HDFN Basics

Most therapies for hemolytic disease of the fetus and newborn (HDFN) aim to reduce the levels of bilirubin in the blood of the baby. 

Bilirubin is a normal by-product of the breakdown of red blood cells (RBCs). In HDFN, the accelerated destruction of RBCs due to the presence of maternal antibodies against the fetal blood results in high levels of bilirubin, which can be dangerous. This happens when the mother’s body perceives the red blood cells of her baby as foreign due to their blood being incompatible.

Treatments that aim to reduce bilirubin levels include phototherapy, intravenous fluids and intravenous immunoglobulin (IVIG). There is also an experimental treatment in development called nipocalimab that aims to reduce the levels of circulating immunoglobulin G (IgG) antibodies that attack the baby’s red blood cells.

Phototherapy

Phototherapy was introduced in the 1970s as a way to manage the buildup of bilirubin in a baby. The American Academy of Pediatrics (AAP) recommends intensive phototherapy for the treatment of HDFN.

The light used in phototherapy transforms bilirubin into a water-soluble molecule that the baby’s kidneys and intestines can excrete without it being processed by the liver. 

The side effects of phototherapy include diarrhea, dehydration, skin rashes and “bronze baby” syndrome, which refers to the development of gray-brown skin discoloration. Some studies have suggested that phototherapy may also increase the risk of certain cancers, but more research is needed to reach a conclusion on the possible link. 

Another downside of phototherapy is that the baby needs to be separated from the mother right after birth for as long as a week.

Intravenous fluids

Intravenous fluids may also help remove extra bilirubin from the baby’s body. They can also ensure the baby stays hydrated. Additionally, intravenous fluids can help raise blood pressure and may be necessary to treat low blood pressure in the baby.

IVIG

IVIG is a treatment that utilizes blood plasma from donors whose blood contains antibodies. It aims to reduce the breakdown of the baby’s red blood cells, thereby lowering the levels of bilirubin in their body.

IVIG is increasingly being used off-label for the treatment of HDFN. However, its use is still controversial, as studies about its benefits have been inconclusive.

Nipocalimab

Nipocalimab, being developed by Janssen Pharmaceutical, is an investigational, fully human monoclonal antibody that is injected into the mother’s bloodstream. It is thought to selectively block the neonatal Fc receptor, which is involved in transporting IgG from the mother to the baby. By blocking the neonatal Fc receptor, nipocalimab aims to reduce levels of circulating IgG, which are known to be associated with HDFN. 

Research has shown that the experimental treatment is well tolerated by both mothers and babies and may lead to a reduction in the need for blood transfusion before or after birth. It is also not associated with unusual infections, even though it lowers levels of IgG during pregnancy. 

If approved, nipocalimab could benefit pregnant women who are at high risk of having a baby affected by HDFN.

Reviewed by Kyle Habet, M.D., on September 27, 2023.