Variations and Opportunities in Postnatal Management of Hemolytic Disease of the Fetus and Newborn

Abstract

Importance: Preventive efforts in pregnancy-related alloimmunization have considerably decreased the prevalence of hemolytic disease of the fetus and newborn (HDFN). International studies are therefore essential to obtain a deeper understanding of the postnatal management and outcomes of HDFN. Taken together with numerous treatment options, large practice variations among centers may exist.

Objectives: To assess variations in postnatal management and outcomes of HDFN among international centers and to identify opportunities to improve care.

Design, setting, and participants: In this international, retrospective, cohort study, 31 expert centers from 22 countries retrieved data on neonates with HDFN managed between January 1, 2006, and July 1, 2021. Statistical analysis was performed from July 19, 2023, to October 28, 2024.

Main outcomes and measures: Main outcomes included the frequency of exchange transfusions, administration of intravenous immunoglobulin, administration of erythropoiesis-stimulating agents, and red blood cell transfusions, as well as the association of gestational age at birth with exchange transfusion frequency and risk factors for adverse neonatal outcomes.

Results: The study included 1855 neonates (median gestational age at birth, 36.4 weeks [IQR, 35.0-37.3 weeks]; 1034 boys [55.7%]), of whom 1017 (54.8%) received any form of antenatal treatment. Most neonates (1447 [78.0%]) had anti-D antibodies. Exchange transfusions were performed in 436 neonates (23.5%), with proportions in exchange transfusion frequency varying from 0% to 78% among centers. Intravenous immunoglobulin was administered to 429 of 1743 neonates (24.6%), with proportions varying from 0% to 100% among centers. A higher gestational age at birth was associated with a reduction in exchange transfusion frequency in neonates with intrauterine transfusion, decreasing from approximately 38.2% (13 of 34) at 34 weeks to 16.8% (18 of 107) after 37 weeks and 0 days. A weekly increase in gestational age at birth was associated with a 43.3% decrease (95% CI, 36.1%-49.7%) in the likelihood of adverse neonatal outcomes, and neonates who received an exchange transfusion were 1.55 (95% CI, 1.10-2.18) times more likely to experience unfavorable outcomes.

Conclusions and relevance: In this cohort study of neonates with HDFN managed at 31 centers in 22 countries, significant practice variations in the postnatal management of HDFN were identified, highlighting the lack of, and need for, consensus. The study suggests that there is a potential beneficial clinical association of waiting for delivery until after 37 weeks and 0 days with frequency of exchange transfusions among neonates with HDFN. The framework to implement international guidelines is provided.

Figure 1.. Bubble Plots of Treatment Frequencies Per Center

A, Frequencies among centers of exchange transfusions (ETs) and intravenous immunoglobulin (IVIG) administration among neonates treated with intrauterine transfusion (IUT). B, Frequencies among centers of ETs and IVIG administration among neonates without antenatal treatment. C, Red blood cell (RBC) transfusions during initial admission. Each bubble represents a center. The size of the bubble indicates the number of cases.

Figure 2.. Exchange Transfusion Frequency by Gestational Age

Shown is the exchange transfusion frequency in neonates treated with intrauterine transfusion (IUT) and neonates without antenatal treatment, by gestational age.

Figure 3.. Adverse Neonatal Outcomes by Gestational Age and Association of Variables With Likelihood of Adverse Neonatal Outcomes

A, Frequency of adverse neonatal outcomes by gestational age at birth. B, Percentage change in the likelihood of adverse neonatal outcomes. Error bars indicate 95% CIs. RDS indicates respiratory distress syndrome. To convert hemoglobin to grams per liter, multiply by 10.0.