Although no laboratory tests were available to prove their suspicions, historians have postulated that in the early 1500s the wife of Henry VIII, Catherine of Aragon's pregnancy history was consistent with RH Disease or HDN. She had five babies who were either stillborn or died early in the newborn period.
Hemolytic disease of the newborn (HDN) was identified in 1939 by Dr. Phillip Levine. Dr. Levine was treating a woman named Mary Sano, whose second pregnancy resulted in a stillborn baby. Afterward, this same woman had a reaction from a transfusion in which she received her husband's blood. Doctors began to understand that her husband and baby had certain antigens in their blood that were not present on the mother's, and further, that she had formed antibodies against their antigens. Ultimately, the blood group antigen was understood to be the Rhesus factor. The concept of Rh-sensitization also began to be examined.
In the 1940s, approximately 10% of all pregnancies in the United States were affected by HDN. At that time, the only preventive therapy was exchange transfusions. These massive transfusions involved total replacement of the baby's blood immediately after birth.
By the mid-1940s, an Rh-positive baby born to an Rh-negative mother had a 1 in 30 chance of developing HDN. Approximately 10,000 babies were affected by HDN each year—half of those were fatal cases. By 1968, about 10,000 babies died as a result of HDN.
In the 1960s, scientists proposed giving Rh-negative pregnant mothers a simple injection of antibodies just after delivery. Within 1 year, 500,000 pregnant women had received the injection. By 1973, it was estimated that 50,000 lives had been saved.
Because of anti-D treatment, the incidence of an Rh-negative pregnant woman becoming sensitized today is approximately 0.1%.
HDN Prevention: A Timeline
Europe
1967 - In June, the Swiss Red Cross Blood Transfusion Service in Zürich commences collection of plasma from 27 Rh-immunized female patients. The plasma was sent to the German Red Cross Blood Transfusion Service in Baden-Baden, Germany, for manufacture. The product was successfully tested in 100 patients, and thereafter, Rh-prophylaxis was introduced in Switzerland. Switzerland is the first country in the world to provide anti-D to all mothers at risk.
1969 - ZLB (Swiss Red Cross) started the production of its commercially available anti-D product for the Swiss market.
Australia
1966 - Following the 1966 Congress of the ISBT (International Society Blood Transfusion), at which there was a roundtable held on The Prevention of Rh Haemolytic Disease, CSL Limited and the Red Cross set up a program to collect anti-D plasma from donors with high-titre antibodies.
1967 - The first doses of anti-D were prepared by CSL in February and national distribution commenced in August. Australia is the second country in the world to provide anti-D to all mothers at risk.
United States
1960 - Three scientists open Rh Antepartum Clinic at Columbia-Presbyterian Medical Center to test their theories for Rh alloimmunization to prevent HDN, a disease that claimed roughly 10,000 infant lives annually.
1961-1962 - They began their first tests on 9 Rh-negative men at Sing Sing Prison.
1965 - They successfully tested 27 additional volunteers.
1966 - First study with pregnant women, RhoGAM® was used successfully in 160 women.
1968 - RhoGAM® used cold ethanol fractionation process to isolate human immune globulins from pooled blood. RhoGAM® became the standard therapy for HDN.