What to Know About Hemolytic Disease of the Newborn

Hemolytic disease of the newborn (HDN), also called erythroblastosis fetalis, is a serious immune reaction that can affect newborn babies. This condition causes rapid and severe hemolysis—the breakdown of the baby’s red blood cells (RBCs). It only occurs when there is a mismatch in blood type between the baby and the pregnant parent.

Usually, screening tests can help identify whether a baby is at risk of HDN. If there’s a risk, certain treatments can help prevent it from occurring. Symptoms of hemolysis can include swelling of the body, pale skin, yellow-appearing skin, low birth weight, and a rapid heart rate.

Timely diagnosis and treatment can help prevent death or lifelong disability that can occur secondary to HDN. Read more to learn about hemolytic disease of the newborn, its risk factors, prevention, and treatment.

What Causes Hemolytic Disease of the Newborn?

There are many causes of hemolysis. A baby is considered a neonate during the four weeks after delivery. The most common cause of hemolysis during the neonatal phase of life is an immune response to blood type incompatibility.

The proteins on the surface of RBCs determine blood type. Every single RBC that a person has in their body has the same blood type. The proteins are defined as A, B, and Rh. A person’s blood type can be identified as A, B, AB, or O (no A or B proteins). Additionally, the presence or absence of Rh protein determines whether a person is Rh positive or Rh negative.

When a pregnant person is Rh negative, exposure to a fetus’s Rh positive blood will cause the pregnant person to produce antibodies (immune proteins) against the fetus’s RBCs. This is called Rh sensitization.

This exposure most often happens during labor and delivery. However, it can occur earlier in pregnancy, including during a miscarriage, pregnancy termination, ectopic pregnancy, or an invasive procedure such as amniocentesis or chorionic villus sampling.

The pregnancy in which the first exposure happens usually is not affected. The pregnant person is treated to prevent antibody formation. If antibodies form, they can affect future pregnancies with an Rh positive fetus. The antibodies can cross the placenta and attack the fetus’s blood, resulting in hemolysis.

The most common cause of HDN is Rh incompatibility—when the fetus is Rh positive, and the pregnant person is Rh negative. Other types of blood type incompatibility involving the A and B blood type markers may cause HDN. But the reaction tends to be milder with A or B incompatibility than it is when it occurs due to Rh incompatibility.

Symptoms of HDN

Your healthcare providers can identify risk factors for HDN before birth, but any symptoms of the condition during pregnancy would be subtle and not specific to HDN. The symptoms of HDN after a baby is born can be more obvious but not necessarily specific to this disorder. Diagnostic testing is necessary to identify the cause of any newborn distress.

Signs or symptoms of HDN before birth may include:

• Lower than normal pregnancy weight gain 
• Low weight of the growing fetus for gestational (pregnancy) age
• Lower than normal fetal activity

The baby may show one or more of these signs or symptoms of HDN after birth:

• General swelling throughout the baby's body
• Enlarged abdomen
• Rapid heart rate
• Pale skin
• Yellowish-appearing skin (jaundice)

Severe complications can include damage to one or more organs in the body, such as the brain or kidneys. This can result in long-term disability or even death of the baby.

Complications Associated With HDN

Anemia (low numbers of healthy red blood cells) can be a serious problem, especially when RBCs break down rapidly before the body can replenish them. A deficiency of RBCs may cause insufficient oxygen supply to the body’s organs.

Bilirubin is a breakdown product of RBCs. Rapid hemolysis causes an accumulation of bilirubin in the body. This material can damage the baby’s organs.

Sometimes a serious complication called kernicterus can develop. This is an accumulation of bilirubin in the brain. It can cause permanent brain damage and may lead to learning disabilities, blindness, epilepsy, and an inability to learn how to walk or control physical movements.

HDN Exams and Tests

In addition to a physical examination, testing is an important part of diagnosing HDN. Blood tests can determine whether a baby has low RBCs, immature RBCs, or antibodies that could be destroying the RBCs. Additionally, some blood tests can identify antibodies in the pregnant person’s blood.

Diagnostic tests that can aid in identifying HDN or some of its complications are:

• Oxygen level: Noninvasive testing with pulse oximetry can determine whether a baby is low in oxygen.
• Heart rate: A rapid heart rate can occur when there is a low blood volume due to anemia. This can be extremely straining for a young baby’s heart.
• Blood pressure: Low blood pressure is one of the effects of anemia.
• Direct Coombs test: This blood test can identify antibodies on the baby’s RBCs.
• Indirect Coombs test: This test can identify the presence of antibodies against RBC proteins in the pregnant person’s blood, and it can help identify the risk of HDN before a baby is born.
• Bilirubin level: A high level of bilirubin in the baby’s blood or urine is a sign of hemolysis. 
• Blood typing: A prenatal blood test can identify whether the pregnant person is Rh negative.
• Complete blood count (CBC): A CBC can identify a low number of RBCs in the baby’s blood.
  
• Reticulocyte count: This is a measure of immature RBCs. A high reticulocyte count is a sign that the body is attempting to replace hemolyzed RBCs.

Other tests that may be necessary if there’s concern about serious complications and organ damage include brain imaging or abdominal computerized tomography (CT) scan.

What Is the Treatment for HDN?

Treatments for HDN include preventive approaches, as well as interventions that can be used if the condition isn’t adequately prevented. Survival has improved as treatments have developed, but life expectancy remains low for babies who develop this condition in areas with low access to treatment.

An Rh negative pregnant person who has developed Rh antibodies will have the pregnancy closely monitored. Ultrasound imaging can assess whether the fetus has signs of anemia.

An amniocentesis may be performed to determine if there is elevated bilirubin in the amniotic fluid surrounding the fetus. The fetus's umbilical cord blood may also be sampled to check for antibodies, bilirubin, and signs of anemia.

Sometimes the fetus is treated with an intrauterine blood transfusion before birth. A baby might need further blood transfusions after birth. Intravenous immunoglobulin may also be given to the baby to help prevent hemolysis and elevated bilirubin.

Phototherapy is a type of light therapy that can help the body eliminate excess bilirubin. Babies who have anemia may also need oxygen supplementation, intravenous fluids, and blood pressure management.

Long-Term Care

A baby who has developed organ failure due to HDN may need lifelong care. This can include anti-seizure medication if they develop epilepsy, dialysis if they develop kidney failure, or a feeding tube if they are unable to eat.

Can HDN Be Prevented?

While HDN is not common, it is recognized as a serious risk during pregnancy and delivery. Prenatal care routinely includes blood typing, which identifies whether a pregnant person is Rh negative, the biggest risk factor for HDN.

Normally it’s recommended for the Rh negative pregnant person to receive treatment with RhoGAM, an immune therapy that prevents antibodies from forming against Rh positive blood. Prevention of antibodies during each pregnancy is crucial so that a subsequent pregnancy will not be affected by antibodies attacking the fetus's RBCs.

RhoGAM is administered around 28 weeks of pregnancy. It is also given within 72 hours of delivery of an Rh positive baby. Sometimes it may need to be administered sooner, such as before an amniocentesis. This invasive diagnostic procedure is safe, but it carries the potential of exposure of the pregnant person to the baby’s blood.

Miscarriage or pregnancy termination can lead to a risk of subsequent HDN, so you might receive RhoGAM if you experience these as well.

What’s the Outlook for a Baby With HDN?

The outlook for a baby who develops HDN is variable. It can be nearly impossible to anticipate the severity of anemia that will develop in response to Rh incompatibility. Without treatment, the outlook can range from mild and easily treatable anemia to severe organ damage or even death.

Hydrops fetalis is a life-threatening condition in which the baby develops severe swelling in the body. Life expectancy is substantially lowered if a baby develops this complication.

When to Talk to a Healthcare Provider

It’s best to get prenatal care as soon as you find out you are pregnant. If you are planning to get pregnant or are at risk of pregnancy, you might be advised to start taking care of your health. This includes starting on prenatal vitamins and avoiding smoking and alcohol.

During early pregnancy, blood tests will identify your blood type. If you are Rh positive, then there is no need to worry or get treatment to prevent HDN.

If you are Rh negative, it’s highly likely that you could be carrying a fetus who is Rh positive because about 90% of the population is Rh positive. It is a dominant trait (is likely to be expressed in the fetus if the other parent is Rh positive).

Your healthcare providers would schedule your preventive treatment during your pregnancy so that you will not develop antibodies against your fetus’s Rh factor proteins.

If you are Rh negative, you need to consult a healthcare provider during each pregnancy to determine if treatment is needed, even if you are not carrying the pregnancy to term.

Summary

Hemolytic disease of the newborn (HDN) is a rare but serious condition that may develop due to blood type incompatibility between a growing fetus and the pregnant parent. The process and steps that lead to this condition usually involve sequential pregnancies of a pregnant person who is Rh negative.

During the first pregnancy, an Rh negative pregnant person develops antibodies to the fetus’s Rh positive blood. During a subsequent pregnancy, the antibodies will attack the RBCs of the developing fetus, causing hemolysis.

This immune reaction may cause anemia, organ failure, or death. Usually, HDN can be prevented with treatment that begins during each pregnancy. However, if a fetus or baby develops this condition, close observation and medical care may prevent serious consequences.