An Overview of Isoimmunization

Understanding your disease is so important to helping get your baby here safely. This page will provide an educational explanation of the disease and what is going on inside your body. As always, discuss everything with your health care team. 

What is Isoimmunization (Iso)?

Isoimmunization (also called alloimmunization), occurs when a woman’s immune system is sensitized to foreign blood cell antigens. This causes the woman to make antibodies that can cross the placenta and destroy baby's blood cells (1).

During pregnancy, some of the mother's antibodies are transported across the placenta and enter the fetal circulation. This is necessary because newborns have only a primitive immune system, and the presence of maternal antibodies helps them survive while their immune system matures. A downside to this protection is that by targeting fetal blood cells, maternal antibodies can also cause HDN (2). Blood production in the fetus begins at about 3 weeks, and the baby's blood cells can have antigens on the red cell membrane as early as 38 days after conception (4).

Antibody? Antigen? What’s my body doing again?

Antigen – foreign protein on red blood cells of dad or baby

Antibody – made by mom to defend her body from the antigen

Antigens are foreign. Antibodies defend the body.

How it works

Dad makes the E antigen and passes it to baby. When baby’s blood and mom’s blood mix, mom’s blood finds the foreign antigen and makes antibodies to defend her body. This is called sensitization. The antibodies then find the foreign cells and destroy them in a process called hemolysis (hemo = cell, lysis = death). The next time mom’s sensitized body finds the E antigen, her antibodies are primed and ready to attack the foreign cells. So when mom has baby #2, who has dad’s E antigen, her antibodies cross the placenta and attack the baby’s blood.

A visual of how antibodies need to match their antigen on the blood cell or they cannot bind. The blood cell has 3 antigens - a star, a diamond, and a hexagon. The pink antibody has diamond shaped receptors, so it needs a diamond antigen to grab onto. No matching antigen = no attack. If the antibody does not have anything to grab on to then it cannot attack the cell. 

How did I become sensitized?

The most common ways maternal sensitization occurs are (1):
Blood transfusion



Ectopic Pregnancy

Fetomaternal hemorrhage

Placental abruption


Chorionic villus sampling

Percutaneous umbilical blood sampling

External cephalic version (trying to turn a breech baby)

Manual removal of the placenta (instead of spontaneous delivery of the placenta)

Why is Iso dangerous?

Isoimmunization is dangerous because the antibodies can cross the placenta during pregnancy and if the fetus is positive for the specific antigens, the fetal red blood cells are destroyed. This can result in anemia, hemolytic disease of the fetus and newborn (HDFN), fetal hydrops (sometimes fatal), and more (1).

Possible Outcomes

If you are sensitized, it is NOT a death sentence for your baby, and it does not mean you cannot have additional children. Advancements in fetal surveillance and treatment allow for successful outcomes for most of the affected fetuses.  For the Rh D- woman, the drug Rhogam has reduced the risk of sensitization to less than 1% of susceptible pregnancies. Because of this other alloantibodies have increased in relative importance. These include antibodies to other antigens of the Rh blood group system (ie, c, C, e, E) and other atypical antibodies known to cause severe anemia, such as anti-Kell (ie, K, k), anti-Duffy (ie, Fya), and anti-Kidd (ie, Jka, Jkb) (1).

How do I know if I have an antibody?

There is only one way to know if you have an antibody, you have to get tested. Routine antibody screening is done in the US on all pregnancies (unless refused) as part of the basic prenatal blood work.

The Exception
The exception to this is if you have had Rhogam recently. Rhogam can stay in your system for months, and usually will not titer higher than 1:4. In this case, your test may be reading the Rhogam antibodies, and not antibodies produced by your own body. If you are going to get Rhogam (please, please get it), then have an indirect antibody screen run before you get the shot. 

What do I do? Where do I start?

Start by keeping a binder or folder. Use this to write down all your questions (and the doctor's answers). No question is silly. It is important that you are informed and able to actively participate in your care and advocate for your baby. Ask for copies of all your test results and keep them in your folder. Don't forget to get a copy of each ultrasound report and MCA scan (complete with all the PSV values, not just the highest or lowest). This way you can see how things are changing and how baby is doing. This is also helpful if you have to have multiple doctors. Sometimes things don't always get passed along between offices, so it is very important to have your own record. It is also a great place to put keepsakes such as ultrasound photos, bracelets, etc. Consider having someone come with you to tests and appointments for support or to drive you home after procedures. The printables on the Info page are a great place to get started with things to put in your folder. 

You also need to get a medical alert card for your wallet or a medical alert bracelet. Mine says “Transfusion Alert: Anti-E”. This is important even after you're not pregnant. If you are ever in an accident or unconscious and need blood, you do not want to have a life threatening transfusion reaction. Some blood banks, hospitals, or doctor's offices will provide them for you. There are also multiple places online (eBay, Etsy, Amazon, etc) where you can order a bracelet, or in the pharmacy section of our local Meijer, there is a USB medical alert card that you can put your entire medical record, not just your antibody status. Some cell phones have an In Case of Emergency or ICE section where you can write your antibody status and include emergency contact information for your MFM too.

If you need a medical alert card, please fill out the Google form and a paper card will be printed and mailed to you.


You are your baby's biggest advocate.
With proper treatment, you have every reason to expect a live baby. 

We have great ways of monitoring baby now and several options for helping earlier than ever. 
Your baby is not automatically going to be anemic, brain damaged, or anything else. 

You can have a perfectly healthy baby when this is over. 

You can have more children.