Haemolytic disease of the foetus and newborn
review article and a retrospective analysis of patients hospitalised at a tertiary neonatal centre during 2007-2016
Haemolytic disease of the foetus and newborn (HDFN) occurs when maternal alloimmune antibodies cross the placenta to the foetal circulation and cause destruction of erythrocytes, resulting in anaemia and hyperbilirubinemia. It can result from naturally present antibodies, such as anti-A and anti-B antibodies, or isoantibodies produced by women previously sensitised during pregnancy or transfusion of incompatible erythrocytes such as anti-D antibodies. RhD antigen is the most immunogenic and causes severe HDFN, while the spectrum of HDFN due to AB0 incompatibility ranges from subclinical to severe, requiring exchange transfusion. Thanks to effective and widely implemented prophylaxis with administration of anti-D immunoglobulin to RhD negative women, the HDFN due to anti-D is nowadays a rare disease.
Present paper provides an overview on the pathophysiology, clinical characteristics, diagnostics, treatment and prevention of HDFN. In the second part of the article we present the results of a cohort retrospective analysis of 109 patients with HDFN hospitalised at the tertiary neonatal unit during 2007–2016. In 84.4 % of cases the underlying cause of HDFN were antibodies anti-A or anti-B, in 9.2 % of cases antibodies anti-D and in 6.4 % other more rare antibodies. HDFN caused by different antibodies did not result in statistically significant differences in the evaluated hematological tests. Direct Coombs test was positive in all patients with HDFN RhD and in 64 % of newborns with HDFN AB0. All patients with HDFN RhD required exchange transfusion or intrauterine transfusion.
Rennie JM. Rennie&Roberton’s TextbookofNeonatology, 5thedition. Keren R, Tremont K, Luan X, Cnaan A. Visual assessment of jaundice in term and late preterminfants. Arch Dis Child Fetal Neonatal Ed. 2009;94(5):F317–22. PMID:19307221
Vir: NIJZ, Perinatalni informacijski sistem Republike. de Alarcon P, Werner E. Neonatal Hematology. Cambridge: Cambridge University Press; 2005.
Luchtman-Jones L, Schwartz AL, Wilson DB. The blood and hematopoietic system. Fanaroff AA, Martin RJ, eds. Neonatal-Perinatal Medicine-Diseases of the Fetus and Infant. 8th ed. St. Louis, Mo: Mosby; 2006. Vol 2: 1287–1356.
Choavaratana R, Uer-Areewong S, Makanantakosol S. Feto-maternal transfusion in normal pregnancy and during delivery. J Med Assoc Thai. 1997 Feb;80(2):96–100. PMID:9078693
Bricl I, Ogrizek-Pelkič K, Vogler A. Hemolitična bolezen ploda in novorojenčka (HBPN) – prikaz primera. Zdrav Vestn. 2003;72:671–3.
Železnik K, Dovč-Drnovšek T, Rožman P, Bricl I. Preventiva in diagnostika hemolitične bolezni ploda in novorojenčka. Zdrav Vestn. 2012;81 supl 2:II-312–21.
Geaghan SM. Diagnostic laboratory technologies for the fetus and neonate with isoimmunization. Semin Perinatol. 2011 Jun;35(3):148–54. https://doi.org/10.1053/j.semperi.2011.02.009 PMID:21641488
Eder AF. Update on HDFN: new information on long-standing controversies. Immunohematology. 2006;22(4):188–95. PMID:17430078
Groleger K, Bratanič B, Veličkovič Perat M. Nekonjugirana hiperbilirubinemija pri novorojenčku. Med Razgl. 1998;37:355–66.
Delaney M, Matthews DC. Hemolytic disease of the fetus and newborn: managing the mother, fetus, and newborn. Hematology (Am Soc Hematol Educ Program). 2015;2015(1):146–51. https://doi.org/10.1182/asheducation-2015.1.146 PMID:26637714
Christensen RD, Yaish HM. Hemolytic Disorders Causing Severe Neonatal Hyperbilirubinemia. Clin Perinatol. 2015 Sep;42(3):515–27. https://doi.org/10.1016/j.clp.2015.04.007 PMID:26250914
Christensen RD, Lambert DK, Henry E, Yaish HM, Prchal JT. End-tidal carbon monoxide as an indicator of the hemolytic rate. Blood Cells Mol Dis. 2015 Mar;54(3):292–6. https://doi.org/10.1016/j.bcmd.2014.11.018 PMID:25624169
Lozar-Krivec J, Bratanic B, Paro-Panjan D. The role of carboxyhemoglobin measured with CO-oximetry in the detection of hemolysis in newborns with ABO alloimmunization. J Matern Fetal Neonatal Med. 2016;29(3):452–6. https://doi.org/10.3109/14767058.2015.1004050 PMID:25604086
Christensen RD, Yaish HM, Henry E, Bennett ST. Red blood cell distribution width: reference intervals for neonates. J Matern Fetal Neonatal Med. 2015 May;28(8):883–8. https://doi.org/10.3109/14767058.2014.938044 PMID:24968099
Christensen RD, Henry E, Andres RL, et al. Neonatal reference ranges for blood concentrations of nucleated red blood cells. Neonatology. 2010;99:289–94. https://doi.org/10.1159/000320148 PMID:21135564
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 Jul-Aug;22(5):341–7. https://doi.org/10.1038/sj.jp.7210702 PMID:12082466
American Academy of Pediatrics Subcommittee on Hyperbilirubinemia. Management of hyperbilirubinemia in the newborn infant 35 or more weeks of gestation. Pediatrics. 2004 Jul;114(1):297–316. https://doi.org/10.1542/peds.114.1.297 PMID:15231951
Bhutani VK, Johnson-Hamerman L. The clinical syndrome of bilirubin-induced neurologic dysfunction. Semin Fetal Neonatal Med. 2015 Feb;20(1):6–13. https://doi.org/10.1016/j.siny.2014.12.008 PMID:25577653
Wong RJ, Stevenson DK. Neonatal hemolysis and risk of bilirubin-induced neurologic dysfunction.
Kaplan M, Bromiker R, Hammerman C. Hyperbilirubinemia, hemolysis, and increased bilirubin neurotoxicity. Semin Perinatol. 2014 Nov;38(7):429–37. https://doi.org/10.1053/j.semperi.2014.08.006 PMID:25284470
Maisels MJ, McDonagh AF. Phototherapy for neonatal jaundice. N Engl J Med. 2008 Feb;358(9):920–8. https://doi.org/10.1056/NEJMct0708376 PMID:18305267
Zwiers C, van Kamp I, Oepkes D, Lopriore E. Intrauterine transfusion and non-invasive treatment options for hemolytic disease of the fetus and newborn - review on current management and outcome. Expert Rev Hematol. 2017 Apr;10(4):337–44. https://doi.org/10.1080/17474086.2017.1305265 PMID:28277805
Sainio S, Nupponen I, Kuosmanen M, Aitokallio-Tallberg A, Ekholm E, Halmesmäki E, et al. Diagnosis and treatment of severe hemolytic disease of the fetus and newborn: a 10-year nationwide retrospective study. Acta Obstet Gynecol Scand. 2015 Apr;94(4):383–90. https://doi.org/10.1111/aogs.12590 PMID:25603954
Lozar Krivec J. Izmenjalna transfuzija pri novorojenčkih. In: Obravnava kritično bolnih- od novorojenčka do odraslega. Zbornik prispevkov: 48. Strokovni seminar; Rogaška Slatina, maj 2015, Slovenija. V Ljubljani: Zbornica zdravstvene in babiške nege Slovenije - Zveza društev medicinskih sester, babic in zdravstvenih tehnikov Slovenije, Sekcija medicinskih sester in zdravstvenih tehnikov v anesteziologiji, intenzivni terapiji in transfuziologiji, 2015.
Louis D, More K, Oberoi S, Shah PS. Intravenous immunoglobulin in isoimmune haemolytic disease of newborn: an updated systematic review and meta-analysis. Arch Dis Child Fetal Neonatal Ed. 2014 Jul;99(4):F325–31. https://doi.org/10.1136/archdischild-2013-304878 PMID:24514437
Daniels G, Finning K, Martin P. Noninvasive fetal blood grouping: present and future. Clin Lab Med. 2010 Jun;30(2):431–42. https://doi.org/10.1016/j.cll.2010.02.006 PMID:20513561
Christensen RD, Nussenzveig RH, Yaish HM, Henry E, Eggert LD, Agarwal AM. Causes of hemolysis in neonates with extreme hyperbilirubinemia. J Perinatol. 2014 Aug;34(8):616–9. https://doi.org/10.1038/jp.2014.68 PMID:24762414
Kristinsdottir T, Kjartansson S, Hardardottir H, Jonsson T, Halldorsdottir AM. [Positive Coomb’s test in newborns; causes and clinical consequences Summary of cases diagnosed in the Blood Bank in the years 2005 to 2012]. Laeknabladid. 2016 Jul;102(7-8):326–31. PMID:27531851
Valsami S, Politou M, Boutsikou Τ, 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 Aug;56(4):256–60. https://doi.org/10.1016/j.pedneo.2014.11.005 PMID:25637293
Sarici SU, Yurdakök M, Serdar MA, Oran O, Erdem G, Tekinalp G, et al. An early (sixth-hour) serum bilirubin measurement is useful in predicting the development of significant hyperbilirubinemia and severe ABO hemolytic disease in a selective high-risk population of newborns with ABO incompatibility. Pediatrics. 2002 Apr;109(4):e53. https://doi.org/10.1542/peds.109.4.e53 PMID:11927726
The Author transfers to the Publisher (Zdravniški vestnik/Slovenian Medical Journal) all economic copyrights following form Article 22 of the Slovene Copyright and Related Rights Act (ZASP), including the right of reproduction, the right of distribution, the rental right, the right of public performance, the right of public transmission, the right of public communication by means of phonograms and videograms, the right of public presentation, the right of broadcasting, the right of rebroadcasting, the right of secondary broadcasting, the right of communication to the public, the right of transformation, the right of audiovisual adaptation and all other rights of the author according to ZASP.
The aforementioned rights are transferred non-exclusively, for an unlimited number of editions, for the term of the statutory
The Author can make use of his work himself or transfer subjective rights to others only after 3 months from date of first publishing in the journal Zdravniški vestnik/Slovenian Medical Journal.
The Publisher (Zdravniški vestnik/Slovenian Medical Journal) has the right to transfer the rights, acquired parties without explicit consent of the Author.
The Author consents that the Article be published under the Creative Commons BY-NC 4.0 (attribution-non-commercial) or comparable licence.