Hemolytic disease of the newborn is an intrauterine immunological conflict caused by incompatibility of fetal and maternal blood for a number of antigens, which leads to hemolysis of the child’s erythrocytes under the influence of maternal antibodies that overcome the placental barrier. Hemolytic disease of the newborn can occur in edematous, jaundice, anemic form and even lead to fetal death in utero. In the diagnosis, amniotic fluid (amniocentesis), umbilical cord blood, bilirubin and hemoglobin in a newborn are examined. Treatment requires phototherapy, intravenous infusion of solutions, exchange blood transfusion.
The pathogenetic basis of hemolytic disease is the processes caused by immunological (antigen-antibody) incompatibility of fetal and maternal blood. In this case, the antigens present in the fetal blood are inherited from the father, and there are no antigens in the mother’s blood. Most often (1 case per 250 pregnancies), fetal hemolytic disease develops with a conflict over the Rh factor; it can also occur with group incompatibility of blood and other less studied antigens. Hemolytic disease of the newborn leads to perinatal mortality in 3.5% of cases.
With hemolytic disease of the newborn, under the influence of maternal antibodies formed to fetal antigens and penetrating through the placenta, the child develops hemolysis of erythrocytes and inhibition of hemipoiesis. The toxic effect of erythrocyte breakdown products on the fetus (newborn) leads to the development of anemia, an increase in bilirubin and blast (immature) erythrocytes.
The immunological conflict leading to hemolytic disease of the fetus most often develops with isoserological incompatibility of blood according to the Rh system (Rh), when the mother has Rh-negative blood, and the fetus has Rh-positive. In this case, it is called rhesus conflict. Isoimmunization in this case can occur in two ways: iatrogenic (with sensitization of a woman by Rh(+) blood transfusions in the past) or with fetal-maternal transplacental transfer of fetal erythrocytes into the maternal bloodstream during pregnancy and childbirth. In the case of Rh incompatibility, fetal hemolytic disease is rarely associated with the first pregnancy; it often develops from the 2nd or 3rd pregnancy with increasing risks with each subsequent gestation.
Another possible cause of hemolytic disease is the incompatibility of fetal and maternal blood according to the AB0 system, i.e. with the mother’s blood group 0 (I), and in the fetus any other. At the same time, antigens A and B from the fetus penetrate through the placenta into the maternal bloodstream and cause the production of immune α- and β-antibodies, followed by an “antigen-antibody” conflict. Hemolytic disease of the newborn with ABO-incompatibility has a lighter course than with Rh-incompatibility. With AB0 incompatibility, hemolytic disease of the newborn can develop already during the 1st pregnancy.
In relatively rare cases, fetal hemolytic disease may be associated with immunological conflicts in the Duffy, Kell, MNSs, Kidd, Lutheran, etc. systems or P, S, N, M antigens.
In pregnant women, there is no specific picture of pathology; sometimes an increase in intrauterine reactions can cause a woman to have a symptom complex similar to gestosis. Hemolytic disease of the newborn can manifest itself in the following ways: stillbirth in the period from 20 to 30 weeks of pregnancy; edematous, jaundice or anemic forms. Common manifestations characteristic of all forms of fetal hemolytic disease are the presence of normochromic anemia with an increase in erythroblasts in the blood, hepatomegaly and splenomegaly.
With the edematous variant of hemolytic disease, the size of the spleen, liver, heart, glands increases in the fetus, and hypoalbuminemia increases. These changes are accompanied by pronounced swelling of subcutaneous fat, ascites, pericarditis, pleurisy, an increase in the weight of the child by 2 times compared to the norm. In the edematous variant of hemolytic disease of the newborn, pronounced anemia is noted (Er -1-1.5 x 1012 / l, Hb 35-50 g / l), erythroblastemia, enlargement and swelling of the placenta. Severe metabolic disorders can cause intrauterine fetal death or the death of a child shortly after birth. The edematous form of hemolytic disease of the fetus is distinguished by an extremely severe course, which in most cases leads to a fatal outcome.
With the jaundice variant of hemolytic disease of the newborn, the child is more often born from urgent labor, full-term, more often with normal skin color. In this case, the hemolytic disease of the fetus manifests itself a few hours after birth – the child’s jaundice skin color is rapidly increasing; less often, jaundice is congenital. In newborns with the jaundice form of hemolytic disease, the spleen, liver, lymph nodes, and sometimes the heart are enlarged, and there is an intensive increase in indirect bilirubin in the blood.
Hyperbilirubinemia is dangerous with the possibility of damage to hepatocytes, cardiomyocytes, nephrons, neurons with the development of bilirubin encephalopathy. With nuclear jaundice (bilirubin intoxication), the child is sluggish, sucks poorly, often regurgitates, he develops hyporeflexia, vomiting, convulsions. The critical level of indirect bilirubin, dangerous in terms of CNS damage, is more than 306-340 mmol/l in full-term and 170-204 mmol/l in premature infants. The consequence of bilirubin encephalopathy may be the death of a child or a subsequent lag in mental development.
In the anemic form of hemolytic disease, the damaging effect on the fetus is usually small. Anemia, pallor of the skin, hepatomegaly and splenomegaly come to the fore. The severity of the manifestations of hemolytic disease of the fetus is determined by the titer of antibodies in a pregnant woman and the degree of maturity of the newborn: the disease is more severe in premature babies.
Currently, obstetrics and gynecology attaches great importance to the timely detection and proper management of pregnancy threatened by the development of hemolytic disease of the newborn. When a pregnant woman is registered, her blood type and Rh factor are determined, similar data of the child’s father are found out, they are interested in a blood transfusion history, the presence of stillborn children in the past, spontaneous miscarriages or children with hemolytic disease of the newborn. With the threat of developing hemolytic disease of the newborn in a woman, the titer of specific antibodies is monitored in dynamics.
Prenatal diagnosis of fetal hemolytic disease includes obstetric ultrasound, dopplerography of uteroplacental blood flow and maximum blood flow in the middle cerebral artery with an assessment of the functional state of the developing child. Characteristic ultrasound criteria of fetal hemolytic disease are placentomegaly, polyhydramnios, umbilical vein dilation; splenic and hepatomegaly, cardiomegaly, the presence of pericardial effusion, hydrothorax.
Considering that hemolytic disease is often accompanied by hypoxia, cardiotocography is performed with an assessment of fetal cardiac activity. In the case of obtaining data for hemolytic disease of the fetus, invasive studies are required – cordocentesis and amniocentesis under the control of ultrasound. At the birth of a child, his rhesus and group affiliation are immediately determined, the content of Hb and bilirubin in umbilical cord blood is examined.
Therapeutic tasks for hemolytic disease of the newborn are the rapid removal of toxic hemolysis factors from the child’s blood – indirect bilirubin and antibodies, as well as increasing the functions of suffering systems and organs. The choice of the method of delivery of women with isoimmunization is determined by the condition of the fetus, the duration of pregnancy, the preparedness of the birth canal. In the absence of data for a severe form of hemolytic disease of the fetus, at a gestation period of more than 36 weeks, maturity of the cervix, natural childbirth is possible. In severe fetal condition, cesarean section is preferable 2-3 weeks before the expected date.
In newborns with hemolytic disease of the newborn, Hb, Ht, and bilirubin indicators are monitored daily. If necessary, correction of anemia by erythrocyte mass, infusion detoxification therapy is carried out. An important component of the treatment of hemolytic disease of the newborn is phototherapy, which contributes to the destruction of indirect bilirubin in the baby’s skin. Phototherapy is carried out in pulsed or continuous mode using fluorescent or blue light lamps.
With more severe manifestations of hemolytic disease of the fetus, drip intragastric fluid injection and replacement blood transfusion are indicated. In case of hemolytic disease of the newborn caused by Rh conflict, one-group Rh (-) blood is used during replacement transfusion. In case of incompatibility with ABO, the erythrocyte mass of group 0 (I) is transfused in accordance with the Rh affiliation of the newborn and the one-group plasma. The development of pulmonary edema and severe respiratory failure requires a ventilator; the presence of ascites dictates the need to perform laparocentesis under ultrasound control.
It consists in preventing Rh-immunization of women – careful blood transfusion, taking into account Rh-affiliation. Women with Rh(-) blood are categorically not recommended to terminate a pregnancy that has occurred for the first time. The method of specific prevention of Rh-conflict in women with Rh(-) blood is the introduction of human immunoglobulin antiresus Rho after abortions, childbirth Rh(+) fetus, ectopic pregnancy, as well as after invasive prenatal diagnosis – chorion biopsy, amniocentesis, cordocentesis.