A common cause of fetal anemia in the United States is RBC alloimmunization. This condition occurs when the RBCs of the mother and those of the fetus are incompatible. Specifically, if fetal RBCs cross into the maternal bloodstream, the mother’s immune system recognizes these cells as foreign and produces antibodies against them. These antibodies remain in the mother’s bloodstream even after pregnancy. In a later pregnancy with a fetus whose RBCs are incompatible with the mother’s RBCs, the antibodies can cross the placenta and target the fetal RBCs. This leads to the destruction of fetal red blood cells, a condition known as hemolytic disease of the fetus and newborn (HDFN).

Fetal anemia can also be caused by parvovirus infection. Also known as “fifth disease,” parvovirus is a common childhood viral infection that causes a rash on the face, trunk, arms, and legs. In a fetus, the virus can attack developing RBCs in the bone marrow. The result can be severe anemia, especially if the infection occurs before 20 weeks of pregnancy. Other infections, including cytomegalovirus (CMV), coxsackie virus, and syphilis, can also cause fetal anemia.

Fetal anemia may occur in certain genetic and metabolic disorders. Some twin pregnancies that share a placenta are also at risk of fetal anemia.

A diagnosis of fetal anemia can be made only by sampling blood from the umbilical cord. This procedure, called cordocentesis, is performed at specialized centers. There is a small risk of pregnancy loss and early delivery. Stillbirth is reported in 1–2% of pregnancies following cordocentesis, which can be related to the procedure or to the underlying anemia in the fetus.

To make the diagnosis of anemia in a fetus, doctors may use ultrasound to check the blood flow in one of the arteries in the fetal brain (called the middle cerebral artery or MCA). One of the fetal responses to anemia is to speed up the blood flow to the brain. This test is used to screen for fetal anemia in several conditions, including RBC alloimmunization and parvovirus. Measurement of MCA blood flow using ultrasound is performed by ultrasonographers, maternal-fetal medicine physicians, or others with special training in the proper technique.

In severe cases of fetal anemia, blood can be given to the fetus. This is called an intrauterine transfusion. This treatment is done by specialists at centers with expertise in this type of therapy. Your healthcare professional will discuss the risks and benefits of intrauterine transfusion with you before the procedure so that you can make an informed decision.

Treatment varies depending on the suspected cause of the disease. If RBC alloimmunization is suspected, a key step is finding out the blood type of the father to determine whether the fetus is at risk. If that is not possible, the fetal blood type can be determined using amniocentesis or, in some cases, by testing a sample of your blood using cell-free DNA technology. If you have antibodies against the fetus’s blood, you will be tested several times during pregnancy to measure your antibody levels. If antibody levels are too high, you may have additional tests such as extra ultrasound exams to evaluate blood flow in the fetal brain or a fetal blood test to check the fetus’s health.

If you’ve had a prior pregnancy complicated by fetal anemia due to maternal antibodies, antibody levels are not helpful in the current pregnancy. Ultrasound or direct testing of fetal RBC levels may be done to find the cause of the fetal anemia.

If you were exposed to parvovirus, your healthcare professional will test to see if you had parvovirus infection in the past and are now immune. But if you haven’t had it in the past, and a current infection is confirmed, you may need close monitoring with ultrasound during your pregnancy to check for signs of fetal anemia.