triple test is about 2 percent.”

Am I reading this correctly? 98% of those who receive a positive test have children who do not have Down Syndrome? How does this jive with a later statement (on the same page) that the test “has a false-positive rate of 5 percent”?

I’m quite confused, as to me it appears that the test has a false-positive rate of 98%.

Thanks for any help with this, as I’m sure you can imagine, my wife is beside herself.

Do you have a cite? It’s also possible you’re getting this from a completely unreliable source.

Good point, info came from this page, part of the American Academy of Family Physicians website.

This is one of those stats-101 examples of what you get when your false-positive rate is much higher than the actual incidence of the disease, and why you have to be careful with screening tests.

Say you’re going to test 1000 pregnant women. On average, about one will actually have a child with Down Syndrome. (And to make this easy, let’s just say that there are no false negatives). Now, 999 will not have children with Down syndrome. But with a 5% false positive rate, ~50 will get a false positive rate. Thus, only 1/50 of positive tests is actually correct. The other 49/50 positive tests will false positives.

Tests like this can be a good screening tool, but that’s all they are. It’s not a true diagnostic – you’ll probably go through a few rounds of test to confirm or refute the initial result.

The test is screening test, not a diagnostic one. It screens for risk only, the results of your wife’s test only indicate that she is at a higher risk of carrying a child with Down Syndrome, not that the child has it.

The test looks at AFP (alpha-fetoprotein), hCG (human chorionic gonadatropin) and estriol in your wife’s blood. The levels of these proteins at certain stages of pregnancy are linked to genetic diseases. If the dating of the pregnancy is accurate and her levels are high or low, the child is at risk for Down, Edwards or neural tube defects.

It is an easy way to screen for risk without using invasive testing like amniocentesis or CVS. Since her test came back with a higher than normal likelihood of Down Syndrome, you now have the choice as to whether you want a diagnostic test performed which is going to be much more accurate, but more invasive and thus more risk of injury is involved.

Down syndrome screening is complicated, because a huge number of different risk factors are taken into account. The lab I used to work for had an entire section devoted to calculating risks based on test results and demographics.

I’m vaguely familiar with this and am just going off what I’m reading, so if someone with more direct expertise shows up, I defer to them. First off, it looks like they’re using the triple test as a screening test, meaning you want to be sure you catch every single Down syndrome pregnancy that comes through (though the reality is that it only catches about 60%, according to that paper). The flip side of this is that a lot of normal pregnancies are also flagged. That’s why, if you look at the scheme in Figure 2, they go on to do a lot more testing to confirm if the triple test is positive. It should be seen as a flag to look further rather than a diagnosis of Down syndrome. 98% of those positive triple tests end up being free of Down syndrome. That’s how a screening test is supposed to work. It sucks that you scare a lot of people, but hopefully you don’t miss very many real cases.

The false positive thing seems confusing, I agree. I think they’re using it in a more technical manner. A “false positive” in this case doesn’t mean “it was positive, but they really didn’t have Down syndrome”. I think it means “we measured the levels of these hormones, and the numbers we saw gave a positive result, but the real hormone levels were within the negative range.” That is, the test itself screwed up due to inherent limitations. All clinical tests are required to measure these rates. You would do this by taking a whole bunch of samples that you know should register as negative and testing them, then seeing how many came up as positive.

What did your doctor talk to you about as far as follow-up testing? Because from what I understand, it definitely should not stop here.

Thanks for the replies, it makes more sense now. I really should have been able to figure this out, but the thinking part of my brain was temporarily in hiding.

I don’t know what we’ll do about follow-up testing. Maybe nothing.

Thanks again!

The issue is that there’s a (very) small risk of miscarriage with an amnio or CVS test. So nowadays they don’t do them as a matter of course. Instead, they do the non-invasive triple test, which as has been discussed, leads to a lot of false positives.

Only if, as in your case, there’s a hit on the triple test, is it considered worth the small risk of miscarriage to do one of the more invasive tests, which are much, much more accurate (and which have no or essentially no risk of false positives).

The bottom line – the overwhelming likelihood is that the fetus doesn’t have Down’s, and that there won’t be any negative conequences from the test. But those numbers are non-zero.

–Cliffy

FWIW, we had the same results on the triple-test when I was pregnant with our son. We knew we wouldn’t want to abort even with Downs, and it had taken us years to get pregnant, so we declined CVS or amnio. Instead we had several more ultrasounds than typical where they monitored things like “neck ridge” (or something like that; it’s been years).

Anyhoo, our son was born perfectly healthy.

Here’s my unsolicited advice – tell no one unless they have a good grasp of statistics. If we had told my mother or MIL, they would have freaked out the entire pregnancy for no good reason.

I had a CVS test in October, due to advanced maternal age. (41) It was scary, and I had some hard cramping afterward, a little bleeding. The results were good news, and I had a normal pregnancy and delivery and I’m nursing my typically developing one month old as I type this. I would have aborted if tests had been positive for chromosome abnormalities, because I’ve no family who would love and properly care for my child if something happens to me. If I were a younger parent, I probably would have skipped any risky tests and hoped for a long life with whatever child nature gave me. I can share details of the test in PM if you need more info.

even a sex chromosome abnormality? Most sex chromosome abnormalities do not mean mental retardation. heck even an autosome chromosome disorder doesn’t automaticly mean mental retardation. They are beginning to find out that not everyone with an autosome disorder is one of those kids in a motorized wheelchair, with a communication board, who has tons of medical problems. there are people with autosome disorders who are very mildly affected, and that you would think just is hard of hearing or has mild but obvious learning disabilties.

No. And no one undergoes such a risky, costly procedure without a thorough understanding of the potential for error or the limits of the test. I still have nightmares about the needle coming so perilously close to the fetus, and nightmares about losing the pregnancy I hoped for and wanted badly.
And before you continue with the lecture, a physical handicap of any degree wouldn’t have discouraged me in the least.

on the other hand Troppus, prenatal counseling is highly highly negative. a lot of times parents will get info that’s straight out of the 1950’s…even about conditions that are relatively common.

Actually, I received very helpful, timely information both from prenatal counseling and from tests and ultrasounds throughout my high risk pregnancy, and I was grateful to have knowledgeable physicians as well as access to up to date statistics and studies to refer to. I didn’t encounter any negative feedback, and everyone who assisted me was positive and reassuring. Mistakes could happen in the lab, tests don’t catch every abnormality, injuries during birth can result in lifelong handicaps, and there are numerous conditions that result in limitations that arise long after birth. However, this knowledge did not prevent me from screening for Trisomy or DS. The screen is a tool a potential parent can use to either make the hardest decision of their life, or prepare for raising a child who may have varying degrees of special needs