Empowered Pregnancy Education - The Placenta - Confined Placental Mosaicism

By: Aunt Doula (02/18/2023)

Welcome! If you have ended up here and have not read the post about the NIPT test found here please consider reading that article first and circling back. A 'positive' NIPT test can be exceptionally scary, and so that post will be a primer for the more in-depth discussion here on one of the more common "false positive/placental true positive" scenarios that can come from an NIPT test. Another great place to post your current situation and get additional help and information is heading over to r/NIPT if you haven't been there already. Check out the articles pinned to have another source of information about certain situations that may also apply to you. This article is not an exhaustive compilation of CPM possibilities by any means and is only meant to be an educational primer to help you start to understand this vast and difficult finding that can be hard to find simpler explanations on.

As is noted in both of these places, a 'positive' is a bit of a mis-nomer; it really means that there is an increased risk of the chromosome issue that flagged on the NIPT. It is also vital to remember that the NIPT test is purely a screening test and it cannot diagnose anything on it's own. It can only indicate that further testing may be pursued to check the finding of possible higher risk.

What is Confined Placental Mosaicism?

The term confined placental mosaicism can be broken down by each word for the basic understanding to begin understanding what's happening. Confined (is in and kept in one place) Placental (relating to the placenta) mosaicism (parts of a whole are made of more than one type, or are different than another part) so CPM is cells that are located only in the placenta that are different from the baby. In the general majority, because the placenta and the fetus both come from the embryo, their genes are almost always the same. Much like if you tested 1 plate and 1 cup that were made from the same source of clay, they should test as the same clay even tho one was turned into a plate and one was turned into a cup. In a genetically normal unaffected pregnancy, the cells of the baby (cup) and the cells of the placenta (plate) would match.

Following this analogy, when something goes wrong during embryogenesis (the development of cells of the embryo) there may be an extra chromosome such as the 13th chromosome for example. Without going to far into the first weeks of development, there are three layers that become the earliest structures - the two most important for this discussion are the layer that becomes the placenta and the layer that becomes the fetus. just before this split into three layers, one of the mechanisms that is employed by embryos to create a healthy baby is to essentially 'detect' that there are cells that are abnormal and break them off and away from the cells that will become the baby. These abnormal cells may also have only been in the layer destined to become the placenta in the first place and is another way that CPM may exist. There are a number of other ways, but however it gets to this point, the most important aspect of this is that the placental tissue DNA is separate and distinct from the baby's DNA and that can mean that you have a healthy baby with a 'positive' NIPT that is only a placenta true positive. In these early days of development as differentiation solidifies and the 3 layers become distinct, the abnormal cells are still capable of becoming anything (they haven't been assigned a role yet) and they can be cast off to the layer that becomes the placenta where that abnormal genetic material can do less harm.

Let's get back to our clay analogy. We have a clump of clay that we will be turning into a cup and a plate - and when we are separating into piles for the cup and plate, we find rocks mixed in and we can't remove them. So we very carefully shift all the clay that contains rocks over into the pile that will become the plate so they can be hidden in the thick bottom of the plate and hopefully not cause much of an issue. If we got rocks in our cup, they might make it impossible for the cup to hold water if the walls couldn't seal around the rocks well, or they could cut a lip if it was on the rim. So now, we have a smooth clay ideal for making a well sealed and normal cup, and a plate with rocks but we can work around them still pretty well. The cup is the baby, the placenta is the plate, the rocks are the trisomy 13 cells. Now our rocks are confined (located in one place) in the plate and can't damage our cup.

I hope this analogy has helped, if not we will now have a brief discussion of the mechanism with the analogy removed. Biology is complicated, and as such in a very complicated process during embryonic development, if the embryo detects abnormal DNA in a layer that becomes the baby, it will do it's very best to push those cells out of that layer and "cast off" the abnormal cells into the next layer outward which is the placental layer of cells. An embryo is a round ball of an egg that has met and been fertilized by a sperm and has begun to divide internally to create life. It divides many times and goes through many stages and changes before it reaches the 3 layer point and the ball actually breaks apart into different structures - connected but no longer without roles. If the process of confined placental mosaicism has succeeded for an embryo with abnormal cells present, the placenta will hold all the abnormal cells, the fetus will have none - but the NIPT will still flag positive as high risk for the trisomy 13 condition - because all the NIPT can test is the "cfdna" aka "fetal fraction" aka "placental debris" which is miniscule bits of the placental tissues make it into the carrying persons blood stream to be found by the lab and tested. The NIPT test only tests place tal DNA, and again, CPM means that the fetus has normal DNA differing from the placenta.

So to recap - sometimes to try and fix an issue like an extra gene coming from the egg, sperm or cell division error, the embryo will isolate and push out the abnormal cells into the layer of cells that will become the placenta before they separate into distinct layers with defined purposes. Clay source with rocks, careful sorting to put all the rocks with the plate clay where they do the least harm and can be worked around, and keep the cup clay free of rocks. A drawing of the 3 most common mosaic presentations is here and is way to show the cup (baby), plate (placenta) and rocks (abnormal chromosome cells) in their possible rearrangements.

The most important thing of note in learning about an NIPT test is that cannot tell you if the condition it detects is confined to the placenta! It can only tell you that it is in the placenta. As the general majority of pregnancies the placental DNA matches the fetal DNA, many OB's and genetic counselors do not even bring up the possibility of CPM or what it is and this is a very unfortunate reality. CPM is rare, but should always be explored under certain circumstances as listed below. Some estimations put CPM as 1-2% of pregnancies, however some estimates put it higher as we are still collecting data with the boom of NIPT testing has been being scrutinized for it's false positive rate and whether it is a case of test failure or CPM. As time goes on and NIPT testing companies are being forced to face the consequences of their rising false positive rates not matching their claimed testing materials, more stringent studies have been launched. As of 2023, one of the largest companies Natera has a lawsuit against them for falsely claimed rates of accuracy.

What comes after a positive NIPT?

When an NIPT test returns 'positive' the two tests available for diagnostic testing are a CVS (Chorionic Villus Sampling) which is testing the cells of the placenta for their DNA make up, or an Amniocentesis which is testing the skin cells of the baby, and therefore the true genetics of the baby. As you may have picked up, if the NIPT can't tell you if the condition is confined to the placenta, why would you test the placental cells? Sometimes, you shouldn't - and that is what we will discuss next.

Criteria to choose CVS or Amnio if:

Mosaicism in the baby is a different type of mosaicism where by our analogy, some of the rocks did stay in the cup clay, but not all of them so some of the clay is rock free - i.e some cells are normal and some cells have the abnormality

So what do I do?

If you have received a 'positive' NIPT or abnormal result I highly encourage you to post your circumstances, story, and results to the r/NIPT sub as a beginning step. You will find support, answers to questions that may not have been included in the article about nipt testing or this one, be able to filter by tags that match your situation and read about stories like your own, and you can also reach out to me directly!

Above all, to the best of your ability, take a deep breath and reach out. A 'positive' NIPT is not the definitive thing many OB's and google may lead you to believe. It is only a screening test, and they have a semi-alarming false positive rate. I am not in the business of giving false hope, but I am also not in the business of falsely crushing your hope, either. I believe in cautious and realistic optimism. If you have any questions please don't hesitate to reach out.

What else should I know?

It is most important to know that if your pregnancy is diagnosed with confined placental mosaicism, it is possible that your placenta may not function as well as a "normal" placenta. This is where the meaning of doing "less harm" comes into play. While it is not a guarantee, CPM pregnancies need to be monitored for IUGR (intrauterine growth restriction) complications later in pregnancy as the abnormal genetics could impact the blood flow or structure of the placenta such that it does not function at peak efficiency.

You may have to advocate strongly to receive an amniocentesis to confirm a CVS finding as in many practices, a CVS confirmation is considered definitive regardless of ultrasound findings. You do not have to do anything you don't want to - you do not have to terminate based on any findings even from an amniocentesis. It is your right to carry your child to term or as long as they are able to grow and be with you. While there may be additional risks with carrying an abnormal pregnancy, it is your choice to do so and if you need someone to talk to to help you pursue any choice you are making from termination to carrying to term, I am a safe and non-judgemental person to speak to. I believe what makes a choice "right" is that you made it. There are no wrong choices in this process, and I will support you in whatever path you decide to go down. Please don't hesitate to reach out.

Join the discussion on r/EmpoweredBirth