Rh Immune Globulin (RhIG)

RhIG Overview: Protecting Rh-Negative Mothers and Babies

Rh Immune Globulin (RhIG)—also known as RhoGAM®, Rhophylac®, WinRho®, HyperRho®, RhIG, or Anti-D—is a life-saving medication used to prevent Rh incompatibility between Rh-negative mothers and their Rh-positive babies. It works by preventing the mother’s immune system from producing harmful antibodies (Anti-D Antibodies) that could cause Hemolytic Disease of the Fetus and Newborn (HDFN). A person is Rh-negative if they have a negative blood type, like O-, A-, B-, or AB-. In most countries, women find out their blood type during their first trimester of pregnancy in order to determine if they need RhIg.

Listen to our Season 3 Podcast Episode about RhIg here.

How Does RhIg Work?

When Rh-negative mothers are exposed to Rh-positive blood during pregnancy or childbirth, their immune system may develop antibodies to fight the foreign blood type. RhIg works by introducing a small amount of anti-D antibodies, tricking the immune system into thinking it has already produced its own antibodies. This prevents the formation of dangerous naturally occurring anti-D antibodies in response to Rh-positive blood. The injected antibodies temporarily circulate in the body before breaking down. RhIg does not cause alloimmunization or sensitization , and it is not a vaccine. It is a preventative medication given via an injection.

History of RhIg: A Groundbreaking Discovery

Before RhIg, HDFN caused several hundred thousand fetal and neonatal deaths and lifelong neurological damage in infants each year. The discovery of RhIg in the 1960s by Dr. Vincent Freda and Dr. John Gorman at Columbia University revolutionized maternal-fetal care. Their breakthrough paved the way for the development of RhIg, which is now responsible for saving countless lives.

Key figures in this discovery included James Harrison, the “man with the golden arm,” who donated over 1,100 plasma donations containing anti-D antibodies. His plasma contributions were critical in the development of RhIG, particularly in Australia.

The routine use of RhIG is responsible for the reduced rate of red cell alloimmunization in more economically developed countries. The postpartum administration of Rh D immune globulin reduced the rate of Anti- D alloimmunization in at-risk pregnancies from approximately 13–16% to approximately 0.5–1.8%. The risk was further reduced to 0.14–0.2% with the addition of routine antepartum administration (American College of Obstetricians and Gynecologists. ACOG Practice Bulletin No. 75: Management of alloimmunization during pregnancy. Obstet Gynecol. 2006;108(2):457-464).

Read more about James Harrison here.

Read more about the discovery of RhIg here.

Safety, Efficacy, and Indications

Effectiveness:

RhIg has been shown to reduce the risk of Rh sensitization to just 0.1-0.2% when administered at 28 weeks of pregnancy and within 72 hours after delivery. It is 99% effective in preventing Anti-D Alloimmunization (Rh disease).

Common Side Effects:

The most common side effects are mild, including swelling, pain, or redness at the injection site and occasional mild fever. Serious side effects are extremely rare, and no deaths have been reported due to RhIg administration for pregnancy-related purposes.

Safety Measures:

The donated plasma used to make RhIg is rigorously screened for diseases such as Hepatitis B, Hepatitis C, and HIV. The process includes viral reduction filtration procedures to ensure no infectious diseases are transmitted, and no cases of viral transmission have been reported.

Indications:

 RhIg is given to Rh-negative mothers under the following circumstances:

  • At 28 weeks of pregnancy
  • Within 72 hours after delivery
  • After miscarriage, abortion, or trauma
  • Following invasive testing like amniocentesis or CVS
  • In cases of vaginal bleeding during pregnancy

When RhIg Is NOT Needed

There are some cases where RhIg is not necessary:

  • You are Rh-positive, so there is no risk of Rh incompatibility.
  • You are Rh-negative, but the fetus is Rh-negative (determined through cffDNA testing or confirmed paternity with an Rh-negative partner). There is a 40% chance that if you are Rh negative, your baby is also Rh negative and you do not need RhIg. 
  • You are Rh-negative, but you have already become alloimmunized (i.e., you have developed anti-D antibodies from a previous pregnancy or exposure).

How RhIg Is Made

RhIg is made from human plasma, specifically from Rh-negative donors who produce anti-D antibodies. These donors are carefully screened for infections, and some even receive injections of the RhD positive red cells to boost their antibody production.

Learn more about how you can help donate to specialty Anti-D programs, in “How you can help” below.

RhIg Administration for First Trimester Losses

There is ongoing debate regarding the need for RhIg after first trimester pregnancy losses. Medical organizations such as Society for Maternal-Fetal Medicine (SMFM), the American College of Obstetricians and Gynecologists (ACOG), the Society for Family Planning  (SFP) and the World Health Organization (WHO) have differing recommendations:

  • SMFM: Recommends RhIg after spontaneous or induced abortion at less than 12 weeks if it is logistically feasible and does not impede access to abortion care.
  • ACOG: Recently updated their guidelines, suggesting that routine Rh testing and RhIg administration may be unnecessary for losses under 12 weeks, though it may be considered on an individual basis in some cases.

Recent studies show a very low risk of Rh sensitization after first trimester losses, but the true threshold for fetal-maternal hemorrhage remains unclear. At Allo Hope Foundation, we are in agreement with SMFM and advocate for RhIg to be given in first trimester pregnancy losses.

Global Shortage of RhIg

Unfortunately, RhIg is not accessible to all women in need worldwide. About 50% of the women who require RhIg do not receive it, and an estimated 3 million women annually go without the medication. As a result, 160,000 fetal/neonatal deaths and 100,000 pediatric disabilities occur every year due to HDFN.

In many developing countries, RhIg is not readily available, and women may be required to purchase it out-of-pocket at unattainably high costs, if it is available at all. This global shortage has been exacerbated by the COVID-19 pandemic, which led to a decrease in plasma donations.

Global Efforts and the Way Forward

Efforts are underway to improve access to RhIG in underserved regions, and new technologies like cell-free fetal DNA (cffDNA) testing are helping determine fetal RhD status before administering RhIg, which will conserve doses. In some countries, like those in Scandinavia, cffDNA is already used to reduce unnecessary RhIG administration during the pregnancy, conserving doses and ensuring they are used when truly needed.

The goal is to make RhIg widely available, affordable, and accessible for all women who need it, helping to prevent the tragedy of Rh incompatibility and its consequences.

How You Can Help

The global shortage of RhIg highlights the critical need for robust plasma donor programs and increased awareness about access to treatment in underserved areas. You can make a meaningful impact by becoming a specialty plasma donor or supporting organizations that work to improve access to RhIg, helping to save lives and reduce the burden of HDFN worldwide. 

Through our AHF Africa Anti-D program, you can provide access to RhIg for women in Kenya and Nigeria who cannot afford it. To donate, please visit our AHF Africa Campaign here .

For more information on how to become a plasma donor or supporting our Africa RhIg program, please contact katie@allohopefoundation.org.

Donor Programs:

Kedrion

Grifols 


What If I Feel Uncomfortable Receiving RhIg?

At The Allo Hope Foundation, we understand that medical decisions during pregnancy are deeply personal and can often feel overwhelming, especially when there are conflicting opinions and complex information to consider. It’s natural to have concerns and questions about any medical intervention. Our organization, founded by alloimmunized mothers, is dedicated to empowering women to make informed decisions throughout their pregnancies.

Some women may have reservations about medical treatments like RhIg due to concerns about the influence that pharmaceutical companies, government regulations, and the broader healthcare system may have on medical interventions like RhIg, which is derived from human plasma and can be viewed as part of a larger industry framework. Others may feel uncomfortable with the pressure to make medical decisions, especially when they come from a variety of sources, including healthcare providers, family, community and society. Additionally, some women are committed to pursuing a more natural approach to pregnancy and may view any medical intervention, including RhIg, as incompatible with their values. While we respect these perspectives, it is important to clarify that RhIg is not a vaccine or invasive treatment, but a targeted medication that does not cause sensitization or alloimmunization. It is designed to prevent these conditions from developing and their associated severe fetal and neonatal risks in future pregnancies.

Our role is to provide the facts and support informed decision-making, empowering women to make the choice that is best for their health and the well-being of their baby.

What Are My Options if I Don’t Want to Receive RhIg?

If you are Rh-negative and have concerns about receiving RhIg, there are options to determine whether your baby is also Rh-Negative , which means you do not require RhIG in that pregnancy. A non-invasive cell free fetal DNA (cffDNA) test can assess whether your fetus carries the RhD antigen, helping to confirm whether RhIG is indicated. Alternatively, if the biological father is confirmed to be Rh-negative and paternity is certain, this may also provide insight into your baby’s Rh status. 

There is approximately a 40% chance that if you are Rh negative, your baby will also be Rh negative, in which case RhIg would not be necessary. The cffDNA test offers a reliable, non-invasive way to confirm your baby’s blood type to help guide your decision about whether to proceed with RhIg. Routine cffDNA testing to drive RhIg administration and conservation efforts is standard of care in countries such as Denmark, Finland, Sweden, Netherlands, and most recently England, Australia and New Zealand. If you are outside of these countries, you can still request cffDNA/NIPT testing for fetal RhD determination through BillionToOne (the Unity screen) or Natera (the Panorama screen).

See more about cffDNA testing here

What Can Happen If I Refuse RhIg and my baby is Rh Positive?

While you have the right to refuse RhIG, it’s important to understand the potential risks associated with this decision. Refusing RhIG increases the chances of sensitization, which can have severe and sometimes fatal consequences in future pregnancies. 

The postpartum administration of RhIG reduces the rate of red cell alloimmunization from 13-16% to approximately 0.5-1.8%. With the addition of routine antepartum administration at 28 weeks gestational age, the risk is further reduced to 0.14-0.2%.

  • Sensitization: After refusing RhIg, there is about a 13-16% chance that you can become sensitized, meaning your body may develop antibodies that can attack any subsequent Rh-positive fetuses, leading to HDFN (which can cause severe anemia, organ damage, and even death).
  • Increased Risk in Future Pregnancies: If sensitization occurs, subsequent pregnancies with an Rh positive baby become high risk. Managing these pregnancies often involve invasive, complex and costly treatments, such as intrauterine blood transfusions as well as extended care in a neonatal intensive care unit (NICU). 

It’s important to weigh these potential risks carefully and discuss your concerns with your healthcare provider, who can help guide you through the decision-making process.

The Bottom Line: Empowerment through Knowledge

We are here to help you make the best decision for you and your baby. We are dedicated to ensuring that patients feel heard, respected, empowered, and supported. If you need support regarding RhIg in your pregnancy, please don’t hesitate to contact us.

Where can I learn more?

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