Red Blood Cell Rh-alloimmunization and Fetal Anemia

Rh alloimmunization is condition in which the mother and the fetus have an immunological incompatibility for the red blood cell Rh factor, such that the mother (Rh-negative) recognizes the red blood cells of the fetus (Rh-positive) as foreign. As a result, the mother develops antibodies (immunological proteins) that can cross the placenta and attach to the Rh-antigens on the red blood cells of the fetus and destroy them. The fetus tries to compensate for the destruction of its red blood cells by producing more red blood cells and releasing them more promptly into the circulation. If the fetus is not able to compensate, it develops various degrees of anemia, but ultimately may go into heart failure and it may die.

How does Rh-alloimmunization occur?

An Rh-negative mother can become sensitized to Rh-positive antigens in several ways. During pregnancy, fetal red blood cells may gain access to the mother’s circulation and generate the immunological reaction. This can occur during a normal pregnancy, but can also occur after a miscarriage or an ectopic pregnancy. Rarely, the patient may become sensitized from blood transfusions or from shared needles. Although the mother may become sensitized during the first pregnancy, the immunological effects on the fetus are not typically seen in that pregnancy.

After the mother has been sensitized in a prior pregnancy, subsequent pregnancies with an Rh-positive fetus may elicit the immunological response and produce various degrees of anemia in the fetus.

How can Rh-alloimmunization be prevented?

Rh-negative mothers should be given Rh(D) immunoprophylaxis after a miscarriage, ectopic pregnancy or within 48 hours after a normal pregnancy. In addition, Rh(D) immunoprophylaxis is given at 28 weeks to prevent alloimmunization during pregnancy but before delivery. If immunoprophylaxis is not given after birth, the risk of alloimmunization is approximately 13%. If immunoprophylaxis is given after birth, the risk of alloimmunization drops to approximately 1.3%. If immunoprophylaxis is given at 28 weeks and after delivery, the risk of alloimmunization is 0.13%.

How is alloimmunization detected?

The maternal blood type and antibody testing is included in the prenatal labs. If the mother is noted to be sensitized to Rh-antigens, the fetus could be at risk. The antibody screen may detect other antibodies, different from the Rh-group, that may or may not affect the fetus. Once the antibody is detected and if it is associated with a risk of fetal anemia, the next step is to determine if the father of the baby may carry the antigen or not. If the father is Rh-positive and has had Rh-negative children, the current pregnancy would have a 50% chance of being Rh-positive. If the father has not had prior children or only Rh-positive children, the Rh-genotype of the father may be assessed. A new test is currently available that can detect whether the fetus is Rh-positive by obtaining a sample of blood from the mother. This avoids the prior practice of having to obtain a sample of placenta, amniotic fluid or fetal blood to determine whether the fetus is Rh-positive.

Prenatal Diagnosis of Fetal Anemia

If the mother is sensitized and the fetus is Rh-positive, the fetus is at risk of developing anemia. Previous methods to determine fetal anemia included repeated (serial) amniocenteses to test for colorimetric changes due to the breakdown of fetal red blood cells, or fetal blood sampling and direct assessment of the fetal hemoglobin count and hematocrit. Measurement of the speed of fetal blood with ultrasound has shown to be superior to the previous methods, in addition to being a non-invasive method. The fetal vessel sampled for this measurement is the middle cerebral artery, as this vessel is typically in an ideal position to assess the maximum (peak) velocity at the ejection of blood from the heart (systole). The observed peak systolic velocity of the middle cerebral artery (MCA-PSV) is compared to the expected value at a particular gestational age, between 18 – 35 weeks. If the value is >1.5 multiples of the mediam (MOM), the fetus is at risk of having severe anemia. Thus, patients at risk for developing fetal anemia should be followed with serial (weekly) MCA-PSV measurements to monitor for the possible development of fetal anemia.

Ultrasound may also detect abnormal fluid collections of fluid within the baby (swelling of the skin, fluid in the chest, around the heart, in the abdomen), which are overt signs of heart failure associated with severe anemia. The presence of fluid accumulation in 2 or more fetal spaces is called hydrops.

What can be done if the fetus is suspected of being anemic?

If the fetus is suspected of being anemic, either from the MCA-PSV Doppler measurements or from the presence of fluid accumulation or hydrops, the management options include either fetal blood transfusion or delivery, depending on the gestational age. In the most common method, fetal blood transfusion is performed by accessing the umbilical cord of the fetus with a thin needle inserted through the mother’s abdomen and uterus under ultrasound guidance. A small sample of fetal blood is obtained and checked for anemia. Transfusion of Rh-negative blood specially prepared for this procedure is then performed to replenish partially or totally the hemoglobin deficit. The procedure may need to be repeated during pregnancy until delivery becomes a better option. Other methods include accessing a vein within the fetal liver where the blood is transfused, or placing the transfused blood into the fetal abdomen, where it is slowly absorbed over time. In some cases, blood is transfused both into a fetal vessel and also into the fetal abdomen. In rare instances, particularly if hydrops develops at such an early gestational age that access to the umbilical cord or other vessels is technically very difficult or impossible, direct transfusion of blood into the fetal heart has also been performed. The overall goal of any technique is to perform as few of them as feasible, while achieving the best gestational age possible.