NIPT* Under Age 35

(*non-invasive prenatal testing)

Fetal DNA testing from the Mother's Blood

Non-invasive prenatal testing (NIPT) is quickly becoming a "game-changer" in the world of prenatal testing for chromosomal abnormalities, such as for Down Syndrome, the most well-known, but certainly not the only chromosomal abnormality that can occur. This new technology allows us to draw the mother's blood after 10 weeks of pregnancy and test her blood for her unborn baby's DNA with close to 99% accuracy.

Conditions such as Trisomy 21 (Down Syndrome), Trisomy 18, Trisomy 13, as well as insufficient or excess X or Y chromosome DNA can now be diagnosed without sending the patient for an invasive procedure such as amniocentesis or chorionic villous sampling (CVS). Oh, and you also find out if it's a boy or a girl!

This new DNA testing technology has some drawbacks.

The first drawback is that the test is less accurate for women under age 35. In this group the conditions being looked for are less common compared to pregnant women 35 and over who are traditionally the group that has chromosomal testing done. It is well known that there is a higher risk of chromosomal disorders in women age 35 and over but given that NIPT poses no risk to the pregnancy, more and more women under age 35 are choosing to have this test done. We want them to understand the issues, so let's go see Dr. Oz.

Pretend you are at a taping of the Dr. Oz Show

Imagine 10,000 (early) pregnant women are invited to a special Dr. Oz show. He stands up on the stage and addresses the enthusiastic crowd.

"Good morning ladies ! How are you all doing this beautiful morning?" asks Dr. Oz.

[The crowd goes wild ! ]

"We are here together to conduct a demonstration. Everyone in this room is under 35 with no prior history of chromosomal birth defects. We are going to illustrate what happens if you have your blood tested for your baby's DNA using the new blood test called NIPT. In this low-risk population, the overall chance of having a baby with Down Syndrome is about 1 out of 1,000."

"Under your seat is a card that says positive or negative. Now everyone with a positive please stand up? 30 women are now standing and thus 9,970 women are still seated. Those standing represent a positive NIPT in this low-risk population. All 30 of these women need to be sent for either amniocentesis or CVS (chorionic villous sampling) to confirm their NIPT results. We need a diagnostic test (invasive testing) to confirm these NIPT findings."

"OK. The results are back so please look at the back of your card. If it says false positive, you can sit down. Take a look around. Only 10 people are left standing and 20 people sat down. Those 20 had a normal result on their amnio or CVS. The 10 left standing are the ones whose final result confirmed Down Syndrome, which is 10 women out of 10,000. Luckily this is only a demonstration !"

"Furthermore, based on probabilities, all 9,970 women whose card showed negative will not later find out that their baby has Down Syndrome. This means that the false negative rate of this test is extremely low, making it a highly sensitive test."

"Despite the fact that this is a great test with almost no risk and extremely accurate results, most health insurers are not covering the cost of the test, which is a few thousand dollars. Some of the NIPT testing labs are keeping the out-of-pocket cost to the patient low because they want this test to be available to all women, regardless of age. Check with your insurer before having the test done to see if it is covered."

Let's try this demonstration with a group of 10,000 pregnant women, 35 or older. In this population, the overall chance of Down Syndrome is about 1 out of 100.

"Under your seat is a card that says positive or negative. Everyone with a positive on their card please stand up? 119 women are now standing and 9,881 remain seated. Those standing represent a positive NIPT in this high-risk population. All 119 of these women need to be sent for either amniocentesis or CVS to confirm their NIPT results. We need a diagnostic test to confirm the NIPT findings."

"Now look at the back of your card. If it says false positive, you can sit down. Take a look around. 99 women are still standing and 20 people sat down. Those 20 had a normal result on their amnio or CVS. The 99 left standing are the ones whose final result confirmed Down Syndrome. OK, everyone can sit down now. Thank you all for your help."

A False Negative Result

"But there is a new concern here in this high-risk population. Everyone in this room who has a negative NIPT result on their card, please look at your card again. If the word negative is in red, please stand up. Look around folks, because 1 person has stood up. This represents a false negative result. One person in this group of 10,000 who has a negative result on her NIPT will find out later on, perhaps after the baby is born, that the baby has Down Syndrome. How can this happen? This is because the test is 99% sensitive. So 1% of the time, if Down Syndrome is present, the test will miss the condition."

In summary

Thank you for your help Dr. Oz, we will take it from here. When using NIPT to test for Down Syndrome, if you are under age 35, 30 women out of 10,000 will be sent for amnio or CVS, 10 of them will get bad news and nobody with a negative test will get bad news later.

If you are 35 or older, 119 women will be sent for amnio or CVS but 99 will get bad news, meaning that the ability of this test to predict the condition is quite high. On the other hand 1 person with a negative result will find out later that their baby has Down Syndrome which is a false negative. Maybe they will find out later in pregnancy or maybe not until after delivery.

However, what if there was no such thing as NIPT? In that case, 10,000 women age 35 and over would be sent for amniocentesis (or CVS). All 100 babies with Down Syndrome would theoretically be discovered. But 40 of those 10,000 women would suffer a procedural complication (1/250) which usually means losing the pregnancy. By not sending all 10,000 women for invasive testing. NIPT has prevented 40 miscarriages in this group.

The Technology Trade-Off

This is the trade-off brought to us by this new DNA technology. If you are over 35 and are considering having an amniocentesis, is finding the 1 additional baby with Down Syndrome out of 10,000 pregnancies worth the risk, which is the loss of 40 normal healthy pregnancies? This is a question that doctors and the medical profession cannot answer.

Only the pregnant woman (or couple) facing the choices above, after being informed of all of the potential risks, can answer the question: "should I have an amnio (or CVS) or should I have NIPT done and choose NOT to have an amnio or CVS if the NIPT comes back negative?

We should also point out that additional testing such as fetal ultrasound can often identify when there is an abnormality, so if something is wrong, it would usually be diagnosed during the pregnancy rather than after the baby is born. One day NIPT will check for the same conditions that can be found on an amnio or CVS. Over time, the cost should come down and the accuracy should further improve. NIPT is probably the greatest medical development for pregnant women since ultrasound, and hopefully every pregnant woman will one day be able to have the option of having this test done at a reasonable cost, and paid for by their health insurance.

*numbers taken from ACOG Committee Opinion 640, September 2015, "Cell-free DNA Screening for Fetal Aneuploidy"