Rh-conflict during pregnancy: treatment

Management of pregnant women (general provisions)

Management of unimmunized pregnant women

• The titer of antibodies should be determined monthly.
• In case of detection of Rh-anti-D-antibodies at any term of pregnancy, the pregnant woman should be kept as pregnant with Rh-immunization.
• In the absence of isoimmunization, the pregnant woman is administered anti-Rh 0 (D) -immunoglobulin at the 28th week of pregnancy.
• If in 28 weeks anti-D-immunoglobulin prophylaxis was carried out, the determination of antibodies in the blood of a pregnant woman is not clinically significant.

Management of Rhesus-Immunized (Sensitized) Pregnant Women

Non-invasive methods for assessing the severity of fetal conditions

[1], [2], [3], [4], [5], [6], [7], [8], [9], [10]

Ultrasound diagnostics

Most accurately, ultrasound is diagnosed with edematous hemolytic disease of the fetus. In the absence of dropsy there are no reliable criteria that would allow detecting signs of severe anemia in the fetus.

When pronounced fetal dropsy note:

• hydropericardium (one of the early signs);
• ascites and hydrothorax in combination with polyhydramnios - a very unfavorable prognostic sign;
• cardiomegaly;
• edema of the scalp (especially pronounced) and skin of the extremities;
• poor contractility and thickened walls of the ventricles of the heart;
• increased intestinal echogenicity due to edema of its walls;
• hypertrophied and thickened from the placenta edema, the placenta structure is homogeneous;
• an unusual pose of the fetus, known as the "pose of the Buddha", in which the spine and limbs of the fetus are diverted from the swollen abdomen;
• a general decrease in motor activity, which is characteristic of a fetus suffering from severe hemolytic disease.

The severity of hemolytic disease of the fetus is indicated by the following ultrasound signs:

• enlargement of the vein of the umbilical cord (more than 10 mm), including an increase in the diameter of its intrahepatic department;
• increase in the vertical size of the liver (compared with the gestational rate);
• thickening of the placenta (by 0.5-1.0 cm and more);
• increase in blood flow velocity in the descending part of the fetal aorta (the rate varies inversely with the level of fetal hemoglobin);
• an increase in the maximum systolic blood flow velocity in the middle cerebral artery of the fetus.

With anemia, there is a significant increase in the rate of blood flow in the middle cerebral artery, which correlates with the severity of anemia, the sensitivity of the method is 100%, false-positive results of 12% in predicting fetal anemia of moderate and severe severity. Blood flow velocity 1.69 MoM indicates severe fetal anemia, 1.32 MoM - anemia of medium degree, not requiring blood transfusion. According to other researchers, the diagnostic value of this parameter needs further study.

In order to determine the first signs of hemolytic disease of the fetus, it is expedient to perform ultrasound examination, starting from the 18-20th week. Until then, ultrasonic signs of GBP, as a rule, are not determined. Secondary ultrasound is performed in 24-26 weeks, 30-32 weeks, 34-36 weeks and immediately before delivery. At each pregnant woman the terms of repeated researches are developed individually. If necessary, the interval between studies is reduced to 1-2 weeks, and in severe forms of pulmonary TB, ultrasound is performed every 1-3 days.

In some situations, the ultrasound method is the only possible way to monitor the fetus; in particular, the leakage of amniotic fluid, the lack of technical facilities for amniocentesis and cordocentesis, with the contamination of amniotic fluid by blood or meconium, when the patient refuses from invasive procedures.

The functional state of the fetus in pregnant women with rhesus sensitization is assessed using cardiotocography and the biophysical profile of the fetus, which is expedient to be performed on an outpatient basis, starting from 30-32 weeks of gestation to delivery. If signs of chronic hypoxia are present, monitoring should be performed daily to detect fetal impairment early.

In CTG, the fetal hypoxia changes are noted, the severity of which increases as the severity of hemolytic disease of the fetus increases. Registration with the CTG curve "sinusoidal" type indicates the presence of edematous form of hemolytic disease and extremely severe fetal condition.

[11], [12], [13], [14], [15]

Amniocentesis

When immunization is detected in significant titers in previously unimmunized pregnant women, the next stage of diagnosis is amniocentesis. Amniocentesis makes it possible to diagnose the severity of hemolytic anemia in the fetus, since the concentration of bilirubin in the amniotic fluid reflects the intensity of the hemolysis occurring.

Indications for amniocentesis

• weighed obstetric anamnesis (ante-, intra- or postnatal death of children from severe forms of GB);
• the presence of children who underwent a replacement blood transfusion (PEP) in connection with GB;
• Detection of ultrasound markers of GBP;
• the antibody titer level is 1:16 and higher.

Given that hemolytic disease of the fetus rarely develops until 22-24 weeks of gestation, an amniocentesis before this period is inappropriate.

The method of choice is an amniocentesis under ultrasound to prevent trauma of the placenta or umbilical cord. With trauma, bleeding occurs in the fetus and the mother, which increases the degree of immunization.

The resulting amniotic fluid (10-20 ml) is rapidly transferred to a dark vessel and subjected to spectrophotometric analysis after centrifugation and filtration.

[16], [17]

Spectrophotometry

The method used to identify and quantify the substances. The method is based on the dependence of the optical density (OP) of the substance solution on the wavelength of light passing through it.

Normally, the change in the OP of the amniotic fluid, depending on the wavelength of the transmitted light, is a smooth curve with maximum absorption on a short wave. If the bilirubin content in the amniotic fluid is increased, the OD values give an absorption peak at 450 nm, the peak size being proportional to the pigment content. The value of the deviation is delta OD (delta OP-450) - the difference between the obtained index and the value of OP on the absorption curve of a normal amniotic fluid at the same wavelength (450 nm). Delta OP-450 is directly proportional to the increase in the concentration of bilirubin derivatives in the amniotic fluid.

Impurities that cause a low peak and can distort the shape of the curve: blood gives sharp peaks at 415, 540 and 580 nm, meconium gives an absorption peak at 412 nm.

Various systems for the evaluation of spectrophotograms (Lily scale, Fred scale, etc.) are proposed and used. They allow to determine the severity of the disease in the fetus and choose the correct tactics of the patient's management-conservative method, early delivery or intrauterine transfusions. However, according to the Lily scale, it is possible to predict the severity of hemolytic disease in the third trimester of pregnancy, in the second trimester the sensitivity is low. In addition, it is possible to diagnose either very severe fetal lesions, or weak, initial signs.

There are 3 prognostic zones (according to the Lily scale).

• Zone I (lower). The fetus usually has no damage and is born with a hemoglobin content in the cord blood above 120 g / l (norm 165 g / l). Such a situation does not require an early delivery.
• Zone II (medium). Early delivery is not performed until the level of bilirubin increases to the border of the dangerous zone III or the fetus does not reach 32 weeks of pregnancy. The level of hemoglobin in the cord blood is usually 80-120 g / l. Early delivery is indicated in the following cases:
  • mild fetuses;
  • previous intrauterine fetal death occurred within the same period;
  • a sharp increase in the delta OP-450 to 0.15 and higher.
• Zone III (upper). Antenatal fetal death is possible within 7-10 days. Blood transfusion should be performed, and in the absence of such a possibility, delivery should be given. The level of cord blood hemoglobin is usually below 90 g / l. The dropping curve of OP-450 nm after the 2nd or 3rd research is a good prognostic sign. If the delta OP-450 nm falls into zone I, further interventions are not required.

The value of the OPB can also be determined using a photoelectric colorimeter (FEC). Applying FEC with a wavelength of 450 nm, amniotic fluid can be examined starting from 34-35 weeks of gestation. The level of optical density of bilirubin is less than 0.1 p.p. Testifies to absence of disease of a fruit. The increase in OCD occurs with the development of GB: the values of 0.1-0.15 indicate an easy degree of disease, 0.15-0.2 - the average, an OCD greater than 0.2 with a high probability suggests the presence of severe form of GBP, which indicates the need delivery.

The concentration of bilirubin is an indirect indicator of hemolysis and anemia in the fetus. More precise information can be obtained by examining the fetal blood obtained directly from the cordocentesis.

Blood from the umbilical cord is taken by an aspiration needle, administered transabdominally under ultrasound control.

The method allows to determine the following parameters in the fetus:

• blood group and Rh factor;
• hemoglobin and hematocrit;
• antibodies associated with fetal erythrocytes (direct Coombs reaction);
• bilirubin;
• number of reticulocytes;
• the level of whey protein;
• CBS.

If the fetus is Rh-negative blood, no further research is done during pregnancy. Cordocenesis is especially important in women with previous Rh immunization, when the level of antibodies can not serve as a criterion for assessing the severity of hemolytic disease of the fetus (at high titers of fetus antibodies, nevertheless, it can be Rh negative).

In most cases, ultrasound diagnosis, assessment of the blood flow velocity in the middle cerebral artery, the results of amniocentesis and cordocentesis make it possible to develop the correct tactics of the patient's management. The plan of care depends on the period of pregnancy, the condition of the fetus and the level of perinatal care in this institution (the possibility of intrauterine blood transfusion and nursing premature babies).

Tactics of pregnancy management depending on the results of the survey

• At the gestational age of more than 34 weeks, if the patient has a delta OP-450 nm in zone III or a fetal hematocrit level below 30%, and also with ultrasound signs of dropsy, delivery should be performed.
• In gestational terms less than 34 weeks with similar indicators, either intrauterine blood transfusion or delivery is required.

The final decision should be made on the basis of assessment of the maturity of the fetal lungs, the data of the obstetric anamnesis and the increase in the level of bilirubin in the amniotic fluid and the possibilities of perinatal service. If there are no conditions for intrauterine blood transfusion, a respiratory distress syndrome should be prevented by corticosteroids within 48 hours. Delivery can be undertaken 48 hours after the first dose of corticosteroids. It must be remembered that after the introduction of corticosteroids, the delta values of 459 nm decrease, while the doctor should not consider this as a sign of improvement in the course of the disease.

If the gestation period is less than 34 weeks, the lungs of the fetus are immature and there is an opportunity for intrauterine blood transfusion, then proceed with their carrying out.

Methods of intrauterine blood transfusion

There are 2 methods of intrauterine hemotransfusion: intraperitoneal - the introduction of erythrocyte mass directly into the abdominal cavity of the fetus (the method is practically not used at present); intravascular - the introduction of erythrocyte mass into the vein of the umbilical cord.

Intravascular blood transfusion is the method of choice due to the lower risk of complications and the ability to monitor the severity of anemia and the effectiveness of treatment. In addition, with intravascular blood transfusion, a larger interval between transfusions and labor can be delayed until the fetus reaches a more mature gestational age.

Intravascular blood transfusion

Equipment. Under the control of ultrasound determine the position of the fetus and the site of the puncture of the vein of the umbilical cord. A 20-gauge or 22-gauge needle transabdominal under ultrasound control punctures the umbilical vein not far from the site of its departure from the placenta. In order to immobilize the fetus intravascularly (through the umbilical vein) or intramuscularly injected muscle relaxants.

Blood transfusion is carried out at an initial rate of 1-2 ml / min, gradually increasing the rate to 10 ml / min. Before and after hemotransfusion, the erythrocyte mass is determined by the hematocrit of the fetus. The final hematocrit determines the adequacy of blood transfusion. The desired final hematocrit (after transfusion) is 45%. In severe fetal anemia with hematocrit below 30%, transfusions allow to maintain hematocrit at a level close to normal for a given gestational age (45-50%).

Requirements for erythrocyte mass: blood group 0, Rhesus negative, tested and negative for hepatitis B, C, cytomegalovirus and HIV, compatible with the mother and fetus, washed in physiological saline to minimize the risk of viral infection.

The interval between transfusions depends on the posttransfusion hematocrit and is on average 2-3 weeks.

Intravascular blood transfusion provides:

• suppression of the production of fetal erythrocytes (in response to a smaller number of Rh positive cells, stimulation of the maternal immune system is reduced);
• prolong the pregnancy to a more mature gestational age of the fetus and prevent complications associated with deep prematurity.

Complications:

• death of the fetus (in the absence of fetal dropsy in 0-2% of cases, with fetal edema in 10-15% of cases);
• bradycardia in the fetus in 8% of cases;
• amnionitis in 0.5% of cases;
• bleeding from the puncture site in 1% of cases;
• premature rupture of membranes in 0.5% of cases. Evaluation of complications is not easy due to the fact that severely ill fruit is treated.

The progression or regress of fetal hydrocephalus can be monitored by ultrasound, which allows to determine the indications for repeated transfusion. In 60-70% of cases after 2-3 weeks, repeated transfusion is required. Amniocentesis is of little value after intrauterine transfusion, when amniotic fluid is usually contaminated with blood. In this case, a false increase in the level of bilirubin in the amniotic fluid is possible.

Childbirth should be taken only when the risk associated with premature birth is less than the risk associated with intrauterine transfusion. In typical cases, this occurs at the 34th week of gestation. Caesarean section is the optimal method of delivery in dropsy and severe anemia in the fetus, when there is a high risk of impairing his condition in childbirth. During labor, a neonatal brigade should be present, which has blood at its disposal for replacement transfusion.