Hemolytic disease of the fetus and newborn (HDFN) caused by RhD incompatibility was uncommon in a 2024 study at a tertiary-care hospital in Pakistan, although some newborns had laboratory evidence of antibodyAntibody A protein made by the immune system that recognizes and attacks foreign substances, such as bacteria, or in HDFN, fetal red blood cells carrying incompatible antigens.-related red blood cell destruction.
The findings, presented recently at the International Society of Blood Transfusion Asian Day Session, suggest that a positive direct antiglobulin testDirect antiglobulin test A blood test used to detect antibodies attached to red blood cells. It helps confirm HDFN in newborns. (DATDirect antiglobulin test A blood test used to detect antibodies attached to red blood cells. It helps confirm HDFN in newborns.) does not necessarily mean a newborn will develop severe HDFN and that clinical and laboratory findings should be considered together.
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“DAT reactivity alone did not predict severity, underscoring the importance of integrating serologic grading with biochemical and clinical parameters,” explained the authors.
The study included all RhD-negative mothers who delivered at Aga Khan University Hospital from January through December 2024. Among 4,840 deliveries, 191 mothers were RhD-negative, with a mean age of 30.3 years. Of 140 RhD-positive newborns, 23 (16.4%) had a positive DAT. Overall, 69.6% of newborns were born at term, 81.7% had normal birth weight and 14.7% required admission to a neonatal intensive care unit.
Among newborns with a positive DAT, 69.6% of mothers had identifiable medical, obstetric or immunologic risk factors. AntibodiesAntibody A protein made by the immune system that recognizes and attacks foreign substances, such as bacteria, or in HDFN, fetal red blood cells carrying incompatible antigens. were detected in 21.7% of mothers, predominantly anti-D. Most DAT-positive newborns (82.6%) had no symptoms. PhototherapyPhototherapy A treatment that uses special blue light to help newborns break down bilirubin and prevent kernicterus. was required for 17.4%, while one newborn developed significant hemolysis, or accelerated destruction of red blood cells.
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Hemoglobin and indirect bilirubinBilirubin A yellow substance produced when red blood cells break down. High bilirubin levels in newborns with HDFN can cause jaundice or, in severe cases, brain damage. levels did not differ significantly between DAT-positive and DAT-negative newborns. However, the strength of the DAT showed a moderate correlation with indirect bilirubin levels, indicating that stronger antibody binding was associated with higher bilirubin. The regression model predicting the need for phototherapy was statistically significant (P =.009).
For patients, the findings reinforce the importance of RhD blood-group testing during pregnancy and timely Anti-D prophylaxis when indicated. RhD incompatibility occurs when an RhD-negative mother carries an RhD-positive fetus, potentially causing maternal antibodies to attack fetal or newborn red blood cells. Although prophylaxis has reduced alloimmunizationAlloimmunization When a person’s immune system develops antibodies against foreign antigens from the same species—such as when an Rh-negative mother’s body forms antibodies against her baby’s Rh-positive red blood cells. rates to less than 0.5% in high-income countries, gaps in screening, Anti-D availability and laboratory monitoring continue to create preventable risks in low- and middle-income countries.
The study concluded that clinically important RhD-mediated HDFN was uncommon in a setting with structured screening and prophylaxis. Because DAT positivity alone did not predict disease severity, coordinated obstetric, transfusion and newborn care remains important. Expanding universal screening and ensuring reliable access to Anti-D could further reduce preventable HDFN-related complications.
