International guidelines regarding the role of IVIG in the management of Rh- and ABO-mediated haemolytic disease of the newborn

Lani Lieberman; Enrico Lopriore; Jillian M Baker; Rachel S Bercovitz; Robert D Christensen; Gemma Crighton; Meghan Delaney; Ruchika Goel; Jeanne E Hendrickson; Amy Keir; Denise Landry; Ursula La Rocca; Brigitte Lemyre; Rolf F Maier; Eduardo Muniz-Diaz; Susan Nahirniak; Helen V New; Katerina Pavenski; Maria Cristina Pessoa Dos Santos; Glenn Ramsey; Nadine Shehata; International Collaboration for Transfusion Medicine Guidelines (ICTMG)

doi:10.1111/bjh.18170

International guidelines regarding the role of IVIG in the management of Rh- and ABO-mediated haemolytic disease of the newborn

Br J Haematol. 2022 Jul;198(1):183-195. doi: 10.1111/bjh.18170. Epub 2022 Apr 12.

Authors

Lani Lieberman^{1

2

3}, Enrico Lopriore⁴, Jillian M Baker^{5

6}, Rachel S Bercovitz⁷, Robert D Christensen^{8

9}, Gemma Crighton¹⁰, Meghan Delaney^{11

12}, Ruchika Goel^{13

14}, Jeanne E Hendrickson¹⁵, Amy Keir^{16

17}, Denise Landry¹⁸, Ursula La Rocca^{19

20}, Brigitte Lemyre²¹, Rolf F Maier²², Eduardo Muniz-Diaz²³, Susan Nahirniak²⁴, Helen V New^{25

26}, Katerina Pavenski²⁷, Maria Cristina Pessoa Dos Santos²⁸, Glenn Ramsey²⁹, Nadine Shehata³⁰; International Collaboration for Transfusion Medicine Guidelines (ICTMG)

Affiliations

¹ Department of Clinical Pathology, University Health Network, Toronto, Ontario, Canada.
² Department of Laboratory Medicine & Pathobiology, University of Toronto, Toronto, Ontario, Canada.
³ Department of Laboratory Medicine and Molecular Diagnostics, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.
⁴ Division of Neonatology, Department of Pediatrics, Leiden University Medical Center, Leiden, The Netherlands.
⁵ Department of Pediatrics, Unity Health Toronto (St. Michael's Hospital), Toronto, Ontario, Canada.
⁶ Division of Haematology-Oncology, The Hospital for Sick Children, Toronto, Ontario, Canada.
⁷ Division of Hematology, Oncology, and Stem Cell Transplant, Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
⁸ Divisions of Neonatology and Hematology/Oncology, University of Utah Health, Salt Lake City, UT, USA.
⁹ Department of Women and Newborn's Research, Intermountain Healthcare, Salt Lake City, Utah, USA.
¹⁰ Department of Haematology, Royal Children's Hospital, Melbourne, Australia.
¹¹ Division of Pathology & Laboratory Medicine, Children's National Hospital, Washington, District of Columbia, USA.
¹² Department of Pathology & Pediatrics, The George Washington University Health Sciences, Washington, District of Columbia, USA.
¹³ Division of Transfusion Medicine, Department of Pathology, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.
¹⁴ Simmons Cancer Institute at SIU School of Medicine, Springfield, Illinois, USA.
¹⁵ Departments of Laboratory Medicine and Pediatrics, Yale University, New Haven, Connecticut, USA.
¹⁶ SAHMRI Women and Kids, South Australian Health and Medical Institute, North Adelaide, South Australia, Australia.
¹⁷ Adelaide Medical School and the Robinson Research Institute, the University of Adelaide, North Adelaide, South Australia, Australia.
¹⁸ Canadian Blood Services, Ottawa, Ontario, Canada.
¹⁹ Department of Translational and Precision Medicine, Sapienza University, Rome, Italy.
²⁰ Italian National Blood Centre, National Institute of Health, Rome, Italy.
²¹ Department of Pediatrics, University of Ottawa, Ottawa, Ontario, Canada.
²² Children's Hospital, University Hospital, Philipps University, Marburg, Germany.
²³ Department of Immunohematology, Blood and Tissue Bank of Catalonia, Barcelona, Spain.
²⁴ Alberta Precision Laboratories and Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, Alberta, Canada.
²⁵ Clinical Directorate, NHS Blood and Transplant, London, UK.
²⁶ Centre for Haematology, Imperial College London, London, UK.
²⁷ Department of Laboratory Medicine and Pathology, Unity Health Toronto (St. Michael's Hospital), Toronto, Ontario, Canada.
²⁸ IFF/Fundação Oswaldo Cruz, Rio de Janeiro, Brazil.
²⁹ Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.
³⁰ Departments of Medicine, Laboratory Medicine and Pathobiology, Institute of Health, Policy Management and Evaluation, University of Toronto, Mount Sinai Hospital, Toronto, Ontario, Canada.

Abstract

Haemolytic disease of the newborn (HDN) can be associated with significant morbidity. Prompt treatment with intensive phototherapy (PT) and exchange transfusions (ETs) can dramatically improve outcomes. ET is invasive and associated with risks. Intravenous immunoglobulin (IVIG) may be an alternative therapy to prevent use of ET. An international panel of experts was convened to develop evidence-based recommendations regarding the effectiveness and safety of IVIG to reduce the need for ETs, improve neurocognitive outcomes, reduce bilirubin level, reduce the frequency of red blood cell (RBC) transfusions and severity of anaemia, and/or reduce duration of hospitalization for neonates with Rh or ABO-mediated HDN. We used a systematic approach to search and review the literature and then develop recommendations from published data. These recommendations conclude that IVIG should not be routinely used to treat Rh or ABO antibody-mediated HDN. In situations where hyperbilirubinaemia is severe (and ET is imminent), or when ET is not readily available, the role of IVIG is unclear. High-quality studies are urgently needed to assess the optimal use of IVIG in patients with HDN.

Keywords: alloimmunization; evidence-based guidelines; haemolytic disease of the newborn; intravenous immunoglobulin; pregnancy.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Blood Group Incompatibility
Erythroblastosis, Fetal* / drug therapy
Exchange Transfusion, Whole Blood
Female
Humans
Immunoglobulins, Intravenous* / therapeutic use
Infant, Newborn
Phototherapy

Substances

Immunoglobulins, Intravenous

Grants and funding

UL1 TR001863/TR/NCATS NIH HHS/United States