Rh Incompatibility

Symptoms

• For the Mother: Rh incompatibility does not cause any symptoms in the mother.
• For the Unborn Baby (detected by monitoring): Anemia (low red blood cell count), often detected by special ultrasound scans.
• For the Unborn Baby (detected by monitoring): Enlarged liver and spleen.
• For the Unborn Baby (detected by monitoring): Fluid buildup in the abdomen (ascites) or around the lungs/heart.
• For the Unborn Baby (detected by monitoring): Severe cases can lead to widespread swelling (hydrops fetalis), which is a serious condition indicating heart failure.
• For the Newborn Baby: Jaundice (yellowing of the skin and eyes) appearing within the first 24 hours after birth.
• For the Newborn Baby: Pallor (unusual paleness) due to anemia.
• For the Newborn Baby: Enlarged liver and spleen.
• For the Newborn Baby: Severe cases may involve widespread swelling (hydrops fetalis) at birth or breathing difficulties.
• For the Newborn Baby: Very high bilirubin levels can lead to serious brain damage (kernicterus), with signs like extreme lethargy, poor feeding, high-pitched crying, arching of the back or neck, and seizures.

Causes & Risk Factors

• The fundamental cause is the exposure of an RhD-negative mother's immune system to RhD-positive fetal red blood cells.
• This exposure, known as a sensitization event or fetomaternal hemorrhage, allows fetal red blood cells to enter the mother's circulation.
• The mother's immune system recognizes the RhD antigen on the fetal red blood cells as foreign and produces antibodies (initially IgM, then IgG).
• In a subsequent pregnancy with another RhD-positive fetus, the maternal IgG antibodies can cross the placenta and bind to the fetal red blood cells.
• These antibodies mark the fetal red blood cells for destruction by the baby's spleen and liver, leading to hemolysis and anemia (Hemolytic Disease of the Fetus and Newborn).
• Mother is RhD-negative.
• Fetus is RhD-positive (requires biological father to be RhD-positive).
• Previous pregnancy with an RhD-positive fetus, especially if Rh immune globulin was not administered.
• Delivery of an RhD-positive infant.
• Ectopic pregnancy.
• Spontaneous or induced abortion.
• Miscarriage after 8 weeks gestation.
• Amniocentesis, chorionic villus sampling (CVS), or other invasive prenatal diagnostic procedures.
• Antepartum hemorrhage (e.g., placenta previa, placental abruption).
• External cephalic version.
• Abdominal trauma during pregnancy.
• Intrauterine fetal death.
• Mismatched blood transfusion with RhD-positive blood (rare).
• Concurrent ABO incompatibility between mother and fetus may offer partial protection against RhD alloimmunization.

Diagnosis

• All pregnant women should have ABO and RhD blood typing and an antibody screen (indirect Coombs test) at their first antenatal visit.
• RhD-negative, unsensitized women will have a repeat antibody screen around 28 weeks' gestation, before routine Rh immune globulin administration.
• If you are RhD-negative and sensitized, your healthcare provider will monitor your antibody levels (titers) regularly, typically every 2-4 weeks after 18-20 weeks of pregnancy.
• A critical antibody titer (often 1:8 to 1:32, depending on the lab and guidelines) indicates a high risk for severe fetal anemia and triggers more intensive monitoring.
• Your partner's RhD status can be tested to determine the likelihood of an RhD-positive fetus.
• Non-invasive fetal RhD genotyping using cell-free fetal DNA from your blood can determine the baby's RhD status before birth, avoiding unnecessary interventions if the baby is RhD-negative.
• Middle Cerebral Artery (MCA) Peak Systolic Velocity (PSV) Doppler is the primary non-invasive ultrasound tool to assess for fetal anemia.
• Serial ultrasounds are used to monitor for signs of hydrops fetalis (fluid buildup in the baby's body).
• Cordocentesis (Percutaneous Umbilical Blood Sampling - PUBS) is an invasive procedure to directly measure fetal hemoglobin/hematocrit, often performed before an intrauterine transfusion.
• At birth, cord blood testing for all infants of RhD-negative mothers includes the infant's ABO and RhD type, a Direct Antiglobulin Test (DAT) / Direct Coombs Test to detect maternal antibodies, and hemoglobin/hematocrit and bilirubin levels.

Treatment Options

• Intrauterine Blood Transfusion (IUT): For severe fetal anemia, O-negative, CMV-negative, irradiated, packed red blood cells are transfused into the umbilical vein under ultrasound guidance. This may be repeated every 2-4 weeks until delivery.
• Phototherapy: For newborns with hyperbilirubinemia (high bilirubin levels), special lights are used to help the baby's body excrete bilirubin.
• Intravenous Immunoglobulin (IVIG): For severe hyperbilirubinemia in newborns, IVIG may be used alongside phototherapy to reduce the need for exchange transfusion.
• Exchange Transfusion: For severe anemia or dangerously high bilirubin levels in newborns unresponsive to phototherapy, the infant's blood is removed and replaced with donor blood to remove bilirubin, maternal antibodies, and correct anemia.
• Immediate resuscitation of a hydropic infant at birth.
• Emergency exchange transfusion for critical hyperbilirubinemia or severe anemia in the newborn.
• Monitoring of bilirubin levels in the newborn.
• Monitoring for late-onset anemia in infants who received intrauterine transfusions or had severe Hemolytic Disease of the Fetus and Newborn (HDFN).
• An RhD-negative pregnant woman with a critical anti-D titer should be referred to a Maternal-Fetal Medicine (MFM) specialist.
• Pregnancies requiring intrauterine transfusion should be managed at a tertiary care center with expertise in this procedure.

Frequently Asked Questions