Am J Perinatol
DOI: 10.1055/a-2255-8772
Original Article

A Description of IVIG Use in Term Neonates with ABO Incompatibility

Michael Daunov
1   Rainbow Babies and Children's Hospital, University Hospitals Cleveland Medical Center, Cleveland, Ohio
2   Case Western Reserve University School of Medicine, Cleveland, Ohio
,
Andrea Schlosser
3   Wexner Medical Center, Nationwide Children's Hospital, Ohio State University, Columbus, Ohio
,
Sindhoosha Malay
1   Rainbow Babies and Children's Hospital, University Hospitals Cleveland Medical Center, Cleveland, Ohio
2   Case Western Reserve University School of Medicine, Cleveland, Ohio
,
Jaclyn Adams
4   Doernbecher Children's Hospital, Oregon Health and Science University, Portland, Oregon
,
Rachael Clark
5   University of Massachusetts, Boston, Massachusetts
,
Lauren Ferrerosa
6   UCSF Benioff Children's Hospital, Oakland, California
,
Irina Pateva
1   Rainbow Babies and Children's Hospital, University Hospitals Cleveland Medical Center, Cleveland, Ohio
2   Case Western Reserve University School of Medicine, Cleveland, Ohio
› Author Affiliations

Abstract

Objective This study aimed to determine if treatment with IVIG of neonates with ABO incompatibility (without Rh incompatibility) results in decreased number of packed red blood cell (pRBC) transfusions and phototherapy use.

Study Design An Institutional Review Board (IRB)-approved, single-institution retrospective study was conducted. Neonates ≥38 weeks' gestational age born between January 1, 2007, and December 31, 2016, with ABO incompatibility were included. The comparison among groups was performed using chi-square and Fisher's exact tests for categorical variables; continuous variables were assessed by Kruskal–Wallis test.

Results Six hundred and sixty-eight neonates with ABO incompatibility met inclusion criteria, 579 were included in the analyses. From these, 431 (74%) neonates had positive Direct Antiglobulin Test (DAT); 98 (17%) received IVIG and 352 (61%) received phototherapy. Thirty-six (6%) neonates received pRBC and 6 (1%) required exchange transfusions. Only 3 (0.5%) infants received pRBC transfusions postdischarge, by 3 months of age. Neonates requiring IVIG had lower initial hemoglobin (13.6 vs. 16.0 g/dL, p ≤ 0.0001) and higher bilirubin at start of phototherapy (9.1 vs. 8.1 mg/dL, p = 0.0064). From the 42 (7%) neonates who received simple and exchange transfusions, IVIG use was not associated with decreased use or number of transfusions (p = 0.5148 and 0.3333, respectively). Newborns with A+ and B+ blood types had comparable initial hemoglobin, DAT positivity, APGAR, and bilirubin. However, infants with B+ blood group were more likely (than A + ) to require phototherapy (p < 0.001), receive IVIG (p = 0.003), and need phototherapy for a longer duration (p = 0.001).

Conclusion The results of this large retrospective study reveal that giving IVIG to neonates with ABO incompatibility was associated with increased simple or exchange transfusions. Newborns with B+ blood type required more phototherapy and IVIG. Further studies are needed to better stratify neonates who would benefit from IVIG use in order to optimize treatment strategies and avoid unnecessary risks and adverse events.

Key Points

  • IVIG use not associated with decreased use of pRBC or exchanges.

  • Phototherapy duration associated with increased IVIG and pRBC use.

  • Newborns with B+ blood type had worse hemolytic anemia.



Publication History

Received: 08 December 2022

Accepted: 26 January 2024

Accepted Manuscript online:
29 January 2024

Article published online:
06 March 2024

© 2024. Thieme. All rights reserved.

Thieme Medical Publishers, Inc.
333 Seventh Avenue, 18th Floor, New York, NY 10001, USA

 
  • References

  • 1 Murray NA, Roberts IA. Haemolytic disease of the newborn. Arch Dis Child Fetal Neonatal Ed 2007; 92 (02) F83-F88
  • 2 Matteocci A, De Rosa A, Buffone E, Pierelli L. Retrospective analysis of HDFN due to ABO incompatibility in a single institution over 6 years. Transfus Med 2019; 29 (03) 197-201
  • 3 Desjardins L, Blajchman MA, Chintu C, Gent M, Zipursky A. The spectrum of ABO hemolytic disease of the newborn infant. J Pediatr 1979; 95 (03) 447-449
  • 4 Zwiers C, Scheffer-Rath ME, Lopriore E, de Haas M, Liley HG. Immunoglobulin for alloimmune hemolytic disease in neonates. Cochrane Database Syst Rev 2018; 3 (03) CD003313
  • 5 Treatment of immune hemolytic anemia with gammaglobulin. J Pediatr 1987; 110 (05) 817-818
  • 6 Mundy CA, Bhatia J. Immunoglobulin transfusion in hemolytic disease of the newborn: place in therapy. Int J Clin Transfus 2015; 3: 41-45
  • 7 Elalfy MS, Elbarbary NS, Abaza HW. Early intravenous immunoglobin (two-dose regimen) in the management of severe Rh hemolytic disease of newborn–a prospective randomized controlled trial. Eur J Pediatr 2011; 170 (04) 461-467
  • 8 Santos MC, Sá C, Gomes Jr SC, Camacho LA, Moreira ME. The efficacy of the use of intravenous human immunoglobulin in Brazilian newborns with rhesus hemolytic disease: a randomized double-blind trial. Transfusion 2013; 53 (04) 777-782
  • 9 Smits-Wintjens VE, Walther FJ, Rath ME. et al. Intravenous immunoglobulin in neonates with rhesus hemolytic disease: a randomized controlled trial. Pediatrics 2011; 127 (04) 680-686
  • 10 Pan J, Zhan C, Yuan T. et al. Intravenous immunoglobulin G in the treatment of ABO hemolytic disease of the newborn during the early neonatal period at a tertiary academic hospital: a retrospective study. J Perinatol 2021; 41 (06) 1397-1402
  • 11 van Klink JM, van Veen SJ, Smits-Wintjens VE. et al. Immunoglobulins in neonates with rhesus hemolytic disease of the fetus and newborn: long-term outcome in a randomized trial. Fetal Diagn Ther 2016; 39 (03) 209-213
  • 12 American Academy of Pediatrics Subcommittee on Hyperbilirubinemia. Management of hyperbilirubinemia in the newborn infant 35 or more weeks of gestation. Pediatrics 2004; 114 (01) 297-316
  • 13 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; 56 (04) 256-260
  • 14 Dillon A, Chaudhari T, Crispin P, Shadbolt B, Kent A. Has anti-D prophylaxis increased the rate of positive direct antiglobulin test results and can the direct antiglobulin test predict need for phototherapy in Rh/ABO incompatibility?. J Paediatr Child Health 2011; 47 (1-2): 40-43
  • 15 Dinesh D. Review of positive direct antiglobulin tests found on cord blood sampling. J Paediatr Child Health 2005; 41 (9–10): 504-507
  • 16 Chen JY, Ling UP. Prediction of the development of neonatal hyperbilirubinemia in ABO incompatibility. Zhonghua Yi Xue Za Zhi (Taipei) 1994; 53 (01) 13-18
  • 17 Hammerman C, Kaplan M, Vreman HJ, Stevenson DK. Intravenous immune globulin in neonatal ABO isoimmunization: factors associated with clinical efficacy. Biol Neonate 1996; 70 (02) 69-74
  • 18 Sato K, Hara T, Kondo T, Iwao H, Honda S, Ueda K. High-dose intravenous gammaglobulin therapy for neonatal immune haemolytic jaundice due to blood group incompatibility. Acta Paediatr Scand 1991; 80 (02) 163-166
  • 19 Rohde JM, Dimcheff DE, Blumberg N. et al. Health care-associated infection after red blood cell transfusion: a systematic review and meta-analysis. JAMA 2014; 311 (13) 1317-1326
  • 20 Patel RM, Knezevic A, Shenvi N. et al. Association of red blood cell transfusion, anemia, and necrotizing enterocolitis in very low-birth-weight infants. JAMA 2016; 315 (09) 889-897
  • 21 dos Santos AM, Guinsburg R, de Almeida MF. et al; Brazilian Network on Neonatal Research. Red blood cell transfusions are independently associated with intra-hospital mortality in very low birth weight preterm infants. J Pediatr 2011; 159 (03) 371-376.e1 , 3
  • 22 Baer VL, Lambert DK, Henry E, Snow GL, Christensen RD. Red blood cell transfusion of preterm neonates with a Grade 1 intraventricular hemorrhage is associated with extension to a Grade 3 or 4 hemorrhage. Transfusion 2011; 51 (09) 1933-1939
  • 23 Rashid N, Al-Sufayan F, Seshia MM, Baier RJ. Post transfusion lung injury in the neonatal population. J Perinatol 2013; 33 (04) 292-296
  • 24 Wang YC, Chan OW, Chiang MC. et al. Red blood cell transfusion and clinical outcomes in extremely low birth weight preterm infants. Pediatr Neonatol 2017; 58 (03) 216-222
  • 25 Schulz S, Wong RJ, Vreman HJ, Stevenson DK. Metalloporphyrins - an update. Front Pharmacol 2012; 3: 68
  • 26 Cariani L, Romano EL, Martínez N. et al. ABO-haemolytic disease of the newborn (ABO-HDN): factors influencing its severity and incidence in Venezuela. J Trop Pediatr 1995; 41 (01) 14-21
  • 27 Bhat YR, Kumar CG. Morbidity of ABO haemolytic disease in the newborn. Paediatr Int Child Health 2012; 32 (02) 93-96
  • 28 Stiller RJ, Herzlinger R, Siegel S, Whetham JC. Fetal ascites associated with ABO incompatibility: case report and review of the literature. Am J Obstet Gynecol 1996; 175 (05) 1371-1372
  • 29 Dufour DR, Monoghan WP. ABO hemolytic disease of the newborn. A retrospective analysis of 254 cases. Am J Clin Pathol 1980; 73 (03) 369-373
  • 30 Ding Z, Zhang X, Li H. Application of IgG antibody titer and subtype in diagnosis and severity assessment of hemolytic disease of the newborn. Transl Pediatr 2022; 11 (09) 1544-1551
  • 31 Brouwers HA, Overbeeke MA, van Ertbruggen I. et al. What is the best predictor of the severity of ABO-haemolytic disease of the newborn?. Lancet 1988; 2 (8612): 641-644
  • 32 Bakkeheim E, Bergerud U, Schmidt-Melbye AC. et al. Maternal IgG anti-A and anti-B titres predict outcome in ABO-incompatibility in the neonate. Acta Paediatr 2009; 98 (12) 1896-1901
  • 33 Watchko JF. ABO hemolytic disease of the newborn: a need for clarity and consistency in diagnosis. J Perinatol 2023; 43 (02) 242-247