Predictive Ability of Direct Antibody Testing in Infants Born to Mothers with Rh(D) and Other Minor Red Blood Cell Antibodies

Abstract

Objective Hemolytic disease of the newborn (HDN) most commonly occurs in neonates whose mothers carry nonpassively acquired antibodies directed against red blood cell (RBC) antigens. Because affected neonates may develop severe hyperbilirubinemia, early identification of at-risk neonates is critically important. We hypothesized that use of the direct antibody test (DAT) would be of high predictive value in identifying those neonates most likely to meet treatment criteria for hyperbilirubinemia.

Study Design We performed a retrospective chart review of all mother–infant pairs in which RBC antibodies were detected on routine prenatal screening during the current pregnancy (2011–2013). We then compared DAT results of neonates who eventually met the treatment criteria for hyperbilirubinemia with those who did not.

Main Results Fifty-sixty neonates were born to mothers with clinically significant antibodies. The sensitivity and specificity of a positive DAT result for meeting the treatment criteria were 87.5 and 93.3%, respectively. The positive and negative predictive values were 77.8 and 96.6%, respectively.

Conclusion The result of a DAT, obtained in neonates of mothers with clinically relevant alloantibodies, is a specific marker with good positive predictive value for identifying those who are most likely to meet the treatment criteria for hyperbilirubinemia.

Keywords

coombs test - fluorescent antibody technique - direct - hemolytic disease of newborn - hyperbilirubinemia - infant - newborn

• References

• 1 James RM, McGuire W, Smith DP. The investigation of infants with RhD-negative mothers: can we safely omit the umbilical cord blood direct antiglobulin test?. Arch Dis Child Fetal Neonatal Ed 2011; 96 (4) F301-F304
• 2 Koelewijn JM, Vrijkotte TG, de Haas M, van der Schoot CE, Bonsel GJ. Risk factors for the presence of non-rhesus D red blood cell antibodies in pregnancy. BJOG 2009; 116 (5) 655-664
• 3 Howard H, Martlew V, McFadyen I , et al. Consequences for fetus and neonate of maternal red cell allo-immunisation. Arch Dis Child Fetal Neonatal Ed 1998; 78 (1) F62-F66
• 4 Kernicterus threatens healthy newborns. Jt Comm Perspect 2001; 21 (6) 10-11
• 5 Johnson L, Bhutani VK, Karp K, Sivieri EM, Shapiro SM. Clinical report from the pilot USA Kernicterus Registry (1992 to 2004). J Perinatol 2009; 29 (Suppl. 01) S25-S45
• 6 American Academy of Pediatrics Subcommittee on Hyperbilirubinemia. Management of hyperbilirubinemia in the newborn infant 35 or more weeks of gestation. Pediatrics 2004; 114 (1) 297-316
• 7 Koelewijn JM, Vrijkotte TG, van der Schoot CE, Bonsel GJ, de Haas M. Effect of screening for red cell antibodies, other than anti-D, to detect hemolytic disease of the fetus and newborn: a population study in the Netherlands. Transfusion 2008; 48 (5) 941-952
• 8 Gooch A, Parker J, Wray J, Qureshi H ; British Committee for Standards in Haematology Blood Transfusion Task Force. Guideline for blood grouping and antibody testing in pregnancy. Transfus Med 2007; 17 (4) 252-262
• 9 Judd WJ ; Scientific Section Coordinating Committee of the AABB. Practice guidelines for prenatal and perinatal immunohematology, revisited. Transfusion 2001; 41 (11) 1445-1452
• 10 US Preventive Services Task Force. Screening of infants for hyperbilirubinemia to prevent chronic bilirubin encephalopathy: US Preventive Services Task Force recommendation statement. Pediatrics 2009; 124 (4) 1172-1177
• 11 Filbey D, Hanson U, Wesström G. The prevalence of red cell antibodies in pregnancy correlated to the outcome of the newborn: a 12 year study in central Sweden. Acta Obstet Gynecol Scand 1995; 74 (9) 687-692
• 12 Bhutani VK, Stark AR, Lazzeroni LC , et al; Initial Clinical Testing Evaluation and Risk Assessment for Universal Screening for Hyperbilirubinemia Study Group. Predischarge screening for severe neonatal hyperbilirubinemia identifies infants who need phototherapy. J Pediatr 2013; 162 (3) 477-482.e1
• 13 Keren R, Luan X, Friedman S, Saddlemire S, Cnaan A, Bhutani VK. A comparison of alternative risk-assessment strategies for predicting significant neonatal hyperbilirubinemia in term and near-term infants. Pediatrics 2008; 121 (1) e170-e179
• 14 Watchko JF, Kaplan M, Stark AR, Stevenson DK, Bhutani VK. Should we screen newborns for glucose-6-phosphate dehydrogenase deficiency in the United States?. J Perinatol 2013; 33 (7) 499-504
• 15 Kaplan M, Hammerman C. Glucose-6-phosphate dehydrogenase deficiency: a hidden risk for kernicterus. Semin Perinatol 2004; 28 (5) 356-364
• 16 Herschel M, Karrison T, Wen M, Caldarelli L, Baron B. Evaluation of the direct antiglobulin (Coombs') test for identifying newborns at risk for hemolysis as determined by end-tidal carbon monoxide concentration (ETCOc); and comparison of the Coombs' test with ETCOc for detecting significant jaundice. J Perinatol 2002; 22 (5) 341-347
• 17 Madan A, Huntsinger K, Burgos A, Benitz WE. Readmission for newborn jaundice: the value of the Coombs' test in predicting the need for phototherapy. Clin Pediatr (Phila) 2004; 43 (1) 63-68
• 18 Stevenson DK, Fanaroff AA, Maisels MJ , et al. Prediction of hyperbilirubinemia in near-term and term infants. Pediatrics 2001; 108 (1) 31-39
• 19 Maisels MJ, Deridder JM, Kring EA, Balasubramaniam M. Routine transcutaneous bilirubin measurements combined with clinical risk factors improve the prediction of subsequent hyperbilirubinemia. J Perinatol 2009; 29 (9) 612-617