Hemolytic disease of the fetus and newborn

Epidemiology

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Etiology

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Pathophysiology

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Feature	ABO HDN	Rh HDN
Frequency	Common (Most common cause of HDN)	Rare (due to RhoGAM prophylaxis)
Scenario	Mom Type O / Baby A or B	Mom Rh(-) / Baby Rh(+)
First Pregnancy?	Yes (Pre-existing IgG)	No (Requires sensitization)
Severity	Mild (Jaundice within 24h)	Severe (Hydrops fetalis, death)
Mechanism	IgG Anti-A/B cross placenta	IgG Anti-D cross placenta
Smear/Labs	Spherocytes, Weak Coombs	Strong + Coombs, No spherocytes
Prevention	None	RhoGAM (Anti-D IgG)

1. The “Sponge” Effect (Antigen Distribution)

• ABO Antigens: Found on RBCs AND other tissues (endothelium, platelets, fetal tissues).
  • Result: Maternal Anti-A/B antibodies crossing the placenta bind to these other tissues, effectively “soaking up” or neutralizing the antibodies before they can significantly destroy RBCs.
• Rh Antigens: Found ONLY on RBCs.
  • Result: Every maternal Anti-D antibody that crosses the placenta targets red blood cells specifically, leading to focused and massive hemolysis.

2. Antigen Maturity

• ABO Antigens: Weakly expressed on fetal RBCs compared to adult RBCs.
  • Result: Less binding sites for antibodies → less hemolysis.
• Rh Antigens: Fully expressed at birth.
  • Result: High density of binding sites allows for rapid destruction (extravascular hemolysis in the spleen).

ABO incompatibility

• Highest risk: mother with blood group O; newborn with blood group A or B
• Maternal antibodies (anti-A and/or anti-B) against nonself antigens of the ABO system are present even if sensitization has not occurred, so fetal hemolysis may occur during the first pregnancy.
  • Combination of predominantly IgM antibodies and late expression of fetal ABO antigens reduces the chances of significant disease.

Clinical features

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Diagnostics

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Treatment

• Prevention (Rh-negative, Unsensitized Mothers):
  1. Anti-D Immune Globulin (RhoGAM, 300 $\mu$g):
     • Administer routinely at 28 weeks gestation. c
     • Administer within 72 hours postpartum if neonate is Rh(D)-positive.
     • Administer after any potential feto-maternal hemorrhage event (spontaneous abortion, ectopic pregnancy, CVS, amniocentesis, abdominal trauma, external cephalic version). c
  2. Kleihauer-Betke (KB) Test / Flow Cytometry:
     • Perform postpartum or post-trauma to quantify feto-maternal hemorrhage volume and calculate required additional doses of RhoGAM.
     • Note: RhoGAM is ineffective once maternal alloimmunization (sensitization) has occurred.
• Antenatal Management (Sensitized Pregnancies):
  1. Surveillance: Serial MCA-PSV Doppler every 1–2 weeks starting at 16–20 weeks gestation.
  2. If MCA-PSV > 1.5 MoM:
     • $<35$ weeks: Intrauterine Erythrocyte Transfusion (IUET) via PUBS into umbilical vein using O-negative, CMV-negative, irradiated, leukoreduced packed RBCs.
     • $\ge 35$ weeks: Proceed to delivery.
• Neonatal Management:
  1. First-line: Intensive Phototherapy (converts hydrophobic unconjugated bilirubin into water-soluble photoisomers/lumirubin).
  2. Second-line / Adjunct: Intravenous Immune Globulin (IVIG) to block neonatal Fc receptors and decrease hemolysis in immune-mediated hyperbilirubinemia.
  3. Refractory / Severe Hyperbilirubinemia: Double-volume Exchange Transfusion if total serum bilirubin exceeds exchange thresholds or if acute bilirubin encephalopathy signs appear.