Rhesus Conflict in Pregnancy - Treatment

Management of pregnant women (general provisions)

Management of non-immunized pregnant women

• Antibody titers should be determined monthly.
• If Rhesus anti-D antibodies are detected at any stage of pregnancy, the pregnant woman should be treated as a pregnant woman with Rhesus immunization.
• In the absence of isoimmunization, the pregnant woman is administered anti-Rh 0 (D) immunoglobulin at the 28th week of pregnancy.
• If anti-D immunoglobulin prophylaxis was performed at 28 weeks, then the determination of antibodies in the pregnant woman’s blood has no clinical significance.

Management of Rh-immunized (sensitized) pregnant women

Non-invasive methods for assessing the severity of fetal condition

[ 1 ], [ 2 ], [ 3 ], [ 4 ], [ 5 ]

Ultrasound diagnostics

The most accurate diagnosis of the edematous form of hemolytic disease of the fetus is made by ultrasound. In the absence of dropsy, there are no reliable criteria that would allow detecting signs of severe anemia in the fetus.

In case of severe fetal hydrops the following is noted:

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

The following ultrasound signs indicate the severity of hemolytic disease of the fetus:

• dilation of the umbilical vein (more than 10 mm), including an increase in the diameter of its intrahepatic section;
• increase in the vertical size of the liver (compared to the gestational norm);
• thickening of the placenta (by 0.5–1.0 cm or more);
• increase in blood flow velocity in the descending part of the fetal aorta (velocity changes inversely proportional to the level of fetal hemoglobin);
• increase in maximum systolic blood flow velocity in the middle cerebral artery of the fetus.

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

In order to detect the first signs of hemolytic disease of the fetus, it is advisable to conduct an ultrasound examination starting from the 18th to 20th week. Before this period, ultrasound signs of HDF are usually not determined. Repeated ultrasound is performed at 24-26 weeks, 30-32 weeks, 34-36 weeks and immediately before delivery. The timing of repeat examinations is developed individually for each pregnant woman. If necessary, the interval between examinations is reduced to 1-2 weeks, and in severe forms of HDF, ultrasound is performed every 1-3 days.

In some situations, the ultrasound method is the only possible way to monitor the condition of the fetus; in particular, when there is leakage of amniotic fluid, there are no technical possibilities for amniocentesis and cordocentesis, when the amniotic fluid is contaminated with blood or meconium, or when the patient refuses invasive procedures.

The functional state of the fetus in pregnant women with Rh sensitization is assessed using cardiotocography and biophysical profile of the fetus, which are appropriate to perform in an outpatient setting, starting from 30-32 weeks of pregnancy until delivery. In the presence of signs of chronic hypoxia, monitoring should be carried out daily for the purpose of early detection of deterioration in the condition of the fetus.

CTG shows changes characteristic of fetal hypoxia, the severity of which increases as the severity of hemolytic disease of the fetus increases. Registration of a "sinusoidal" type curve during CTG indicates the presence of an edematous form of hemolytic disease and an extremely severe condition of the fetus.

[ 6 ], [ 7 ], [ 8 ]

Amniocentesis

If immunization is detected in significant titers in a previously unimmunized pregnant woman, the next diagnostic step is amniocentesis. Amniocentesis allows diagnosing 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

• burdened obstetric history (ante-, intra- or postnatal death of children from severe forms of hypertension);
• the presence of children who have undergone exchange blood transfusion (EBT) due to hypertension;
• detection of ultrasound markers of GBP;
• antibody titer level 1:16 or higher.

Considering that hemolytic disease of the fetus rarely develops before 22–24 weeks of pregnancy, performing amniocentesis before this time is inappropriate.

The method of choice is ultrasound-guided amniocentesis to prevent trauma to the placenta or umbilical cord. Trauma causes bleeding in the fetus and mother, which increases the degree of immunization.

The resulting amniotic fluid (10–20 ml) is quickly transferred into a dark vessel and, after centrifugation and filtration, is subjected to spectrophotometric analysis.

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Spectrophotometry

A method used for the identification and quantitative analysis of substances. The method is based on the dependence of the optical density (OD) of a substance solution on the wavelength of light passing through it.

Normally, the change in the OP of amniotic fluid depending on the wavelength of the transmitted light is a smooth curve with maximum absorption at a short wavelength. If the bilirubin content in the amniotic fluid is elevated, the OP values show an absorption peak at a wavelength of 450 nm, and the peak size is proportional to the pigment content. The deviation value is the delta OP (delta OP-450) - the difference between the obtained value and the OP value on the absorption graph of 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 appearance of the curve: blood gives sharp peaks at 415, 540 and 580 nm, meconium gives an absorption peak at 412 nm.

Various systems for assessing spectrophotograms have been proposed and used – the Lily scale, the Fred scale, etc. They allow determining the severity of the disease in the fetus and choosing the correct tactics for managing the patient – a conservative method, early delivery, or intrauterine transfusions. However, the Lily scale can 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 is usually undamaged and is born with a cord blood hemoglobin level above 120 g/l (normal is 165 g/l). This situation does not require early delivery.
• Zone II (medium). Early delivery is not performed until the bilirubin level rises to the border of the dangerous zone III or the fetus reaches 32 weeks of pregnancy. The hemoglobin level in the umbilical cord blood is usually 80-120 g/l. Early delivery is indicated in the following cases:
  • the fetal lungs are ripe;
  • the previous intrauterine death of the fetus occurred within the same time frame;
  • a sharp increase in delta OP-450 to 0.15 and higher.
• Zone III (upper). Antenatal death of the fetus is possible within 7-10 days. Blood transfusion should be performed, and if this is not possible, delivery should be performed. The cord blood hemoglobin level is usually below 90 g/l. A descending OP-450 nm curve after the 2nd or 3rd study is a good prognostic sign. If the delta OP-450 nm values fall into zone I, no further interventions are required.

The value of the optical density of bilirubin can also be determined using a photoelectrocolorimeter (PEC). Using a PE 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 less than 0.1 relative units indicates the absence of fetal disease. An increase in the optical density of bilirubin occurs with the development of hypertension: values of 0.1-0.15 indicate a mild degree of the disease, 0.15-0.2 - moderate, PE of more than 0.2 with a high probability suggests the presence of a severe form of GBP, which indicates the need for delivery.

Bilirubin concentration is an indirect indicator of hemolysis and anemia in the fetus. More accurate information can be obtained by examining the fetus's blood directly, obtained by cordocentesis.

Blood is collected from the umbilical cord using an aspiration needle inserted transabdominally under ultrasound guidance.

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

• blood type and Rh factor;
• hemoglobin and hematocrit;
• antibodies associated with fetal red blood cells (direct Coombs reaction);
• bilirubin;
• reticulocyte count;
• whey protein level;
• KOS.

If the fetus has Rh-negative blood, no further testing is performed during pregnancy. Cordocentesis is especially important in women with previous Rh immunization, when the antibody level cannot serve as a criterion for assessing the severity of hemolytic disease of the fetus (with high antibody titers, the fetus may nevertheless be Rh-negative).

In most cases, ultrasound diagnostics, assessment of blood flow velocity in the middle cerebral artery, results of amniocentesis and cordocentesis allow to develop the correct tactics of patient management. The management plan depends on the gestational age, the condition of the fetus and the level of perinatal service in a given institution (the possibility of intrauterine blood transfusions and nursing of premature babies).

Pregnancy management tactics depending on the examination results

• If the patient has a delta OP of 450 nm in zone III or a fetal hematocrit level below 30%, or if there are ultrasound signs of fetal hydrops, delivery should be undertaken after 34 weeks of pregnancy.
• In a gestational period of less than 34 weeks with similar indicators, either intrauterine blood transfusion or delivery is required.

The final decision should be made based on the assessment of fetal lung maturity, obstetric history, and the increase in bilirubin levels in the amniotic fluid, as well as the capabilities of the perinatal service. If intrauterine blood transfusions are not possible, respiratory distress syndrome should be prevented with corticosteroids for 48 hours. Delivery can be attempted 48 hours after the first dose of corticosteroids. It should be remembered that delta 459 nm values decrease after the administration of corticosteroids, but the physician should not consider this a sign of improvement in the course of the disease.

If the gestation period is less than 34 weeks, the fetal lungs are immature and there is a possibility of performing intrauterine blood transfusions, then they begin to be performed.

Methods of performing intrauterine blood transfusions

There are two methods of performing intrauterine blood transfusions: intraperitoneal - introduction of red blood cell mass directly into the abdominal cavity of the fetus (this method is currently practically not used); intravascular - introduction of red blood cell mass into the umbilical vein.

Intravascular 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 transfusion, a longer interval between transfusions is possible and delivery can be delayed until the fetus reaches a more mature gestational age.

Intravascular blood transfusion

Technique. Under ultrasound control, the position of the fetus and the puncture site of the umbilical vein are determined. Using a 20- or 22-gauge needle, the umbilical vein is punctured transabdominally under ultrasound control near the place where it departs from the placenta. In order to immobilize the fetus, muscle relaxants are administered intravascularly (through the umbilical vein) or intramuscularly to the fetus.

Blood transfusion is performed at an initial rate of 1–2 ml/min, gradually increasing the rate to 10 ml/min. Before and after blood transfusion of red blood cells, the fetal hematocrit is determined. The final hematocrit determines the adequacy of the blood transfusion. The desired final hematocrit (after transfusion) is 45%. In severe fetal anemia with a hematocrit below 30%, transfusions allow maintaining the hematocrit at a level close to normal for a given gestational age (45–50%).

Requirements for red blood cells: blood group O, Rh negative, tested and negative for hepatitis B, C, cytomegalovirus and HIV, compatible with mother and fetus, washed in saline to minimize the risk of viral contamination.

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

Intravascular blood transfusion provides:

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

Complications:

• fetal death (in the absence of fetal hydrops in 0–2% of cases, with fetal hydrops in 10–15% of cases);
• fetal bradycardia 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. It is difficult to assess complications due to the fact that seriously ill fetuses are being treated.

Progression or regression of hydrops fetalis can be monitored by ultrasound, which allows determining the indications for repeat transfusion. In 60–70% of cases, repeat transfusion is required after 2–3 weeks. Amniocentesis is of little value after intrauterine blood transfusion, when the amniotic fluid is usually contaminated with blood. In this case, a false increase in bilirubin levels in the amniotic fluid is possible.

Delivery should be attempted only when the risk of preterm delivery is less than the risk of intrauterine transfusion. Typically, this occurs by 34 weeks of gestation. Caesarean section is the optimal method of delivery for hydrops and severe fetal anemia, when there is a high risk of compromise during labor. A neonatal team with blood for exchange transfusion should be present during delivery.