What is the significance of Rhesus (Rh) factor in pregnancy?

From the Guidelines

Rhesus (Rh) factor management is crucial during pregnancy to prevent complications, and Rh-negative pregnant women should receive anti-D immunoglobulin (RhoGAM) at 28 weeks gestation and again within 72 hours after delivery if their baby is Rh-positive, as well as after potentially sensitizing events like amniocentesis, vaginal bleeding, trauma, or miscarriage, with a standard dose of 300 micrograms intramuscularly, as recommended by the most recent study 1.

Key Considerations

• All pregnant women should be tested for Rh status at their first prenatal visit, and if Rh-negative, antibody screening should be performed 1.
• If a woman has already been sensitized (developed anti-Rh antibodies), she will need specialized monitoring with serial ultrasounds and possibly intrauterine transfusions if the fetus shows signs of anemia 1.
• The use of RhD immune globulin (RhIg) has reduced the burden of perinatal morbidity and mortality attributable to RhD alloimmunization, with a postpartum dose decreasing the rate of postpartum anti-D alloimmunization from between 13% and 17% to 1% to 2%, and an additional dose in the mid-trimester reducing the antepartum rate of alloimmunization from 1.8% to between 0.1% and 0.2% 1.

Management of Specific Situations

• In cases of spontaneous or induced abortion at less than 12 weeks of gestation, the administration of RhIg may be recommended to reduce the risk of RhD alloimmunization, although the specific point estimate has not been determined 1.
• For threatened abortion, the risk of fetomaternal hemorrhage is lower, and the need for prophylaxis is less clear, but it may be prudent to administer anti-D immunoglobulin when there is “heavy” bleeding or associated abdominal pain, or when the event occurs near 12 weeks’ gestation 1.

Prevention of Complications

• Proper Rh management has dramatically reduced the incidence of Rh disease, making this once-common complication now relatively rare with appropriate preventive care 1.
• The recommended dose of anti-D immunoglobulin for potentially sensitizing events is 50 μg for first-trimester events and 300 micrograms for second- and third-trimester events 1.

From the FDA Drug Label

Although a lesser degree of protection is afforded if Rh antibody is administered beyond the 72-hour period, HyperRHO S/D Full Dose may still be given. For antenatal prophylaxis, one full dose syringe of HyperRHO S/D Full Dose (1500 IU; 300 mcg) is administered at approximately 28 weeks’ gestation. This must be followed by another full dose (1500 IU; 300 mcg) , preferably within 72 hours following delivery, if the infant is Rh positive HyperRHO S/D Full Dose is used to prevent isoimmunization in the Rho(D) negative individual exposed to Rho(D) positive blood as a result of a fetomaternal hemorrhage occurring during a delivery of an Rho(D) positive infant, abortion (either spontaneous or induced), or following amniocentesis or abdominal trauma

• Rhesus in pregnancy: Rh immune globulin (IM) is used to prevent isoimmunization in Rho(D) negative individuals exposed to Rho(D) positive blood.
• Administration: One full dose syringe of HyperRHO S/D Full Dose (1500 IU; 300 mcg) is administered at approximately 28 weeks’ gestation, followed by another full dose within 72 hours after delivery if the infant is Rh positive 2.
• Mechanism of action: HyperRHO S/D Full Dose acts by suppressing the immune response of Rho(D) negative individuals to Rho(D) positive red blood cells 2.

From the Research

Rhesus in Pregnancy

• Rhesus (Rh) incompatibility can cause hemolytic disease of the fetus and newborn (HDFN), a condition where the mother's immune system produces antibodies against the fetus's red blood cells 3.
• The use of Rh immune globulin (RhIG) has been shown to prevent maternal sensitization to RhD, reducing the risk of HDFN 3.
• In cases where HDFN occurs, treatment options include intrauterine fetal transfusion, intravenous immune globulin (IVIG), and therapeutic plasma exchange (TPE) 4, 5.
• IVIG administration has been used to successfully treat severe Rh disease, with favorable outcomes reported in several case studies 4, 5.
• A combined regimen of TPE, IVIG, and intrauterine transfusion has been shown to be effective in managing severe maternal red blood cell alloimmunization and HDFN 5.

Management of Rhesus Incompatibility

• Antenatal injection of RhIG is indicated for pregnant Rh-negative women to prevent maternal sensitization to RhD 3, 6.
• Detection of anti-D in a mother's plasma can be complicated by the presence of RhIG, which can interfere with compatibility testing 6.
• A combination of qualitative and quantitative test methods, as well as a complete clinical history, is necessary for accurate diagnosis and patient management in cases where RhIG is detected 6.

Treatment Outcomes

• Successful management of severe HDFN has been reported using a combination of TPE, IVIG, and intrauterine transfusion, with all five women in one case series delivering healthy infants 5.
• The use of fully phenotypically matched red blood cells for intrauterine transfusion may help prevent further red blood cell alloimmunization in complex cases of HDFN 5.