Your Pregnancy Matters

RhoGAM shortage: Managing Rh incompatibility in pregnancy

Your Pregnancy Matters

Pregnant woman getting an IV
Amid a critical RhIg shortage, non-invasive prenatal testing and partner testing can help save doses.

Rh incompatibility describes a condition in pregnancy where the mother and fetus have different blood types, specifically of the Rh factor. A possible, serious result of this mismatch is Rh isoimmunization, when the mother produces antibodies to Rh-positive fetal red blood cells during pregnancy. The destruction of fetal red blood cells can lead to anemia or death in a fetus or newborn.

The medication Rho(D) immune globulin (RhIg) has been given to women for decades to reduce the risk of isoimmunization. Women who are Rh-negative generally get a dose at 28 weeks of pregnancy and again within 72 hours of labor. In 1968, Time magazine heralded the invention of RhoGAM®, a popular formulation of the medication, as something obstetricians would “insist on” for their patients. The two-dose strategy reduced the rate of isoimmunization from about 15% to 0.2% in at-risk pregnancies.

But in March 2024, the U.S. Food and Drug Administration, the American Society of Health-System Pharmacists (ASHP), and the Association for the Advancement of Blood & Biotherapies, announced a major shortage in the U.S. of RhoGAM.

As new information unfolds, your provider may treat Rh incompatibility with other effective medications, including HyperRHO S/D or Rhophylac, and offer other screening strategies, such as expanding the scope of non-invasive prenatal testing (NIPT).

Most patients will not need RhIg, but for those who do, it can be lifesaving for the baby. Let’s discuss the basics of Rh incompatibility, how we treat it, and what to ask your doctor if you may be at risk.

What is Rh incompatibility?

The Rh blood group is complicated, but when we talk about patients being Rh-negative or Rh-positive, we are generally referring to the presence of a protein on red blood cells – the D antigen. If your cells have the D antigen, you’re considered Rh-positive. If you don’t, you’re considered Rh-negative. Based on a study of blood donors, an estimated 15% of people in the U.S. are Rh-negative; this varies significantly by race and ethnicity.

When a mother is Rh-negative and a fetus is Rh-positive, their blood types are considered Rh incompatible.

blood cells
A woman’s immune system can be exposed to Rh-positive red blood cells either during pregnancy and delivery or if she were to accidentally receive a transfusion of Rh-positive blood.

Genes control the production of D antigen on the red blood cell surface; women who are negative don’t have this protein on the surface of their red blood cells. But people who are Rh-positive may carry one or two copies of the gene making the protein, either making them heterozygous or homozygous. This becomes important when assessing potential risk to a pregnancy. If a woman who is Rh-negative has a child with a man who is Rh-negative, all of their children will be Rh-negative. But if the man is Rh-positive, the fetus could be Rh-positive or negative, depending on what genes he carries.

A woman’s immune system can be exposed to Rh-positive red blood cells either during pregnancy and delivery or if she were to accidentally receive a transfusion of Rh-positive blood. If this happens, the mother’s immune system will recognize the blood as foreign. It will then mount an immune response and deploy antibodies against the fetal cells.

Rh incompatibility doesn’t harm the mother and rarely affects a first pregnancy. However, it can complicate future pregnancies. The mother’s immune system remembers the incompatibility and can mount an immune response against fetal cells sooner. This can cause severe problems for the fetus, including jaundice and hemolytic disease of the newborn (HDFN), a serious form of anemia that can lead to death or severe brain damage in the baby. Babies with HDFN may need a blood transfusion or early delivery to reduce antibody exposure.

Screening and treatment for Rh incompatibility

Rh immune globulin is an injectable (intramuscular or intravenous) medicine that treats Rh incompatibility between a mother and fetus. It’s a solution of anti-D antibodies that helps prevent the Rh-negative mother’s immune system from recognizing the foreign cells as intruders and blocks her immune system from making antibodies.

Exposure to fetal blood can happen at different times during a pregnancy. To prevent isoimmunization, Rh-negative mothers get an injection of Rh immune globulin during specific events like a threatened miscarriage or an invasive test like amniocentesis. Because fetal blood can escape into the maternal circulation in later pregnancy and we don’t usually know the Rh status of a fetus, women also get a dose around 28 weeks of pregnancy. Mothers who give birth to a Rh-positive baby typically get another dose within 72 hours of delivery, to reduce the risk of developing antibodies that may cause fetal harm in a future pregnancy.

We, along with our colleagues, are employing several tactics to lessen the impact of the shortage of RhoGAM:

  • Close inventory monitoring: UT Southwestern Ob/Gyns are keeping careful count of our RhIg stores, how much we’re using, and how much we predict will be necessary.
  • Alternate medications: Injections such as HyperRHO S/D and Rhophylac can also treat Rh incompatibility – the names just aren’t as familiar as RhoGAM to most patients.
  • Paternal testing (in the setting of certain paternity): If an Rh-negative woman’s partner is also Rh-negative, their offspring will not be Rh-positive, so there's no need for RhIg. That’s why fertility clinics usually select sperm from an Rh-negative donor if donor sperm are necessary in an Rh-negative woman. And if your partner is Rh-positive, he can have genetic testing help determine whether there is a possibility that the fetus is Rh-negative.
  • Non-invasive prenatal testing (NIPT): While Rh-negative mothers should get RhIg at 28 weeks, that dose is not needed if their baby is also Rh-negative. NIPT assesses DNA fragments in maternal blood to determine the risk of certain chromosomal disorders. It can also tell the baby’s Rh status, providing another option to save Rh immune globulin doses for patients carrying babies who may be Rh-positive.
  • Triage of administration. If supplies become more scarce, we may have to alter the traditional indications for these therapies.

If you know you are Rh-negative or if you are unsure of your status, talk with your doctor or midwife about their plan to reduce your baby’s risk of complications. Planning can grant you peace of mind and give your care team extra time to make your delivery as safe as possible.

To talk with an Ob/Gyn or certified nurse-midwife, call 214-645-8300 or request an appointment online.