Hemolytic disease of the newborn is a type of anemia that begins during pregnancy. It can cause serious illness in a newborn, but it may be diagnosed during prenatal screening and treated to avoid complications.

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Hemolytic anemia is low hemoglobin caused by the destruction of your red blood cells.

In newborns, hemolytic anemia can result from a mismatch between maternal and fetal blood types. This mismatch provokes the maternal immune system to attack fetal red blood cells.

The resulting hemolytic disease of the fetus and newborn (HDFN) can cause your baby to develop anemia and jaundice. Symptoms can begin during pregnancy or after delivery, and range from mild to life threatening.

However, doctors can screen, identify, and closely monitor pregnancies at high risk of HDFN. Preventive therapy is also available for some blood group mismatches.

If your baby has been diagnosed with hemolytic disease of the newborn, effective treatment is available.

Learn more about hemolytic anemia.

When you’re pregnant, some of your antibodies cross the placenta and enter your baby’s bloodstream to help protect your newborn.

But if your baby has a different blood type than you, this can become a problem. In this case, your antibodies can attack your baby’s red blood cells, causing hemolytic disease of the fetus and newborn (HDFN), also known as erythroblastosis fetalis.

We’re all born with blood type O, A, B, or AB, determined by the antigen proteins on our red blood cells. Everyone’s blood is also either positive or negative for the Rhesus (Rh) antigen. There are also many less-common blood group antigens.

ABO blood type mismatch occurs in up to 25% of pregnancies. But HDFN only develops in about 1% of these pregnancies, usually when birth parents with type O blood carry babies with blood type A or B. This type of HDFN is caused by pre-existing, naturally occurring anti-A or B antibodies found in people with type O blood.

Rh antigen mismatch happens when an Rh-negative parent carries an Rh-positive baby. In Rh mismatches, HDFN is triggered by fetomaternal hemorrhage. If even a tiny amount (as little as 0.1 mL) of Rh+ fetal blood enters the maternal bloodstream during the pregnancy or delivery, the maternal immune system can recognize it as foreign and begin producing antibodies against the baby’s red blood cells.

To help prevent and monitor for HDFN, your doctor will test your blood type, Rh antigen, and red blood cell antibodies early in your pregnancy.

Symptoms of HDFN can appear during pregnancy or after birth.

During pregnancy, babies with HDFN can develop:

Newborns with HDFN might also have:

  • pale skin
  • difficulty breathing
  • lethargy
  • edema
  • jaundice

Jaundice is yellow discoloration of the skin and eyes caused by excess bilirubin in the bloodstream. Many healthy newborns develop mild jaundice.

But in HDFN, many red blood cells are bursting and rapidly releasing their bilirubin, so jaundice can quickly become severe. Left untreated, this can lead to neurologic complications (kernicterus).

During pregnancy, doctors will review your medical and obstetric history, determine your blood type, and check for pre-existing red blood cell antibodies that could affect your baby.

If your tests reveal a risk for HDFN, your doctors might:

  • test your partner or baby’s blood type
  • monitor your antibody levels
  • perform ultrasounds and labs checking for fetal anemia
  • perform amniocentesis to check for bilirubin in your amniotic fluid
  • give you preventive RhoGAM injections (to stop Rh-negative mothers from developing antibodies against Rh antigen)

If you have type O blood but otherwise normal prenatal testing, your baby’s blood type and direct antibody test will still be checked shortly after birth to check for newborn hemolytic disease.

If your newborn develops symptoms of HDFN, doctors will monitor blood counts and bilirubin levels, and order further blood tests to clarify the diagnosis.

If your newborn has received a diagnosis of HDFN, doctors may recommend:

When HDFN is diagnosed prenatally, doctors will monitor using ultrasounds, amniocentesis, and fetal and maternal blood tests. Depending on severity, doctors might recommend:

  • intrauterine transfusion of red blood cells to the fetus
  • maternal plasma exchange or intravenous immunoglobulin (IVIg) infusions
  • early delivery, when feasible

Left untreated, HDFN can result in marked anemia and/or jaundice. In the most severe cases, this results in hydrops fetalis, organ failure (including heart failure), and brain damage.

The good news is that when HDFN is identified early and treated promptly, doctors can help manage any risks to your baby.

Some circumstances increase the risk of HDFN:

  • maternal blood type O or Rh-negative
  • positive maternal blood group antibody screening (usually A/B/O or Rhesus (Rh) antigen; or rare minor blood group antigens like Kell or Duffy)
  • maternal history of blood transfusion
  • known fetomaternal hemorrhage
  • history of HDFN or hydrops fetalis in a previous pregnancy
  • lack of prenatal care

With advances in prenatal screening and treatment, the outlook is good for most babies with hemolytic disease.

Research has shown that 94% of fetuses diagnosed with HDFN will survive with treatment (including intrauterine transfusions). Even in cases with prenatal evidence of early hydrops fetalis, survival is 74%.

A 2023 study found that 22% of newborns with HDFN required phototherapy for jaundice, 1% required blood transfusion, and 0.5% required exchange transfusion or IVIg infusion.

What’s the most common cause of hemolytic disease in newborns?

Though it’s declined since the advent of RhoGAM, Rh antigen incompatibility remains the most common cause of serious HDFN.

The number of people with Rh-negative blood types varies between countries around the globe ranging from 2.4% to 17%. With prenatal screening and RhoGAM treatment, about 1 per 3000 Rh-negative birthing parents still develop Rh antibodies, placing their future pregnancies at risk of HDFN.

The most common cause of HDFN overall is ABO blood group incompatibility. But because maternal A/B antibody levels can be low, and fetal red blood cells do not express A/B antigen at a high level, this type of HDFN is often milder.

Is hemolytic anemia of the newborn life threatening?

Severe HDFN can lead to critical anemia and hydrops fetalis, which is a life threatening condition. However, treatment is readily available and can significantly reduce the risk to your baby.

Hemolytic disease of the fetus and newborn (HDFN) occurs during pregnancy when your antibodies cross the placenta and attack your baby’s red blood cells. This process can be triggered by a variety of different blood antigen mismatches between you and your baby but is most often due to ABO or Rh incompatibility.

Signs and symptoms of HDFN can begin in utero or neonatally. They include fetal or newborn anemia, hyperbilirubinemia, and in severe cases, life threatening hydrops fetalis.

With prompt identification and treatment, the majority of babies with HDFN survive and thrive.