What are the considerations for Rhesus (Rh) factor in pregnancy?

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From the Guidelines

Rh Considerations in Pregnancy are Crucial to Prevent Hemolytic Disease of the Newborn All Rh-negative pregnant women should receive Rh immune globulin (RhIg) at 28 weeks of gestation and within 72 hours of delivery if the baby is Rh-positive 1. Additionally, RhIg should be administered after any potential sensitizing events, such as miscarriage, ectopic pregnancy, or amniocentesis, with a dose of 50 micrograms if the pregnancy is less than 12 weeks, and 300 micrograms if the pregnancy is beyond 12 weeks 1.

Key Considerations

  • Screening for Rh Antibodies: All Rh-negative women should be screened for Rh antibodies at the beginning of pregnancy and again at 28 weeks 1.
  • Dose and Administration: A 50 mg dose of RhIg within 72 hours of spontaneous or induced abortion is adequate to cover the volume of potential feto-maternal hemorrhage in the first trimester, but a 300 mg dose may be used if the lower dose is unavailable 1.
  • Prevention of Alloimmunization: The goal of RhIg administration is to prevent the formation of Rh antibodies, which can lead to hemolytic disease of the newborn in future pregnancies 1.
  • Risk of Alloimmunization: Although the incidence of RhD alloimmunization arising from spontaneous or induced abortion at <12 weeks of gestation is low, it is not likely to be negligible at the population level, and prevention is critical 1.

Recommendations

  • RhD testing and RhIg administration should be offered for spontaneous and induced abortion at <12 weeks of gestation in unsensitized, RhD-negative individuals, if logistically and financially feasible 1.
  • Local surveillance of anti-D alloimmunization rates should be considered to determine the impact of selective first-trimester RhIg administration 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. One full dose syringe of HyperRHO S/D Full Dose provides sufficient antibody to prevent Rh sensitization if the volume of red blood cells that has entered the circulation is 15 mL or less. In instances where a large (greater than 30 mL of whole blood or 15 mL red blood cells) fetomaternal hemorrhage is suspected, a fetal red cell count by an approved laboratory technique (e.g., modified Kleihauer-Betke acid elution stain technique) should be performed to determine the dosage of immune globulin required. 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 acts by suppressing the immune response of Rho(D) negative individuals to Rho(D) positive red blood cells.

The considerations for Rhesus (Rh) factor in pregnancy include:

  • Preventing isoimmunization: Administering Rh immune globulin (e.g., HyperRHO S/D Full Dose) to Rh-negative mothers to prevent isoimmunization after exposure to Rh-positive blood due to fetomaternal hemorrhage, abortion, amniocentesis, or abdominal trauma 2.
  • Dosage requirements: The dosage of immune globulin required depends on the volume of red blood cells that have entered the maternal circulation, with one full dose syringe providing sufficient antibody to prevent Rh sensitization if the volume is 15 mL or less 2.
  • Antenatal prophylaxis: Administering one full dose syringe of HyperRHO S/D Full Dose at approximately 28 weeks’ gestation, followed by another full dose within 72 hours after delivery if the infant is Rh-positive 2.
  • Fetomaternal hemorrhage: Performing a fetal red cell count by an approved laboratory technique to determine the dosage of immune globulin required in cases of suspected large fetomaternal hemorrhage 2.
  • Mechanism of action: HyperRHO S/D Full Dose acts by suppressing the immune response of Rh-negative individuals to Rh-positive red blood cells 2.

From the Research

Considerations for Rhesus (Rh) Factor in Pregnancy

  • The Rhesus (Rh) factor is a protein found on red blood cells, and if an Rh-negative mother is exposed to Rh-positive blood, she may develop antibodies against the Rh factor, leading to complications in future pregnancies 3, 4, 5, 6, 7.
  • To prevent this, Rh immune globulin (RhIG) is administered to Rh-negative women at 26-30 weeks' gestation and again within 72 hours of delivery, which has been shown to be highly effective in preventing maternal Rh alloimmunization 3.
  • The guidelines for the administration of RhIG vary, but most recommend routine administration at 28 weeks' gestation and after delivery, as well as after potentially sensitizing events such as miscarriage, abortion, or invasive prenatal procedures 4, 5, 7.
  • The dose of RhIG also varies, but most guidelines recommend a dose of 300 micrograms at 28 weeks' gestation and after delivery, with additional doses given after potentially sensitizing events if necessary 4, 5, 6.
  • It is also important to note that the detection of anti-D after administration of RhIG should be viewed with suspicion if it occurs more than 100 days after administration, as this may indicate that the dose was not adequate for antepartum protection 6.
  • There are some discrepancies between guidelines regarding the management of women with weak D blood type and the optimal dose and regimen for routine antenatal prophylaxis, highlighting the need for further studies and consistent evidence-based protocols 7.

Timing and Dosage of RhIG Administration

  • Routine administration of RhIG at 28 weeks' gestation and after delivery is recommended by most guidelines 3, 4, 5, 7.
  • Additional doses of RhIG may be given after potentially sensitizing events, such as miscarriage, abortion, or invasive prenatal procedures, with the dose and timing varying depending on the specific event and the guidelines being followed 4, 5, 6, 7.
  • The optimal dose and regimen for routine antenatal prophylaxis is still a topic of debate, with some guidelines recommending administration between 28 and 34 weeks, while others recommend specifically at 28 weeks 7.

Special Considerations

  • Women with weak D blood type should not receive anti-D, as this may cause an adverse reaction 4, 5.
  • The need for prophylaxis after some sensitizing events, such as threatened, spontaneous, or surgical miscarriage, termination of pregnancy, and molar and ectopic pregnancy, is still a topic of debate, with different guidelines recommending different approaches 7.
  • The optimal dose of anti-D globulin after invasive antenatal procedures, abdominal trauma, external cephalic version, and postnatal prophylaxis is also still a topic of debate, highlighting the need for further studies and consistent evidence-based protocols 7.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Rh(O)D immune globulin products for prevention of alloimmunization during pregnancy.

American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists, 2015

Research

Prevention of Rh alloimmunization.

Journal of obstetrics and gynaecology Canada : JOGC = Journal d'obstetrique et gynecologie du Canada : JOGC, 2003

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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