Researchers investigate first potential drug treatment for blood-type incompatibility during pregnancy

Advocate Children’s Hospital is the first site in Illinois to join Phase 3 study of hemolytic disease of the fetus and newborn

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Researchers investigate first potential drug treatment for blood-type incompatibility during pregnancy

Advocate Children’s Hospital – Park Ridge is the first site in Illinois to join a clinical trial evaluating whether an investigational nonsurgical treatment can reduce the risk of hemolytic disease in unborn and newborn babies.

“Hemolytic disease of the fetus and newborn, or HDFN, happens when the blood type of the pregnant individual and the unborn baby are not compatible,” said Suwan Mehra, MD, a high risk obstetrician, gynecologist and fetal surgeon and Advocate Aurora Research Institute’s principal investigator for the study. “This is typically seen when the one parent’s blood type is different from the other’s, and that difference is passed on to the fetus in some way. In alloimmune-mediated conditions such as HDFN, the pregnant individual’s immune system sees the baby’s blood type as a threat and begins producing alloantibodies to fight it. This is more common and often more severe after the first pregnancy, because the pregnant individual’s immune system has already been primed to attack their fetus’ incompatible blood type.”

Mild cases of HDFN often cause jaundice during the baby’s early life. But in severe cases, the mother’s antibodies pass through the placenta during pregnancy or at delivery and attack the fetus’ red blood cells so rapidly that the unborn baby or newborn infant requires medical attention to prevent fetal anemia, which can cause organ failure and death.

“In the absence of timely recognition and intervention this can be devastating to the family,” Dr. Mehra said.

The clinical trial will assess whether the drug nipocalimab, when given to the mother during pregnancy, can reduce the number of these harmful antibodies in her bloodstream and also reduce the number of harmful alloantibodies that cross the placenta to the fetus.

Although HDFN was once responsible for thousands of infant deaths each year, it is now relatively uncommon in the U.S., as advancements in early detection have made some types of HDFN highly preventable.

“Everyone has a blood type – A, B, AB or O. Everyone also has a what’s called an Rh factor – either positive for negative,” Dr. Mehra said. “The most severe cases of HDFN occur when there are differences in Rh factor between the mother and fetus. Use of the well-known drug RhoGAM can prevent HDFN in these cases, but only if it is administered at the correct time during pregnancy. And there is currently no immunization against HDFN caused by differences in the ABO type.”

There are also no nonsurgical treatments approved for the treatment of HDFN once it has been diagnosed.

“In cases where HDFN cannot be or is not prevented, doctors will sometimes perform intrauterine blood transfusions from a matched donor,” said Cheryl Lefaiver, PhD, RN, Director of the Center for Child and Family Research at the Research Institute. “But this is a highly invasive, risky and resource-intensive procedure that is typically only possible at major medical centers, and it is not a cure-all, which is why researchers like ours are searching for alternative treatments.”

The clinical trial, “A Phase 3 study of nipocalimab in pregnancies at risk for severe hemolytic disease of the fetus and newborn (HDFN) (AZALEA),” is sponsored by Janssen Research & Development, a Johnson & Johnson company.

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About Advocate Aurora Research Institute

Advocate Aurora Research Institute is a not-for-profit, limited liability company of Advocate Aurora Health. Advocate Aurora has emerged as a national destination for patient-centered bench, translational and clinical research, and the Research Institute unifies the innovative research efforts throughout the health system. Advocate Aurora researchers focus on rapidly translating new discoveries from the scientist’s bench to the patient’s bedside and into the community we serve to improve options and outcomes that change not only the lives of individuals, but transform the health of populations.