What is Rhesus (Rh) incompatibility between a mother and child?

Rhesus Incompatibility Between Mother and Child

Rhesus incompatibility occurs when an RhD-negative mother is exposed to the RhD antigen from her RhD-positive fetus, triggering the production of anti-D antibodies that can cause hemolytic disease in subsequent RhD-positive pregnancies. 1

What is Rhesus (Rh) Factor?

The Rhesus (Rh) factor is a protein found on the surface of red blood cells. People who have this protein are Rh-positive, while those who lack it are Rh-negative. The RhD antigen is particularly important in pregnancy due to its high immunogenicity.

• Approximately 15% of the population is Rh-negative
• The RhD antigen is well-developed in fetuses by 6 weeks' gestation 1
• Among all blood group antigens, the D antigen exhibits the highest immunogenicity after A and B antigens 2

Mechanism of Rhesus Incompatibility

Rhesus incompatibility develops through the following process:

1. Initial exposure: An RhD-negative mother carries an RhD-positive fetus
2. Fetomaternal hemorrhage: Small amounts of fetal blood containing RhD-positive cells enter the maternal circulation
3. Maternal sensitization: The mother's immune system recognizes the RhD antigen as foreign and produces anti-D antibodies
4. Subsequent pregnancies: In later pregnancies with RhD-positive fetuses, maternal anti-D antibodies cross the placenta and attack fetal red blood cells

Key Facts About Fetomaternal Hemorrhage

• Fetal red cells are found in the circulation of 50% of all postpartum patients
• Fetal cells are found in maternal circulation in 7% of pregnancies in the first trimester, 16% in the second trimester, and 29% in the third trimester 1
• As little as 0.1 mL of RhD-positive blood can cause sensitization in RhD-negative individuals 1
• Fetomaternal hemorrhage can occur during delivery, abortion, amniocentesis, abdominal trauma, or ectopic pregnancy 3, 2

Consequences of Rhesus Incompatibility

When an RhD-negative mother becomes sensitized, subsequent RhD-positive pregnancies are at risk for hemolytic disease of the fetus and newborn (HDFN). Untreated, HDFN has poor fetal and neonatal outcomes 4.

Fetal and Neonatal Complications

• Fetal anemia (particularly severe early-onset anemia)
• Fetal hydrops (fluid accumulation in fetal tissues)
• Hyperbilirubinemia in newborns
• Bilirubin-induced neurological dysfunction
• Neonatal jaundice
• Early and late postnatal anemia 4

Long-term Complications

• Neurodevelopmental impairment
• Potential cardiovascular disease in adulthood 4

Prevention of Rhesus Incompatibility

The cornerstone of prevention is RhD immune globulin (RhIg) administration to unsensitized RhD-negative mothers.

When to Administer RhD Immune Globulin

RhD immune globulin should be administered to unsensitized RhD-negative women in the following situations:

• Within 72 hours after delivery of an RhD-positive infant
• After spontaneous or induced abortion
• Following ruptured ectopic pregnancy
• After amniocentesis or abdominal trauma
• At 28 weeks' gestation (antenatal prophylaxis) 3

Effectiveness of RhD Immune Globulin

• Postpartum administration reduces alloimmunization from 13-17% to 1-2%
• Additional antenatal dose at 28 weeks further reduces alloimmunization to 0.1-0.2% 1, 3
• RhIg must be administered within 72 hours of potential exposure to RhD-positive blood for maximum effectiveness 3

Important Considerations

• Once maternal sensitization occurs, it is irreversible and persists for life 5
• RhIg is only effective for prevention, not treatment of established sensitization 2
• RhIg works by suppressing the maternal immune response to RhD-positive red blood cells, though the complete mechanism is not fully understood 3
• If the father's blood type is known to be RhD-negative, RhIg administration is not necessary 3

Management of Affected Pregnancies

When a sensitized RhD-negative mother carries an RhD-positive fetus:

• Close monitoring for signs of fetal anemia
• Intravascular intrauterine transfusion (IUT) in specialized centers for severe fetal anemia
• Early delivery when appropriate
• Neonatal exchange transfusions may be required after birth 4, 6

Pitfalls and Caveats

• Failure to identify RhD status: Always determine maternal RhD status early in pregnancy
• Missing the window for prophylaxis: RhIg should be administered within 72 hours of potential exposure
• Overlooking first-trimester events: Even early pregnancy events like miscarriage can cause sensitization
• Assuming low risk in early pregnancy: The RhD antigen is present from 6 weeks' gestation, making sensitization possible early in pregnancy 1
• Neglecting subsequent pregnancies: Once sensitization occurs, all future RhD-positive pregnancies are at risk