Rh-conflict during pregnancy: symptoms

The mechanism of Rh immunization

Immune anti-Rh antibodies appear in the body in response to the Rh-antigen, either after transfusion of Rh-incompatible blood or after delivery of the Rh-positive fetus. The presence of Rh-negative anti-Rh antibodies in the blood indicates that the body is sensitized to the Rh factor.

The mother’s primary response to RH antigens entering the bloodstream is to produce IgM antibodies that do not penetrate the placental barrier to the fetus due to the high molecular weight. The primary immune response after the D-antigen enters the mother’s bloodstream occurs after a certain time, which ranges from 6 weeks to 12 months. With the repeated ingress of Rh antigens into a sensitized mother's organism, there is a rapid and massive production of IgG, which, due to its low molecular weight, is able to penetrate the placental barrier. In half of the cases, 50–75 ml of erythrocytes are sufficient for the development of the primary immune response, and 0.1 ml for the secondary.

Sensitization of the mother's body increases with the continued action of the antigen.

Passing through the placental barrier, Rh antibodies destroy fetal red blood cells, causing hemolytic anemia and the formation of a large amount of indirect bilirubin (jaundice). The result is a compensatory extramedullary hematopoiesis, the foci of which are located mainly in the liver of the fetus and inevitably lead to a violation of its functions. Portal hypertension, hypoproteinemia, fetal dropsy develop, i.e. A complex of disorders called fetal erythroblastosis.

During hemolysis in the body, the concentration of bilirubin in the fetus increases. Hemolytic anemia develops and, as a result, erythropoietin synthesis is stimulated. When the formation of red blood cells in the bone marrow cannot compensate for their destruction, extramedullary hematopoiesis occurs in the liver, spleen, adrenal glands, kidneys, placenta and intestinal mucosa of the fetus. This leads to obstruction of the portal and umbilical cord veins, portal hypertension, disruption of the protein-synthesizing function of the liver. Colloid-osmotic blood pressure decreases, resulting in edema.

The severity of fetal anemia depends on the number of circulating IgG, the affinity of maternal IgG to fetal erythrocytes, the fruiting compensation of anemia.

Hemolytic disease of the fetus and newborn (synonym for fetal erythroblastosis) is classified in 3 degrees depending on the severity of hemolysis and the ability of the fetus to compensate for hemolytic anemia without developing hepatocellular lesions, portal obstruction and generalized edema.

They distinguish mild hemolytic disease (half of all diseased fetuses), moderate (25–30%) and severe (20–25%).

With a mild disease, hemoglobin concentration in cord blood is 120 g / l and above (the norm for childbirth is 160–180 g / l), with a hemolytic disease of a moderate degree - 70–120 g / l, with a severe one - below 70 g / l.

In domestic practice using the system for assessing the severity of hemolytic disease of the newborn, presented in the table.

System for assessing the severity of hemolytic disease of the newborn

Clinical signs	Severity of hemolytic disease
	I	II	III
Anemia (Hb in cord blood)	150 g / l (> 15 g%)	149–100 g / l (15.1–10.0 g%)	100 g / l (10 g%)
Jaundice (bilirubin in cord blood)	85.5 µmol / L (<5.0 mg%)	85.6-136.8 μmol / L (5.1-8.0 mg%)	136.9 μmol / L (8.1 mg%)
Edematous syndrome	Pastos subcutaneous tissue	Pastoznost and ascites	Universal swelling

Rhesus immunization during the first pregnancy

• Before birth, Rh immunization during the first pregnancy occurs in 1% of Rh-negative women who are pregnant with Rh-positive fetus.
• The risk increases with increasing gestational age.
• The erythrocytes penetrate the placental barrier in 5% of cases during the first trimester, in 15% - during the second trimester and in 30% - at the end of the third trimester. However, in the overwhelming majority of cases, the number of fetal cells entering the mother’s blood is small and insufficient for the development of an immune response.
• The risk increases with the use of invasive procedures and abortion.
• Fetal maternal bleeding during amniocentesis in II and III trimesters is noted in 20% of pregnant women, and in spontaneous or induced abortions in 15%.

[1], [2], [3], [4]

Rhesus immunization during labor

Rhesus immunization of the mother is a consequence of the erythrocytes of the fetus entering the mother’s bloodstream during labor. However, even after childbirth, isoim-munification is observed only in 10–15% of Rh-negative women giving birth to Rh-positive children.

Factors affecting the occurrence of Rh immunization during the first pregnancy and first birth:

• Fetal maternal transfusion: the more antigens enter the bloodstream, the higher the likelihood of immunization. When fetal maternal bleeding is less than 0.1 ml, the probability of immunization is less than 3%, from 0.1 to 0.25 ml - 9.4%, 0.25–3.0 ml - 20%, more than 3 ml - up to 50 %;
• mismatch between mother and fetus in the AB0 system. If a pregnant woman has a blood group of 0, and the father has A, B, or AB, then the frequency of Rh isoimmunization is reduced by 50–75%;
• the presence during this pregnancy of trauma to the placenta during amniocentesis, as well as bleeding in the normal and low location of the placenta, manual separation of the placenta and the allocation of the placenta, caesarean section;
• genetic features of the immune response: about 1/3 of women are not immunized with the Rh antigen during pregnancy.

If a woman’s pregnancy is not the first, spontaneous and / or induced abortions and operations to remove an ovum during ectopic pregnancy affect the increase in the risk of Rh immunization, in addition to the above factors.

The risk factors for Rh immunization not related to pregnancy include transfusion of Rh-incompatible blood (by mistake or without rhesus factor determination), use of a single syringe by drug addicts.

[5], [6]

[7]