Learn The BasicsHemolytic disease of the fetus and newborn (HDFN) is a disorder in which a pregnant woman’s immune system attacks her baby’s red blood cells, leading to their destruction and resulting in severe anemia, also known as erythroblastosis fetalis. In severe cases, HDFN can be associated with permanent damage to the baby’s brain or even death before the baby is born due to high levels of bilirubin, also called kernicterus.
What causes HDFN?
HDFN results from incompatibility between the blood of the mother and the baby. The incompatibility can be between blood types and/or Rh factor, in which case the disease is called Rh disease.
The baby may inherit antigens—substances that are capable of stimulating an immune response —from their father that do not exist in the mother’s body. In such cases, the mother’s immune system may produce antibodies against these antigens.
Normally, the blood of the mother and the baby do not mix during pregnancy. However, in cases of miscarriage, prenatal testing, and labor when the placenta breaks, the baby’s blood may be exposed to the blood of the mother, who starts producing antibodies that target red blood cells for destruction. It takes some time for these antibodies to mature, which is why HDFN occurs more commonly in a second pregnancy than in a first pregnancy.
What are the symptoms of HDFN?
The main symptom of HDFN before birth is hydrops fetalis. This is the presence of extra fluid in the abdomen, around the lungs and the heart, in the scalp and in the skin of the fetus.
After birth, symptoms of HDFN in the baby include:
- Pale skin.
- Enlarged liver and/or spleen.
- Jaundice.
- Very dark urine.
- Rapid breathing and heart rate.
How do doctors diagnose HDFN?
HDFN may be diagnosed before or after the baby is born. Diagnostic tests include:
- A maternal blood test to assess the presence of antibodies.
- An ultrasound to assess whether the baby’s organs are enlarged.
- A Doppler ultrasound to measure the peak systolic velocity of the middle cerebral artery in the brain of the fetus.
- A cordocentesis, in which blood is drawn from the umbilical cord to confirm the baby’s blood type, blood count, and the number of antibodies attached to their red blood cells to predict disease severity.
How is HDFN treated?
Treatment options for HDFN include a blood transfusion. This can be done before birth, also known as intrauterine, or after birth.
Once the baby is born, it may undergo phototherapy or bright light therapy and receive intravenous fluids to help reduce the extra bilirubin that forms as a result of the breakdown of red blood cells.
Intravenous immunoglobulin, or IVIG, in the infant, may be used to reduce the breakdown of red blood cells and levels of bilirubin. However, according to the National Institutes of Health (NIH), this method is less common, as its use is still controversial.
There is also a potential new treatment in development called nipocalimab that could reduce levels of circulating antibodies associated with HDFN. If successful, the treatment, which is injected into the mother’s bloodstream, could benefit pregnant women who are at high risk of having a baby affected by HDFN.
Some cases of HDFN may be prevented by injecting Rh antibodies either during pregnancy or within 72 hours of birth to decrease the risk of the mother’s next baby contracting HDFN. Also known as an anti-D injection, this treatment can prevent the mother’s body from producing antibodies against the baby’s red blood cells. Women who are Rh- should have these shots after a miscarriage or ectopic pregnancy if the baby’s father is Rh+. However, this approach will not be effective if the mother already has antibodies against the RhD antigen.
The takeaway
HDFN occurs when the blood of a mother and child are incompatible, causing the mother’s immune system to attack her baby’s red blood cells. Though HDFN is a rare, debilitating and sometimes deadly disease, there are ways to treat babies suffering from this disease, and there are steps mothers and their physicians can take to prevent a baby from contracting it.
There are several different treatment options currently available for babies diagnosed with HDFN, and researchers are actively testing and developing new treatments to help those who are most at risk.
Reviewed by Debjyoti Talukdar, M.D., on September 18, 2023.
