Is Direct Antiglobulin Test Crucial in the Evaluation of Neonatal Hyperbilirubinemia? (2015)

Neonatal hyperbilirubinemia remains a public health concern as documented by recent reports of kernicterus in otherwise healthy term and near-term newborns. Fetal-maternal blood group incompatibility, a previously affected sibling, glucose-6-phosphate dehydrogenase deficiency, cephalohematomas/bruising, and nonoptimal sucking/nursing are major risk factors for hyperbilirubinemia in term newborns.1Porter M.L. Dennis B.L. Hyperbilirubinemia in the term newborn.Am Fam Physician. 2002; 65: 599-606PubMed Google Scholar Clinical data and morphologic features of erythrocytes have been used to predict and diagnose neonatal hyperbilirubinemia.2Huang H.C. Yang H.I. Chang Y.H. Chang R.J. Chen M.H. Chen C.Y. et al.Model to predict hyperbilirubinemia in healthy term and near-term newborns with exclusive breast feeding.Pediatr Neonatol. 2012; 53: 354-358Abstract Full Text Full Text PDF PubMed Scopus (13) Google Scholar, 3Christensen R.D. Yaish H.M. Lemons R.S. Neonatal hemolytic jaundice: morphologic features of erythrocytes that will help you diagnose the underlying condition.Neonatology. 2014; 105: 243-249Crossref PubMed Scopus (39) Google Scholar However, no single test can determine the cause of neonatal hyperbilirubinemia. The direct antiglobulin test (DAT), also known as direct Coombs test, is a screening technique used to detect nonagglutinating antibodies on human red blood cells (RBCs). When a pregnant woman's serum includes a clinically significant immunoglobulin G (IgG) antibody directed against an antigen on the RBCs of her fetus, placental transfer of the antibody into the fetal circulation may result in the destruction of fetal RBCs, leading to hemolytic disease of the newborn (HDN). DAT is considered to be an important test to identify neonates who are at risk of HDN. Positive or negative DAT results have been discussed in many studies conducted during the neonatal period. A positive DAT is a strong predictor of hyperbilirubinemia in ABO-incompatibility, Rhesus (Rh) disease, and antibodies against other blood groups in newborns. Nevertheless, there is a debate over the role of DAT screening in predicting HDN. In this issue of Pediatrics and Neonatology, Valsami et al4Valsami S. Politou M. Boutsikou T. Briana D. Papatesta M. Malamitsi-Puchner A. Importance of direct antiglobulin test (DAT) in cord blood: causes of DAT (+) in a cohort study.Pediatr Neonatol. 2015; 56: 256-260Abstract Full Text Full Text PDF Scopus (17) Google Scholar retrospectively reviewed routine DAT results in cord blood and correlated the results with blood type, development of hyperbilirubinemia, and the need for phototherapy. They found 70 positive DAT cases in 2695 cord blood samples. Sixty-seven cases of DAT positivity were attributed to ABO incompatibility, three cases were attributed to maternal alloimmunization (anti-Fya and anti-JKb), and one case to maternal IgG autoantibodies that developed after methyldopa treatment. The strength of DAT positivity tends to correlate with the need for and duration of phototherapy. The results were consistent with previous studies that positive DAT is associated with a fourfold increased risk of neonatal hyperbilirubinemia and that the grades of positivity are associated with the duration of phototherapy.5Oztekin O. Kalay S. Tezel G. Barsal E. Bozkurt S. Akcakus M. et al.Is the strength of direct antiglobulin test important for the duration of phototherapy?.J Matern Fetal Neonatal Med. 2014; 27: 534-536Crossref PubMed Scopus (7) Google Scholar Among the limitations of this study that have been acknowledged by the authors are the predictive value and cost-benefit information of routine DAT. A positive DAT has only 23% predictive value for ABO HDN.6Dinesh D. Review of positive direct antiglobulin tests found on cord blood sampling.J Paediatr Child Health. 2005; 41: 504-507Crossref PubMed Scopus (51) Google Scholar A negative DAT does not rule out ABO HDN or exclude a nonimmune hemolytic etiology underlying clinically significant hyperbilirubinemia. Some institutions consider routine DAT is a cost-ineffective strategy and it is not supported by clinical guidelines.7American Academy of Pediatrics Subcommittee on Hyperbilirubinemia Management of hyperbilirubinemia in the newborn infant 35 or more weeks of gestation.Pediatrics. 2004; 114: 297-316Crossref PubMed Scopus (2037) Google Scholar Although some clinical practice guidelines recommend that if the maternal blood is group O, Rh-positive, it is an option to test the cord blood for the infant's blood type and DAT, however, it is not required if there is adequate surveillance, risk assessment prior to discharge, and appropriate follow up.7American Academy of Pediatrics Subcommittee on Hyperbilirubinemia Management of hyperbilirubinemia in the newborn infant 35 or more weeks of gestation.Pediatrics. 2004; 114: 297-316Crossref PubMed Scopus (2037) Google Scholar Many technical pitfalls including Wharton jelly in cord blood specimens, spontaneous RBC agglutination, and poor washing techniques can result in a false-positive DAT. In this issue of Pediatrics and Neonatology, Valsami et al4Valsami S. Politou M. Boutsikou T. Briana D. Papatesta M. Malamitsi-Puchner A. Importance of direct antiglobulin test (DAT) in cord blood: causes of DAT (+) in a cohort study.Pediatr Neonatol. 2015; 56: 256-260Abstract Full Text Full Text PDF Scopus (17) Google Scholar directly punctured the umbilical vein and implemented a fully automated method to avoid Wharton jelly contamination and to overcome technical pitfalls, respectively. The investigation of neonatal hyperbilirubinemia should be individualized, and infants with early-onset or severe hyperbilirubinemia need more aggressive study. The combined results of DAT and its strength of reaction may be useful in early detection of infants with the risk of severe jaundice. Further research is needed to determine the sensitivity and specificity of the DAT and its role in newborn infants with particular hematologic abnormalities. The author declares no conflicts of interest.