Is jaundice in a newborn with Rh positive blood, whose mother has Rh negative blood, due to a congenital inheritance disorder or an acquired factor, specifically Rh incompatibility leading to hemolytic disease of the newborn (HDN)?

Jaundice in Rh-Positive Newborns with Rh-Negative Mothers is an Acquired Factor Due to Rh Incompatibility

Jaundice in a newborn with Rh-positive blood whose mother has Rh-negative blood is primarily caused by an acquired factor - specifically Rh incompatibility leading to hemolytic disease of the newborn (HDN) - rather than a congenital inheritance disorder.

Pathophysiology of Rh Incompatibility

Rh incompatibility occurs when an Rh-negative mother carries an Rh-positive fetus. This blood type incompatibility creates a specific sequence of events:

1. Maternal Sensitization: The Rh-negative mother is exposed to Rh-positive fetal red blood cells, typically during delivery, abortion, trauma, or invasive procedures 1
2. Antibody Production: The mother's immune system recognizes the Rh antigen as foreign and produces anti-D antibodies
3. Subsequent Pregnancies: In future pregnancies with Rh-positive fetuses, these maternal antibodies cross the placenta and attack fetal red blood cells 1

Clinical Presentation and Diagnosis

Newborns with hemolytic disease due to Rh incompatibility typically present with:

• Jaundice within the first 24 hours of life (pathologic jaundice)
• Anemia of varying severity
• Positive direct Coombs test 1
• Elevated bilirubin levels requiring intervention

The severity of hemolytic disease can be categorized based on fetal hemoglobin concentrations, with severe anemia potentially leading to hydrops fetalis and fetal death 1.

Prevention of Rh Alloimmunization

Prevention is the cornerstone of management:

• Prenatal Testing: All pregnant women should be tested for ABO and Rh(D) blood types with serum screening for unusual isoimmune antibodies 1
• RhD Immune Globulin (RhIg): Administration to Rh-negative mothers prevents sensitization
  • Given within 72 hours after delivery of an Rh-positive infant
  • Reduces incidence of Rh isoimmunization from 12-13% to 1-2% 2
  • Also recommended after spontaneous or induced abortion, amniocentesis, or abdominal trauma 1
  • Two-dose protocol (28 weeks' gestation and post-delivery) can further reduce sensitization to less than 0.1% 2

Management of Affected Newborns

For newborns with jaundice due to Rh incompatibility:

1. Bilirubin Monitoring: Measure total serum bilirubin (TSB) every 8-12 hours until levels are clearly declining 3
2. Phototherapy: Initiate when TSB reaches thresholds based on age, gestational age, and risk factors 3
3. IVIG: Consider intravenous immunoglobulin (0.5-1 g/kg over 2 hours) if TSB is rising despite intensive phototherapy 3
4. Exchange Transfusion: Prepare if TSB ≥25 mg/dL or reaches exchange level per guidelines 3
5. Follow-up: Schedule follow-up at 2-4 weeks to check hemoglobin levels, especially with rare antibodies, to monitor for late-onset anemia 3

Important Distinctions

It's important to note that while Rh incompatibility is an acquired factor, there are congenital inheritance disorders that can also cause neonatal jaundice and anemia, including:

• Alpha-thalassemia
• Glucose-6-phosphate dehydrogenase deficiency
• Pyruvate kinase deficiency 1

However, in the specific case of an Rh-positive newborn with an Rh-negative mother presenting with jaundice, the primary cause is the acquired Rh incompatibility rather than these inherited conditions.

Clinical Pearls

• Not all cases of jaundice in Rh-incompatible pregnancies are due to Rh incompatibility - always consider other causes
• The RhD antigen is well developed by 6 weeks' gestation, making first-trimester exposure a potential risk 1
• Alloimmunization can occur with as little as 0.1 mL of injected Rh-positive cells 1
• While Rh incompatibility is the prototype of maternal alloimmunization, other antigens capable of causing alloimmunization and hemolytic disease include c, Kell, and Fya 4

With proper prevention through RhIg administration and appropriate management of affected newborns, the perinatal mortality from hemolytic disease has been dramatically reduced over the past decades 4.