Background: The aim of this study was to determine the frequency and o
rigin of additional alloantibodies directed against red cells (RBCs) a
fter intrauterine transfusion (IUT). Study Design and Methods: Between
March 1987 and December 1992, fetuses with severe hemolytic disease (
n = 91) received a total of 280 ultrasound-guided IUTs of RBCs from un
related donors. The specificity of alloantibodies to RBCs in maternal
serum was determined both before and after each IUT. If additional all
oantibodies directed against RBCs were detected, their origin was dete
rmined by phenotyping the fetal, donor, and paternal RBCs for each par
ticular antigen. The study included a control group of 69 pregnant wom
en who underwent either amniocentesis or fetal blood sampling. Results
: Production of additional alloantibodies directed against RBC antigen
s was detected in 24 women (26%). The source of the immunizing antigen
, either donor or fetus, was identified in 14 patients. The additional
alloantibodies were directed against fetal antigens in 11 women and a
gainst donor antigens in 3. One additional alloantibody directed again
st donor antigen clearly reduced the survival of donor RBCs. The fetus
and the donor shared the immunizing antigen in four cases, and in one
case, the antibody occurred naturally. In five cases, the source of t
he immunizing antigen was not determined. In the control group, additi
onal antibodies were detected in two patients. Conclusion: IUT therapy
is associated with a high incidence of additional alloantibodies. In
the majority of patients, the use of maternal RBCs for IUT would not h
ave prevented additional formation of alloantibody to RBCs.