Background:
Maternal–infant blood group incompatibility is an important cause of early-onset neonatal hyperbilirubinemia and hemolytic disease of the newborn. Although ABO incompatibility accounts for most cases, less common Rh and minor blood group incompatibilities may be associated with more severe disease.
Objective:
To characterize neonatal immune hemolytic disease according to the type of maternal–infant blood group incompatibility and to compare disease severity and treatment requirements across incompatibility types.
Methods:
We conducted a retrospective observational study of 147 neonates with indirect hyperbilirubinemia attributed to maternal–infant blood group incompatibility admitted to the Neonatal Centre, Vietnam National Children’s Hospital, from January 2024 to April 2025. Clinical presentation, hematological findings, type of blood group incompatibility, treatment modalities, and outcomes were analysed and compared across incompatibility groups.
Results:
Jaundice developed predominantly within the first 24 hours of life, and 83.0% of infants were term. Anemia was present in 53.7%, with a median reticulocyte percentage of 9.1% (IQR, 4.5–12.7). ABO incompatibility was the most common cause (87.1%), followed by minor Rh(D) blood group (8.8%) and Rh(C, c, E, e) incompatibility (4.1%). Intravenous immunoglobulin (IVIG) was more frequently used in neonates with ABO incompatibility than in those with non-ABO (Rh(D) or minor Rh blood group) incompatibility (91.5% vs. 65.5%, p=0.002), whereas exchange transfusion was required more frequently in neonates with Rh(D) incompatibility (13.8% vs. 2.4%, p=0.039) or minor Rh blood group incompatibilities (20.7% vs. 6.1%, p=0.034). Neonates who received IVIG had a higher rate of anemia at follow-up than those who did not (89.0% vs. 4.0%, p<0.001), with a trend toward more frequent readmission for blood transfusion within the first month of life (21.9% vs. 4.0%, p=0.063).
Conclusions: ABO incompatibility was the predominant cause of hemolytic disease in newborn and was managed more often with with IVIG, whereas Rh(D) and minor Rh blood group incompatibilities, though less common, were associated with more severe disease requiring exchange transfusion. The higher rate of anemia at follow-up among IVIG-treated neonates likely reflects more severe underlying hemolysis in this group rather than a direct treatment effect, highlighting the importance of close post-discharge hematological follow-up regardless of incompatibility type.