Maternal isoimmunisation due to Rh incompatibility, what are the risks?

By (gynaecologist) and (embryologist).
Last Update: 06/16/2023

In addition to the 4 main blood groups(A, B, AB and O), it is well known that, depending on the Rh factor, a person can be Rh positive or Rh negative. Rh is an antigen that can be found on the surface of red blood cells.

In the event that the red blood cells present such an antigen, the person is said to be Rh positive. If, on the other hand, this antigen is absent, the person will be Rh negative.

If an Rh-negative woman becomes pregnant with an Rh-positive baby, there will be an Rh incompatibility that can lead to serious problems, especially in a subsequent pregnancy.

What is Rh isoimmunization?

Maternal isoimmunization due to Rh incompatibility can occur when an Rh-negative woman becomes pregnant and her baby is Rh-positive (because she inherited it from the father).

In this case, the Rh-positive red blood cells of the fetus may be recognized as foreign by the maternal immune system. This would trigger the production of anti-Rh antibodies in the mother, which is known as isoimmunizationo rh sensitization.

For this to occur, the baby's blood must come into contact with the mother's blood. Although it can happen towards the end of pregnancy, this can happen especially at the time of delivery. For this reason, Rh isoimmunization does not usually affect the fetus in the first pregnancy.

However, it is important to mention that isoimmunization can occur even if the pregnancy is terminated or is an ectopic pregnancy. Similarly, the Rh-negative woman may become sensitized to the Rh factor for reasons unrelated to pregnancy, such as an Rh-positive blood transfusion (which is currently very rare).

Rh isoimmunization and second pregnancy

When the woman is isoimmunized, it can have serious consequences for a second pregnancy (if the fetus is Rh positive again).

After isoimmunization, maternal antibodies can cross the placenta in a subsequent pregnancy and eventually destroy the Rh-positive red blood cells of the fetus. This can lead to anemia in the baby and other serious complications that can even be fatal. This is called perinatal hemolytic disease perinatal hemolytic disease.

On the other hand, in subsequent pregnancies, the amount of anti-Rh antibodies in the woman will be higher, so complications for the baby may be more severe.

Perinatal hemolytic disease

Maternal anti-Rh antibodies can destroy Rh-positive red blood cells in the fetus, resulting in perinatal (or newborn) hemolytic disease. Among the main symptoms the baby may have are:

  • Anemia
  • Jaundice: yellowing of the skin and whites of the eyes. It is due to bilirubin produced by the destruction of red blood cells.
  • Heart failure.
  • Severe edema, hydrops fetalis (fluid accumulation).
  • Kernicterus: is brain damage caused by elevated bilirubin levels and its accumulation in the brain.

As mentioned, these complications can even lead to the death of the baby. Therefore, it is essential to know if there is a risk of maternal isoimmunization and to do everything possible to avoid it.

How to prevent it?

To try to avoid Rh isoimmunization, at the first gestational consultation, the woman's blood group, Rh factor and the presence of antibodies are determined to see if the woman is isoimmunized by the indirect Coombs test. In addition, this test will be performed several times throughout the pregnancy.

If the woman is Rh negative and is not sensitized for Rh, she will be given an injection of Rh immune globulin, which is known to many as the Rh vaccine. This vaccine is usually given in the 28th week of pregnancy, regardless of the Rh factor of the couple.

However, Rh immune globulin may not be given if the infant's Rh is known (through fetal DNA study in maternal blood or amniotic fluid) and the infant is Rh negative.

On the other hand, the vaccine will also be administered in the first 72 hours after delivery (vaginal or cesarean section) if the baby is Rh positive and, in addition, after any of the following situations:

  • Ectopic pregnancy.
  • Miscarriage or voluntary termination of pregnancy.
  • Amniocentesis, chorionic villus biopsy and other invasive procedures.
  • External cephalic version.
  • Vaginal bleeding in pregnancy.
  • Trauma or blow to the abdomen while pregnant.

The purpose of this injection is to prevent the mother from producing anti-Rh antibodies. This avoids the serious complications that could result from maternal isoimmunization and the development of perinatal hemolytic disease.

How to treat it?

If the woman is isoimmunized, periodic repetition of the indirect Coombs' test will serve to monitor the amount and increase of antibodies produced. If the antibodies reach a certain level or critical value, there is an increased risk of hemolytic disease in the baby.

However, in these cases it is very important to know the Rh factor of the baby through the study of fetal DNA in maternal blood (or amniocentesis if performed for another indication), since if the baby is Rh negative, strict control is not necessary.

Evaluation of the baby for signs of anemia is often performed by Doppler ultrasound.

If the baby should be affected by Rh incompatibility, treatment will depend on the particular situation and severity. In a mild case, jaundice will be closely monitored after birth and phototherapy may be applied.

In other more severe cases, when severe anemia is detected in the baby, the baby may require intrauterine or postpartum fetal transfusions (neonatal exchange transfusion) or may have to be delivered prematurely.

FAQs from users

To avoid isoimmunisation of the Rh-negative female, can Rh-negative donor sperm be used if the male is Rh-positive?

By Rocío Rodríguez Martín M.D. (gynaecologist).

Sperm from an Rh-negative donor could be used to reduce the risk of isoimmunisation by this antigen. This ensures that the foetus will be Rh negative. However, there are patients who prefer the blood group of the sperm donor to be the same as that of the future father.
Read more

Is there incompatibility if the foetus is Rh negative and the mother is Rh positive?

By Silvia Azaña Gutiérrez B.Sc., M.Sc. (embryologist).

No. In this case there would be no Rh incompatibility even if they are different. The reason is that if the foetus is Rh negative, it does not have the Rh antigen on the surface of its red blood cells, so it cannot trigger the production of maternal anti-Rh antibodies.

Rh isoimmunisation only occurs if the mother is Rh negative and the foetus is Rh positive (because it has inherited it from the father). For this reason, there is sometimes talk of Rh incompatibility in the couple, since for this to occur (the baby being Rh positive while the mother is Rh negative) the father must be Rh positive.

What are the risk factors for maternal-fetal isoimmunisation?

By Silvia Azaña Gutiérrez B.Sc., M.Sc. (embryologist).

Maternal-fetal isoimmunisation of an Rh-negative mother pregnant with an Rh-positive fetus can occur in the third trimester of pregnancy, but occurs especially at the time of delivery.

Other times of risk for maternal isoimmunisation to occur include:

  • After an ectopic pregnancy.
  • After a miscarriage or voluntary termination of pregnancy.
  • When an invasive procedure is performed in pregnancy.
  • If an external cephalic version is required.
  • When vaginal bleeding occurs in pregnancy.
  • If a trauma or blow to the womb occurs while pregnant.

Therefore, at 28 weeks gestation, after delivery and after all these situations, Rh-negative women who are not isoimmunised will be administered Rh immunoglobulin to try to prevent isoimmunisation.

Suggested for you

In this article we have mentioned the study of fetal DNA in maternal blood. If you want to know more about this non-invasive prenatal test, you can visit the following link: Non-invasive prenatal maternal blood test: advantages and indications.

On the other hand, in this article you can read information about some possible complications that may arise in pregnancy: What are the most common pregnancy complications?

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FAQs from users: 'To avoid isoimmunisation of the Rh-negative female, can Rh-negative donor sperm be used if the male is Rh-positive?', 'Is there incompatibility if the foetus is Rh negative and the mother is Rh positive?' and 'What are the risk factors for maternal-fetal isoimmunisation?'.

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Authors and contributors

 Rocío Rodríguez Martín
Rocío Rodríguez Martín
Rocío Rodríguez Martín has a degree in Medicine from the University of Seville. In addition, Rocío has several Master's degrees, including one in Assisted Human Reproduction from the Hospital Virgen del Rocío and Ginemed. Dr. Rodríguez is currently working at Next Fertility Sevilla. More information about Rocío Rodríguez Martín
Licence: 414116713
 Silvia Azaña Gutiérrez
Silvia Azaña Gutiérrez
B.Sc., M.Sc.
Graduate in Health Biology from the University of Alcalá and specialized in Clinical Genetics from the same university. Master in Assisted Reproduction by the University of Valencia in collaboration with IVI clinics. More information about Silvia Azaña Gutiérrez
License: 3435-CV

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