Rh disease (also Rhesus disease, Haemolytic Disease of the Newborn (HDNB) or Morbus haemolyticus neonatorum or erythroblastosis) is a condition that occurs when a Rh negative mother has given birth to a Rh positive baby and subsequently becomes pregnant with another Rh positive child. About 5% of at-risk pregnancies would result in still births or extremely sick babies. Many who managed to survive would be severely retarded. Once a woman gives birth to a baby with the disease, all subsequent babies would also have it. The connection between the Rh antigen and erythroblastosis was made in 1941 by Dr. Philip Levine. The treatment that came to be developed for the disease was blood transfusion, which was often ineffective or only partially ameliorative because the damage had already been done. Severely retarded children often resulted.

During the first pregnancy and the act of birth a small amount of the baby's blood may enter the mother's body. If the mother is Rh negative, her body produces antibodies (including IgG) against the Rhesus antigens on her baby's erythrocytes, if the baby is Rh positive. During the second pregnancy the IgG is able to pass through the placenta into the fetus, where it leads to agglutination and destruction of erythrocytes. The means to prevent this harmful disease is to vaccinate the mother immediately after the birth of her first child: she is treated with anti-Rh antibodies, so that the fetal erythrocytes are destroyed before her immune system can discover them.

This explanation of the etiology of the disease was first worked in 1960 out by Dr. Ronald Finn, a Liverpool, England native, who applied a microscopic technique for detecting fetal cells in the mother's blood. It lead him to propose that the disease might be prevented by injecting the at-risk mother with an antibody against fetal red blood cells. He proposed this for the first time to the public on February 18, 1960. A few months later, he proposed at a meeting of the British Genetical Society, that the antibody be anti-Rh. Nearly simultaneously with him, a group of researchers from New York City Columbia-Presbyterian Medical Center, John Gorman, Vince Freda, and Bill Pollack came to the same realization, and set out to prove it by injecting a group of male prisoners at Sing Sing Correctional Facility with anti-body supplied by Ortho Pharmaceutical Corporation. Dr. Gorman's daughter-in-law was the first at risk woman to receive a prophylactic injection on January 31, 1964. Clinical trials by the two rival groups, and others quickly confirmed their hypothesis, and the vaccine was finally approved in England and the United states in 1968. Within a year or so, it had been injected with great success into more than 500,000 women. Time magazine picked it as one of the top ten medical achievements of the 1960's. By 1973, it was estimated that in the US alone, over 50,000 baby's lives had been saved.

Importance of the Rh factor

The Rh factor, a blood protein, plays a critical role in some pregnancies. If an Rh negative woman is pregnant with a fetus who is Rh positive, her body will produce antibodies against the fetus's blood. This can cause Rh disease, also known as hemolytic disease of the newborn, or erythroblastosis fetalis, in the baby. In severe cases, Rh disease leads to brain damage and even death.

Rh factor is important only during a pregnancy in which an Rh negative woman is carrying an Rh positive fetus . This can occur when an Rh negative woman conceives a baby with an Rh positive man. The gene for Rh positive blood is dominant over the gene for Rh negative blood, so their baby will be Rh positive. If the Rh positive father also carries the gene for Rh negative blood, his children have a 50% chance of inheriting Rh negative blood and a 50% chance of inheriting Rh positive blood. If both parents are Rh negative, their offspring will always be Rh negative. In order to protect their future children from Rh disease, all women of childbearing age should know their Rh status before becoming pregnant.

Rh factor in pregnancy

The conditions allowing for Rh disease are established when the blood of an Rh negative mother is exposed to the Rh positive blood of her first baby, prompting the mother's immune system to build up antibodies to fight the foreign blood protein. Since this exposure usually occurs at birth, the first child is generally unaffected, but any fetus the mother carries afterward will develop Rh disease unless preventative measures are taken. Mixing of blood also occurs during an abortion or miscarriage and results in the same sensitization. Certain prenatal tests, such as amniocentesis and chorionic villi sampling, can also result in maternal exposure to fetal blood.

The attack of a mother's antibodies on the red blood cells of her Rh positive fetus results in several serious conditions. The first, anemia , refers to a reduction in red blood cells and is marked by weakness and fatigue. Another consequence is the buildup of a reddish yellow fluid called bilirubin, which in turn causes jaundice . If the bilirubin level gets high enough, brain damage can result. The most severe form of Rh disease, called hydrops fetalis, is marked by profound anemia and edema. Infants with hydrops fetalis are usually stillborn or only survive a few hours after birth.

Treatment for Rh disease

Since 1968 a vaccine has existed which prevents sensitization from even occurring. The vaccine is considered the best way to eliminate Rh disease because it prevents the mother's body from making antibodies against the fetus's blood. The vaccine, called Rh immune globulin (RhoGAM), is available by injection. RhoGAM blocks the action of the antibodies and prevents the mother's antibodies from attacking the baby's blood. To be effective, the vaccine must be given any time fetal blood mixes with maternal blood: after birth, abortion, miscarriage, or prenatal tests like amniocentesis and chorionic villus sampling. The vaccine is typically given within 72 hours of any of these events. Since mixing of the blood may occur during the last three months of pregnancy, some health care providers recommend receiving the vaccine at 28 weeks of pregnancy.

If a woman has become sensitized during a previous pregnancy, she can still take steps to prevent future babies who are Rh positive from developing Rh disease. Unfortunately, once the harmful antibodies are in a woman's blood, they cannot be removed.

A pregnant woman who has already been sensitized from a previous pregnancy should be carefully monitored throughout her pregnancy for the level of antibodies in her blood. As long as the antibody levels remain relatively low, no problem exists. However, if those levels rise, the fetus will need special attention. High antibody levels indicate that the fetus's red blood cells are being attacked and destroyed.

In these circumstances, the fetus will need a blood transfusion while it is still in the uterus. Two or three transfusions may be necessary before the baby is born. If the fetus shows signs of illness close to its anticipated birth, the physician may elect to deliver the baby early, either through an induced birth or cesarean section. The baby will then receive a transfusion after birth.

Eliminating Rh disease

Until the introduction of RhoGAM, Rh disease could not be prevented. Prior to widespread use of the vaccine in the early 1970s, researchers reported that approximately 45 babies per 10,000 births developed Rh disease yearly. The number of newborns with Rh disease has dropped dramatically ever since the introduction of the vaccine; about 10 per 10,000 in the early 1990s. The prevention of Rh disease is one of the triumphs of modern medicine.

Nevertheless, a relatively high number of newborns with Rh disease are still delivered each year in the United States. Clearly, the disease is not completely eradicated. Further steps must be taken since this is a preventable disease. The majority of Rh disease cases of are the result of women not receiving the vaccine at the appropriate time. Poor women, particularly those without health insurance, are the ones most at risk for inadequate prenatal care. Older women may have become sensitized before the vaccine was available. Foreign-born women may not have had access to the vaccine. With further diligence, health care providers hope to eradicate Rh disease.

Gale Encyclopedia of Childhood & Adolescence. Gale Research, 1998.

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