Hemolytic Disease of the Fetus and Newborn (HDFN): Symptoms, Causes, and Treatment

Written by Stephanie Watson, Christine Loconti
Medically Reviewed by Kecia Gaither, MD, MPH on May 22, 2025
10 min read

Hemolytic disease of the fetus and newborn (HDFN) is a blood disorder that happens when your blood type doesn't match your baby's blood type during pregnancy. This mismatch causes your immune system to attack and damage your fetus or newborn's red blood cells. Red blood cells carry oxygen to all the organs and tissues. Having too few of these cells is called anemia.

When red blood cells break down, they produce a yellow substance called bilirubin. Babies' bodies can't get rid of bilirubin easily, so it builds up in their blood and tissues. This is called hyperbilirubinemia.

Without treatment, HDFN could be very serious or life-threatening. But thanks to improved screening, doctors can detect this condition during pregnancy and prevent it with medicine. Only about 4,000 babies are born with HDFN each year.

Erythroblastosis fetalis is another name for hemolytic disease of the fetus and newborn.

Symptoms are different in each baby. They happen as red blood cells get damaged and the baby's body tries to make more of these cells.

What is the first sign of hemolytic disease of the fetus and newborn?

The first signs start before your baby is born. You won’t notice any symptoms during your pregnancy, but your doctor may spot symptoms like these during a prenatal test:

  • Mild anemia. A low red blood cell count reduces the amount of oxygen that reaches the baby's organs and tissues.
  • Jaundice. A buildup of bilirubin in the blood turns the amniotic fluid and umbilical cord yellow.
  • Severe swelling. As your baby’s body tries to make more red blood cells, their liver and spleen swell up. If anemia causes the baby's heart to fail, large amounts of fluid can build up in their organs and tissues and make them swell too. Doctors call this hydrops fetalis.

Other symptoms of hemolytic disease of the fetus and newborn

After birth, babies with this condition may have symptoms like these:

  • Jaundice – yellow color to the eyes, skin, or umbilical cord
  • Pale skin
  • Swollen liver or spleen
  • Severe swelling of the body
  • Trouble breathing
  • Seizures, vomiting, or a lack of energy from kernicterus — leaking of bilirubin into the brain

How long do symptoms last?

Hemolytic disease of the fetus and newborn is temporary. With the right treatment, symptoms should go away within the first 8 to 12 weeks of the baby's life.

This condition has two types, which are based on the cause:

  • Isoimmune hemolytic disease is the most common type. It happens when your blood type isn't compatible with your baby's blood type. Your immune system makes proteins called antibodies that attack your baby's red blood cells.
  • Nonimmune hemolytic disease happens because of another condition, such as an inherited problem with red blood cells or an autoimmune disease like lupus in the mother.

Hemolytic disease of the fetus and newborn happens when the mother's blood type isn't compatible with the baby's blood type. Everyone has a blood type: A, B, AB, or O. Along with a type, you also have an Rh factor, which is a protein on the surface of red blood cells. If you have this protein, you're Rh-positive. If you don't have this protein, you're Rh-negative.

Rh factor incompatibility is the most common cause of HDFN. If the baby is Rh-positive, there can be problems if even a tiny amount of the baby's red blood cells cross the placenta to the mother. This can happen during a prenatal test like amniocentesis or during delivery. When the two blood types meet, the mother's immune system recognizes the Rh-positive blood cells as foreign and makes antibodies against them. Those antibodies attack and damage the baby's red blood cells.

ABO incompatibility is another common cause of HDFN. It can happen if the mother's blood type is O and the baby's is type A, B, or AB. This type is less severe than Rh factor incompatibility.

Hemolytic disease of the fetus and newborn doesn't usually affect the baby in a first pregnancy. The mother becomes sensitized during the first pregnancy, which can then affect a later pregnancy.

Is hemolytic disease of the fetus and newborn contagious?

No. This condition isn't contagious. It happens when the mother's immune system reacts to the baby's blood type.

Your baby is more likely to have this condition if their blood type is Rh-positive and yours is Rh-negative. Hemolytic disease of the fetus and newborn is more common in a second or third pregnancy than in a first pregnancy. It affects white babies three times more often than it does Black babies.

Your doctor can do tests before your baby is born and after their birth to diagnose HDFN.

Tests for hemolytic disease of the fetus and newborn

These are the tests doctors use to detect HDFN during pregnancy:

  • Blood test. This will show whether your immune system is making antibodies against your baby's red blood cells. Every pregnant person gets this blood test at their first prenatal doctor visit.
  • Amniocentesis. Your doctor will place a needle through your belly and remove a small amount of amniotic fluid from around your baby. A lab will test the fluid for chromosome or genetic disorders.
  • Ultrasound. This test uses sound waves to take pictures of your growing baby. It can show if the fetus has swelling from fluid buildup or enlarged organs.
  • Cordocentesis. The doctor places a needle through your belly and removes a small blood sample from the umbilical cord to test for antibodies, bilirubin, and anemia.

Doctors carefully monitor babies with this condition. After your baby is born, their doctor will look for symptoms like anemia, swelling, and jaundice. The doctor may do tests like these:

  • Umbilical cord blood test for antibodies, red blood cell count, and Rh factor.
  • Blood test to check the baby's bilirubin levels. 

What to know when your child is diagnosed

Your baby will need careful monitoring with blood tests and ultrasounds during your pregnancy and blood tests for the first 12 weeks after their birth.

Once you have antibodies, you have them for life. This means you could have a future baby with hemolytic disease. You could also have a dangerous reaction after a blood transfusion if the donor's blood doesn't match your antibodies. That's why it's important to tell all of your doctors that you have HDFN.

How to deal with a diagnosis

A diagnosis of hemolytic disease of the fetus and newborn can be overwhelming. You'll feel more empowered once you understand the condition. Ask the doctor a lot of questions and learn all you can about the monitoring and treatments your baby will need. Starting on the right treatment as soon as possible could lead to a better outcome. 

Learning that your baby has a condition like HDFN can be scary and overwhelming. Ask for emotional support if you need it. Friends, family, your medical team, and mental health professionals are all good sources of support.

A group of specialists like these will provide care during your pregnancy and after your baby is born:

  • Obstetrician/gynecologist (OB/GYN). This doctor may diagnose hemolytic disease of the fetus and newborn. Your OB/GYN will help care for you and your growing baby during your pregnancy.
  • Maternal-fetal medicine specialist or perinatologist. This specialist diagnoses and manages high-risk pregnancies. They will monitor your pregnancy and care for you until you deliver.
  • Neonatologist. This doctor treats newborns with inherited diseases and other serious conditions.
  • Transfusion medicine doctor and nurse. These specialists manage blood transfusions. They'll make sure the donor's blood matches your baby's blood and will monitor for any problems after the transfusion. 

The type of HDFN treatment depends on whether doctors detect it before or after birth. If your doctor finds hemolytic disease of the newborn during pregnancy, your fetus can have a blood transfusion to treat anemia. The doctor will use a needle to deliver the blood to your fetus through your belly or the umbilical cord. Transfusions usually continue until the fetus fully develops and can be safely delivered. 

If your fetus has complications from HDFN in the womb, the doctor may induce labor early, as long as your baby is mature enough. Your doctor may give you steroid medicine to help your baby’s lungs develop more quickly for an early delivery. 

After birth, the choice of treatment depends on your baby's health and symptoms. 

Blood transfusions for hemolytic disease of the fetus and newborn

Blood transfusions treat severe anemia. Your baby will get blood from a matched donor. 

Exchange transfusion is a procedure to treat a high bilirubin level. It removes some of your baby's blood through a vein or artery and replaces it with donor blood that has a healthy bilirubin level and red blood cell count.

Medications for hemolytic disease of the fetus and newborn

Some of the medicines that treat this condition in newborns are:

Intravenous immunoglobulin (IVIG). This fluid contains antibodies from donors. IVIG prevents damage to your baby's red blood cells and helps lower their bilirubin levels. 

Surfactant. This medicine coats the air sacs in the baby's lungs to help them breathe more easily. Some babies also need oxygen or a machine to help them breathe.

The doctor may also recommend giving extra fluid through a vein (IV) or medicine to treat low blood pressure.

Light therapy for hemolytic disease of the fetus and newborn

This treatment exposes your baby to a special blue light. The light converts extra bilirubin into a form that's easier for their body to remove.

HDFN complications range from mild to severe. They happen when red blood cells break down and bilirubin builds up in your baby's body. 

Complications of severe HDFN include:

Cyanosis. The baby's fingers and toes turn blue because there is too little oxygen in their blood.

Anemia. A drop in red blood cells prevents organs and tissues from getting enough oxygen. Anemia can be mild or severe. As the baby's spleen and liver try to make more new blood cells, these organs swell up.

Hydrops fetalis. This is when fluid builds up in your fetus's organs and tissues in the womb. It can cause stillbirth.

Heart failure. Severe anemia prevents the baby's heart from getting enough oxygen-rich blood. Eventually the heart becomes so damaged that it can't pump out enough blood.  

Kernicterus. When too much bilirubin builds up in the brain, it can cause brain damage, seizures, and hearing loss. Kernicterus can be life-threatening.

HDFN is a temporary condition, but its health effects can sometimes last longer. During your child's treatment you may spend a lot of time seeing doctors and visiting the hospital.

Hemolytic disease of the fetus and newborn cost

The costs of doctor and hospital visits, as well as treatments needed to manage this condition, can add up. One study from Israel found that the cost of care during pregnancy, the first year of life, and childhood add up to almost $27,000.

How is hemolytic disease of the fetus and newborn managed?

Your doctor will monitor your growing baby's health during pregnancy and after they're born. Treatment can help manage complications and prevent your child from having long-term complications.

These are some of the organizations that support families of children with HDFN.

Fetal Health Foundation. This organization funds research, spreads awareness, and offers information on HDFN and other fetal syndromes.

Global Foundation for the Care of Newborn Infants. This international organization is dedicated to improving outcomes for newborns with serious medical conditions.

HDFN can cause complications like anemia and hyperbilirubinemia. But with the right treatment, the outlook is good. Better screening and monitoring are helping doctors diagnose this condition early, when treatment is most effective.

Can hemolytic disease of the fetus and newborn be cured?

This condition is curable. With treatment, the antibodies that attack the baby's red blood cells should go away within three months.

Hemolytic disease of the fetus and newborn is preventable. During prenatal care visits, your doctor will most likely do a blood test to learn your blood type. If you test positive for antibodies, the doctor can give you a medication called Rh immunoglobulin (RhoGAM) at around 28 weeks to stop the antibodies from attacking your fetus’s red blood cells.

Hemolytic disease of the fetus and newborn is a disorder that happens when your blood type isn't compatible with your baby's blood type. It can cause problems like anemia and high bilirubin levels in the fetus and newborn. Today HDFN is preventable with early detection and treatment. Your doctor will likely do a blood test during your pregnancy to see whether your body makes antibodies against your baby's blood, and if so, treat you with RhoGAM.

Which condition would result in hemolytic disease of the fetus and newborn?

Hemolytic disease happens because of an incompatible Rh factor or ABO blood type during pregnancy.

Which blood types are not compatible for pregnancy?

Rh-negative and Rh-positive blood types aren't compatible. Neither are type O with types A, B, or AB.

What is the survival rate for hemolytic disease of the fetus and newborn?

Hyperbilirubinemia — high bilirubin levels — causes the most serious side effects. But with the right treatment, the survival rate for hyperbilirubinemia is as high as 98%.