Rh Disease (Rh Incompatibility in Pregnancy)

What Rh factor means

The Rh factor, or RhD, is a protein on the surface of red blood cells. If you have it, you are Rh-positive; if not, Rh-negative. In the US, about 15% of white people and a smaller share of Black, Hispanic and Asian people are Rh-negative. Being Rh-negative is harmless on its own. It matters only in pregnancy and transfusions.

How Rh disease develops

1. Sensitization: an Rh-negative person is exposed to Rh-positive red cells. This usually happens during delivery of an Rh-positive baby, when some of the baby's blood enters the mother's circulation. It can also happen after miscarriage, abortion, ectopic pregnancy, bleeding in pregnancy, an injury to the belly, amniocentesis, turning a breech baby, or an incompatible transfusion.
2. Antibody formation: the mother's immune system makes anti-D antibodies. The first baby is usually unaffected because antibodies form too late.
3. Later pregnancy: in a future pregnancy with an Rh-positive baby, these IgG antibodies cross the placenta and coat the baby's red cells, which are destroyed in the baby's spleen.

If the baby is Rh-negative, it is not affected. If the father is Rh-negative, the baby will be Rh-negative too.

Effects on the baby

• Anemia: a form of hemolytic anemia. The baby's bone marrow and liver try to keep up, enlarging the liver and spleen.
• Hydrops fetalis: severe anemia leads to heart failure with fluid in the belly, chest and skin. This can be fatal without treatment.
• Jaundice after birth: before birth, the placenta clears bilirubin from red cell breakdown. After birth the baby's immature liver cannot, so bilirubin rises quickly. Very high levels can cause brain damage called kernicterus.
• Late anemia in the weeks after birth, as antibodies linger.

Each affected pregnancy tends to be more severe than the last.

Rh disease vs ABO incompatibility

Prevention: Rh immune globulin (RhoGAM)

Rh immune globulin is a blood product containing anti-D antibodies. Given to an Rh-negative person who is not yet sensitized, it clears any Rh-positive fetal cells before the immune system can respond. It has reduced Rh disease dramatically since the late 1960s.

You will usually be offered it:

• at about 28 weeks of pregnancy
• within 72 hours after delivery if the baby is Rh-positive; a blood test on the mother estimates how much fetal blood has crossed, to see if extra doses are needed
• after miscarriage, abortion, ectopic or molar pregnancy (guidance for losses before 12 weeks has changed recently, so ask your provider)
• after bleeding in pregnancy (including placental abruption), belly injury, amniocentesis, chorionic villus sampling or external version of a breech baby

Rh immune globulin does not help once antibodies have already formed. Side effects are usually mild, such as soreness at the injection site. It has been screened and treated to remove infections.

In some places, a blood test of the mother can detect the baby's RhD type from fetal DNA, so Rh immune globulin can be targeted to those carrying an Rh-positive baby.

Monitoring a sensitized pregnancy

If your blood test shows anti-D antibodies:

• Antibody levels (titers) are measured every 2 to 4 weeks.
• The baby's Rh type is checked with cell-free DNA from your blood or, sometimes, amniocentesis. Testing the father's blood type can also help.
• Doppler ultrasound of blood flow in the baby's brain (middle cerebral artery peak velocity) shows whether the baby is becoming anemic, without a needle.
• Ultrasound for signs of hydrops.

Care is led by a maternal-fetal medicine specialist.

Treatment

Before birth

• Intrauterine transfusion: if the baby is significantly anemic, Rh-negative donor blood is transfused through a needle into the umbilical cord vein, guided by ultrasound. It may be repeated every 2 to 4 weeks. Survival for babies who need these transfusions is now high in experienced centers.
• Early delivery, usually between 37 and 38 weeks, or earlier if needed.
• IVIG and plasma exchange in the mother are occasionally used in very severe cases with past fetal loss.

After birth

• Phototherapy with blue light to break down bilirubin
• Exchange transfusion to replace the baby's blood when bilirubin is dangerously high
• IVIG for the baby in some cases to slow red cell destruction
• Top-up transfusions for anemia that can develop over the following weeks
• Follow-up blood counts for 2 to 3 months

Outlook

When Rh immune globulin is given correctly, Rh sensitization is now rare. For pregnancies already affected, modern monitoring and in-womb transfusions mean most babies survive and develop normally. Babies who had severe hydrops or very high bilirubin face a higher risk of complications such as hearing loss or developmental problems.

Frequently asked questions

Does Rh disease affect the first baby?

Usually not. In a first pregnancy, antibodies typically form at delivery, too late to affect that baby. It can affect a first pregnancy if the mother was sensitized earlier, for example by a past miscarriage, abortion, ectopic pregnancy or transfusion without Rh immune globulin.

What happens if an Rh-negative mother does not get RhoGAM?

After carrying an Rh-positive baby, roughly 1 in 6 unprotected Rh-negative mothers develop antibodies. Future Rh-positive babies could then develop anemia, jaundice or hydrops. Once antibodies form, the injection no longer helps, which is why it is given routinely.

Is the RhoGAM shot safe?

Yes. Rh immune globulin has been used for decades and is considered very safe for both mother and baby. It is made from donated plasma that is screened and treated to remove infections. Side effects are usually limited to a sore arm or mild fever.

What if both parents are Rh-negative?

If both parents are Rh-negative, the baby will be Rh-negative too, so Rh disease cannot occur. However, paternity is not always certain, so many providers still recommend Rh immune globulin unless the baby's Rh type is confirmed negative.

Can Rh disease be cured?

The mother's antibodies are permanent once formed, but the baby can be treated. Transfusions before birth, early delivery, phototherapy and exchange transfusions treat the baby's anemia and jaundice. The baby's own blood production replaces the damaged cells, and the mother's antibodies clear from the baby within a few months.