The History of Alloimmunization & Treatment Options
The History of Alloimmunization and HDFN
For centuries leading up to the development of modern medicine, infant mortality rates were extremely high and the cause of these newborn deaths remained a tragic mystery. In 1609, a French midwife named Louise Bourgeois reported a twin birth that many believe to be the first documented case of HDFN. One of the newborns was very swollen and died soon after birth, while the other developed severe jaundice and died several days later. We now understand the swelling as hydrops, and the severe jaundice as kernicterus; both of which are components of Hemolytic Disease of the Fetus and Newborn (HDFN). Back then there was no treatment and very little hope for babies with HDFN.
The turning point came in the 20th century. The 1901 discovery of ABO blood groups improved transfusion safety, and in 1940, researchers identified the Rh factor, the key culprit in severe HDFN cases. By the 1950s, amniotic fluid analysis provided insight into fetal anemia, and in 1963, Dr. Liley pioneered the first intrauterine transfusion (IUT), injecting donor blood into a fetus’s abdomen—guided only by X-rays and paper clips taped to the mother’s belly.
In 1968, a game-changer arrived: RhoGAM©, the first preventative treatment for Rh alloimmunization. This dramatically reduced cases of Rh disease in developed countries, but with over 245 known red cell antigens, alloimmunization remains largely unpreventable.
Advancements continued through the 1980s and 90s. Intravascular IUTs improved fetal survival rates, and Dr. Giancarlo Mari’s breakthrough in 1995—the MCA Doppler scan—eliminated the need for invasive amniocentesis to detect fetal anemia. By 1997, fetal DNA was detected in maternal blood, paving the way for noninvasive fetal antigen testing.
Today, survival rates for babies treated at specialized centers exceed 97%, yet many women still struggle to access proper care. And in regions without affordable access to RhIG, an estimated 114,000 babies die from preventable HDFN each year.
The future is promising. New therapies like Nipocalimab, a monoclonal antibody that blocks maternal antibodies from crossing the placenta, could make invasive treatments obsolete. Our hope for the future: no more lost babies, no more preventable suffering. The journey isn’t over, but the progress we’ve made is nothing short of extraordinary
