Rhesus conflict in pregnancy - Symptoms

Mechanism of Rhesus immunization

Immune anti-Rhesus antibodies appear in the body in response to the Rhesus antigen either after a transfusion of Rhesus-incompatible blood or after delivery of an Rhesus-positive fetus. The presence of anti-Rhesus antibodies in the blood of Rhesus-negative individuals indicates sensitization of the body to the Rhesus factor.

The mother's primary response to the entry of Rh antigens into the bloodstream is the production of IgM antibodies, which do not penetrate the placental barrier to the fetus due to their high molecular weight. The primary immune response after the entry of D antigen into the mother's bloodstream manifests itself after a certain time, which ranges from 6 weeks to 12 months. When Rh antigens enter the sensitized mother's body again, there is a rapid and massive production of IgG, which, due to their low molecular weight, is able to penetrate the placental barrier. In half of the cases, the entry of 50-75 ml of erythrocytes is enough to develop the primary immune response, and 0.1 ml for the secondary one.

Sensitization of the mother's body increases as the antigen continues to act.

Passing through the placental barrier, Rh antibodies destroy fetal erythrocytes, causing hemolytic anemia and the formation of large amounts of indirect bilirubin (jaundice). As a result, compensatory extramedullary hematopoiesis occurs, the foci of which are localized mainly in the fetal liver and inevitably lead to a disruption of its functions. Portal hypertension, hypoproteinemia, fetal hydrops develop, i.e. a complex of disorders called fetal erythroblastosis.

During hemolysis, the concentration of bilirubin in the fetus's body increases. Hemolytic anemia develops and, as a result, the synthesis of erythropoietin is stimulated. When the formation of erythrocytes 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 veins, portal hypertension, and disruption of the protein-synthesizing function of the liver. The colloid osmotic pressure of the blood decreases, resulting in edema.

The severity of fetal anemia depends on the amount of circulating IgG, the affinity of maternal IgG for fetal red blood cells, and fetal compensation for anemia.

Hemolytic disease of the fetus and newborn (synonym - erythroblastosis fetalis) is classified into 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.

Hemolytic disease is classified as mild (half of all sick fetuses), moderate (25–30%), and severe (20–25%).

In mild cases of the disease, the concentration of hemoglobin in the umbilical cord blood is 120 g/l or higher (the norm for childbirth is 160–180 g/l), in moderate hemolytic disease - 70–120 g/l, in severe cases - below 70 g/l.

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

Hemolytic disease of the newborn severity scoring system

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%)
Edema syndrome	Subcutaneous tissue pastosity	Pastosity and ascites	Universal edema

Rhesus immunization during first pregnancy

• Before delivery, Rh immunization during the first pregnancy occurs in 1% of Rh-negative women pregnant with an Rh-positive fetus.
• The risk increases with increasing gestational age.
• 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 vast 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 with termination of pregnancy.
• Fetal-maternal bleeding during amniocentesis in the second and third trimesters is observed in 20% of pregnant women, and in 15% of spontaneous or induced abortions.

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Rhesus immunization during childbirth

Rhesus immunization of the mother is a consequence of the fetus's red blood cells entering the mother's bloodstream during labor. However, even after labor, isoimmunization is observed only in 10–15% of Rhesus-negative women giving birth to Rhesus-positive children.

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

• volume of fetal-maternal transfusion: the more antigens enter the bloodstream, the higher the probability of immunization. With fetal-maternal bleeding 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 according to the AB0 system. If the pregnant woman has blood group 0, and the father has A, B or AB, then the frequency of Rh isoimmunization decreases by 50–75%;
• the presence during this pregnancy of placental trauma during amniocentesis, as well as bleeding with normal and low location of the placenta, manual separation of the placenta and discharge of the placenta, cesarean section;
• genetic features of the immune response: about 1/3 of women are not immunized with the Rh antigen during pregnancy.

If a woman is not pregnant for the first time, in addition to the above factors, spontaneous and/or artificial abortion, and operations to remove the ovum during an ectopic pregnancy, increase the risk of Rh immunization.

Risk factors for Rh immunization not related to pregnancy include transfusion of Rh-incompatible blood (by mistake or without determining the Rh factor) and sharing of syringes by drug addicts.

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