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PEDIATRICS Vol. 110 No. 1 July 2002, pp. 127-130

Isoimmunization Is Unlikely to Be the Cause of Hemolysis in ABO-Incompatible but Direct Antiglobulin Test-Negative Neonates

Marguerite Herschel, MD*, Theodore Karrison, PhD{ddagger}, Ming Wen, MS{ddagger}, Leslie Caldarelli, MD* and Beverly Baron, MD§

* Departments of Pediatrics
{ddagger} Health Studies
§ Pathology, the University of Chicago Pritzker School of Medicine, Chicago, Illinois

Objective. It is stated that the direct antiglobulin (Coombs’) test (DAT) may be negative in ABO hemolytic disease of the newborn. Thus, significant jaundice in neonates who are A-B incompatible with their mothers but DAT test negative is often attributed to isoimmunization and another diagnosis is not sought. We wished to determine the rate of bilirubin production, as an objective measure of hemolysis, in 2 groups of DAT-negative neonates—ABO-compatible and ABO-incompatible—and in DAT-positive ABO-incompatible neonates.

Methods. In consecutive, term, healthy newborns who were admitted to the general care nursery, we measured the level in parts per million (ppm) of end-tidal breath carbon monoxide (CO), corrected for inspired CO (ETCOc), an index of the rate of bilirubin production. We compared the levels in DAT-negative ABO-incompatible neonates with those in ABO-compatible neonates and with the levels in DAT-positive ABO-incompatible neonates. Statistical analysis was performed using 2-sample t and {chi}2 tests.

Results. There was no significant difference between the mean 12-hour ETCOc levels in DAT-negative ABO-incompatible neonates (n = 60, 2.2 ± 0.6 ppm) versus DAT-negative ABO-compatible neonates (n = 171, 2.1 ± 0.6 ppm), although there was a difference between the mean levels in DAT-positive ABO-incompatible neonates (n = 14, 3.4 ± 1.8 ppm) and the DAT-negative groups. Four DAT-negative ABO-incompatible neonates had elevated ETCOc levels; in 2, we diagnosed a specific hematologic abnormality, namely, glucose-6-phosphate dehydrogenase deficiency in 1 and elliptocytosis in the other.

Conclusion. In DAT-negative newborns with significant jaundice or increased bilirubin production, even if ABO-incompatible, a cause other than isoimmunization should be sought.

Key Words: direct antiglobulin test • Coombs’ test • end-tidal carbon monoxide • neonatal jaundice • ABO incompatibility

Abbreviations: DAT, direct antiglobulin test • IgG, immunoglobulin G • ETCOc, end-tidal carbon monoxide corrected for ambient CO • G6PD, glucose-6-phosphate dehydrogenase

Received for publication Oct 5, 2001; Accepted Jan 28, 2002.