Case Presentation:

A 7-day-old female born at 37 WGA presented with continued jaundice since birth.  Pregnancy was complicated by maternal preeclampsia requiring early induction of labor.  Both parents’ blood types were A+ and the mother had a negative antibody screen six months prior to delivery.  There was no history of maternal blood transfusion or antenatal trauma or bleeding.

Baby was jaundiced soon after birth and was discharged home at two days of life with a bilblanket.  She required hospitalization for phototherapy on day of life 3 and responded well before discharge home within 24 hours.  At 7 days of life her parents felt she looked much more jaundiced so brought her to the Emergency Department.

In the ED, VS were: HR 180; Temp 37.2; BP 68/42; RR 36.  She was diffusely jaundiced with an otherwise normal exam.  Her bilirubin was 20.3 mg/dL (0.0 mg/dL conjugated).  Hematology was consulted and she was admitted to the hospitalist service for further management.  She was found to be Coombs positive with HgB of 11.1 g/dL and 1.5% reticulocytes.  Antibody assay revealed that anti-c antibodies were causing her hemolytic disease of the newborn (HDN).

Her bilirubin responded to phototherapy in the hospital and she was discharged after two days. She followed up with hematology as an outpatient and, while bilirubin remained appropriate, she has required multiple packed red blood cell transfusions due to continued hemolysis and worsening anemia.


This case illustrates the clinical significance of non-RhD antigens in HDN.  Anti-c antibodies are estimated to be present in ~80% of people in the United States.  It has been reported that little-c antibody-mediated processes can cause HDN as well as acute and delayed hemolytic transfusion reactions.

One study reviewed 108,000 reports of antibody testing during pregnancy and identified 214 women who had clinically significant non-RhD antibodies.  Out of these 214 women, 52 had anti-c antibodies, and 8 of the little-c antibody cohort’s children developed severe HDN.  In all cases of severe HDN in women with a history of maternal red blood cell transfusion, little-c antibodies were implicated as mediating the HDN.  There has been a case report published in which a woman developed anti-c antibodies in the latter part of her pregnancy with no history of transfusion.


HDN can be severe and life threatening unless promptly identified and treated.  In a patient with recurrent hyperbilirubinemia, antibody mediated HDN should be considered even when parental RhD blood types are matched.  While maternal history of red blood cell transfusion is an important risk factor for anti-c antibody generation, HDN mediated by anti-c can occur without a history of maternal transfusions.  Children who are anti-c positive require ongoing follow up to evaluate the need for transfusion and additional phototherapy.