Introduction to the Hemolytic Disease of the New Born (HDN)
Hemolytic Disease of the New Born (HDN) occurs when the blood type of the mother is incompatible with the blood type of her new born child. The blood type incompatibility is due to the presence of RhD (rhesus D) antigens in the red blood cells (RBCs) of the child and their absence in the RBCs of the mother. The child is said to be RhD positive while the mother is said to be RhD negative. The RhD antigens of the infant RBCs are recognized by the mother’s immune system as foreign objects; consequently, the mother produces anti-RhD antibodies to destroy the infant red blood cells through hemolysis. The disease is characterized by erythroblastosis (production of immature red blood cells), severe anemia, jaundice, and hydrops fetalis (edema or fluid build up). If no medical treatments or procedures are administered, the disease could lead to the death of the child.
HDN was first observed by a French midwife in a set of twins in 1609. Doctors waited for more than 300 years for an explanation of the causes of the disease, which started to appear during the discovery of the Rh blood group system in 1940 by Landsteiner and Weiner. In 1953, Dr. Bruce Chown found out that the antibodies of an Rh negative mother destroy the RBCs of her child. Further detailed explanations of the etiology of HDN have been presented since then.
The Genetics of the Hemolytic Disease of the New Born
The Rh antigens are determined by two homologous but distinctive proteins associated in the membrane of red blood cells. These Rh antigen proteins are encoded by two separate genes located in the short arm of chromosome number 1. Each of these genes is as long as 10 exons combined. Moreover, the two genes have 96% structural similarities (e.g. nucleotide sequence similarity). The D protein is an example of a protein encoded by the Rh gene. A person who has the D protein in RBCs is said to be RhD positive while a person who has no D protein is said to be RhD negative. A person becomes RhD negative if there is no inheritance of the RhD gene from the parents. Without the RhD gene no RhD protein is expressed in RBCs.
The Causes of the Hemolytic Disease of the New Born
Hemolytic Disease of the New Born occurs when an RhD negative mother produces a RhD positive child. The child is RhD positive because it inherited the RhD gene from the father. HDN is not a problem in the first pregnancy of the mother. It becomes a problem in any subsequent pregnancies of the mother especially if she is already sensitized to the RhD antigen in her first child.
Sensitization is the process wherein the mother produces antibodies (immunoglobulin M, IgM) against the RhD antigen of the child’s RBCs. IgM antibodies are produced once RBCs of the child is mixed with the mother’s blood. IgM antibodies are incapable of crossing the placenta so the first child is safe from hemolytic disease.
The exposure of the mother to RhD positive RBCs of her second child triggers the production of immunoglobulin G (IgG) antibodies that are capable of crossing of the placenta and mix with the child’s blood. IgG antibodies destroys the child’s RBCs until the level of RBCs is inadequate to meet the child’s oxygen demand. The child develops severe anemia and the bone marrow and spleen are forced to produce red blood cells that are immature and non-functional. These two organs became enlarged as the level of RBCs is dropping. The destruction of the RBCs also result from the production of too much bilirubin in the body, a condition called hyperbilirubinemia. Bilirubin, a yellow colored substance, causes yellowing of the infant, a condition commonly known as jaundice.
Hemolytic Disease of the New Born References
*Emedicine’s Hemolytic Disease of the New Born. Retrieved May 14, 2009 from https://emedicine.medscape.com/article/974349-overview
*New England Journal of Medicine: RhD Hemolytic Disease of the New Born. Retrieved May 14, 2009 from https://content.nejm.org/cgi/content/extract/339/24/1775.
*University of Virginia Health System: HemolyticDisease of the New Born. Retrieved May 14, 2009 from https://www.healthsystem.virginia.edu/uvahealth/peds_hrnewborn/hdn.cfm