Clinical Characteristics and Prognosis of Hemolytic Disease of the Newborn Caused by Irregular Antibodies: A 13-Year Retrospective Analysis

Overview

Journal Children (Basel)

Specialty Health Services

Date 2025 Jan 8

PMID 39767838

Authors

Hui Wu

Rui Li

Hongling Wei

Weiwei Zhu

Yan Xing

Affiliations

Soon will be listed here.

Abstract

Background/objectives: The clinical characteristics and outcomes of hemolytic disease of the newborn (HDN) caused by irregular antibodies remain unclear. Herein, we analyzed the clinical features and prognosis of HDN.

Methods: Children admitted to our institution between June 2009 and December 2022 with a definite diagnosis of HDN were evaluated. Patients with irregular antibodies were matched in a 1:3 ratio to those with ABO incompatibility. Children with confirmed Rh-incompatibility hemolytic disease were divided into the RhD subgroup (hemolysis induced by Rh anti-D) and the non-RhD group (hemolysis induced by other Rh antibodies).

Results: The irregular antibody and ABO incompatibility group included 32 and 96 patients, respectively. Compared to the ABO incompatibility group, the irregular antibody group showed earlier jaundice; higher incidence of liver and spleen enlargement and anemia; higher direct antiglobulin test (DAT) positivity; earlier and more severe anemia; higher rates of enhanced phototherapy, blood transfusion, and blood exchange; and longer hospital stay (all < 0.05). Compared to the non-RhD group, the RhD subgroup showed an earlier occurrence of jaundice and a higher incidence of liver and spleen enlargement (both < 0.05). The multiple irregular antibody subgroup further showed earlier occurrence of jaundice and a higher rate of enhanced phototherapy, blood transfusion, and blood exchange than the single-antibody group (both < 0.05).

Conclusions: HDN caused by irregular red blood cell antibodies is rare, but clinical manifestations are serious. It is important to pay attention to the screening of irregular antibodies during pregnancy, to strengthen monitoring, and to provide intrauterine treatment and early intervention as necessary.

References

Ree I, Smits-Wintjens V, van der Bom J, van Klink J, Oepkes D, Lopriore E . Neonatal management and outcome in alloimmune hemolytic disease. Expert Rev Hematol. 2017; 10(7):607-616. DOI: 10.1080/17474086.2017.1331124. View

Li S, He Z, Mo C, Ji Y, Luo Y, Fang Q . Hyporegenerative anemia in anti-M-associated hemolytic disease of the fetus. Transfusion. 2021; 61(6):1908-1915. DOI: 10.1111/trf.16350. View

Brinc D, Lazarus A . Mechanisms of anti-D action in the prevention of hemolytic disease of the fetus and newborn. Hematology Am Soc Hematol Educ Program. 2009; :185-91. DOI: 10.1182/asheducation-2009.1.185. View

Alsaleem M . Intravenous Immune Globulin Uses in the Fetus and Neonate: A Review. Antibodies (Basel). 2020; 9(4). PMC: 7709108. DOI: 10.3390/antib9040060. View

Li M, Blaustein J . Persistent hemolytic disease of the fetus and newborn (HDFN) associated with passive acquisition of anti-D in maternal breast milk. Transfusion. 2017; 57(9):2121-2124. DOI: 10.1111/trf.14171. View

Wang H, Wang Y, Liang X, Zhang C, Guo B . Value of red cell distribution width-to-platelet ratio as a predictor for morbidity and mortality in neonatal intensive care unit. Clin Hemorheol Microcirc. 2022; 81(4):281-291. DOI: 10.3233/CH-221388. View

Subramaniyan R . Early-onset hypoproliferative anemia in an intrauterine-transfused neonate with severe Rh hemolytic disease. Med J Armed Forces India. 2023; 79(3):344-347. PMC: 10182267. DOI: 10.1016/j.mjafi.2021.05.004. View

Delaney M, Matthews D . Hemolytic disease of the fetus and newborn: managing the mother, fetus, and newborn. Hematology Am Soc Hematol Educ Program. 2015; 2015:146-51. DOI: 10.1182/asheducation-2015.1.146. View

Brouwers H, Overbeeke M, Van Ertbruggen I, Schaasberg W, Alsbach G, van der Heiden C . What is the best predictor of the severity of ABO-haemolytic disease of the newborn?. Lancet. 1988; 2(8612):641-4. DOI: 10.1016/s0140-6736(88)90466-7. View

10.

Andersen L, Jacob E, McThenia S, Tauscher C, Patterson E, Oliveira J . Hemolytic disease and reticulocytopenia of the newborn attributable to maternal immunoglobulin G anti-M reacting optimally at cold temperatures. Transfusion. 2021; 61(3):974-978. DOI: 10.1111/trf.16252. View

11.

Moise Jr K . Diagnosing hemolytic disease of the fetus--time to put the needles away?. N Engl J Med. 2006; 355(2):192-4. DOI: 10.1056/NEJMe068071. View

12.

Laks M, Cohen T . Noninvasive diagnosis of fetal anemia by Doppler ultrasonography. N Engl J Med. 2000; 343(1):66-7; author reply 67-8. View

13.

Elfarargy M, Al-Ashmawy G, Abu-Risha S, Khattab H . Study of Cord Blood Levels of Erythropoietin, Bilirubin and Reticulocyte Count as Early Predictors of Neonatal Hyperbilirubinemia. Endocr Metab Immune Disord Drug Targets. 2020; 21(9):1641-1648. DOI: 10.2174/1871530321666201229152019. View

14.

Castleman J, Kilby M . Red cell alloimmunization: A 2020 update. Prenat Diagn. 2020; 40(9):1099-1108. DOI: 10.1002/pd.5674. View

15.

Wang S, Wu Y, Wu W, Lee M, Lin W, Ma G . Polyhydramnios as a sole ultrasonographic finding for detecting fetal hemolytic anemia caused by anti-c alloimmunization. Taiwan J Obstet Gynecol. 2022; 61(4):722-725. DOI: 10.1016/j.tjog.2022.04.006. View

16.

Singh B, Chaudhary R, Katharia R . Title: Effect of multiple maternal red cell alloantibodies on the occurrence and severity of Hemolytic Disease of the Fetus and Newborn. Transfus Apher Sci. 2020; 60(1):102958. DOI: 10.1016/j.transci.2020.102958. View

17.

Zheng Y, Hong Q, Wang Q . [Investigation and Analysis of Non-ABO Hemolytic Disease of the Newborn]. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2021; 29(4):1330-1333. DOI: 10.19746/j.cnki.issn.1009-2137.2021.04.050. View

18.

Zwiers C, Scheffer-Rath M, Lopriore E, de Haas M, Liley H . Immunoglobulin for alloimmune hemolytic disease in neonates. Cochrane Database Syst Rev. 2018; 3:CD003313. PMC: 6494160. DOI: 10.1002/14651858.CD003313.pub2. View

19.

Leonard A, Hittson Boal L, Pary P, Mo Y, Jacquot C, Luban N . Identification of red blood cell antibodies in maternal breast milk implicated in prolonged hemolytic disease of the fetus and newborn. Transfusion. 2019; 59(4):1183-1189. DOI: 10.1111/trf.15154. View

20.

Arthur C, Patel S, Smith N, Bennett A, Kamili N, Mener A . Antigen Density Dictates Immune Responsiveness following Red Blood Cell Transfusion. J Immunol. 2017; 198(7):2671-2680. PMC: 5777137. DOI: 10.4049/jimmunol.1601736. View