Fetal erythroblastosis

Fetal erythroblastosis (EP) is a hemolytic anemia of the fetus and newborn, resulting from transplacental transmission of maternal antibodies against the background of maternal and fetal blood incompatibility according to the Rh factor (80-85% of cases) or according to the blood groups of the ABO system (15-20% of cases) and rare blood factors. The term erythroblastosis is associated with the presence of immature erythrocytes in the peripheral blood due to increased hematopoiesis.

Frequency

• • An Rh-positive fetus in an Rh-negative mother is observed in 9% of all pregnancies.
  • In babies with blood type A (I), erythroblastosis occurs 4 times more often than in babies with blood type B (III).

Genetic Aspects

• • Occurs when the fetus inherits the father’s blood type Ag, which is absent from the mother
  • The most commonly involved Rh-D Ar
  • In ABO conflict, agglutinogen A or B is present in the child’s erythrocytes and is absent from the mother. Causes – mainly isoimmunization of pregnant antigens of the Rh and ABO systems, less often due to incompatibility in other erythrocyte antigens (Kell, Duffy, Kidd, M, S, Diego), very rarely incompatibility of blood groups in other systems (C, E), congenital insufficiency erythrocyte enzymes, erythrocyte membrane pathology, infection or deficiency of vitamins (vitamin E, etc.)
  • Rh-isoimmunization is a humoral immune response to erythrocyte antigens of the Rh-rpynpy fetus. Sensitization to Rh-Ar occurs either during transfusion of Rh-positive blood, or during previous or current pregnancies. Under the influence of maternal AT (IgG anti-D), hemolysis of Rh-positive fetal erythrocytes and the breakdown of Hb, the formation of a large amount of bilirubin, and the development of anemia occur. With the predominance of hemolysis over hematopoiesis, foci of extramedullary hematopoiesis appear in the liver, spleen and other organs. Obstruction of the portal and umbilical veins develops, portal hypertension, impaired liver function, a decrease in oncotic blood pressure, causing tissue edema
  • ABO incompatibility softens the course of pregnancy with Rh-conflict. Rh-conflict often occurs if the pregnant woman and the fetus have the same or ABO-compatible blood groups. With incompatibility according to the ABO system, fetal erythrocytes, entering the body of a pregnant woman, are quickly destroyed, so anti-Rh ATs do not have time to be synthesized. Risk factors
  • Previous transfusions of incompatible blood
  • Pregnancy with an Rh-positive fetus in an Rh-negative woman
  • The risk of sensitization is:
  • Without prophylactic immunotherapy during pregnancy – 16%
  • With spontaneous abortions – within 3%
  • With surgical abortions – 5-6%
  • Fetal blood sensitization occurs during ectopic pregnancy, amniocentesis, examination of chorionic villi, manipulations on the placenta.

Options

• • By severity
  • Light – most often. The level of Hb in cord blood is 120-150 g/l (the norm for full-term pregnancy is 160-180 g/l), the concentration of cord blood bilirubin is less than 3.5 mg% (the norm is less than 2 mg%). In the neonatal period, the level of indirect bilirubin in plasma does not exceed 20 mg%, and the concentration of Hb is not lower than 80 g/l.
  • Average – 25-30% of cases. Anemia of moderate severity with the level of Hb 70-120 g/l. An increase in the amount of indirect bilirubin in the blood. The defeat of the central nervous system – bilirubin encephalopathy (nuclear jaundice).
  • Heavy – 20-25%. Severe anemia is characteristic, a decrease in Hb is less than 70 g / l, intrauterine generalized edema – dropsy of the fetus (edema of the subcutaneous tissue of the head, limbs, pleural and pericardial effusion,

ascites). Hepatosplenomegaly, portal hypertension, chronic heart failure.

• • Clinical Options
  • The edematous form is the most severe, children are often born dead or die in the first hours of life
  • Waxy pallor, slight yellowness or cyanosis of the skin
  • Edema of the subcutaneous tissue, free fluid in the cavities (pleural, pericardial, abdominal)
  • Hemorrhagic syndrome (bruising, petechiae, bleeding)
  • Hepatosplenomegaly.

•

• • Icteric form – from mild forms to severe
  • Jaundice appears immediately after birth or in the first days of life
  • Amniotic fluid and lubrication are yellow
  • Hepatosplenomegaly
  • Auscultation – heart sounds are muffled
  • The phenomena of intracranial hypertension (tilting the head, stiff neck, tonic convulsions, tremor of the limbs)
  • Symptom of the setting sun, monotonous cry
  • With stem disorders – bradycardia, bradypnea.
  • Anemia is the mildest form.
  • Paleness of the skin occurs by 7-10 days after birth
  • Moderate enlargement of the liver and spleen.

Laboratory research

• • Edematous form: Hb – less than 100 g / l, erythrocytes – 1.5-1.7×1012 / l and less, reticulocytosis, erythroblastosis, leukocytosis, myelocytes
  • Icteric form: Hb -150-160 g / l, bilirubin – more than 52 μmol / l, anemia in the peripheral blood, macrocytosis, leukocytosis, reticulocytosis, erythroblastosis, myeloblasts and myelocytes, a moderate increase in ESR. The content of direct bilirubin in cord blood is 60-171 µmol/l, the hourly increase is over 6 µmol/l. The content of direct bilirubin in the blood over 324 µmol / l in full-term babies is considered toxic to the central nervous system. The direct and indirect van der Berg reactions are positive. Urinalysis – dark urine, Gmelin’s test is positive
  • The anemic form is a non-cardinal decrease in the number of Hb and erythrocytes, microcytosis, anisocytosis, reticulocytosis, erythroblastosis, polychromasia are not always present. Color index – 1. A slight nuclear shift in the leukocyte formula to the left
  • In all newborns with erythroblastosis, when examining blood taken from the umbilical cord, a positive direct Coombs test is determined (may be positive at the preclinical stage). Special Studies
  • Fetal ultrasound: special measurements are taken – the diameter of the veins of the umbilical cord, the vertical size of the liver (more than 45 mm – a pathological indicator), the thickness of the placenta, the blood flow velocity in the descending part of the fetal aorta (the rate is inversely proportional to the content of Hb in the fetus), reveals hepatomegaly, ascites, signs of dropsy
  • Amniocenez : determine the severity of anemia in the fetus
  • Cordocentesis – taking blood from the fetal umbilical cord through the anterior abdominal wall of a pregnant woman: a fetal blood test is performed to determine a number of indicators (Hb and Ht, blood group and Rh factor, bilirubin content, serum protein, reticulocyte count). Differential Diagnosis
  • Fetal anemia associated with blood loss
  • Transfusion between fraternal twins
  • Arteriovenous or cardiac malformations of the fetus
  • congenital hemolytic anemia
  • Hemolytic anemia stimulated by various drugs
  • Non-immune dropsy of the fetus.

Treatment: Management Tactics

• • Determination of AT titer after a few weeks during pregnancy. A titer of 1:16 and above necessitates further investigation.
  • Periodic amniocentesis to determine the level of bilirubin in the amniotic fluid in pregnant women with an elevated titer of AT. The results determine the severity of hemolysis in the fetus and will need to be in the study of umbilical cord blood.
  • Percutaneous examination of umbilical cord blood (cordocentesis) to determine the fetal blood type, Ht, reticulocyte count, presence of erythroblasts.
  • Control determination of fetal heart rate.
  • Intrauterine transfusion – if the gestation period is less than 34 weeks, intrauterine transfusion is necessary (can be performed from 18 weeks of pregnancy).
  • Delivery may be considered if the risk associated with preterm birth does not exceed the risk associated with intrauterine transfusion (not earlier than 34 weeks of gestation).
  • Exchange transfusion of blood to the newborn.
  • Absolute readings
  • Increasing the content of bilirubin more than 342 µmol/l a The rate of increase of bilirubin is more than 6 µmol/l/h
  • The concentration of bilirubin in cord blood is above 60 µmol/l
  • Anemia with Hb content less than 130 g/l (first day of life)
  • Reticulocytosis above 3%, normoblastosis, erythroblastosis
  • The content of indirect bilirubin is above 171 µmol/L.
  • Relative indications are bacterial or viral sepsis. In this case, in addition to the content of bilirubin in the blood, the clinical picture should be taken into account. :
  • Phototherapy for icteric and anemic forms. Drug treatment – phenobarbital at a dose of 10 mg / kg / day, magnesium sulfate, vikasol, diuretics, cardiotonic drugs, treatment of anemia.

Complications

• • Fetal distress syndrome associated with emergency delivery
  • intrauterine fetal death
  • ICE
  • Miscarriage associated with umbilical cord blood sampling
  • Miscarriage associated with intrauterine transfusion
  • Asphyxia
  • Anemia of the newborn associated with suppression of hematopoiesis after intrauterine transfusion
  • Pulmonary edema
  • Chronic heart failure
  • Nuclear jaundice. Current and forecast. Maternal AT titer and obstetric history predict the severity of EP during pregnancy in 62% of cases. Accuracy increases to 89% with amniocentesis and ultrasound. With an anti-Rh-AT titer of more than 1:16, the risk of intrauterine fetal death reaches 10%. At a low titer (1:2, 1:4), both mild and severe forms of hemolytic disease of the newborn appear equally often. At the same time, with a high titer of AT, mild forms do not appear .. Prevention
  • The introduction of Rh-negative pregnant women with Rh-positive fetus of anti-Rhesus y-globulin products at 28-32 weeks of gestation (in the absence of signs of sensitization according to the results of a serological study), during childbirth, and also in the first 72 hours after childbirth (simultaneous administration of AT and Ag prevents the development of an immune response)
  • Artificial insemination with syaerma of an Ar-negative donor of an isoimmunized woman married to an Ar-positive man
  • Births will need to be taken in a clinic with equipment for exchange transfusion (even if mild fetal damage is predicted).

Synonyms

• • Erythroblastosis of newborns
  • Hemolytic disease of the newborn
  • Congenital anemia of newborns
  • Fetal immune hydrops
  • Malignant jaundice of newborns

Reduction. EP – fetal erythroblastosis

ICD

• P55 Hemolytic disease of the fetus and newborn
• P55.0 Rh isoimmunization of the fetus and newborn
• P55.1 ABO isoimmunization of the fetus and newborn
• P55.8 Other hemolytic disease of fetus and newborn
• P56 Fetal dropsy due to hemolytic disease
• P57 Nuclear jaundice