The contemporary management of haemolytic disease of the fetus and newborn

Abstract

Haemolytic disease of the fetus and newborn (HDFN) remains an important cause of perinatal mortality and morbidity. The pathogenesis underlying this condition is maternal red cell alloimmunization, with immunoglobulin G (IgG) antibodies produced in response to ‘non‐self’, inherited paternal antigens expressed upon fetal erythrocytes. The IgG antibodies cross the placenta into the fetal circulation causing red cell destruction and fetal anaemia. Intrauterine transfusion (IUT) remains the cornerstone therapy with fetal survival rates up to 97%, but it is an invasive, technically challenging surgical procedure performed at specialized medical centres. The procedure‐related risk of IUTs is increased at gestational age before 24 weeks. This has stimulated interest in maternal medical therapies that attenuate the risk of severe fetal anaemia, increase the gestational age of first IUTs, and reduce perinatal mortality and morbidity. This review summarizes current evidence for such treatments: intravenous immunoglobulin therapy and neonatal fragment crystallizable (Fc) receptor blockade for managing severe HDFN.

In Utero Molecular-Targeted Drug Therapies: Translational Principles, Pharmacologic Considerations, and Emerging Clinical Applications

“…Concurrently, it decreases transplacental IgG transfer, thereby limiting fetal exposure to pathogenic antibodies. This dual mechanism targets an early step in disease pathogenesis, shifting management from treatment of established fetal injury to prevention of disease progression [71,80,82].…”

In Utero Molecular-Targeted Drug Therapies: Translational Principles, Pharmacologic Considerations, and Emerging Clinical Applications

“…Concurrently, it decreases transplacental IgG transfer, thereby limiting fetal exposure to pathogenic antibodies. This dual mechanism targets an early step in disease pathogenesis, shifting management from treatment of established fetal injury to prevention of disease progression [71,80,82].…”

FcRn Blockade as a Targeted Therapeutic Strategy in Antibody-Mediated Autoimmune Diseases: A Focus on Warm Autoimmune Hemolytic Anemia

“…While RhD is the most common trigger, other antigens like Kell, Duffy, Kidd, and additional Rh antigens (C, c, E, e) have also been implicated [ 72 ]. Intrauterine transfusions (IUT) are the mainstay of therapy, but are invasive, technically complex, and limited to specialized centers [ 73 , 74 ]. Risks, including preterm premature rupture of membranes (pPROM) and fetal death, are higher when performed before 24 weeks of gestation [ 74 , 75 ].…”

“…Intrauterine transfusions (IUT) are the mainstay of therapy, but are invasive, technically complex, and limited to specialized centers [ 73 , 74 ]. Risks, including preterm premature rupture of membranes (pPROM) and fetal death, are higher when performed before 24 weeks of gestation [ 74 , 75 ]. Early-onset severe HDFN—defined as occurring at or before 24 weeks’ gestation—is linked to significant fetal and neonatal morbidity and mortality.…”

In Utero Molecular-Targeted Drug Therapies: Translational Principles, Pharmacologic Considerations, and Emerging Clinical Applications

“…Concurrently, it decreases transplacental IgG transfer, thereby limiting fetal exposure to pathogenic antibodies. This dual mechanism targets an early step in disease pathogenesis, shifting management from treatment of established fetal injury to prevention of disease progression [71,80,82].…”

FcRn Blockade as a Targeted Therapeutic Strategy in Antibody-Mediated Autoimmune Diseases: A Focus on Warm Autoimmune Hemolytic Anemia

“…While RhD is the most common trigger, other antigens like Kell, Duffy, Kidd, and additional Rh antigens (C, c, E, e) have also been implicated [ 72 ]. Intrauterine transfusions (IUT) are the mainstay of therapy, but are invasive, technically complex, and limited to specialized centers [ 73 , 74 ]. Risks, including preterm premature rupture of membranes (pPROM) and fetal death, are higher when performed before 24 weeks of gestation [ 74 , 75 ].…”

“…Intrauterine transfusions (IUT) are the mainstay of therapy, but are invasive, technically complex, and limited to specialized centers [ 73 , 74 ]. Risks, including preterm premature rupture of membranes (pPROM) and fetal death, are higher when performed before 24 weeks of gestation [ 74 , 75 ]. Early-onset severe HDFN—defined as occurring at or before 24 weeks’ gestation—is linked to significant fetal and neonatal morbidity and mortality.…”

In Utero Molecular-Targeted Drug Therapies: Translational Principles, Pharmacologic Considerations, and Emerging Clinical Applications

“…Concurrently, it decreases transplacental IgG transfer, thereby limiting fetal exposure to pathogenic antibodies. This dual mechanism targets an early step in disease pathogenesis, shifting management from treatment of established fetal injury to prevention of disease progression [71,80,82].…”

FcRn Blockade as a Targeted Therapeutic Strategy in Antibody-Mediated Autoimmune Diseases: A Focus on Warm Autoimmune Hemolytic Anemia

“…While RhD is the most common trigger, other antigens like Kell, Duffy, Kidd, and additional Rh antigens (C, c, E, e) have also been implicated [ 72 ]. Intrauterine transfusions (IUT) are the mainstay of therapy, but are invasive, technically complex, and limited to specialized centers [ 73 , 74 ]. Risks, including preterm premature rupture of membranes (pPROM) and fetal death, are higher when performed before 24 weeks of gestation [ 74 , 75 ].…”

“…Intrauterine transfusions (IUT) are the mainstay of therapy, but are invasive, technically complex, and limited to specialized centers [ 73 , 74 ]. Risks, including preterm premature rupture of membranes (pPROM) and fetal death, are higher when performed before 24 weeks of gestation [ 74 , 75 ]. Early-onset severe HDFN—defined as occurring at or before 24 weeks’ gestation—is linked to significant fetal and neonatal morbidity and mortality.…”