Fetal anemia is a condition where a developing baby has a lower-than-normal amount of red blood cells or hemoglobin, the protein responsible for carrying oxygen. A low count means the fetus is not getting enough oxygen, forcing the heart to work harder and faster to circulate the limited supply of oxygen-carrying blood. This overexertion can lead to heart failure and a dangerous condition called hydrops fetalis, which is an abnormal accumulation of fluid in multiple body areas.
Maternal Immune System Responses
One of the most common causes of severe fetal anemia is alloimmunization, an immune response where the mother’s body produces antibodies against the red blood cells of the fetus. This typically happens when fetal red blood cells cross into the maternal bloodstream, often during a previous pregnancy, delivery, or a procedure like amniocentesis. The mother’s immune system recognizes the fetal red blood cell antigens as foreign and creates antibodies to attack them.
The most widely known example is Rhesus (Rh) incompatibility, where an Rh-negative mother is sensitized by an Rh-positive fetus. In subsequent pregnancies, the maternal antibodies (IgG) cross the placenta and coat the fetal red blood cells. These coated cells are then destroyed in the fetal spleen by specialized immune cells, a process called hemolysis, leading to anemia.
While Rh disease is now largely preventable, other non-Rh antibodies can still cause similar issues. Antibodies against other red blood cell antigens, such as Kell, Duffy, and Kidd, can also cross the placenta and destroy the fetus’s red blood cells. Kell antibodies are particularly concerning because they not only cause red blood cell destruction but can also suppress the production of new red blood cells in the fetal bone marrow, leading to a more profound anemia.
Viral and Bacterial Infections
Infections that cross the placenta can also cause fetal anemia, primarily by suppressing the bone marrow’s ability to produce new red blood cells, resulting in an aplastic crisis. The most frequent infectious cause of severe fetal anemia is Parvovirus B19, commonly known as Fifth Disease. This virus specifically targets and destroys the erythroid progenitor cells, which are the precursors to red blood cells, in the fetal bone marrow and liver.
The fetus is especially vulnerable to Parvovirus B19 infection before 20 weeks of gestation because the red blood cells have a shorter lifespan, and the virus attacks the rapidly dividing precursor cells. The direct destruction of these cells causes a temporary halt in red blood cell production. The resulting anemia can be severe, leading to heart failure and hydrops fetalis. Other infections like Cytomegalovirus (CMV), toxoplasmosis, and syphilis are also known to potentially cause fetal anemia, though they are less common causes of severe cases compared to Parvovirus B19.
Inherited Blood Cell Disorders
Genetic conditions passed down from the parents can lead to fetal anemia by causing intrinsic defects in the red blood cells themselves. These disorders cause chronic hemolysis, where the red blood cells are improperly formed or are fragile and destroyed prematurely.
One severe example is Alpha-Thalassemia, specifically the most serious form known as Hemoglobin (Hb) Barts syndrome, which results from the absence of all four alpha-globin genes. Alpha-globin is a component of hemoglobin, and its absence means the fetus cannot produce functional adult hemoglobin, leading to severe anemia and hydrops fetalis, often resulting in stillbirth or death shortly after birth without intervention.
Another inherited cause is Sickle Cell Disease, which is caused by a single amino acid error in the beta-globin chain, resulting in abnormal hemoglobin S. This abnormal hemoglobin causes red blood cells to take on a sickle shape under certain conditions, leading to their premature destruction and chronic anemia.
Fetal Hemorrhage and Circulatory Problems
Fetal anemia can also result from the physical loss of blood or an unequal distribution of blood volume between twins. Feto-Maternal Hemorrhage (FMH) occurs when a significant amount of the fetus’s blood transfers into the mother’s circulation through a breach in the placental barrier. While small amounts of fetal blood routinely enter the mother’s bloodstream, a massive FMH can acutely deplete the fetus’s blood volume, causing severe anemia. This can occur spontaneously or follow trauma or certain obstetric complications.
Another circulatory issue is Twin-to-Twin Transfusion Syndrome (TTTS), which affects identical twins who share a single placenta. In TTTS, abnormal connections between the blood vessels in the shared placenta cause blood to be unequally distributed. This results in one twin, the donor, becoming anemic and growth-restricted, while the recipient twin receives too much blood, leading to polycythemia and fluid overload.