Hemolytic Disease of the Fetus and Newborn (HDFN)

Pathophysiology & Antibodies

• Maternal IgG alloantibodies cross the placenta targeting fetal red blood cell antigens, leading to profound hemolysis, fetal anemia, and hydrops fetalis.
• RhD Incompatibility: Most severe classical form. Occurs in Rh-negative mother with Rh-positive fetus (subsequent pregnancies if unsensitized).
• ABO Incompatibility: Occurs typically in Type O mothers with Type A or B infants. Less severe because A/B antigens are also present on non-erythroid tissues, diluting antibody effect.
• Minor Antigens: Anti-Kell ('Kell kills' by simultaneously destroying RBCs and suppressing fetal bone marrow erythropoiesis), Anti-c, Anti-E.

Diagnostic Workup & MCA Doppler

• Prenatal: Serial Middle Cerebral Artery (MCA) Peak Systolic Velocity (PSV) ultrasounds. PSV > 1.5 Multiples of the Median (MoM) dictates immediate fetal blood sampling/intrauterine transfusion.
• Postnatal immediate labs (Cord Blood): Blood type, Direct Antiglobulin Test (DAT/Coombs - usually strongly positive), CBC (to assess baseline hemoglobin), Reticulocyte count (highly elevated >> 5-10%).
• Smear morphology: Spherocytes prominent in ABO incompatibility; nucleated RBCs (erythroblasts) prominent in Rh disease.

Acute Neonatal Management

• Immediate intensive phototherapy pending lab results if HDFN is suspected, utilizing maximum irradiance (> 30 µW/cm²/nm).
• Intravenous Immunoglobulin (IVIG): 0.5 to 1.0 g/kg administered IV over 2-4 hours if TSB is rising aggressively despite phototherapy (>0.5 mg/dL/hr) or is within 2 mg/dL of exchange threshold. Reduces need for exchange transfusion by blocking Fc receptors on macrophages.
• Double-Volume Exchange Transfusion (DVET): Removes sensitized RBCs, circulating maternal antibodies, and unbound bilirubin. Replaces with matched, irradiated, CMV-safe, O-negative fresh whole blood.

Late Complications Management

• Late Hyporegenerative Anemia: Maternal antibodies continue destroying infant RBCs for up to 6-12 weeks, while infant bone marrow response remains blunted.
• Monitor Hemoglobin weekly/bi-weekly for 2-3 months.
• Symptomatic anemia (poor feeding, tachycardia, lethargy): Provide simple PRBC top-up transfusions (10-15 mL/kg O-negative PRBCs crossed against maternal serum).
• Folic Acid supplementation (1 mg/day) to support intense compensatory erythropoiesis.

Diagnostic & Management Algorithm

• HDFN Exchange Transfusion Logic: [START] Rh Sensitized + rapidly rising bilirubin -> [DECISION] Bilirubin within 2mg/dL of exchange? -> [YES] Give IVIG -> [DECISION] Bilirubin > exchange threshold? -> [YES] DVET

References

1. Pegoraro V, et al. Hemolytic disease of the fetus and newborn due to Rh(D) incompatibility: A preventable disease that still produces significant maternal and neonatal morbidity. PLoS One.