What are Rh incompatibility and isoimmunization?

Risk Factors

Risk factors for Rh incompatibility and isoimmunization include being a pregnant woman with Rh-negative blood who had a prior pregnancy with a fetus that was Rh positive; being a pregnant woman who had a prior blood transfusion or amniocentesis; and being a pregnant woman with Rh-negative blood who did not receive Rh immunization prophylaxis during a prior pregnancy with an Rh-positive fetus.

Etiology and Genetics

The Rh locus on the short arm of chromosome 1 at position 1p36.2-p34 actually consists of two genes, RHD and
RHCE, that are organized in tandem and are so similar in sequence that it is clear that they evolved from the duplication of a common ancestral gene. There are two phenotypes, Rh positive and Rh negative, that are distinguished by the presence or absence of the RhD antigen (the protein product of the RHD gene) on the surface of red blood cells. The RHCE gene encodes both the RhC and RhE proteins, but since these do not confer antigenic properties on the cell, they do not contribute to the Rh phenotype. Most individuals who are Rh negative have a deletion of the entire RHD gene and retain only the RHCE gene.

The Rh-positive allele is dominant to the Rh-negative allele, so Rh-positive individuals have either one or two copies of the RHD gene. Rh-negative individuals lack the RHD gene on both of their copies of chromosome 1. Two Rh-positive individuals who are both heterozygous (having only one copy of the RHD gene) have a 25 percent chance of having an Rh-negative child and a 75 percent chance of having an Rh-positive child. In all cases of Rh incompatability, the mother is Rh negative and both the father and the developing fetus are Rh positive.

Symptoms

Symptoms and complications affect only the fetus and/or newborn. They occur when standard preventive measures are not taken and can vary from mild to very serious. The mother’s health is not affected.

Symptoms of the fetus or newborn baby include anemia and swelling of the body (also called hydrops fetalis), which may be associated with heart failure and respiratory problems. Another symptom is kernicterus (a neurological syndrome), which can occur in stages.

Symptoms in the early stage include a high bilirubin level (greater than 18 milligrams/cubic centimeters), extreme jaundice, an absent startle reflex, a poor suck, and lethargy. Symptoms in the intermediate stage include a high-pitched cry, an arched back with neck hyperextended backward (opisthotonos), a bulging fontanel (soft spot), and seizures. Late-stage symptoms include high-pitched hearing loss, mental retardation, muscle rigidity, speech difficulties, seizures, and movement disorder.

Screening and Diagnosis

There are not any physical symptoms that would allow women to detect on their own if they are Rh incompatible with any given pregnancy. If women are pregnant, it is standard procedure for their health care providers to order a blood test that will determine whether they are Rh positive or Rh negative. If the blood test indicates that they have developed Rh antibodies, their blood will be monitored regularly to assess the level of antibodies it contains. If the levels are high, an amniocentesis would be recommended to determine the degree of impact on the fetus.

Treatment and Therapy

Since Rh incompatibility is almost completely preventable with the use of prophylactic immunization (immune globulin injection of RhoGAM), prevention remains the best treatment.

Women will be given an injection of Rho immune globulin at week twenty-eight of their pregnancy. This desensitizes their blood to Rh-positive blood. They will also have another injection of immune globulin within seventy-two hours after delivery (or miscarriage, induced abortion, or ectopic pregnancy). This injection further desensitizes their blood for future pregnancies.

Treatment of a pregnancy or newborn depends on the severity of the condition. If the condition is mild, treatment includes aggressive hydration and phototherapy using bilirubin lights.

Treatment for hydrops fetalis includes amniocentesis to determine severity, an intrauterine fetal transfusion, and early induction of labor. A direct transfusion of packed red blood cells (compatible with the infant’s blood) and exchange transfusion of the newborn may be done to rid the infant’s blood of the maternal antibodies that are destroying the red blood cells. Treatment may also include control of congestive failure and fluid retention.

Treatment for kernicterus includes exchange transfusion (which may require multiple exchanges) and phototherapy.

Full recovery is expected for mild Rh incompatibility. Both hydrops fetalis and kernicterus represent extreme conditions caused by the breakdown of red blood cells, called hemolysis. Both have guarded outcomes; hydrops fetalis has a high risk of mortality. Long-term problems can result from severe cases, including cognitive delays, movement disorders, hearing loss, and seizures.

Prevention and Outcomes

Rh incompatibility is almost completely preventable. Rh-negative mothers should be followed closely by their obstetricians during pregnancy. If the father of the infant is Rh-positive, the mother is given a midterm injection of RhoGAM and a second injection within a few days of delivery. These injections prevent the development of antibodies against Rh-positive blood. This effectively prevents the condition. Routine prenatal care should help identify, manage, and treat any complications of Rh incompatibility.

Bibliography

Beers, Mark H., ed. The Merck Manual of Medical Information. 2d home ed., new and rev. Whitehouse Station, N.J.: Merck Research Laboratories, 2003.

EBSCO Publishing. Health Library: Rh Incompatibility and Isoimmunization. Ipswich, Mass.: Author, 2009. Available through http://www.ebscohost.com.

Moise, K. J., Jr. “Management of Rhesus Alloimmunization in Pregnancy.” Obstetrics and Gynecology 112, no. 1 (July, 2008): 164-176.

Smits-Wintjens, V. E., F. J. Walther, and E. Lopriore. “Rhesus Haemolytic Disease of the Newborn: Postnatal Management, Associated Morbidity, and Long-Term Outcome.” Seminars in Fetal and Neonatal Medicine 13, no. 4 (August, 2008): 265-271.