Emily Oster

9 min Read Emily Oster

Emily Oster

Prenatal Testing Deep Dive

A review of the options for trisomy detection

Emily Oster

9 min Read

The landscape of prenatal testing is confusing, partly because its evolution has been so rapid. When I was pregnant the first time, which was both a long time ago and not that long ago, there were ultrasound-based screening procedures and invasive tests. When I was pregnant the second time, cell-free fetal DNA testing had been added. Since then, that testing has improved, the set of conditions it can screen for has improved, and on and on. It can be quite difficult to figure out how, exactly, these all fit together.

Here’s an example question from the mailbox:

I just had my 19-week ultrasound, and the doctor told me our baby has dilated renal pelvis (4.9 millimeters, which is over the standard max. of 4mm). Even though my cell-free DNA test came back as negative for trisomy 21, they said the chance our baby has Down syndrome has increased from 1 in 10,000 to 1 in 5,200. In the end, dilated renal pelvis is pretty common. Any insight on your end as to how worried we should be that our baby has Down syndrome? I want to avoid invasive testing if at all possible.

This person has had two tests — a cell-free screening and an ultrasound. How do they combine? How should they be combined? Is invasive testing necessary? Where do these numbers even come from?

Today we’ll dive into a review of this testing. The space is big, so we’re going to limit the scope. I’m going to focus on testing for the three most common trisomies (genetic conditions in which there is an extra, third, copy of a chromosome) — trisomy 21, 18, and 13. I’ve written before about the expansion of cell-free testing to other conditions, here. I’ll talk through the various ways these can be detected, the accuracy rates, and how it all gets put together. (There is a little bit of TL;DR at the end, if you want to skip down.)

Testing options

Cell-free fetal DNA testing

Cell-free fetal DNA testing began to be used in the mid-2010s. These tests make use of the fact that some fetal DNA circulates in the maternal bloodstream. Treated correctly, a sample of blood from the pregnant person can be used to detect abnormalities in the fetus. To somewhat simplify, the approach is to look for evidence of DNA that wouldn’t otherwise be in the mother.

For example: Let’s say you wanted to know the baby’s sex. The pregnant person typically has two X chromosomes. A male baby will have an XY, and a female will have XX. If you sample mom’s blood and find evidence of circulating Y chromosomes in the cell-free DNA, this indicates a male fetus (since the mom’s own cell-free DNA wouldn’t contain a Y chromosome).

These tests can be used to detect an infant’s sex and the three primary trisomies (Down syndrome, trisomy 13, and trisomy 18). Detecting a trisomy means, effectively, looking for an imbalance in the presence of these chromosomes in the cell-free DNA. Assuming the pregnant person has two copies of each chromosome, if you observe an excess of chromosome 21 in the cell-free DNA, it suggests this must be due to an excess of chromosome 21 in the fetus, which would suggest Down syndrome.

Cell-free testing relies on a maternal blood sample, typically taken at around 10 or 11 weeks of pregnancy (testing too early can lead to inconclusive results, since the amount of fetal DNA increases over time).

These tests are extremely accurate. Based on a 2017 meta-analysis, cell-free testing would detect 99.4% of trisomy 21 cases, 97.7% of trisomy 18 cases, and 90.6% of trisomy 13 cases. The false-positive rates are also quite low — 0.1% for all three. Because these conditions are rare, even these relatively small false-positive rates mean that a reasonable share of positive tests are false positives, but the overall performance of the test is excellent. In particular, an enormous share of the cases of these three conditions are detected based on these tests.

Invasive testing: amniocentesis and CVS tests

There are two approaches to invasive prenatal testing: amniocentesis, where a sample of amniotic fluid is used for testing, and chorionic villus sampling (CVS), in which a sample is taken from the placenta.

In either of these cases, the accuracy of the tests performed is close to 100%. Because you are directly sampling DNA, it is possible to actually look directly at the chromosomal makeup. These tests can also be used for other conditions beyond trisomies, since you can look at the full set of chromosomes.

The main concern with invasive testing is possible risks to the fetus, notably miscarriage. Women are often quoted procedure-related miscarriage risks of 1 in 100 or 1 in 200. These are overestimates. A 2019 review suggests that when an appropriate control group is used, neither amniocentesis nor CVS is associated with a significantly higher miscarriage risk (and the point estimates are very small or negative).

Because these are invasive procedures, it is hard to say they have no risk at all, but in the data their risks seem to be negligible.

PGT 

If you got pregnant through IVF, you may have done preimplantaion genetic testing (PGT). Similar to the invasive testing options, this is close to 100% accurate for these trisomies (it can be wrong in very rare cases).

Other ultrasound and blood-test-based screenings

There are a number of ultrasound-based tests that can be used as a screen for trisomies. The best-known one is NT (nuchal translucency) testing. At around 12 weeks, an ultrasound can take a measurement of fluid behind the neck. Fetuses with trisomy 21  are more likely to have more fluid behind the neck. A high reading on this test therefore suggests a higher risk of the fetus being affected. This is typically combined with a blood test, which has some screening value. The measurements are also combined with individual age. All together, they generate a risk value based on the screening and people either “screen positive” (meaning they are above some risk cutoff) or “screen negative” (meaning they are below).

These tests are substantially less accurate than cell-free fetal DNA testing.  The NT + blood testing would detect perhaps 80% of cases, depending on maternal age, with a high false-positive rate (about 4% on average). The reason for this is fairly simple — although fetuses with trisomy 21 are more likely to have a large amount of fluid, a lot of other babies do too. This is just not a super-accurate marker.

There are a large number of markers like this. There are results from blood tests and ultrasound findings that are more common when a fetus has a trisomy. It’s important to note, though, that these all have fairly weak predictive power. None of them comes anywhere close in accuracy to the cell-free options, which is why they are increasingly less used.

Combining metrics

Given this option set, we can think about what we learn at any given stage of testing. Big picture:

  • Each new piece of information helps us learn something, but how much we learn depends on what we thought before.
  • We need Bayes’ rule.

This is perhaps best illustrated by going back to a version of the question we started with. Let’s say at your 20-week ultrasound, there is evidence of a “soft marker” (a finding that may indicate an increased risk) for Down syndrome. How much do we learn from that? The answer depends tremendously on what you knew before.

Scenario 1: You’ve done PGT or some type of invasive testing, and it is negative

If you have a full DNA test from your fetus, the chance that they have trisomy 21 is essentially zero. The soft marker that you observe on the ultrasound is something that occurs in some babies with normal chromosomes and at higher rates in babies with Down syndrome. However, since you know your baby has a normal set of chromosomes, there is nothing to learn here. The chance is still essentially zero.

Scenario 2: You have a cell-free fetal DNA test, and it is negative

The cell-free testing detects a huge share of Down syndrome cases, but not all. Therefore, the risk is not zero. So we need some numbers.

Beginning at the beginning: Based on maternal age, there is some baseline risk of Down syndrome. Let’s assume it’s 1 in 500. The cell-free fetal DNA test detects 99.4% of cases. This means that after a negative test, the remaining chance is 0.006 per 500, or about 1 in 83,333.

Now we imagine you’ve got a soft marker signal on ultrasound — to be specific, let’s go with dilated renal pelvis. This is a condition that appears in about 17% of fetuses with Down syndrome and about 2.5% of fetuses without it. This information, together with the baseline risk, is enough to make a calculation of the chance that your fetus has Down syndrome given a positive test. This calculation relies on Bayes’ rule; there are more details on this in the post linked above. But the overall concept involves taking the baseline risk and adjusting based on the value of the new information.

With this new information, the risk is increased from 1 in 83,333 to 1 in 12,255. This is higher, but it is still extremely small. It’s an increase from 0.0012% to 0.0081%. These numbers are both tiny.

Scenario 3: You have no testing before

A third possibility is that you encounter one of these soft markers without any prior information.

We can continue with the dilated renal pelvis example. We imagine now that there was no testing done before, so the starting risk is 1 in 500 (your basic, baseline risk). With a positive test — applying Bayes’ rule — the updated risk is 1 in 74. This is still a very small number but much higher. And the actual increase in risk is much bigger in this case than in the prior one.

There is no really correct answer as to how to combine these tests, because so much of the right choice depends on individual preference. Faced with scenario 2, some people would choose to get an invasive test to be sure. Others will not.

There is, I think, an interesting question about whether these soft markers are useful at this point if someone has already had cell-free fetal DNA testing. On one hand, they do provide some additional information. On the other hand, I suspect it will rarely be the case that this information will be enough to push someone into more invasive testing.

Bottom line

  • If you want to be sure about trisomy detection, either amniocentesis or CVS testing is necessary. These carry minimal risks.
  • Cell-free fetal DNA testing is extremely accurate for detecting the primary trisomies (21, 13, 18). Although there are a small number of false negatives, it is very rare.
  • Ultrasound findings rarely provide much information if you’ve already had cell-free fetal DNA testing, and no additional information if you have had invasive testing.

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Do you brand things a certain way to get your kid to accept it? Like calling carrots “rabbit popsicles”? Or telling them to put on their “super speed socks” in the morning? Share your rebrands in the comments below! You never know who you might be helping out 👇

#emilyoster #funnytweets #relatabletweets #parentingjokes #kidssaythedarndestthings
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Have you ever panic-googled a parenting question when everyone else is asleep? If so, you’re not alone. 

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Have you ever panic-googled a parenting question when everyone else is asleep? If so, you’re not alone.

Today is the first episode of a new biweekly series on my podcast: Late-Night Panic Google. On these mini-episodes, you’ll hear from some familiar names about the questions keeping them up at night, and how data can help. First up: @claireholt!

Listen and subscribe to ParentData with Emily Oster in your favorite podcast app 🎧

#parentdata #emilyoster #claireholt #parentingstruggles #parentingtips #latenightpanicgoogle
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Sun safety is a must for all ages, especially babies! Here are my tips for keeping your littlest ones protected in the sunshine:
☀️ Most importantly, limit their time out in hot weather. (They get hotter than you do!)
☀️ Keep them in the shade as much as possible when you’re out.
☀️ Long-sleeve but lightweight clothing is your friend, especially on the beach, where even in the shade you can get sunlight reflecting off different surfaces.
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Comment “Link” for a DM to an article on the data around sun and heat exposure for babies.

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Sun safety is a must for all ages, especially babies! Here are my tips for keeping your littlest ones protected in the sunshine:
☀️ Most importantly, limit their time out in hot weather. (They get hotter than you do!)
☀️ Keep them in the shade as much as possible when you’re out.
☀️ Long-sleeve but lightweight clothing is your friend, especially on the beach, where even in the shade you can get sunlight reflecting off different surfaces.
☀️ If you want to add a little sunscreen on their hands and feet? Go for it! But be mindful as baby skin tends to more prone to irritation.

Comment “Link” for a DM to an article on the data around sun and heat exposure for babies.

#sunsafety #babysunscreen #babyhealth #parentdata #emilyoster
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I’m calling on you today to share your story. I know that many of you have experienced complications during pregnancy, birth, or postpartum. It’s not something we want to talk about, but it’s important that we do. Not just for awareness, but to help people going through it feel a little less alone.

That’s why I’m asking you to post a story, photo, or reel this week with #MyUnexpectedStory and tag me. I’ll re-share as many as I can to amplify. Let’s fill our feeds with these important stories and lift each other up. Our voices can create change. And your story matters. 💙

#theunexpected #emilyoster #pregnancycomplications #pregnancystory

I’m calling on you today to share your story. I know that many of you have experienced complications during pregnancy, birth, or postpartum. It’s not something we want to talk about, but it’s important that we do. Not just for awareness, but to help people going through it feel a little less alone.

That’s why I’m asking you to post a story, photo, or reel this week with #MyUnexpectedStory and tag me. I’ll re-share as many as I can to amplify. Let’s fill our feeds with these important stories and lift each other up. Our voices can create change. And your story matters. 💙

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OUT NOW: My new book “The Unexpected: Navigating Pregnancy During and After Complications” is available on April 30th. All of my other books came out of my own experiences. I wrote them to answer questions I had, as a pregnant woman and then as a new parent. “The Unexpected” is a book not to answer my own questions but to answer yours. Specifically, to answer the thousands of questions I’ve gotten over the past decade from people whose pregnancies were more complicated than they had expected. This is for you. 💛 Order now at my link in bio! ...

OUT NOW: My new book “The Unexpected: Navigating Pregnancy During and After Complications” is available on April 30th. All of my other books came out of my own experiences. I wrote them to answer questions I had, as a pregnant woman and then as a new parent. “The Unexpected” is a book not to answer my own questions but to answer yours. Specifically, to answer the thousands of questions I’ve gotten over the past decade from people whose pregnancies were more complicated than they had expected. This is for you. 💛 Order now at my link in bio!

OUT NOW: My new book “The Unexpected: Navigating Pregnancy During and After Complications” is available on April 30th. All of my other books came out of my own experiences. I wrote them to answer questions I had, as a pregnant woman and then as a new parent. “The Unexpected” is a book not to answer my own questions but to answer yours. Specifically, to answer the thousands of questions I’ve gotten over the past decade from people whose pregnancies were more complicated than they had expected. This is for you. 💛 Order now at my link in bio! ...

OUT NOW: My new book “The Unexpected: Navigating Pregnancy During and After Complications” is available on April 30th. All of my other books came out of my own experiences. I wrote them to answer questions I had, as a pregnant woman and then as a new parent. “The Unexpected” is a book not to answer my own questions but to answer yours. Specifically, to answer the thousands of questions I’ve gotten over the past decade from people whose pregnancies were more complicated than they had expected. This is for you. 💛 Order now at my link in bio!

OUT NOW: My new book “The Unexpected: Navigating Pregnancy During and After Complications” is available on April 30th. All of my other books came out of my own experiences. I wrote them to answer questions I had, as a pregnant woman and then as a new parent. “The Unexpected” is a book not to answer my own questions but to answer yours. Specifically, to answer the thousands of questions I’ve gotten over the past decade from people whose pregnancies were more complicated than they had expected. This is for you. 💛 Order now at my link in bio! ...

Is side sleeping important during pregnancy? Comment “Link” for a DM to an article on whether sleep position affects pregnancy outcomes.

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Sources:
📖 #ExpectingBetter pp. 160-163
📈 Robert M. Silver et al., “Prospective Evaluation of Maternal Sleep Position Through 30 Weeks of Gestation and Adverse Pregnancy Outcomes,” Obstetrics and Gynecology 134, no. 4 (2019): 667–76. 

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Is side sleeping important during pregnancy? Comment “Link” for a DM to an article on whether sleep position affects pregnancy outcomes.

Being pregnant makes you tired, and as time goes by, it gets increasingly hard to get comfortable. You were probably instructed to sleep on your side and not your back, but it turns out that advice is not based on very good data.

We now have much better data on this, and the bulk of the evidence seems to reject the link between sleep position and stillbirth or other negative outcomes. So go ahead and get some sleep however you are most comfortable. 💤

Sources:
📖 #ExpectingBetter pp. 160-163
📈 Robert M. Silver et al., “Prospective Evaluation of Maternal Sleep Position Through 30 Weeks of Gestation and Adverse Pregnancy Outcomes,” Obstetrics and Gynecology 134, no. 4 (2019): 667–76.

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...

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My new book, “The Unexpected: Navigating Pregnancy During and After Complications” is available for preorder at the link in my bio!

I co-wrote #TheUnexpected with my friend and maternal fetal medicine specialist, Dr. Nathan Fox. The unfortunate reality is that about half of pregnancies include complications such as preeclampsia, miscarriage, preterm birth, and postpartum depression. Because these are things not talked about enough, it can not only be an isolating experience, but it can also make treatment harder to access.

The book lays out the data on recurrence and delves into treatment options shown to lower risk for these conditions in subsequent pregnancies. It also guides you through how to have productive conversations and make shared decisions with your doctor. I hope none of you need this book, but if you do, it’ll be here for you 💛

#pregnancy #pregnancycomplications #pregnancyjourney #preeclampsiaawareness #postpartumjourney #emilyoster
...

We are better writers than influencers, I promise. Thanks to our kids for filming our unboxing videos. People make this look way too easy. 

Only two weeks until our book “The Unexpected” is here! Preorder at the link in my bio. 💙

We are better writers than influencers, I promise. Thanks to our kids for filming our unboxing videos. People make this look way too easy.

Only two weeks until our book “The Unexpected” is here! Preorder at the link in my bio. 💙
...

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While doctors have long said Tylenol was safe, confusing studies, panic headlines, and even a lawsuit have continually stoked fears in parents. As a result, many pregnant women have chosen not to take it, even if it would help them.

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Exciting news! We have new, high-quality data that says it’s safe to take Tylenol during pregnancy and there is no link between Tylenol exposure and neurodevelopmental issues in kids. Comment “Link” for a DM to an article exploring this groundbreaking study.

While doctors have long said Tylenol was safe, confusing studies, panic headlines, and even a lawsuit have continually stoked fears in parents. As a result, many pregnant women have chosen not to take it, even if it would help them.

This is why good data is so important! When we can trust the data, we can trust our choices. And this study shows there is no blame to be placed on pregnant women here. So if you have a migraine or fever, please take your Tylenol.

#tylenol #pregnancy #pregnancyhealth #pregnancytips #parentdata #emilyoster
...

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For this graph, researchers used a standardized measure of vocabulary size. Parents were given a survey and checked off all the words and sentences they have heard their child say.

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How many words should kids say — and when? Comment “Link” for a DM to an article about language development!

For this graph, researchers used a standardized measure of vocabulary size. Parents were given a survey and checked off all the words and sentences they have heard their child say.

They found that the average child—the 50th percentile line—at 24 months has about 300 words. A child at the 10th percentile—near the bottom of the distribution—has only about 50 words. On the other end, a child at the 90th percentile has close to 600 words. One main takeaway from these graphs is the explosion of language after fourteen or sixteen months.

What’s valuable about this data is it can give us something beyond a general guideline about when to consider early intervention, and also provide reassurance that there is a significant range in this distribution at all young ages.

#cribsheet #emilyoster #parentdata #languagedevelopment #firstwords
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