Rh incompatibility is a condition which develops when a pregnant woman has an Rh-negative blood type and the fetus she carries has Rh-positive blood type.
The Rh factor (ie, rhesus factor) is an red blood cell surface antigen that was named after the monkeys in which it was first discovered. Rh incompatibility, also known as Rh disease, is a condition that occurs when a woman with Rh-negative blood type is exposed to Rh-positive blood cells, leading to the development of Rh antibodies.
Rh incompatibility can occur by two main mechanisms. The most common type occurs when an Rh-negative pregnant mother is exposed to Rh-positive fetal red blood cells secondary to fetomaternal hemorrhage during the course of pregnancy from spontaneous or induced abortion, trauma, invasive obstetric procedures, or delivery. Rh incompatibility can also occur when an Rh-negative female receives a blood transfusion that contains Rh antigens. In part, this is the reason that blood banks prefer using blood type “O-negative” or “type-O, Rh negative,” as the universal donor type, especially in females.
The most common cause of Rh incompatibility is exposure to an Rh-negative mother by Rh-positive fetal blood during pregnancy or delivery, whereby red blood cells from the fetal circulation leak into the maternal circulation. After a significant exposure, sensitization occurs and maternal antibodies are produced against the foreign Rh antigen.
Once produced, maternal Rh immunoglobulin G (IgG) antibodies may cross freely from the placenta to the fetal circulation, where they form antigen-antibody complexes with Rh-positive fetal erythrocytes and eventually are destroyed, resulting in a fetal alloimmune-induced hemolytic anemia. Although the Rh blood group systems consist of several antigens (eg, D, C, c, E, e), the D antigen is the most immunogenic; therefore, it most commonly is involved in Rh incompatibility.
Causes, incidence, and risk factors
During pregnancy, red blood cells from the fetus can get into the mother’s bloodstream as she nourishes her child through the placenta. If the mother is Rh-negative, her system cannot tolerate the presence of Rh-positive red blood cells.
In such cases, the mother’s immune system treats the Rh-positive fetal cells as if they were a foreign substance and makes antibodies against the fetal blood cells. These anti-Rh antibodies may cross the placenta into the fetus, where they destroy the fetus’s circulating red blood cells.
First-born infants are often not affected — unless the mother has had previous miscarriages or abortions, which could have sensitized her system — as it takes time for the mother to develop antibodies against the fetal blood. However, second children who are also Rh-positive may be harmed.
Rh incompatibility can cause symptoms ranging from very mild to fatal. In its mildest form, Rh incompatibility causes hemolysis (destruction of the red blood cells) with the release of free hemoglobin into the infant’s circulation.
Hemoglobin is converted into bilirubin, which causes an infant to become yellow (jaundiced). The jaundice of Rh incompatibility, measured by the level of bilirubin in the infant’s bloodstream, may range from mild to dangerously high levels of bilirubin.
Hydrops fetalis is a complication of a severe form of Rh incompatibility in which massive fetal red blood cell destruction (a result of the Rh incompatibility) causes a severe anemia resulting in fetal heart failure, total body swelling, respiratory distress (if the infant has been delivered), and circulatory collapse. Hydrops fetalis often results in death of the infant shortly before or after delivery.
Kernicterus is a neurological syndrome caused by deposition of bilirubin into the brain (CNS) tissues. Kernicterus develops in extremely jaundiced infants, especially those with severe Rh incompatibility.
It occurs several days after delivery and is characterized initially by loss of the Moro (startle) reflex, poor feeding, and decreased activity. Later, a high-pitched shrill cry may develop along with unusual posturing, a bulging fontanel, and seizures. Infants may die suddenly of kernicterus.
If they survive, they will usually later develop decreased muscle tone, movement disorders, high-pitched hearing loss, seizures, and decreased mental ability.
Rh incompatibility develops only when the mother is Rh-negative and the infant is Rh-positive. Special immune globulins, called RhoGAM, are now used to prevent this sensitization. In developed countries such as the US, hydrops fetalis and kernicterus have decreased markedly in frequency as a result of these preventive measures.
The amount of fetal blood necessary to produce Rh incompatibility varies. In one study, less than 1 mL of Rh-positive blood has been shown to sensitize volunteers with Rh-negative blood. Conversely, other studies have suggested that 30% of persons with Rh-negative blood never develop Rh incompatibility, even when challenged with large volumes of Rh-positive blood. Once sensitized, it takes approximately one month for Rh antibodies in the maternal circulation to equilibrate in the fetal circulation. In 90% of cases, sensitization occurs during delivery. Therefore, most firstborn infants with Rh-positive blood type are not affected because the short period from first exposure of Rh-positive fetal erythrocytes to the birth of the infant is insufficient to produce a significant maternal IgG antibody response.
The risk and severity of sensitization response increases with each subsequent pregnancy involving a fetus with Rh-positive blood. In women who are prone to Rh incompatibility, the second pregnancy with an Rh-positive fetus often produces a mildly anemic infant, whereas succeeding pregnancies produce more seriously affected infants who ultimately may die in utero from massive antibody-induced hemolytic anemia.
Risk of sensitization depends largely upon the following 3 factors:
1. Volume of transplacental hemorrhage
2. Extent of the maternal immune response
3. Concurrent presence of ABO incompatibility
The incidence of Rh incompatibility in the Rh-negative mother who is also ABO incompatible is reduced dramatically to 1-2% and is believed to occur because the mother’s serum contains antibodies against the ABO blood group of the fetus. The few fetal red blood cells that are mixed with the maternal circulation are destroyed before Rh sensitization can proceed to a significant extent.
Rh incompatibility is only of medical concern when transfusion is needed and during pregnancy. Rh positive antibodies circulating in the bloodstream of an Rh-negative woman have no adverse effect in the nonpregnant state.