Rh-incompatible pregnancy

Disease Description (Causes and Symptoms)

• Definition: A condition in which, when the pregnant woman is Rh(D)-negative and the fetus is Rh(D)-positive, IgG antibodies produced after maternal sensitization to the D antigen on fetal red blood cells cross the placenta and cause hemolysis of fetal red blood cells.
• Causes/pathophysiology: After initial exposure (delivery, miscarriage, invasive procedures, trauma, etc.), the mother forms anti-Rh(D) antibodies. In subsequent pregnancies, IgG antibodies cross the placenta and destroy fetal red blood cells → fetal and neonatal anemia, compensatory extramedullary hematopoiesis (enlargement of the liver and spleen), and hyperbilirubinemia due to hemolysis. In severe cases, heart failure and hydrops fetalis may occur, with possible intrauterine death.
• Main symptoms (fetus/newborn): Anemia (pallor, lethargy), jaundice (yellowing of the skin and sclera in newborns), hepatomegaly and splenomegaly, ascites, pleural effusion, and skin edema (hydrops), respiratory distress, pulmonary hemorrhage, heart failure, and, in severe cases, kernicterus (brain damage) and neonatal seizures.

Treatment Methods (Standard Treatment, Medications, Procedures, Lifestyle Management, and Precautions)

• Prevention (most important)
  • Administration of Rh immune globulin (Rho(D) Ig; e.g., RhoGAM): The standard is a single dose at around 28 weeks of pregnancy (generally 300 µg), with an additional dose within 72 hours after delivery when the mother is Rh(-) and the newborn is Rh(+). It is also administered after events with a risk of sensitization, such as miscarriage, ectopic pregnancy, invasive procedures (CVS, amniocentesis), and abdominal trauma.
• Prenatal management and intervention
  • Maternal testing: Blood type and Rh, indirect Coombs test (antibody screening), antibody identification, and antibody titer measurement (recommended monthly until 24 weeks after initial confirmation, then at 2-week intervals). The critical titer varies by institution and testing method, but levels of 1:16–1:32 or higher are generally considered concerning titers.
  • Fetal monitoring: Interventional testing when fetal anemia is suspected
    • Doppler MCA (middle cerebral artery) peak systolic velocity (PSV): Significant anemia is suspected if >1.5 MoM.
    • Confirmation and treatment: Fetal hemoglobin is assessed by cord blood testing (cordocentesis), and intrauterine transfusion (IUT) is performed when necessary.
  • Consider early delivery if severe hemolysis or hydrops develops.
• Newborn treatment
  • Phototherapy: Treatment of hyperbilirubinemia.
  • Exchange transfusion: Used for severe hyperbilirubinemia or severe anemia, with fresh Rh-negative type O blood.
  • In some cases, neonatal IVIG (for the purpose of neutralizing antibodies) is attempted to reduce the need for exchange transfusion.
• Other (in cases of severe sensitization)
  • Attempts may be made to reduce the effects of antibodies using antenatal high-dose IVIG or autologous blood and pre-transplant treatment (in specific situations), but application is selective and referral to a specialized center is required.
• Precautions/risks of complications/self-care
  • Keep accurate records of Rho(D) Ig administration, like vaccination records (timing and dose).
  • If sensitization has occurred, the risks of hydrops fetalis and intrauterine death increase. Newborns are at risk of neurological complications caused by kernicterus.
  • Consult medical staff immediately after an invasive procedure or trauma to determine whether Rho(D) Ig should be administered.
  • Prenatal care should be provided closely with a specialist (maternal-fetal medicine center).

Checkpoints Before an Outpatient Visit (Including Items to Bring and Example Questions)

• Items to bring to the appointment
  • Copies of past and current blood type (Rh) test results and antibody test (indirect Coombs test) results
  • Previous pregnancy history: previous miscarriages and deliveries (including the newborns’ blood types), history of intrauterine transfusion or hydrops, and whether exchange transfusion was performed
  • Records of Rho(D) Ig administration (date and dose)
  • Recent ultrasound and MCA Doppler results, and examination dates
  • List of medications currently being taken and history of allergies
  • Whether recent trauma or invasive procedures (amniocentesis, CVS, etc.) occurred and the dates
• Items useful to record for the outpatient visit
  • Changes in symptoms during pregnancy, such as decreased fetal movement, edema, fever, and bleeding
  • Trends in changes in previous antibody titers
• Example questions (questions the patient can ask the doctor directly)
  • (For preparation before the appointment begins) "Could you check my blood type and antibody test results? What is my current antibody titer?"
  • "Is there a time or situation during this pregnancy when I need to receive Rho(D) Ig?"
  • "Did the recent ultrasound show hydrops fetalis or an elevated MCA PSV?"

General Example Questions to Ask the Doctor

• "What does my current antibody titer mean as the pregnancy progresses? At what level would you recommend additional testing?"
• "If fetal anemia is suspected, what tests will you perform and when? What are the indications and risks of intrauterine transfusion?"
• "How likely is it that the newborn will need treatment for jaundice or anemia after delivery? How will the necessary treatment (phototherapy/exchange transfusion) be determined?"

Disease-Specific Example Questions

• "Is my antibody titer (e.g., 1:16) at a dangerous level for my current gestational age? Once it reaches this level, what additional tests (MCA Doppler, amniocentesis, cord blood testing) will be performed?"
• "I received Rho(D) Ig in the past; do I need to receive the same dose in this pregnancy as well? After a miscarriage or trauma, how soon and how much additional Rho(D) Ig should I receive?"