Prenatal Treatments

In every class there is always some discussion about the worse case scenarios. This page is the hard to read one that everyone hopes does not happen to them. It shows the scary cases and the problems that can happen with HDFN. This may be hard to read, but remember that most babies today survive and thrive. Many antibody babies do not have any of these things happen, and you can have a pregnancy without these worst case scenarios. Infants born to moms with antibodies are getting better care today than they were even 5 years ago. Antibodies are not a death sentence, and knowing about the things that can/do sometimes happen can help you to be better prepared.


Fetal Anemia

Fetal anemia is when the baby is anemic (not enough blood). If the baby is too anemic, a blood transfusion is needed. You can find out if your baby is anemic by having an MCA scan and looking at the numbers from that, or from taking a sample of the baby’s blood (in utero), and checking the hemoglobin level. With an MCA scan, you will get PSV values. Ask for them if they aren’t given to you, or look at the screen during the scan. These PSV values are then plugged into a formula to find your MoM number. You can get a great calculator here: https://medicinafetalbarcelona.org/calc/

A MoM of 1.0 is normal. 1.3 is considered mildly anemic. 1.5 is considered moderately anemic (requires treatment). If fetal anemia is not treated in a timely manner (when the MoM reaches 1.5), then ascites (fluid build up) and hydrops (fluid build up in 3 or more places) can occur. In both cases, the fluid build up is a sign of heart failure due to untreated anemia. If these occur, the survival rate plummets from >90% down to 25%. Untreated fetal anemia is almost always fatal. Even with treatment, it is still possible for the baby to die.

Two of the best outcomes involve baby not being anemic enough to need treatment, or making it to delivery with the help of IUTs. Just because you make it to delivery though, does not mean you’re out of the woods. Babies with HDFN are at risk of developing late onset anemia from 3 – 12 weeks old, so it is important to have your baby’s hemoglobin levels checked until they are at least 12 weeks old.

Plasmapheresis

The treatment that reduces mom’s antibody levels.

Plasmapheresis is the removal of the blood plasma. It is then replaced with antibody free plasma or a plasma substitute. Plasmapheresis is usually initiated at 12 weeks and can be done in the hospital, outpatient infusion center, or doctor’s office.

Why is it done?
Plasmapheresis is done to remove the antibodies from the body. Because antibodies are found in the blood plasma, removing the plasma removes the antibodies. The fewer antibodies there are, the less baby will be attacked. Plasmapheresis does not remove the blood itself. Blood is returned to the patient. Once the antibodies are removed, plasmapheresis is usually followed with IVIG to block any remaining antibodies from crossing the placenta and to keep antibody production down.

How often is it done?
Frequency varies by case, but generally it is done 3 times the first week. This will hopefully remove a majority of the antibodies from Mom’s system.

How is it done?
An IV or port is placed in a good artery. This will remove the plasma. A machine separates the plasma from the blood. The blood and replacement plasma will be returned through a second needle placed in the arm or foot 32.


Intravenous Immunoglobulin (IVIG)

The treatment that prevents or delays the onset of fetal anemia.

IVIG stands for intravenous immunoglobulin. It is a product made from human blood plasma. IVIG is usually done between 12 and 20 weeks 5. It is also used after birth to treat high bilirubin 31. Occasionally doctors will use IVIG when doing an IUT, but this is rare. There was also one case report of giving IVIG to the baby at 30 weeks with anti-M. IVIG can be administered at the hospital, outpatient infusion center, doctor’s office, or sometimes at your home.

Why is it done?
IVIG blocks some of the receptors in the placenta and makes it so that the antibodies cannot cross over to the baby. It also makes it so that you will produce less antibodies because your body sees IVIG as an antibody and decides that it doesn’t need to make any more. 5

How often is it done?
IVIG is usually done once per week 5.

How is it done?
IVIG is administered slowly through an IV, or possibly a port depending on how often you need to receive treatment. It can cause side effects like headache, nausea, vomiting, fever and fatigue. Many women report getting multi-day headaches from the IVIG. Your doctor can sometimes give you something for the pain.

Note: Some women have an allergic reaction to the IVIG. If this is the case, talk with your doctor about trying a different brand. Some women have no reaction when they switch brands.

Intrauterine Blood Transfusion (IUT)

The only way to treat fetal anemia once it has developed.

An IUT is an Intrauterine Transfusion. It is a blood transfusion for the baby while they are still inside of you. Doctor’s usually have great results with IUTs. About 75% of babies with hydrops survive, while more than 90% of babies without hydrops survive 19.

When is it done?
IUTs are generally done between 18 and 35 weeks. Sometimes an IUT can be done as early as 15-16 weeks, but it is very difficult to do before 18 weeks. After 35 weeks, there is more risk with doing an IUT compared with delivery and a transfusion after birth 20.

Where is it done?
IUTs are done in the hospital. Usually in a surgical suite.

Why is it done?
An IUT is done to prevent baby from dying. When the baby is anemic, they do not have enough red blood cells for their body to work properly. Just like how we would die if we lost too much blood, the baby is losing too much blood and needs a transfusion.

How often is it done?
IUTs are done anytime the baby is anemic (not just for HDFN). For most doctors, an IUT will be done any time a baby’s MoM reaches 1.5 or higher. Some doctor’s also do them on a schedule since the baby will need more blood as it grows (which is approximately every 3 weeks). Many doctors use a formula to calculate how long the blood will last based on starting and ending counts. How often an IUT is done depends on each individual case and the doctor. Ask your doctor when he thinks an IUT will need to be performed, and how often.

How is it done?
IUT procedures vary by doctor and hospital. In general, you can expect sedation for you and baby (sometimes paralytic for baby to prevent injury), and pain medication and anesthesia to numb the area.

The doctor will use an ultrasound to guide the needle into the umbilical cord of the baby and to monitor his health. If the baby is under too much stress, the procedure will be stopped and further action may be taken.

Once the needle is in, a sample of baby’s blood will be taken and the hemoglobin (or sometimes hematocrit) will be checked. This is called a cordocentesis or percutaneous umbilical cord blood sampling (PUBS for short), and tells the doctor how anemic the baby is and how much blood will be needed.

Once the amount of blood is decided, the doctor gives that exact amount to the baby and takes a final hemoglobin reading to see how successful the transfusion was. The needle is removed and it is off to recovery to rest and wait for the medications to wear off.

The doctor will probably continue to monitor baby for a few hours before sending you home. Some doctors prefer an overnight stay, while others do not. Depending on the doctor, you may be asked to be on bed rest, or reduced activity for a day or two before resuming your normal routine.

What do the numbers mean?
Normal hemoglobin increases from about 10 to 11 g/dL at 17 weeks, to about 14 to 15 g/dL at term. If baby’s hemoglobin is 2 g/dL lower than normal, he is considered mildly anemic, 2-7 g/dL lower is considered moderately anemic, and anything 7 g/dL or more below normal is considered severely anemic 20.

Additional Information
IUTs suppress the bone marrow. This means that baby will not make as many red blood cells. In many ways this is good because there will not be baby’s own blood to be attacked by the antibodies. Instead, it will be donor blood that will be safe from attack. Because the bone marrow is suppressed, babies with HDFN are at risk for late onset anemia. Additional tests after birth will be used to closely monitor baby.

Note: If your baby has had IUTs, the state required newborn blood screening may be off (it may be testing donor blood and not baby’s blood), and should be repeated at 1 year of age.


Nipocalimab

The experimental treatment for HDFN.

There’s a new clinical trial going on for pregnant women with anti-D and anti-K antibodies. Many doctors do not know about this study, so if you think you are a candidate, please follow the link below to print the information and get it to your doctor ASAP. 

M281 Trial Criteria

  • Anti-D antibodies with a titer of 1:32 or higher     – OR –   anti-K antibodies with a titer of 1:4 or higher. 
  • Between 8 and 13 weeks gestation with only one baby.
  • Previous pregnancy with problems occurring at or before 24 weeks including: 
  • Severe anemia at the time of IUT    – OR –
  • Hydrops fetalis with MoM over 1.5     – OR –  
  • Loss with placenta/pathology reports indicating severe HDFN.

Please visit  https://clinicaltrials.gov/ct2/show/NCT03842189?cond=m281&rank=3 and https://unityhdfn.com/ for more information about the M281 trial and contact information for the study. Sites are opening up all the time and they will pay for travel expenses and lodging. 

What Is M281?
M281 is a monoclonal antibody that is also called  Nipocalimab. It is designed to prevent Hemolytic Disease of the Fetus and Newborn by reducing how many antibodies are in mom’s system (lowering titers), and by blocking the antibodies from crossing the placenta. It is an IV infusion given every week. While the study is only for anti-D and anti-K, the two most aggressive antibodies, it should work for all antibodies once the trial is finished and the drug given final approval. 


Erythropoietin

The option for patients who oppose the use of blood products.

Erythropoietin is a hormone produced by the kidneys. It promotes the formation of red blood cells by the bone marrow. It can be made in a laboratory and used as a treatment for anemia 35.

When is it done?
Erythropoietin can be done prenatally, or after birth. It appears to be most effective after 24 weeks gestation 34.

Where is it done?
Erythropoietin can be administered at the hospital, outpatient infusion center, or doctor’s office.

Why is it done?
Erythropoietin is done to help prevent anemia. Treatment of HDFN with Erythropoietin is experimental, not very successful, and should only be used as a last resort by those who are unable to receive blood products. There are a handful of cases in the medical literature about Jehova’s Witnesses using Erythropoietin to successfully deliver a live baby with HDFN.

How is it done?
Erythropoietin is administered slowly through an IV, or possibly a port depending on how often you need to receive treatment.


Other Medications for HDFN

Phenobarbital

The medication that can mature baby’s liver and reduce bilirubin issues.

Phenobarbital is an oral medication that is typically taken 3 times per day in the last 10 days of pregnancy.

Why is it done?
Phenobarbital improves liver function. When blood cells break down, they turn into bilirubin, which is removed by the liver. Getting the liver to mature faster can help reduce the amount of bilirubin and reduce jaundice.


Steroids

While not a treatment for HDFN, many alloimmunized women are given steroids.

Steroid shots are an injection of corticosteroids, a synthetic form of natural human steroids. They are usually injected into your arm, leg, or buttocks between 25 and 33 weeks, but may be done later depending on situation 36. Steroid shots are done to help baby’s lungs mature more quickly. This reduces the risk of complications and death from prematurity 36.

How often is it done?
Steroid shots are done in “courses”. One course is 2 injections given about 24 hours apart 36.

Additional Information:
Expert opinion holds that steroids will artificially lower your MoM score from the MCA scans enough to make doctors think baby is not anemic and does not need a transfusion. This is not the case. Steroids do not treat anemia, and if baby was anemic before the steroids, baby will still be anemic after the steroids.The doctor needs to take this into account and not assume that baby is no longer anemic if you have had a dose of steroids. Multiple physicians have recommended that steroids only be administered after the decision to transfuse has been made and a planned IUT should not be altered due to a decrease in MoM values after steroid administration. Steroids are also only effective within a couple of days of delivery. You may need another round of steroids before early IUTs or before early delivery if your last round was more than 2 weeks prior.

Steroids do affect the fetal blood flow and can falsely lower the MoM score. Below are some articles that talk about steroids effects on blood flow. Also, Progesterone (oral or as a shot like Makena) can lower the PSV on the MCA scan as well (see the last article listed). 

Antenatal corticosteroid therapy: a comparative study of dexamethasone and betamethasone effects on fetal Doppler flow velocity waveforms.
Urban R et al
Conclusion: Our results indicate significant decrease in fetal middle cerebral artery impedance at 72 h after maternal administration of the first dose of dexamethasone. 

The short term fetal cardiovascular effects of corticosteroids used in obstetrics
Amanda Henry, MPH, FRANZCOG, B.Med. (Hons)
Talks about the average MoM drop is 0.3 after steroids.

Effect of antenatal betamethasone therapy on maternal-fetal Doppler velocimetry.
Piazze JJ, Anceschi MM, La Torre R, Amici F, Maranghi L, Cosmi EV.
Conclusion: Betamethasone treatment is associated with a significant, although transient, reduction of MCA PI, especially at gestational ages <32 weeks’.

The combined effect of betamethasone and ritodrine on the middle cerebral artery in low risk third trimester pregnancies.
Piazze J, Anceschi MM, Cerekja A, Cosmi E, Meloni P, Alberini A, Pizzulo S, Argento T, Cosmi EV.
Conclusion: In low risk pregnancies, betamethasone therapy in the third trimester is related to a significant but transient reduction of MCA PI, which is more pronounced during tocolytic therapy. Although the physiological basis of this effect is currently unclear, it could be related to the local regulation of intracerebral blood flow. 

The effect of betamethasone and dexamethasone on fetal heart rate patterns and biophysical activities. A prospective randomized trial.
Rotmensch S, Liberati M, Vishne TH, Celentano C, Ben-Rafael Z, Bellati U.
Conclusions: Both betamethasone and dexamethasone induce a profound, albeit transient, suppression of fetal heart rate characteristics and biophysical activities in the preterm fetus. However, the effect of betamethasone is more pronounced.

Effect of antenatal corticosteroid administration on Doppler flow velocity parameters in pregnancies with absent or reverse end-diastolic flow in the umbilical artery.
Müller T, Nanan R, Dietl J.
In contrast, there was an overall drop of pulsatility in the middle cerebral artery.

Effects of maternal dexamethasone administration on fetal Doppler flow velocity waveforms.
Chitrit Y, Caubel P, Herrero R, Schwinte AL, Guillaumin D, Boulanger MC.
Conclusions: The current study finds in healthy fetuses a transient, significant and unexplained decrease in fetal middle cerebral artery impedance on the fourth day following maternal dexamethasone administration. Further basic research and clinical studies including larger sample sizes or pregnancies with fetoplacental dysfunction are needed.

Changes in fetoplacental vessel flow velocity waveforms following maternal administration of betamethasone.
Edwards A, Baker LS, Wallace EM.
Saw a decrease in MoM at 24 hours. 

Vaginal versus intramuscular progesterone in the prevention of preterm labor and their effect on uterine and fetal blood flow
Azza A.Abd El Hameed
A statistically significant decrease in fetal MCA-PI was noted after progesterone administration both vaginally and IM.


Remember…

  • We try to cover as much as possible so you can be informed about both current and past testing options. Individual doctors may or may not use some of these things. They choose the care plan that they (and you) are most comfortable with; we just provide information for your personal understanding about what has been used successfully in the literature.
  • With proper monitoring, you have every reason to expect a live baby.
  • You are your baby’s biggest advocate. If you do not feel like your needs are being met, seek a second opinion.
  • You can have a perfectly healthy baby when this is over. 
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