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Transfusion. 2019 Apr;59(4):1183-1189. doi: 10.1111/trf.15154. Epub 2019 Feb 5.

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

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Center for Cancer and Blood Disorders, Children's National Health System, Washington, District of Columbia.
Divisions of Hematology and Laboratory Medicine and Pathology, Children's National Health System, Department of Pediatrics, George Washington University School of Medicine and Health Sciences, Washington, District of Columbia.



Alloantibodies against more than 50 non-ABO blood group antigens have been implicated in hemolytic disease of the fetus and newborn (HDFN) and are expected to wane within weeks after delivery. Persistent anemia leads to the hypothesis of continued exposure to red blood cell (RBC) alloantibodies via breast milk, which has been shown in a murine model and suggested in rare case reports.


We report three cases of prolonged HDFN in two neonates with anti-D HDFN and one with anti-Jka HDFN. Patient 1 demonstrated 4+ anti-D serologic testing beyond 2 months; therefore, antibody testing was performed on maternal breast milk.


Maternal serum samples were tested for the presence of unexpected antibodies using standard Ortho gel card and 37 °C 60 minutes with anti-human globulin (AHG) tube saline methods. Antibody titrations were performed using the standard 37 °C 60 minutes to AHG tube saline method. Fresh breast milk samples were tested using the standard 37 °C 60 minutes to AHG tube saline method for both unexpected antibodies and titration study. Fresh breast milk from an O-positive, antibody-negative donor was used as control for any reactivity that may have been due to milk solids or proteins alone.


Using a known methodology applied in a novel way to test breast milk for RBC alloantibodies, antibodies against fetal RBCs were identified in the maternal breast milk of three patients.


Maternal RBC alloantibodies are present in breast milk and may be clinically significant in patients with prolonged recovery from HDFN.


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