Karl Landsteiner studied blood types in Europe and in the United States in the late nineteenth and early twentieth centuries. Landsteiner won the Nobel Prize in Physiology or Medicine in 1930 for detailing immunological reactions in the ABO blood group system. The ABO blood group system divides human blood into one of four types based on the antibodies that are present on each cell. Landsteiner's work with blood types led physicians to safely perform blood transfusions and organ transplants. Additionally, Landsteiner researched the Rh blood factor, a protein marker on the surface of blood cells and that can impact pregnancy.

William Thornton Mustard was a surgeon in Canada during the twentieth century who developed surgical techniques to treat children who had congenital heart defects. Mustard has two surgeries named after him, both of which he helped to develop. The first of these surgeries replaces damaged or paralyzed muscles in individuals who have polio, a virus that can cause paralysis. The other technique corrects a condition called the transposition of the great arteries (TGA) that is noticed at birth. Surgeons worldwide adopted that technique, leading to increased survival rates in infants afflicted with the condition. Mustard also published over 100 articles on congenital heart defects, surgical techniques, and the preparation of an artificial heart lung machine. Mustard helped perform the first blood transfusion of a newborn whose red blood cells (RBCs) had degraded, a condition called hemolytic anemia. Throughout his career, Mustard developed surgical techniques that increased the survival rates of infants and children with congenital and developmental disorders.

Exchange transfusion is the replacement of blood from newborn infants with elevated bilirubin level in their blood stream with donor blood containing normal bilirubin levels. Newborn infants that experience jaundice, the yellowing of the skin and eyes, have a buildup of bilirubin, a chemical that occurs during red blood cell breakdown, or hemolysis. Exchange transfusion is a therapy developed throughout the 1940s by Louis Diamond and a group of surgeons at the Children’s Medical Center in Boston, Massachusetts. During exchange transfusion, a physician inserts a plastic tube called a catheter through the umbilical vein of the infant to slowly remove infant blood and sequentially replace it with donor blood. Exchange transfusion was the first definitive treatment for hyperbilirubinemia in the US and it helped reduce the incidence of kernicterus, a type of brain damage caused by elevated bilirubin levels.

Neonatal jaundice is the yellow discoloration of the skin and eyes due to elevated bilirubin levels in the bloodstream of a newborn. Bilirubin is a byproduct of the breakdown of red blood cells. Jaundiced infants are unable to process bilirubin at a normal rate or they have an abnormally high amount of bilirubin in their bloodstream, resulting in a buildup of the yellow colored bilirubin. That build up is called hyperbilirubinemia and is the cause of jaundice. Jaundice can lead to kernicterus, a rare neurological disorder that results in hearing loss, permanent brain damage, and sometimes death. Research into the causes of jaundice and kernicterus began in the late eighteenth century in Paris, France. By the middle of the twentieth century, scientists developed treatments for jaundice that successfully treated infants afflicted with the condition, phototherapy and blood exchange transfusion, due to these treatments, the risk for an infant in developing kernicterus is very low.