For centuries, women with a certain rare blood type suffered mysterious miscarriages or delivered stillborn babies due to an unexplained condition known as hemolytic disease of the newborn (HDN). The development of Rh immune globulin (brand name RhoGAM) in 1968 is estimated to have prevented the deaths of 10,000 babies each year in the United States alone.

Between 1 and 15 percent of US females have Rh-negative blood—meaning they lack a certain protein, D antigen, on the surface of their red blood cells. If an Rh-negative woman carries a baby who is Rh-positive, the mother’s immune system will recognize the baby’s blood cells as foreign and produce antibodies to destroy those cells. Usually a first baby is not affected, because the antibodies need time to multiply and strengthen. During subsequent pregnancies, however, the antibodies can lower babies’ red blood cell counts and cause jaundice, anemia, mental retardation, heart failure, and death.

In 1939, doctors first discovered that HDN stemmed from an incompatibility between a mother’s and baby’s blood; they were tipped off when a woman had a stillborn birth and then, later, a bad reaction to a transfusion of her husband’s blood. At that time, HDN affected about 10 percent of all pregnancies, and the infant’s only chance of survival was a massive transfusion involving total replacement of the baby’s blood immediately after birth. In the 1960s, scientists proposed giving Rh- negative pregnant women an injection of antibodies instead.

The medicine Rh immune globulin was developed in 1968 by doctors at Columbia University in New York City and a Johnson and Johnson laboratory in Raritan, New Jersey. RhoGAM blocks the mother’s immune system from identifying the foreign fetal blood cells so she will not become “sensitized” and make antibodies. Millions of doses have been administered since, and the incidence of Rh-negative pregnant women becoming sensitized today has dropped to approximately 0.1 percent.

ADDITIONAL FACTS

  1. The American College of Obstetrics and Gynecology has hailed the development of RhoGAM as one of the top achievements in 50 years of women’s health.
  2. One famous historical personage who may have been Rh-negative was Catherine of Aragon (1485–1536), the first wife of King Henry VIII(1491–1547). Five of her six children were either born stillborn or died in infancy, telltale signs of the disease. Whatever the reason, Catherine’s inability to bear a male heir had a momentous impact on history: when the pope refused to allow Henry to divorce Catherine to seek a more fertile queen, he responded by repudiating Roman Catholicism and founding the Church of England, a major event in the Protestant Reformation of the 16th century.
  3. Rh factor is short for rhesus factor, because the antigen was first identified in rhesus monkeys.