Rh sensitization occurs during pregnancy when an Rh-negative mother is exposed to Rh-positive blood from her fetus. The Rh factor, specifically the D antigen, is a protein on the surface of red blood cells; people who have it are Rh-positive, and those without it are Rh-negative. Rh incompatibility arises when the mother’s immune system perceives the fetal red blood cells as foreign invaders. This sensitization process creates antibodies that can pose a danger to the baby in the current or future pregnancies.
The Biological Mechanism of Rh Sensitization
The immune response begins when Rh-positive fetal red blood cells enter the Rh-negative mother’s circulation. These cells carry the D antigen, which the mother’s immune system does not recognize as “self.” The initial exposure causes the mother’s B-cells to activate, beginning the process of sensitization.
The maternal immune system develops anti-Rh antibodies, specialized proteins designed to target and destroy the D antigen. These antibodies are primarily Immunoglobulin G (IgG), which are small enough to pass through the placenta into the fetal bloodstream. The first exposure typically results in a slow, mild immune response, and the first Rh-positive fetus is often unaffected.
However, this initial event primes the mother’s immune system by creating immune memory. In subsequent pregnancies with an Rh-positive fetus, if a second exposure occurs, the immune system launches a rapid and massive secondary response, immediately producing large quantities of IgG antibodies. These antibodies readily cross the placenta and begin destroying the fetal red blood cells, leading to severe health consequences.
Events That Trigger Maternal Exposure
The mixing of maternal and fetal blood, known as fetomaternal hemorrhage, is the event that triggers the sensitization process. The most common time for this mixing to occur is during the birth of an Rh-positive baby, as the placenta separates from the uterine wall.
Sensitization can also be triggered by events that disrupt the placental barrier earlier in the pregnancy. These include a miscarriage, an abortion, or an ectopic pregnancy, even if they occur early in gestation. Invasive prenatal procedures, such as amniocentesis or chorionic villus sampling (CVS), also pose a risk of blood mixing.
Other potential triggers include significant abdominal trauma to the mother during pregnancy or the manual turning of a breech baby, known as external cephalic version. Unexplained bleeding during the second or third trimester is also considered a potential exposure event that requires medical intervention.
Health Consequences for the Fetus and Newborn
Once the maternal anti-Rh antibodies cross the placenta, they attach to the Rh-positive fetal red blood cells, marking them for destruction. This process, called hemolysis, leads to Hemolytic Disease of the Fetus and Newborn (HDFN). The rapid destruction of red blood cells causes severe anemia in the fetus, reducing the blood’s oxygen-carrying capacity.
To compensate for the anemia, the fetal body attempts to produce red blood cells at an accelerated rate, leading to the enlargement of the liver and spleen. The severe anemia can eventually cause the fetal heart to struggle and fail, leading to a dangerous buildup of fluid in the baby’s tissues and organs, a condition called hydrops fetalis. This complication can result in stillbirth.
After birth, the newborn continues to break down red blood cells, which releases a yellow pigment called bilirubin. Since the newborn’s immature liver cannot process the large amounts of bilirubin quickly enough, it builds up in the blood, causing severe jaundice. Extremely high levels of bilirubin can cross into the brain, potentially causing permanent neurological damage known as kernicterus.
Modern Prevention and Management
The medical community prevents Rh sensitization through the use of Rh immune globulin (RhoGAM). This medication is made from donated blood plasma and contains passive anti-Rh antibodies. The injection is administered to the Rh-negative mother at specific times when blood mixing is likely to occur.
The injection works by destroying any Rh-positive fetal red blood cells that have entered the mother’s bloodstream before her own immune system can recognize them. By clearing the D antigen from the circulation, RhoGAM prevents the mother’s B-cells from activating and forming permanent immune memory. Typically, an Rh-negative mother receives a prophylactic injection around the 28th week of pregnancy and another dose shortly after delivery if the baby is found to be Rh-positive.
For mothers who have already become sensitized, prevention is no longer possible, and management shifts to protecting the fetus. These pregnancies are closely monitored using specialized ultrasound scans, such as Doppler studies of the fetal middle cerebral artery, to assess the degree of fetal anemia. If the fetus develops severe anemia, blood can be administered directly into the fetal circulation through a procedure called an intrauterine transfusion.