Rh-conflict during pregnancy: diagnosis

Careful collection and analysis of anamnesis

I. Determination of blood type, Rh factor of spouses, Rh-antibodies.

II. Assessment of anamnestic risk factors for Rhesus immunization.

1. Factors related to previous pregnancies:
   • ectopic pregnancy;
   • interruption of pregnancies (spontaneous abortion, artificial abortion, antenatal fetal death);
   • Invasive procedures during previous pregnancies (amniocentesis, cordocentesis);
   • bleeding during previous pregnancies (detachment of normal and low-lying placenta, abdominal injury, pelvis);
   • features of delivery (caesarean section, manual examination of the postpartum uterus, manual removal of the placenta and the discharge of the placenta); carrying out prophylaxis of Rhesus immunization during previous pregnancies or in the puerperium (what drug, in what doses).
2. Factors not related to pregnancy:
   • Blood transfusion without Rhesus factor, use of one syringe by drug addicts.

III. Information about previous children or outcomes of previous pregnancies, special emphasis is placed on the severity of hemolytic disease in the previous child.

• In connection with the increasing risk for the fetus during subsequent pregnancy, it is important to find out at what gestational age the signs of hemolytic disease in the previous child and the severity of the hemolytic disease of the newborn have appeared.
• The features of the therapy of the previous child, in particular, whether the replacement blood transfusion (how many times) or phototherapy, indirectly indicate the degree of hyperbilirubinemia and anemia.

[1], [2], [3], [4], [5], [6]

Evaluation of rhesus 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 when a pregnant woman with Rhesus-negative blood has a partner with Rh-positive blood, the next step is to determine the titer of antibodies in dynamics.
• The availability of information on previous antibody titers is necessary to decide whether there has been immunization to date or has developed in this pregnancy.
• A rare cause of sensitization (about 2% of all cases), called "grandmother's theory", is the sensitization of a woman with Rh-negative blood at birth, due to contact with Rh-positive red blood cells of her mother.
• Definition of the class of antibodies: IgM (complete antibodies) do not represent risk of fetal pregnancy, IgG (partial antibodies) can cause hemolytic disease of the fetus, so detection of antibody titer is necessary.

In the presence of prior immunization, hemolytic disease of the fetus may develop during the first pregnancy.

[7], [8]

Risk factors for Rhesus Immunization

• Spontaneous abortion - 3-4
• Artificial abortion - 2-5
• Ectopic pregnancy <1
• Pregnancy of a term before delivery is 1-2
• Childbirth (for compatibility with the ABO system) - 16
• Childbirth (with AB0 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 direct and indirect Coombs probes with the use of antiglobulin serum. The activity of antibodies is usually judged by their titre, but the titre 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 saline medium. They are usually detected in the early stages of the immune response and refer to the IgM fraction. The molecules of complete antibodies are of large size. The relative molecular weight of complete antibodies is 1 000 000, which prevents their passage 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 colloidal medium, serum, albumin. They belong to the IgG and IgA fractions. Blocking antibodies sensitize erythrocytes without agglutination.

Rhesus sensitization is determined at a titer of 1: 4 and more. In pregnancy, complicated by Rh-sensitization, 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, because once found a titre of maternal antibodies 1:16 determines the risk of fetal death in 10% of cases.

The titre of an indirect Coombs test of 1:32 or more is significant. The determination of the level of antibodies should be carried out in the same laboratory.

The critical level of the titer should be determined for each laboratory (it means that as a result of hemolytic disease, fetal death did not occur 1 week before delivery if the titer did not exceed the critical level). According to different authors, the critical level of antibodies ranges between 1:16 - 1:32 and above.

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

With the use of amniocentesis and ultrasound diagnostics, the prediction accuracy is increased to 89%.

At the development stage there are methods for determining the Rh factor of the fetus antenatally (during pregnancy) by circulating blood of the mother of the Rh rhesus D gene by the polymerase chain reaction method. With the successful implementation of the technique, it will be possible not to conduct diagnostic, preventive and curative measures in mothers, the fruits of which are Rh-negative.