Hemolytic disease of the fetus and newborn: managing the mother, fetus, and newborn

Abstract

Hemolytic disease of the fetus and newborn (HDFN) affects 3/100 000 to 80/100 000 patients per year. It is due to maternal blood group antibodies that cause fetal red cell destruction and in some cases, marrow suppression. This process leads to fetal anemia, and in severe cases can progress to edema, ascites, heart failure, and death. Infants affected with HDFN can have hyperbilirubinemia in the acute phase and hyporegenerative anemia for weeks to months after birth. The diagnosis and management of pregnant women with HDFN is based on laboratory and radiographic monitoring. Fetuses with marked anemia may require intervention with intrauterine transfusion. HDFN due to RhD can be prevented by RhIg administration. Prevention for other causal blood group specificities is less studied. Learning Objectives• Explain the fetal and infant clinical findings associated with hemolytic disease of the fetus and newborn (HDFN) • Describe the approach to pregnancy management when a mother has red cell alloimmunization • Discuss the prevention strategies for HDFN Hemolytic disease of the fetus and newborn (HDFN) is rare condition that occurs when maternal red blood cell (RBC) or blood group antibodies cross the placenta during pregnancy and cause fetal red cell destruction. The fetal physiological consequences of severe anemia in the fetus can also lead to edema, ascites, hydrops, heart failure, and death. In less severe cases, the in utero red cell incompatibility can persist postnatally with neonatal anemia due to hemolysis, along with hyperbilirubinemia and erythropoietic suppression. Epidemiology and pathophysiologyThere are an estimated 3/100 000 to 80/100 000 cases of HDFN per year in the United States. 1 The maternal blood group antibodies that cause HDFN can be naturally occurring ABO antibodies (isohemagglutinins), or develop after exposure to foreign RBC; the latter are called blood group alloantibodies. For HDFN to occur, the fetus must be antigen positive (paternally inherited) and the mother must be antigen negative. Several studies have investigated the prevalence of red cell sensitization. In a large series of 22 102 females in the US, 254 (1.15%) of the women were found to have a red cell alloantibodies, of whom 18% had more than one alloantibody. 2 In the Netherlands, the prevalence of red cell alloantibodies detected in the first trimester was 1.2%. 3 The most common cause of blood group incompatibility results from the ABO blood group system, with incompatibility present in up to 20% of infants. 4 However, because anti-ABO antibodies are predominantly IgM class, most are not effectively transported across the placenta. In addition, the A and B antigens are not well developed on fetal red blood cells. Together, this results in a low rate of clinically severe HDFN due to ABO compatibility, although

Identification of red blood cell antibodies in maternal breast milk implicated in prolonged hemolytic disease of the fetus and newborn

“…D antigen is a complex, highly immunogenic, multipass transmembrane RBC protein and remains the most common cause of HDFN . While the incidence of D sensitization has declined markedly with maternal antenatal and postnatal D immunoprophylaxis, alloantibodies against more than 50 non‐ABO blood group antigens other than D have been implicated in HDFN .…”

“…1 D antigen is a complex, highly immunogenic, multipass transmembrane RBC protein and remains the most common cause of HDFN. 2 While the incidence of D sensitization has declined markedly with maternal antenatal and postnatal D immunoprophylaxis, alloantibodies against more than 50 non-ABO blood group antigens other than D have been implicated in HDFN. 3 RBC sensitization can occur because of exposure to antigenically dissimilar RBCs during prior pregnancy, therapeutic transfusion, organ transplant, or, less frequently, needle sharing.…”

Hemolytic Disorders of the Newborn, Current Methods of Diagnosis and Treatment: A Review Study

“…The diagnosis and management of pregnant women with HDFN is based on laboratory and radiographic monitoring [66]. Antenatal diagnosis and postnatal management of fetuses/neonates affected by red blood cell allo-immunisation continues to require close cooperation between obstetric, neonatal and hematology teams.…”

Hemolytic disease by isoimmunization in Rh and ABO systems in newborns. A clinical study

“…Before the introduction of anti-D immunoglobulin for isoimmunization prophylaxis during pregnancy, HDN by Rh incompatibility affected 9-10% of pregnancies and represented a major cause of perinatal mortality and morbidity. Nevertheless, Rh isoimmunization remains a serious issue, continuing to affect about 2% of pregnancies in Romania (9,10,11) . Out of 7127 newborn infants in the Neonatal Premature Baby Department over a period of 2 years (1 January 2012 till 31 December 2013), a number of 76 newborn infants were diagnosed with hemolytic disease by isoimmunization.…”