ABO Haemolytic Disease of the Newborn

ABO haemolytic disease of the newborn is haemolysis of an infant's red cells by maternal IgG anti-A or anti-B antibodies that cross the placenta. It almost always affects group A or B infants of group O mothers and is usually mild.

It is the commonest cause of neonatal haemolytic jaundice. ABO incompatibility occurs in a substantial minority of pregnancies, but clinically significant haemolysis occurs in only a small proportion of them. The first pregnancy can be affected.

Haemolysis is less severe than in Rh disease because A and B antigens are weakly expressed on neonatal red cells and are also found on other tissues. Hydrops is rare.

Pathophysiology.

Maternal IgG anti-A or anti-B coats the infant's red cells and removes them in the spleen. Haemolysis releases bilirubin that the immature liver conjugates slowly.

Jaundice appears in the first 24 hours, bilirubin rises rapidly and anaemia can develop later. Late anaemia at 2 to 6 weeks is caused by persisting antibody and a poor marrow response.

• Jaundice within 24 hours of birth, or rapidly rising bilirubin over 8.5 micromol/L/h in the first days.
• Pallor, mild hepatosplenomegaly and reticulocytosis.
• Late anaemia with pallor and poor feeding at 2 to 6 weeks.

Red flags.

• Jaundice in the first 24 hours of life.
• Bilirubin rising over 8.5 micromol/L/h or close to the exchange transfusion threshold.
• Lethargy, high pitched cry, poor feeding or abnormal tone, suggesting bilirubin neurotoxicity.

• Maternal and infant blood groups, and direct antiglobulin test on the infant. The test is weakly positive or negative in many cases, so a negative result does not exclude disease.
• Full blood count with blood film (spherocytes), reticulocyte count, serial total and conjugated bilirubin, and albumin.
• G6PD enzyme assay when the course is atypical, as G6PD deficiency can coexist.

Differential diagnosis. Rh haemolytic disease, other red cell antibody disease, G6PD deficiency, hereditary spherocytosis, sepsis, bruising and polycythaemia.

• Phototherapy using gestation specific and age specific bilirubin charts, starting at the phototherapy threshold. Use intensive (double sided) phototherapy when bilirubin rises quickly or is near the exchange threshold.
• Hydration and frequent feeding, with IV fluids if intake is inadequate.
• IV immunoglobulin 500 mg/kg over 4 hours if bilirubin continues to rise despite intensive phototherapy, repeated once at 12 hours if required. Evidence for benefit is limited in ABO disease.
• Double volume exchange transfusion (160 to 180 mL/kg) when bilirubin reaches the gestation specific exchange threshold or signs of bilirubin encephalopathy appear, using group O red cells of the infant's Rh type, cross-matched against the mother, and irradiated where intrauterine transfusion occurred.
• Folic acid 500 micrograms daily by mouth for 4 to 6 weeks is used by many centres in haemolysis. Evidence is limited.

Monitoring. Bilirubin every 4 to 6 hours during phototherapy, then daily after stopping, and 12 to 24 hours after stopping to check for rebound. Haemoglobin weekly for 4 to 6 weeks after discharge, and transfusion if under 80 g/L with symptoms.

Referral and escalation. Early neonatal unit review for jaundice in the first 24 hours. Refer to a centre able to perform exchange transfusion when bilirubin approaches the threshold.