Erythroblastosis fetalis also known as Rh disease or hemolytic disease of the new born (HDN) is a condition which occurs when a mother with Rh negative blood type has contact with Rh positive blood cells from the fetus. Rh factor is a antigen present on the surface of red blood cells. Those have this antigen are called Rh positive and the population group in which it is absent is called Rh negative. This exposure can occur any time during pregnancy such as abortion, miscarriage, delivery or other invasive obstetric procedures. This leakage of blood from fetal to maternal circulation causes sensitization i.e development of anti Rh antibodies.These maternal Rh immunoglobulin G (IgG) antibodies once they had been produced are there for the entire lifetime and in subsequent pregnancies can freely cross the placental barrier into fetal circulation. If the fetus is Rh positive the Rh antigen present on erythrocyte surface will interact with these antibodies forming antigen antibody complexes. This will ultimately lead to destruction of these erythrocytes causing fetal allo immune induced hemolytic anemia. Among the various subtypes of Rh antigen i.e D, C,c . E , e type D is most frequently responsible for Rh incompatibility as it is highly immunogenic as compared to other subtypes. It accounts for 85 % cases of intrauterine transfusions. It is followed by anti c and anti E responsible for 10 % and 3.5 % cases respectivelyHISTORY? The first reported case of this disease was by a French midwife in 1609 in a set of twins. ? In 1932 the relation between fetal hydrops (abnormal accumulation of fluid in fetal compartments including ascites, pleural effusion, pericardial effusion, and skin edema), jaundice ,anemia and circulation of erythroblasts (immature nucleated erythrocytes) was discussed by diamond and colleagues? The Rh blood system was discovered in 1940 after Landsteiner and Weiner in 1940 ? Chown later confirmed in 1953 that this condition was the result of placental leakage of Rh posiive fetal RBCs into circulation of Rh negative mother. PATHOPHYSIOLOGYKleihauer-Betke acid elution is a technique that helps determines the proportion of fetal RBCs in maternal circulation. Using this technique it has been determined that 75% of pregnancies carry the risk of feto maternal hemorrhage. Advancement in gestational period increases occurrence and amount of hemorrhage. Reported to be about 7%, 16%, and 29% in first, second and third trimesters, respectively. The risk increases with pregnancy associated complications such as placental abruption, miscarriage, abortion, toxemia, cesarean delivery and ectopic pregnancy. The amount of fetal blood for producing this reaction is variable. According to different studies in some subjects less than 1 ml of Rh positive blood produced sensitization while nearly 30 % volunteers were not sensitized even when infused with larger volumes of Rh positive blood. After initial exposure the maternal immune system produces immunoglobulin M (IgM) antibodies that do not themselves cross the placental barrier but are capable of producing IgG antibodies that are capable of crossing the barrier. Among the various subtypes of IgG antibodies IgG 3 can bind more efficiently to reticuloendothelial cells resulting in hemolysis. Macrophages and natural killer cells are capable of destroying these antibody coated RBCs with the help of lysosymes. STAGES OF HEMOLYSIS:? When Fetal hemoglobin drops more than 2mg/dl in comparison with gestational standards the process of reticulocytosis starts. ? Further drops in Hb level lead to tissue hypoxia.? Increases in umbilical arterial lactate with fetal Hb less than 8 g/ dL.? Hydrops fetalis develops at fetal b level less than 7g/Dl. Initially it will present as fetal ascites and will gradually develop into pleural effusions and generalized edema.? High degree hemolysis will increase severity of anemia stimulating erythrocyte production in liver spleen, bone marrow, skin and placenta etc.? Normal hepatic parenchyma cells can be replaced by erthroid cells resulting in liver dysfunction and hypoproteinemia.? Hemolysis of RBCs leads to to hyperbilirubinemia which only becomes apparent at birth because in gestational stage bilirubin is metabolized to a great extent by placenta.SENSITIZATION RISK:The risk of this condition increases with every oncoming pregnancy involving Rh positive fetus. Next time such type of pregnancy may result in mildly anemic baby. But subsequent pregnancies with repeated sensitization of mother may even result in utero fetal death due to massive antibody induced hemolytic anemia. ABO COMPATIBILITY AND SENSITIZATION RISK:If Rh negative mothers are ABO incompatible with Rh positive fetus than the risk of sensitization is only 1-2 %. This is due to the fact that the mother already contains antibodies against the ABO blood group of the fetus and the fetal RBCs are rapidly destroyed by these antibodies prior to development of significant sensitization reactions. However this increases to 16 % in cases of ABO compatibility. Even abortion carries a risk of 2-5 %.EPIDEMIOLOGYFrequency of Rh negativity in different races is as follows? Whites: 15%? Blacks: 5%? Hispanics: 8 %? Eskimos, native Americans, Japanese, Asians, Chinese: RareThis disease affects nearly 3-80 in 100000 patients annually. Before use of prophylactic therapy nearly 1% of all pregnant women developed sensitization reactions. However since advent of use of prophylactic therapy in high risk women number of reported cases have decreased from 45 cases per 10000 births to 10.2 cases per 10000 births. .MORTALITY/MORBIDITYThe binding of fetal Rh positive erythrocytes with maternal antibodies resulting in erythrocyte breakdown causes large amount of bilirubin to be produced which are transferred to mother via placenta and subsequently secreted. However in infants low levels of glucuronyl transferase are not capable of handling large amounts of bilirubin and severe in severe hyperbilirubinemia and jaundice.Nearly 50% of the affected newborns are mildly or moderately affected have little or no anemia, may exhibit only hyperbilirubinemia , jaundice and have no development issues. Nearly 25 % If untreated become heavily jaundiced. Among them 90 % will die and 10 % will develop kernicterus.