Fetal anemia of unknown cause--a diagnostic challenge

Purpose: To assess the spectrum of underlying diseases in cases of fetal anemia in which the cause was unknown at the time of first and second transfusion or thereafter.

Materials and methods: All patients who underwent intrauterine transfusion were identified in the perinatal databases of two tertiary referral centers for prenatal medicine and treatment between 2002 and June 2010.

Results: 82 fetuses received intrauterine transfusion in the study period. A total of 356 transfusions were performed in these patients. The causes of fetal anemia in our cohort were alloimmunization (32), parvovirus infection (23), feto-fetal transfusion syndrome (9), sacrococcygeal teratoma (2) and cytomegalovirus infection (1). In the remaining 15 cases, the cause of fetal anemia was unknown at the time of first and second transfusion, and could only be ascertained in the further course of pregnancy, in the postnatal period or was ultimately left in doubt. In all cases markedly elevated peak systolic velocities in the middle cerebral artery accurately predicted fetal anemia. The final diagnosis in these cases was fetomaternal hemorrhage (4), Blackfan-Diamond anemia (1), diffuse neonatal hemangiomatosis with chorangioma (1), kaposi-like hemangioendothelioma (1), elliptocytosis (1), neonatal hemochromatosis (1), mucopolysaccharidosis type VII (1) and in 5 cases the cause of fetal anemia remained unexplained. The latter 5 cases had an uneventful postnatal course and did not require further transfusions in infancy.

Conclusion: In cases of fetal anemia with negative indirect Coombs test and TORCH serology, rare causes of anemia have to be considered. Fetal studies should therefore include reticulocyte count, parameters of hemolysis, peripheral blood smear and fetal liver function tests. Maternal studies should involve a search for fetal red cells using flow cytometry rather than Kleihauer-Betke test.