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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Milestones. We celebrate them in pregnancy, in parenting, and they’re a fun thing to celebrate at work too. Just a couple years ago I couldn’t have foreseen what this community would grow into. Today, there are over 400,000 of you here—asking questions, making others feel seen wherever they may be in their journey, and sharing information that supports data > panic. 

It has been a busy summer for the team at ParentData. I’d love to take a moment here to celebrate the 400k milestone. As I’ve said before, it’s more important than ever to put good data in the hands of parents. 

Share this post with a friend who could use a little more data, and a little less parenting overwhelm. 

📷 Me and my oldest, collaborating on “Expecting Better”

Milestones. We celebrate them in pregnancy, in parenting, and they’re a fun thing to celebrate at work too. Just a couple years ago I couldn’t have foreseen what this community would grow into. Today, there are over 400,000 of you here—asking questions, making others feel seen wherever they may be in their journey, and sharing information that supports data > panic.

It has been a busy summer for the team at ParentData. I’d love to take a moment here to celebrate the 400k milestone. As I’ve said before, it’s more important than ever to put good data in the hands of parents.

Share this post with a friend who could use a little more data, and a little less parenting overwhelm.

📷 Me and my oldest, collaborating on “Expecting Better”
...

I spend a lot of time talking people down after they read the latest panic headline. In most cases, these articles create an unnecessary amount of stress around pregnancy and parenting. This is my pro tip for understanding whether the risk presented is something you should really be worrying about.

Comment “link” for an article with other tools to help you navigate risk and uncertainty.

#emilyoster #parentdata #riskmanagement #parentstruggles #parentingstruggles

I spend a lot of time talking people down after they read the latest panic headline. In most cases, these articles create an unnecessary amount of stress around pregnancy and parenting. This is my pro tip for understanding whether the risk presented is something you should really be worrying about.

Comment “link” for an article with other tools to help you navigate risk and uncertainty.

#emilyoster #parentdata #riskmanagement #parentstruggles #parentingstruggles
...

Here’s why I think you don’t have to throw away your baby bottles.

Here’s why I think you don’t have to throw away your baby bottles. ...

Drop your toddlers favorite thing right now in the comments—then grab some popcorn.

Original thread source: Reddit @croc_docs

Drop your toddlers favorite thing right now in the comments—then grab some popcorn.

Original thread source: Reddit @croc_docs
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Just keep wiping.

Just keep wiping. ...

Dr. Gillian Goddard sums up what she learned from the Hot Flash  S e x  Survey! Here are some key data takeaways:

🌶️ Among respondents, the most common s e x u a l frequency was 1 to 2 times per month, followed closely by 1 to 2 times per week
🌶️ 37% have found their sweet spot and are happy with the frequency of s e x they are having
🌶️ About 64% of respondents were very or somewhat satisfied with the quality of the s e x they are having

Do any of these findings surprise you? Let us know in the comments!

#hotflash #intimacy #midlifepleasure #parentdata #relationships

Dr. Gillian Goddard sums up what she learned from the Hot Flash S e x Survey! Here are some key data takeaways:

🌶️ Among respondents, the most common s e x u a l frequency was 1 to 2 times per month, followed closely by 1 to 2 times per week
🌶️ 37% have found their sweet spot and are happy with the frequency of s e x they are having
🌶️ About 64% of respondents were very or somewhat satisfied with the quality of the s e x they are having

Do any of these findings surprise you? Let us know in the comments!

#hotflash #intimacy #midlifepleasure #parentdata #relationships
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Here’s what we know from a data standpoint:
✈️ The risk of injury to a child on a plane without a carseat is very small (about 1 in 250,000)
✈️ A JAMA Pediatrics paper estimates about 0.4 child air crash deaths per year might be prevented in the U.S. with car seats 
✈️ Cars are far more dangerous than airplanes! The same JAMA paper suggests that if 5% to 10% of families switched to driving, then we would expect more total deaths as a result of this policy. 

If you want to buy a seat for your lap infant, or bring a car seat for an older child, by all means do so! But the additional protection based on the numbers is extremely small.

#parentdata #emilyoster #flyingwithkids #flyingwithbaby #carseats #carseatsafety

Should your kid be in a car seat on the plane? The AAP recommends that you put kids under 40 pounds into a car seat on airplanes. However, airlines don’t require car seats.

Here’s what we know from a data standpoint:
✈️ The risk of injury to a child on a plane without a carseat is very small (about 1 in 250,000)
✈️ A JAMA Pediatrics paper estimates about 0.4 child air crash deaths per year might be prevented in the U.S. with car seats
✈️ Cars are far more dangerous than airplanes! The same JAMA paper suggests that if 5% to 10% of families switched to driving, then we would expect more total deaths as a result of this policy.

If you want to buy a seat for your lap infant, or bring a car seat for an older child, by all means do so! But the additional protection based on the numbers is extremely small.

#parentdata #emilyoster #flyingwithkids #flyingwithbaby #carseats #carseatsafety
...

SLEEP DATA 💤 PART 2: Let’s talk about naps. Comment “Link” for an article on what we learned about daytime sleep!

The first three months of life are a chaotic combination of irregular napping, many naps, and a few brave or lucky souls who appear to have already arrived at a two-to-three nap schedule. Over the next few months, the naps consolidate to three and then to two. By the 10-to-12-month period, a very large share of kids are napping a consistent two naps per day. Over the period between 12 and 18 months, this shifts toward one nap. And then sometime in the range of 3 to 5 years, naps are dropped. What I think is perhaps most useful about this graph is it gives a lot of color to the average napping ages that we often hear. 

Note: Survey data came from the ParentData audience and users of the Nanit sleep monitor system. Both audiences skew higher-education and higher-income than the average, and mostly have younger children. The final sample is 14,919 children. For more insights on our respondents, read the full article.

SLEEP DATA 💤 PART 2: Let’s talk about naps. Comment “Link” for an article on what we learned about daytime sleep!

The first three months of life are a chaotic combination of irregular napping, many naps, and a few brave or lucky souls who appear to have already arrived at a two-to-three nap schedule. Over the next few months, the naps consolidate to three and then to two. By the 10-to-12-month period, a very large share of kids are napping a consistent two naps per day. Over the period between 12 and 18 months, this shifts toward one nap. And then sometime in the range of 3 to 5 years, naps are dropped. What I think is perhaps most useful about this graph is it gives a lot of color to the average napping ages that we often hear.

Note: Survey data came from the ParentData audience and users of the Nanit sleep monitor system. Both audiences skew higher-education and higher-income than the average, and mostly have younger children. The final sample is 14,919 children. For more insights on our respondents, read the full article.
...

Happy Father’s Day to the Fathers and Father figures in our ParentData community! 

Tag a Dad who this holiday may be tricky for. We’re sending you love. 💛

Happy Father’s Day to the Fathers and Father figures in our ParentData community!

Tag a Dad who this holiday may be tricky for. We’re sending you love. 💛
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“Whilst googling things like ‘new dad sad’ and ‘why am I crying new dad,’ I came across an article written by a doctor who had trouble connecting with his second child. I read the symptoms and felt an odd sense of relief.” Today we’re bringing back an essay by Kevin Maguire of @newfatherhood about his experience with paternal postpartum depression. We need to demystify these issues in order to change things for the better. Comment “Link” for a DM to read his full essay.

#parentdata #postpartum #postpartumdepression #paternalmentalhealth #newparents #emilyoster

“Whilst googling things like ‘new dad sad’ and ‘why am I crying new dad,’ I came across an article written by a doctor who had trouble connecting with his second child. I read the symptoms and felt an odd sense of relief.” Today we’re bringing back an essay by Kevin Maguire of @newfatherhood about his experience with paternal postpartum depression. We need to demystify these issues in order to change things for the better. Comment “Link” for a DM to read his full essay.

#parentdata #postpartum #postpartumdepression #paternalmentalhealth #newparents #emilyoster
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What does the data say about children who look more like one parent? Do they also inherit more character traits and mannerisms from that parent? Let’s talk about it 🔎

#emilyoster #parentdata #parentingcommunity #lookslikedaddy #lookslikemommy

What does the data say about children who look more like one parent? Do they also inherit more character traits and mannerisms from that parent? Let’s talk about it 🔎

#emilyoster #parentdata #parentingcommunity #lookslikedaddy #lookslikemommy
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SLEEP DATA 💤 We asked you all about your kids’ sleep—and got nearly 15,000 survey responses to better understand kids’ sleep patterns. Comment “Link” for an article that breaks down our findings!

This graph shows sleeping location by age. You’ll notice that for the first three months, most kids are in their own sleeping location in a parent’s room. Then, over the first year, this switches toward their own room. As kids age, sharing a room with a sibling becomes more common. 

Head to the newsletter for more and stay tuned for part two next week on naps! 🌙

#parentdata #emilyoster #childsleep #babysleep #parentingcommunity

SLEEP DATA 💤 We asked you all about your kids’ sleep—and got nearly 15,000 survey responses to better understand kids’ sleep patterns. Comment “Link” for an article that breaks down our findings!

This graph shows sleeping location by age. You’ll notice that for the first three months, most kids are in their own sleeping location in a parent’s room. Then, over the first year, this switches toward their own room. As kids age, sharing a room with a sibling becomes more common.

Head to the newsletter for more and stay tuned for part two next week on naps! 🌙

#parentdata #emilyoster #childsleep #babysleep #parentingcommunity
...

Weekends are good for extra cups of ☕️ and listening to podcasts. I asked our team how they pod—most people said on walks or during chores. What about you?

Comment “Link” to subscribe to ParentData with Emily Oster, joined by some excellent guests.

#parentdata #parentdatapodcast #parentingpodcast #parentingtips #emilyoster

Weekends are good for extra cups of ☕️ and listening to podcasts. I asked our team how they pod—most people said on walks or during chores. What about you?

Comment “Link” to subscribe to ParentData with Emily Oster, joined by some excellent guests.

#parentdata #parentdatapodcast #parentingpodcast #parentingtips #emilyoster
...

Humility. That’s why. That’s the whole reason.

#emilyoster #secondbaby #parentingjokes #parentinghumor

Humility. That’s why. That’s the whole reason.

#emilyoster #secondbaby #parentingjokes #parentinghumor
...

Bug season is upon us. Besides annoyance, this can bring up safety concerns, particularly with ticks. They are carriers of diseases, most notably Lyme disease. So what’s the best course of action?

Prevention is key! I suggest:
⭐ Regular tick checks
⭐ Using bug sprays with DEET 
⭐ Wearing long sleeves and pants in the woods

Some parents worry about DEET, but repellants with up to 30% DEET are recommended by both the CDC and AAP. The data says you’re in the clear, so go for it. Enjoy your summer!

#parentdata #emilyoster #tickseason #bugbites #bugspray

Bug season is upon us. Besides annoyance, this can bring up safety concerns, particularly with ticks. They are carriers of diseases, most notably Lyme disease. So what’s the best course of action?

Prevention is key! I suggest:
⭐ Regular tick checks
⭐ Using bug sprays with DEET
⭐ Wearing long sleeves and pants in the woods

Some parents worry about DEET, but repellants with up to 30% DEET are recommended by both the CDC and AAP. The data says you’re in the clear, so go for it. Enjoy your summer!

#parentdata #emilyoster #tickseason #bugbites #bugspray
...