Erythroblastosis Fetalis
Basics
Description
- Hemolytic anemia of the fetus or newborn is caused by transplacental transmission of maternal IgG antibodies against fetal red blood cells (RBCs).
- When severe, fetal anemia may result in extramedullary hematopoiesis, secondary organ dysfunction, heart failure, hydrops (generalized edema), and fetal demise.
- The term erythroblastosis refers to the presence of immature erythrocytes in the peripheral blood from accelerated hematopoiesis.
- System(s) affected: cardiovascular, hematologic, lymphatic, immunologic, nervous
- Synonym(s): erythroblastosis neonatorum; hemolytic disease of the fetus and newborn (HDFN); congenital anemia of the newborn; immune hydrops fetalis
Epidemiology
- Predominant age: affects the fetus and newborn
- Predominant sex: none, male = female
- Most frequent populations: Basques, Caucasians in North America and Europe
Incidence
Universal screening for Rh sensitization and widespread use of Rho(D) immunoglobulin (RhIG) in 3rd trimester and/or at birth have made this disease relatively rare at <1% (1)[C]. In developing countries, it is more common with 14% of affected pregnancies resulting in stillbirths.
Etiology and Pathophysiology
- Alloimmunization occurs when maternal blood is exposed to an antigen that is not present on her RBCs; can occur with as little as <0.1 to 0.5 mL of blood exchange (1)[C]
- Can occur during RBC transfusion or fetomaternal bleeding (abortion, ectopic pregnancy, vaginal bleeding due to placental previa or abruption, trauma, external cephalic version, delivery)
- Alloimmunization has also been reported to occur with shared needles and platelet transfusion.
- Only IgG alloantibodies can cross the placenta and thus cause erythroblastosis fetalis.
- Erythroblastosis fetalis is more common with alloantibodies to RhD, Rh(c), Rh(e), and Kell blood group antigens.
- Once the IgG antibodies cross the placental barrier to the fetal circulation, they attach to fetal RBCs and lead to hemolysis.
- Extramedullary hematopoiesis is stimulated by the hemolysis and resultant anemia.
Risk Factors
- Prior transfusion or inadvertent transfusion with Rh-positive blood
- Not receiving Rh immunoglobulin when indicated
Pregnancy Considerations
- Any pregnancy with an Rh-positive fetus in an Rh-negative woman can cause alloimmunization (~9% of pregnancies have an Rh-negative mother with an Rh-positive fetus).
- Without prophylactic immunotherapy (RhIG), risk of Rh sensitization is up to 16% during or after term pregnancy, ~3% for spontaneous abortion, and 5–6% for surgical abortion.
- Prophylaxis with RhIG drastically reduces risk of sensitization to <1% of susceptible pregnancies.
- Universal screening for Rh sensitization and widespread use of RhIG in 3rd trimester and/or at birth have made this disease relatively rare.
Genetics
- 55% of the population are heterozygous for the RhD locus, and 50% of their offspring will be Rh positive (2)[C].
- The RhD antigen is most frequently implicated, but other antibodies may be the source of alloimmunization.
- Cell-free fetal DNA in maternal plasma can be used as early as 10 weeks’ gestational age (more commonly performed at 16 to 20 weeks) to determine RhD and other blood group antigens (3)[C].
General Prevention
- For pregnant patients:
- Administer anti-D immunoglobulin (i.e., RhoGAM) to Rh-negative pregnant women at increased risk of fetomaternal hemorrhage at 28 weeks’ gestational age and within 72 hours of birth of an Rh-positive infant.
- For nonpregnant patients who are of childbearing age:
- Crossmatching of all transfused blood products is standard of care in developed countries. Rh-negative women should be treated with anti-D immunoglobulin if they receive Rh-positive RBCs in error or in emergency transfusions.
- Platelets can contain small amounts of RBCs. Prophylactic anti-D immunoglobulin should be considered in Rh-negative women of childbearing age who are receiving Rh-positive platelets.
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Citation
Domino, Frank J., et al., editors. "Erythroblastosis Fetalis." 5-Minute Clinical Consult, 33rd ed., Wolters Kluwer, 2025. Medicine Central, im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/1688490/1.0/Erythroblastosis_Fetalis.
Erythroblastosis Fetalis. In: Domino FJF, Baldor RAR, Golding JJ, et al, eds. 5-Minute Clinical Consult. Wolters Kluwer; 2025. https://im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/1688490/1.0/Erythroblastosis_Fetalis. Accessed December 10, 2024.
Erythroblastosis Fetalis. (2025). In Domino, F. J., Baldor, R. A., Golding, J., & Stephens, M. B. (Eds.), 5-Minute Clinical Consult (33rd ed.). Wolters Kluwer. https://im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/1688490/1.0/Erythroblastosis_Fetalis
Erythroblastosis Fetalis [Internet]. In: Domino FJF, Baldor RAR, Golding JJ, Stephens MBM, editors. 5-Minute Clinical Consult. Wolters Kluwer; 2025. [cited 2024 December 10]. Available from: https://im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/1688490/1.0/Erythroblastosis_Fetalis.
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