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Monitoring During Pregnancy

Monique Notes: I kind of feel like this is really similar to the timeline Bethany is making. If we are going to keep this page we should either merge it with the timeline, or make it different somehow. Maybe make this less sound byte bullet points and more of an explanation in simple terms. 


Let’s take a minute to talk about how an alloimmunized pregnancy usually goes. If you have had a previously affected pregnancy, things will look a little different than for women experiencing their first sensitized pregnancy. The key difference is that in first affected pregnancies, titers are an accurate indicator of the risk for anemia. In subsequent pregnancies, titers are not an accurate and care should be based on MCA scans.

If you know that you already have antibodies, you can request a preconception appointment with a Maternal Fetal Medicine specialist. This is a great time to go over a care plan and to do some initial testing. Don’t worry if you haven’t had time for a preconception appointment, or if you just found out about your antibodies in mid pregnancy - you can still have these tests run at any time. There will be two main tests that the MFM will run at a preconception appointment: an antibody screen for mom, and an antigen phenotype for dad.

The first test is an antibody screen with reflex for ID and Titer. This is a blood draw for mom and  will give you a starting point for antibody levels prior to pregnancy. It may also detect any new antibodies that have developed due to last delivery. If titers are already at critical levels, it may indicate a need for early MCA ultrasounds. High titer levels may also be eligible for IVIG and plasmapheresis, both of which are started during the first trimester. The disadvantage to doing an antibody screen at a preconception appointment is that the test may not show all of your antibodies and you may negative antibody screen despite prior history of alloimmunization. This does not mean that your antibodies have went away or that you’re “cured”. It simply means that the level of antibodies in your blood is so low that the antibodies are undetectable. Low titer levels pre-pregnancy cannot rule out the need for MCA ultrasounds. 

The second test that will be run at a preconception appointment is an antigen phenotype. This test is a blood draw for dad. If mother has an alloantibody, pre-pregnancy is a good time to have dad’s antigen phenotype run. This will show if he is homozygous for the antigen, heterozygous, or homozygous without the antigen. These results can determine if all children with the same partner are at risk from maternal alloimmunization, if 50% may be antigen positive and at risk, or if there is no risk to any children with this partner. This test provides information about potential risk to baby. Having the results of an antigen phenotype can help you make an informed decision about having future children. It can also lead to more testing (ie heterozygous father means cffDNA testing on the fetus may be an option). The results can determine if there is a need for RhD Immune Globulin (Rhogam). Antigen phenotypes require absolute certainty of paternity - testing anyone besides the baby’s father will be useless. Laboratories may mistakenly run an antibody screen instead of the antigen phenotype, so the results must be checked carefully.

Once you are pregnant, your initial pregnancy blood work will include an antibody screen with reflex to id and titer. This test will be repeated every 4 weeks until 28 weeks, then every 2 weeks until 36 weeks. From 36 weeks until delivery titers are run weekly. Your antibody titer provides a starting point for antibody levels in early pregnancy. If a four-fold increase is found, or if titers hit critical level (4 for Kell, 16 for all other antibodies), then special ultrasounds (MCA scans) will be done to check for anemia.  It is common for antibody levels to increase in the third trimester as both maternal and fetal blood volumes increase, this is why titers are drawn more frequently after 28 weeks. The third trimester is a time when titer levels for many women increase. In some cases, maternal antibodies may not recognize the fetal antigens until late third trimester and then rapidly increase. If titers increase, it may mean it’s time for an early delivery.

MCA scans are used to monitor pregnancies where the mother has had a previously affected baby or if the titers have hit critical level. MCA scans are usually done every 1-2 weeks from 20 weeks onward, or earlier depending on your past history. MCA scans can be done as early as 14-16 weeks, though Intrauterine Transfusions (IUT), the treatment for anemia, are not available until 16/18 weeks depending on the provider’s skill level. Anemia requiring IUT is possible at titers below 4 with anti-Kell. Some doctors debate if there is a critical level for anti-Kell, or if scans should be initiated regardless of titer with anti-Kell. If MCA scans show an elevated MoM of 1.3, it is technically considered mild anemia and weekly scans are warranted. If MCA scans show an elevated MoM of 1.5, it is moderate anemia and the mother should be rescanned within 1-2 days and prepped for an IUT. 

There is an optional test called the cell free fetal DNA test (cffDNA). This is another blood draw for mom, but it can determine baby’s antigen status. If baby is negative, then he will be safe and MCA scans are not needed. This can reduce the amount of appointments that mom has, and decrease the cost as well. The cffDNA test provides confirmation of if the baby is antigen negative (no risk) or antigen positive (at risk). If the baby is negative, weekly MCA scans are unnecessary. If the baby is antigen positive, MCA scans may be required depending on titer levels. The cffDNA test can also help your doctor decide on when to deliver baby (ie an at risk fetus would be delivered at earlier gestation than an antigen negative fetus). The results can also help determine if there is a need for RhD Prophalaxysis (Rhogam) in an Rh- mother. Unfortunately in the USA, this test will not be covered by insurance unless the provider writes a letter requesting it and providing information about the disease, the cost of the test, and the cost of the weekly ultrasounds which can be spared if the fetus is antigen negative. While this test is available to women all over the world regardless of where they live, in most cases the blood drawn for testing must be shipped overseas to the UK or Netherlands. There is a slight risk of the test being incorrect, but overall accuracy is over 99%. Test may need repeated if you do the test early (9-14 weeks).

Having antibodies does not mean you will have to have a c section. It does mean that you will probably be induced early. If you have had an IUT, the goal is to get you to 35 weeks before delivering; anything after 35 is a bonus. If you have not needed an IUT, you will probably be induced at 37-38 weeks. The ACOG Practice Bulletin 192 says delivery is between 37 and 38 weeks is reasonable if there are signs of mild hemolysis. This could be an increase in titers, or an MoM of 1.3 or higher. The exact timing of your delivery will depend on your unique case and your doctor. Women with antibodies are usually not allowed to go to 40 weeks due to increased risk of stillbirth and the increased difficulty monitoring baby.