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Rhesus conflict in pregnancy - Diagnosis

, medical expert
Last reviewed: 03.07.2025
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Careful collection and analysis of anamnesis

I. Determination of blood group, Rh factor of spouses, Rh antibodies.

II. Assessment of anamnestic risk factors for Rh immunization.

  1. Factors related to previous pregnancies:
    • ectopic pregnancy;
    • termination of pregnancy (spontaneous miscarriage, induced abortion, antenatal death of the fetus);
    • invasive procedures during previous pregnancies (amniocentesis, cordocentesis);
    • bleeding during previous pregnancies (abruption of normal and low-lying placenta, abdominal and pelvic trauma);
    • features of childbirth (caesarean section, manual examination of the postpartum uterus, manual separation of the placenta and discharge of the placenta); implementation of prophylactic Rh immunization during previous pregnancies or in the postpartum period (with what drug, in what doses).
  2. Non-pregnancy related factors:
    • Blood transfusions without taking into account the Rh factor, sharing of syringes by drug addicts.

III. Information on previous children or outcomes of previous pregnancies, with particular emphasis on the severity of hemolytic disease in the previous child.

  • Because of the increased risk to the fetus in subsequent pregnancies, it is important to determine the gestational age at which signs of hemolytic disease appeared in the previous child and the severity of hemolytic disease of the newborn.
  • The characteristics of the previous child's therapy, in particular whether exchange transfusion was performed (how many times) or phototherapy, indirectly indicate the degree of hyperbilirubinemia and anemia.

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Evaluation of Rh immunization in pregnant women

  • If the mother and father have Rh-negative blood, there is no need for further dynamic determination of antibody levels.
  • In the case where a pregnant woman with Rh-negative blood has a partner with Rh-positive blood, the next step should be determining the antibody titer over time.
  • Having information on previous antibody titers is necessary to decide whether immunization has occurred before or has developed during a given pregnancy.
  • A rare cause of sensitization (about 2% of all cases), called the "grandmother theory", is sensitization of a woman with Rh-negative blood at birth due to contact with her mother's Rh-positive red blood cells.
  • Determination of the antibody class: IgM (complete antibodies) do not pose a risk to the fetus during pregnancy, IgG (incomplete antibodies) can cause hemolytic disease of the fetus, therefore, if they are detected, it is necessary to determine the antibody titer.

In the presence of previous immunization, hemolytic disease of the fetus can develop during the first pregnancy.

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Risk factors for Rh immunization

  • Spontaneous abortion - 3-4
  • Induced abortion - 2–5
  • Ectopic pregnancy < 1
  • Full-term pregnancy to delivery - 1–2
  • Childbirth (with compatibility according to the ABO system) - 16
  • Childbirth (with ABO incompatibility) - 2–3.5
  • Amniocentesis - 1–3
  • Transfusion of Rh-positive blood - 90–95

Special research methods

The most common method for detecting antibodies is the direct and indirect Coombs test using antiglobulin serum. The activity of antibodies is usually judged by their titer, but titer and activity do not always coincide.

According to serological properties, antibodies are divided into complete, or salt, agglutinins and incomplete. Complete antibodies are characterized by the ability to agglutinate erythrocytes in a salt medium. They are usually detected in the early stages of the immune response and belong to the IgM fraction. The molecules of complete antibodies are large. The relative molecular weight of complete antibodies is 1,000,000, which prevents them from passing through the placental barrier. Therefore, they do not play a significant role in the development of hemolytic disease in the fetus. Incomplete antibodies (blocking and agglutinating) react with erythrocytes in a colloidal medium, serum, albumin. They belong to the IgG and IgA fractions. Blocking antibodies sensitize erythrocytes without agglutinating them.

Rhesus sensitization is determined at a titer of 1:4 or more. In pregnancy complicated by Rhesus sensitization, the antibody titer is used to assess the risk of hemolytic disease of the fetus.

The risk to the fetus is significant at an antibody titer of 1:16 or more and indicates the need for amniocentesis, since a maternal antibody titer of 1:16, once detected, determines the risk of intrauterine fetal death in 10% of cases.

An indirect Coombs titer of 1:32 or more is significant. Determination of antibody levels should be performed in the same laboratory.

The critical titer level should be determined for each laboratory (it means that the fetus did not die as a result of hemolytic disease 1 week before delivery if the titer did not exceed the critical level). According to different authors, the critical level of antibodies fluctuates within the range of 1:16 - 1:32 and higher.

The titer of maternal antibodies in combination with obstetric history data allows predicting the severity of hemolytic disease of the fetus during pregnancy in approximately 62% of cases.

When using amniocentesis and ultrasound diagnostics, the accuracy of prediction increases to 89%.

Methods for determining the fetal Rh factor antenatally (during pregnancy) by the circulation of the fetal Rh D gene in the mother's blood using the polymerase chain reaction method are under development. If the method is successfully implemented, it will be possible to avoid diagnostic, preventive and therapeutic measures for mothers whose fetuses are Rh negative.

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