Rh Incompatibility and Its Implications During Pregnancy


Pharmacists should understand what Rh incompatibility during pregnancy is and how it is treated. 

Rh incompatibility is often asymptomatic in pregnant women, but it's a condition with serious implications for the unborn child if it goes untreated.

By understanding this condition, its implications, and treatments, pharmacists can be better prepared to help the patients they serve.

Defining Rh Incompatibility

Mothers who are Rh negative have erythrocytes that don't express the RhD antigen.

According to the National Heart, Lung and Blood Institute (NHLBI), Rh incompatibility occurs during pregnancy in mothers who have Rh-negative blood and are carrying a baby with Rh-positive blood.

"This phenomenon becomes clinically significant if a mother that is Rh-negative becomes sensitized to the D antigen and, subsequently, produces anti-D antibodies (i.e., alloimmunization) that can bind to and potentially lead to the destruction of Rh-positive erythrocytes," wrote John Costumbrado and Sassan Ghassemzadeh, in a paper on Rh incompatibility.

This condition often doesn't present signs or symptoms in the mother, but can have serious consequences for the fetus. Due to the large number of Rh-positive blood cells in the fetus that are destroyed, hemolytic disease of the newborn (HDN) can develop. According to Costumbrado and Ghassemzadeh, this can be moderate or severe and can range from self-limited hemolytic anemia to severe hydrops fetalis, a dangerous build-up of fluid.

Diagnosing the Condition

The U.S. Preventative Services Task Force recommends that all pregnant women be given a blood test to determine RhD blood typing and antibody testing during their first pregnancy-related visit to identify whether this could be a concern during the pregnancy.

If a woman is identified as unsensitized Rh-negative, the task force recommends repeated RhD antibody testing at 24 to 28 weeks gestation. This testing may not be necessary if the biological father is known to be Rh-negative.


Pregnant women who are diagnosed with Rh incompatibility will need special treatment to protect the health of the baby.

During the seventh month of pregnancy and again within 72 hours of delivery, women are treated with Rh immune globulin (RhIG), which contains Rh antibodies that attach to Rh-positive blood cells and prevent the body from producing Rh antibodies.

Eric M. Tichy, PharmD, MBA, BCPS, FCCP, associate director of clinical pharmacy services at Yale-New Haven Health System tells Drug Topics that RhIG is a costly product. Currently, four different RhIG products are on the market, each with its own attributes.

"Pharmacists should be able to answer questions from other clinicians and cross-check orders to ensure safety for the receiving patient and the fetus," Tichy said.

"Once you have formed Rh antibodies, the medicine will no longer help. That's why a woman who has Rh-negative blood must be treated with [RhIG] with each pregnancy or any other event that allows her blood to mix with Rh-positive blood," states the NHLBI on its website.

Side effects from the injection, which typically occurs in the arm or buttock or intravenously, include soreness at the injection site or a fever.

"The recommendations of the American College of Obstetricians and Gynecologists (ACOG) for the dosing of RhIg vary depending on the scenario of potential fetomaternal hemorrhage," Costumbrado wrote. "Smaller doses are considered for events that occur earlier in the pregnancy since the total fetal-placental blood volume is 3 mL (1.5 mL of fetal erythrocytes) at 12 weeks; therefore, at least 50 mcg should be considered for first-trimester events and 300 mcg if after 12 weeks."

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