ABO Blood Type Incompatibility in Newborns: Pathophysiology, Clinical Features, and Management


ABO blood type incompatibility is a common cause of neonatal jaundice and hemolysis in the first days of life. It occurs when a mother’s blood type is O and the newborn inherits either A or B antigens from the father. Maternal anti-A or anti-B IgG antibodies can cross the placenta and lead to hemolysis of fetal red blood cells. Although often mild, ABO incompatibility can sometimes cause significant hyperbilirubinemia, requiring careful evaluation and management to prevent complications such as bilirubin encephalopathy (kernicterus).

Pathophysiology

  • The ABO blood group system includes four types: A, B, AB, and O.
  • Type O mothers naturally produce IgG antibodies against A and B antigens.
  • When the fetus expresses A or B antigens, maternal IgG can cross the placenta, bind to fetal red blood cells, and trigger immune-mediated hemolysis.
  • This hemolysis increases unconjugated bilirubin, which the immature neonatal liver may struggle to metabolize efficiently, resulting in jaundice.
  • Severity is influenced by maternal antibody titers, infant blood type, and gestational age.

Incidence

  • ABO incompatibility affects 10–20% of all pregnancies.
  • Only 1–2% of newborns develop clinically significant hemolytic disease.
  • It is more common in firstborn infants, as sensitization can occur in utero without prior pregnancies.

Risk Factors

  • Maternal blood type O with anti-A or anti-B antibodies.
  • Infant blood type A or B.
  • Prematurity, as preterm infants have immature hepatic conjugation capacity.
  • Previous pregnancies with ABO incompatibility, although sensitization is often mild in ABO systems compared to Rh incompatibility.

Clinical Presentation

  1. Jaundice
    • Appears within 24–72 hours of life.
    • Starts on the face and sclera and may progress to the trunk and extremities.
  2. Anemia
    • Mild to moderate due to hemolysis.
    • Severe anemia is rare compared to Rh incompatibility.
  3. Laboratory Findings
    • Elevated unconjugated bilirubin.
    • Positive direct antiglobulin test (DAT/Coombs test) in 10–20% of cases.
    • Reticulocytosis may be mild.
    • Hemoglobin usually mildly decreased; severe anemia is uncommon.

Table 1. Laboratory Profile in ABO Incompatibility

ParameterTypical FindingNotes
Total serum bilirubinElevated, mainly unconjugatedPeaks around 3–5 days
Direct Coombs testPositive in some infantsConfirms maternal antibody-mediated hemolysis
HemoglobinMildly decreasedRarely <12 g/dL in term infants
Reticulocyte countMildly elevatedReflects red cell turnover
Peripheral smearSpherocytes may be seenIndicative of hemolysis

Management
Management depends on bilirubin levels, hemolysis severity, and infant gestational age.

  1. Phototherapy
    • First-line therapy for hyperbilirubinemia.
    • Converts unconjugated bilirubin to water-soluble isomers for excretion.
    • Frequent bilirubin monitoring is essential to guide therapy duration.
  2. Intravenous Immunoglobulin (IVIG)
    • Considered in infants with rapidly rising bilirubin or hemolysis unresponsive to phototherapy.
    • IVIG blocks maternal antibodies from destroying red cells.
  3. Exchange Transfusion
    • Reserved for severe hyperbilirubinemia or bilirubin approaching neurotoxic levels.
    • Reduces bilirubin levels quickly and removes antibody-coated red cells.
  4. Supportive Care
    • Adequate hydration and feeding to promote bilirubin excretion.
    • Monitoring hematocrit and hemoglobin for anemia.
    • Follow-up for late-onset anemia if significant hemolysis occurs.

Prognosis

  • Most cases are mild and resolve with phototherapy alone.
  • Severe complications like kernicterus are rare with modern monitoring and early intervention.
  • Term infants generally tolerate ABO incompatibility well; preterm infants may require closer monitoring.

Differential Diagnosis

  • Rh incompatibility: Usually more severe hemolysis and anemia.
  • G6PD deficiency: May present with jaundice triggered by oxidative stress.
  • Sepsis: Can cause early jaundice and anemia.
  • Hereditary spherocytosis: Rare cause of hemolytic jaundice.

Table 2. Comparison of ABO vs Rh Incompatibility in Newborns

FeatureABO IncompatibilityRh Incompatibility
Maternal antibodiesAnti-A or anti-B IgGAnti-D IgG
Onset of jaundiceUsually 1–3 daysOften delayed, more severe
Severity of anemiaMild to moderateSevere
Risk of kernicterusLow if managedHigher without treatment
FrequencyCommonLess common

Parental Education

  • Educate parents to monitor for jaundice, lethargy, poor feeding, or dark urine.
  • Reinforce the importance of timely bilirubin checks.
  • Provide reassurance that most infants respond well to phototherapy and do not develop long-term complications.

Socioeconomic Considerations

  • In the U.S., routine bilirubin screening and phototherapy are widely available, reducing the risk of complications.
  • Families with limited access to care may face challenges in timely diagnosis and management, emphasizing the importance of early pediatric follow-up.

Conclusion
ABO blood type incompatibility is a common cause of mild hemolytic disease and neonatal jaundice. Early recognition, laboratory evaluation, and management with phototherapy prevent complications. Most term infants have an excellent prognosis, though preterm infants or those with rapidly rising bilirubin require closer monitoring. Educating parents and providing timely access to neonatal care are essential to ensure optimal outcomes.