Rh incompatibility is an immunological incompatibility of the Rh-factor of the blood of a Rh-negative mother and a Rh-positive fetus, characterized by sensitization of the maternal organism. The cause of Rh conflict is the transplacental penetration of fetal erythrocytes carrying a positive Rh factor into the bloodstream of a Rh-negative mother. Rh incompatibility can cause fetal death in utero, miscarriage, stillbirth and hemolytic disease of the newborn.
General information
Rh conflict can occur in women with Rh negative during pregnancy or during childbirth if the child has inherited the positive Rh of the father. Rh factor (Rh) of human blood is a special lipoprotein (D-agglutinogen) in the rhesus system, located on the surface of red blood cells. It is present in the blood of 85% of the representatives of the human population who are Rh-positive Rh (+), and 15% who do not have Rh factor belong to the Rh-negative Rh (-) group.
Causes
Isoimmunization and Rh incompatibility are caused by the ingress of Rh-incompatible blood of the child into the mother’s bloodstream and largely depend on the outcome of the first pregnancy in Rh (–) women. Rhesus conflict during the first pregnancy is possible if a woman has previously had a blood transfusion without taking into account Rh compatibility. The occurrence of rhesus conflict is facilitated by previous abortions of pregnancy: artificial (abortions) and spontaneous (miscarriages).
The entry of the baby’s umbilical cord blood into the mother’s bloodstream often occurs during childbirth, making the mother’s body susceptible to Rh antigen and creating the risk of Rh conflict in the next pregnancy. The probability of isoimmunization increases with cesarean delivery. Bleeding during pregnancy or childbirth due to detachment or damage to the placenta, manual separation of the placenta can provoke the development of Rh conflict.
After invasive prenatal diagnostic procedures (chorion biopsy, cordocentesis or amniocentesis), Rh sensitization of the maternal organism is also possible. In a pregnant woman with Rh (-), suffering from gestosis, diabetes, who has had the flu and acute respiratory infections, there may be a violation of the integrity of the chorionic villi and, as a consequence, activation of the synthesis of antiresus antibodies. The cause of Rh–conflict may be a long-standing intrauterine sensitization of Rh(-) women, which occurred at her birth from Rh(+) mother (2% of cases).
The mechanism of rhesus conflict development
The Rh factor is inherited as a dominant trait, therefore, Rh (-) mothers with homozygous (DD) Rh (+) father –child is always Rh (+), which is why the risk of Rh conflict is high. In the case of heterozygosity (Dd) of the father, the chances of having a child with a positive or negative rhesus are the same.
The formation of fetal hematopoiesis begins from the 8th week of intrauterine development, at this time fetal erythrocytes in small quantities can be detected in the mother’s bloodstream. At the same time, the Rh antigen of the fetus is foreign to the Rh (-) immune system of the mother and causes sensitization (isoimmunization) of the maternal organism with the production of antiresus antibodies and the risk of Rh conflict.
Rh (–) sensitization of a woman during the first pregnancy occurs in isolated cases and the chances of her bearing in Rh conflict are quite high, since the antibodies (Ig M) formed in this case have a small concentration, do not penetrate the placenta well and do not pose a serious danger to the fetus.
The probability of isoimmunization during delivery is greater, which can lead to Rh conflict in subsequent pregnancies. This is due to the formation of a population of long-lived immune memory cells, and in the next pregnancy, with repeated contact even with a small volume of Rh-antigen (no more than 0.1 ml), a large number of specific antibodies (Ig G) are released.
Due to the small size of IgG, they are able to penetrate into the fetal bloodstream through the hematoplacental barrier, cause intravascular hemolysis of Rh (+) red blood cells of the child and inhibition of the hematopoiesis process. As a result of the Rh conflict, a severe, life-threatening condition develops for the unborn child – hemolytic fetal disease characterized by anemia, hypoxia and acidosis. It is accompanied by damage and excessive enlargement of organs: liver, spleen, brain, heart and kidneys; toxic damage to the child’s central nervous system – “bilirubin encephalopathy”. Without timely preventive measures, Rh conflict can lead to intrauterine fetal death, spontaneous miscarriage, stillbirth, or the birth of a child with various forms of hemolytic disease.
Symptoms
Rh conflict does not cause specific clinical manifestations in a pregnant woman, but is detected by the presence of antibodies to the Rh factor in her blood. Sometimes rhesus conflict can be accompanied by functional disorders similar to gestosis.
Rh incompatibility is manifested by the development of hemolytic disease of the fetus, which at an early onset can lead to its intrauterine death from the 20th to the 30th week of pregnancy, miscarriage, stillbirth, premature birth, as well as the birth of a full-term child with anemic, jaundice or edematous form of this disease. Common manifestations of Rh incompatibility in the fetus are: anemia, the appearance of immature red blood cells in the blood (reticulocytosis, erythroblastosis), hypoxic damage to important organs, hepatomegaly and spelenomegaly.
The severity of the manifestations of rhesus conflict can be determined by the amount of antiresus antibodies in the mother’s blood and the degree of maturity of the child. The edematous form of fetal hemolytic disease can be extremely difficult with rhesus conflict – with an increase in the size of organs; pronounced anemia, hypoalbuminemia; the appearance of edema, ascites; thickening of the placenta and an increase in the volume of amniotic fluid. With rhesus conflict, fetal dropsy, edematous syndrome of the newborn, an increase in the weight of the child by almost 2 times can develop, which can lead to a fatal outcome.
A small degree of pathology is observed in the anemic form of hemolytic disease; the jaundice form is expressed by jaundice of the skin, enlargement of the liver, spleen, heart and lymph nodes, hyperbilirubinemia. Bilirubin intoxication in rhesus conflict causes damage to the central nervous system and is manifested by the child’s lethargy, poor appetite, frequent regurgitation, vomiting, decreased reflexes, convulsions, which can subsequently lead to a lag in his mental and mental development, hearing loss.
Diagnostics
The diagnosis of Rh conflict begins with the determination of the Rh belonging of a woman and her husband (preferably before the onset of the first pregnancy or at its earliest stage). If the future mother and father have negative rhesus, there is no need for further examination.
For the prognosis of Rh conflict in Rh (-) women, data on blood transfusions carried out in the past without Rh affiliation, previous pregnancies and their outcomes (the presence of spontaneous miscarriage, medical abortion, intrauterine fetal death, the birth of a child with hemolytic disease) are important, which may indicate possible isoimmunization.
The diagnosis of rhesus conflict includes the determination of the titer and class of antiresus antibodies in the blood, which is carried out during the first pregnancy for women who are not sensitized by rhesus – every 2 months; sensitized – up to 32 weeks of gestation every month, from 32-35 weeks – every 2 weeks, from 35 weeks – weekly. Since there is no direct dependence of the degree of fetal lesion on the titer of antiresus antibodies, this analysis does not give an accurate idea of the condition of the fetus in Rh conflict.
To monitor the condition of the fetus, ultrasound examination is carried out (4 times in the period from the 20th to the 36th week of pregnancy and immediately before childbirth), which allows to observe the dynamics of its growth and development. In order to predict rhesus conflict, ultrasound assesses the size of the placenta, the size of the fetal abdomen (including liver and spleen), reveals the presence of polyhydramnios, ascites, umbilical cord veins.
Conducting electrocardiography (ECG), fetal phonocardiography (FKG) and cardiotocography (CTG) allows the gynecologist conducting pregnancy to determine the degree of fetal hypoxia in Rh conflict. Important data is provided by prenatal diagnosis of rhesus conflict by amniocentesis (amniotic fluid examination) or cordocentesis (umbilical cord blood examination) in dynamics under ultrasound control. Amniocentesis is performed from the 34th to the 36th week of pregnancy: the titer of antiresus antibodies, the sex of the unborn child, the optical density of bilirubin, the degree of maturity of the fetal lungs are determined in the amniotic fluid.
To accurately determine the severity of anemia in rhesus conflict allows cordocentesis, which helps to determine the fetal cord blood blood group and Rh factor; hemoglobin, bilirubin, serum protein levels; hematocrit, the number of reticulocytes; antibodies fixed on fetal erythrocytes; blood gases.
Treatment
To weaken the Rh conflict, all Rh (-) pregnant women at 10-12, 22-24 and 32-34 weeks of gestation undergo courses of nonspecific desensitizing therapy, including vitamins, metabolic agents, calcium and iron preparations, antihistamines, oxygen therapy. At a gestation period of more than 36 weeks, in the presence of Rh sensitization of the mother and a satisfactory condition of the fetus, independent delivery is possible.
If a severe fetal condition is noted with rhesus conflict, a planned caesarean section is performed at a period of 37-38 weeks. If this is not possible, an intrauterine blood transfusion through the umbilical vein is performed to the fetus under ultrasound control, which allows partially compensating for the phenomena of anemia and hypoxia and prolonging pregnancy.
In Rh incompatibility, it is possible to prescribe plasmapheresis to a pregnant woman in the second half of gestation in order to reduce the titer of antibodies to Rh (+) fetal erythrocytes in the mother’s blood. In case of severe hemolytic damage to the fetus, immediately after delivery, the child is given a procedure for replacement transfusion of single-group Rh-negative blood or plasma or erythrocyte mass of group I; treatment of hemolytic disease of the newborn is started.
Breastfeeding of a child with signs of hemolytic disease is not allowed for 2 weeks after delivery, so as not to worsen the baby’s condition. If there are no symptoms of this disease in a newborn with rhesus conflict, then after the injection of antiresus immunoglobulin to the mother, breast–feeding is carried out without restrictions.
Prevention
In order to avoid very serious consequences for a child with Rh-incompatible pregnancy, the primary task in gynecology is to prevent the development of Rh-immunization and Rh incompatibility. Of great importance for the prevention of Rh conflict in Rh (–) women is taking into account Rh compatibility with the donor during blood transfusion, the mandatory preservation of the first pregnancy, the absence of abortions in the anamnesis.
Pregnancy planning plays an important role in preventing rhesus conflict, with the examination of a woman for blood type, Rh factor, for the presence of antiresus antibodies in the blood. The risk of developing rhesus conflict and the presence of antibodies to rhesus in a woman’s blood is not a contraindication to pregnancy and a reason for its termination.
A specific prevention of Rh conflict is intramuscular injection of antiresus immunoglobulin (RhoGAM) from donated blood, which is prescribed to women with Rh (-), not sensitized to Rh antigen. The drug destroys Rh (+) red blood cells that may have entered the woman’s bloodstream, thereby preventing her isoimmunization and reducing the likelihood of Rh conflict. For the high effectiveness of the preventive action of RhoGAM, it is necessary to strictly observe the timing of administration of the drug.
The administration of antiresus immunoglobulin Rh (-) to women for the prevention of Rh conflict is carried out no later than 72 hours after transfusion of Rh (+) blood or platelet mass; artificial termination of pregnancy; spontaneous miscarriage, surgery associated with ectopic pregnancy. Antiresus immunoglobulin is prescribed to pregnant women belonging to the risk category of rhesus conflict at 28 weeks of gestation (sometimes again at 34 weeks) for the prevention of hemolytic disease of the fetus. If a pregnant woman with Rh (-) had bleeding (with placental abruption, abdominal trauma), invasive manipulations were performed with the risk of Rh conflict, antiresus immunoglobulin is administered at 7 months of gestation.
In the first 48-72 hours after delivery, in the case of the birth of Rh (+) baby and the absence of antibodies to rhesus in the mother’s blood, the injection of RhoGAM is repeated. This avoids Rh sensitization and Rh incompatibility in the next pregnancy. The effect of immunoglobulin lasts for several weeks and with each subsequent pregnancy, if there is a chance of the birth of a Rh (+) child and the development of Rh incompatibility, the drug must be administered again. For Rh(-) women already sensitized to Rh–antigen, RhoGAM is not effective.
