$Unique_ID{BRK04187} $Pretitle{} $Title{Rh Disease} $Subject{Rh Disease Erythroblastosis Fetalis Erythroblastosis Neonatorum Hemolytic Disease of Newborn Hemolytic Anemia of Newborn Congenital Anemia of Newborn Icterus Gravis Neonatorum Hydrops Fetalis Rhesus Incompatibility Rh Incompatibility Rh Factor Incompatibility } $Volume{} $Log{} Copyright (C) 1986, 1989, 1992 National Organization for Rare Disorders, Inc. 251: Rh Disease ** IMPORTANT ** It is possible the main title of the article (Rh Disease) is not the name you expected. Please check the SYNONYMS listing to find the alternate names and disorder subdivisions covered by this article. Synonyms Erythroblastosis Fetalis Erythroblastosis Neonatorum Hemolytic Disease of Newborn Hemolytic Anemia of Newborn Congenital Anemia of Newborn Icterus Gravis Neonatorum Hydrops Fetalis Rhesus Incompatibility Rh Incompatibility Rh Factor Incompatibility General Discussion ** REMINDER ** The information contained in the Rare Disease Database is provided for educational purposes only. It should not be used for diagnostic or treatment purposes. If you wish to obtain more information about this disorder, please contact your personal physician and/or the agencies listed in the "Resources" section of this report. Rh disease is an Rh incompatibility between the blood of a mother and fetus. It causes anemia and other more serious conditions. Red blood cells are broken down (hemolysis) because of the incompatibility. Symptoms During the first pregnancy of an Rh-negative woman carrying an Rh-positive fetus, there are rarely any symptoms. However, the risks of sensitization increase with each subsequent pregnancy when the fetus is Rh-positive. In Rh disease, red blood cells from the fetus cross the placenta and enter into the mother's circulation during pregnancy. This stimulates maternal antibody formation against the Rh factor. These antibodies reach the fetus via the placenta and cause destruction of the fetal red blood cells (hemolysis). This consequently causes anemia in the fetus. To overcome this anemia, the fetal bone marrow releases immature red blood cells (erythroblasts) into the fetal circulation. The hemoglobin from the destroyed red blood cells is broken down to bilirubin, which is cleared from the fetal circulation by crossing the placenta into the mother's blood. After birth, however, bilirubin builds up in the newborn's circulation and high levels of bilirubin may sometimes be deposited in the basal ganglia of the brain causing Kernicterus. (For more information, please choose "kernicterus" as your search term in the Rare Disease Database.) In women who have developed Rh-sensitization, succeeding pregnancies with Rh incompatibility produce progressively more seriously affected infants, unless treatment with an anti-Rh-gammaglobulin (RhoGAM) is given to the mother within 72 hours after each childbirth or termination of pregnancy. The more severely affected fetuses develop profound anemia in the womb and are delivered with gross edema (swelling) of the entire body (hydrops fetalis). This may be suspected before delivery if excessive fluid around the fetus in the amnion sac (polyhydramnios) is present (detected through x-rays). Sometimes a picture of the fetus in the uterus (amniogram) reveals severe scalp edema. Newborn infants with Rh disease are extremely pale and may have severe generalized edema, including the presence of liquid in the pleural cavity around the lungs (pleural effusion) and an accumulation of serous fluid in the abdominal cavity (ascites). The liver and spleen are enlarged because of production of red blood cells outside the bone marrow. Congestive heart failure may sometimes occur. Because of anemia and prematurity, lack of oxygen in the lungs (asphyxia) is likely during labor and delivery. The prematurity and asphyxia along with an abnormal decrease of the amount of protein in the blood (hypoproteinemia) may predispose the infant to respiratory distress syndrome (RDS), the signs of which may be difficult to distinguish from those of congestive heart failure. Less severely affected newborn infants may be anemic, but do not have edema or other signs of hydrops. Others may have little or no anemia at birth. Affected infants usually develop severe hyperbilirubinemia shortly after delivery because of the continuing hemolytic effect of Rh-antibodies that have crossed the placenta. Succeeding pregnancies tend to produce more seriously affected fetuses. Erythroblastosis can be prevented by injecting the mother with a high-titer anti-Rh-gammaglobulin preparation within 72 hours after delivery to prevent her from developing antibodies. (For more information, see Therapies: Standard.) Causes Rh incompatibility occurs when a woman with Rh-negative blood conceives a child with Rh-positive blood. Red blood cells from the fetus cross the placenta and enter into the mother's circulation stimulating maternal antibody formation against the Rh factor. These antibodies reach the fetus via the placenta and cause destruction of the fetal red blood cells, consequently causing anemia and bilirubin in the fetal blood (jaundice) which makes the infant appear yellow. Rh-negative and -positive blood types are determined by genetic factors. Affected Population Rh Disease occurs only in infants who have Rh-positive blood and whose mothers have Rh-negative blood. In the U.S. only about 13% of marriages result in pairing of an Rh-positive man and an Rh-negative woman. Only 1:27 children born to these couples will suffer from Rh disease. Related Disorders Kernicterus is a condition characterized by an excess of bilirubin in the blood which is deposited in the basal ganglia of the brain and in the brainstem nuclei. (For more information, choose "Kernicterus" as your search term in the Rare Disease database.) Therapies: Standard An infant with hydrops fetalis or severe erythroblastosis fetalis (without hydrops) due to Rh disease is usually critically ill and should be treated in a perinatal intensive care facility whenever possible. Fetal heart rate should be monitored during labor. If signs of lack of oxygen (asphyxia) occur, or if the infant is severely affected, cesarean section delivery should be performed. The mainstay of treatment is "exchange transfusion." This is a blood transfusion using twice the infant's calculated blood volume which removes 85% of the infant's blood, including circulating antibodies, sensitized red blood cells, accumulated bilirubin, and replenishes red blood cells. In hydrops fetalis, profound anemia should be corrected immediately by giving a partial (1-volume or less) exchange transfusion using packed red blood cells. After the infant's condition stabilizes, a 2-volume exchange transfusion should be performed. In addition, digoxin and diuretics for heart failure, alkali therapy for metabolic acidity of the body tissues (acidosis), and supportive treatment for RDS may be required. When an Rh-negative sensitized woman delivers a less severely ill infant, umbilical cord blood should be examined immediately to determine the infant's blood type, and the direct Coombs' test for the presence of antibodies should be performed. If the infant is Rh-positive and the Coombs' test is positive, the infant's percentage of red blood cell volume in the blood (and reticulocyte count) should be determined. A blood smear should be obtained to check for reticulocytes and red blood cells with nuclei. The bilirubin level in umbilical cord blood should also be determined. Laboratory and clinical evaluations of some infants suggest such a severe rate of hemolysis that exchange transfusion will almost certainly be required in the future. If the infant's condition is stable, an early exchange transfusion removes sensitized red blood cells and antibodies before hemolysis produces large amounts of bilirubin and may avert the need for multiple transfusions at a later time. If an exchange transfusion is not needed immediately, the infant can be monitored, determining both the bilirubin and red blood cell count in the blood (hematocrit). Should bilirubin levels become dangerously elevated or should significant anemia develop, an exchange transfusion is normally indicated. Some sensitized Rh-positive infants do not require an exchange transfusion in the newborn period. However, the hematocrit must be followed serially for several weeks or months as severe anemia may develop because of slow, ongoing hemolysis. Such infants may require a simple transfusion with packed red blood cells at a later time. Erythroblastosis can be prevented by injecting a high-titer anti-Rh-gammaglobulin preparation into the mother within 72 hours after each birth or termination of pregnancy. This preparation prevents the formation of maternal antibodies. During pregnancy of an Rh-negative mother (when the father is Rh-positive), maternal Rh antibody levels should be measured at monthly intervals. If the titers are higher than 1:32 a surgical entry into the abdomen to obtain amniotic fluid (amniocentesis) for measurement of bilirubin concentration in amniotic fluid, should be conducted usually at 2- week intervals. If bilirubin levels are elevated, the fetus can be given blood transfusions inside the uterus at 10-day to 2-week intervals, generally until the 32nd to 34th week of pregnancy at which time delivery may be performed. Therapies: Investigational Clinical trials are underway to study Human Parvovirus Infection and it's sequelae in Iowa and Northwestern Illinois. Interested persons may wish to contact: Stanley J. Naides, M.D. Division of Rheumatology, GH E400 Dept. of Internal Medicine University of Iowa Iowa City, IA 52242 (319) 356-2430 to see if further patients are needed for this research. This disease entry is based upon medical information available through January 1992. Since NORD's resources are limited, it is not possible to keep every entry in the Rare Disease Database completely current and accurate. Please check with the agencies listed in the Resources section for the most current information about this disorder. Resources For more information on Rh Disease, please contact: National Organization for Rare Disorders (NORD) P.O. Box 8923 New Fairfield, CT 06812-1783 (203) 746-6518 NIH/National Institute of Child Health and Human Development (NICHHD) 9000 Rockville Pike Bethesda, MD 20892 (301) 496-5133 NIH/National Heart, Lung and Blood Institute (NHLBI) 9000 Rockville Pike Bethesda, MD 20892 (301) 496-4236 For information on genetics and genetic counseling referrals, please contact: March of Dimes Birth Defects Foundation 1275 Mamaroneck Avenue White Plains, NY 10605 (914) 428-7100 Alliance of Genetic Support Groups 35 Wisconsin Circle, Suite 440 Chevy Chase, MD 20815 (800) 336-GENE (301) 652-5553 References CECIL TEXTBOOK OF MEDICINE, 18th ed.: James B. Wyngaarden, and Lloyd H. Smith, Jr., Eds.: W.B. Saunders Co., 1988. P. 948. THE MERCK MANUAL 15th ed: R. Berkow, et al: eds; Merck, Sharp & Dohme Research Laboratories, 1987. Pp. 1766, 1875.