Reassessing critical maternal antibody threshold in RhD alloimmunization: a 16-year retrospective cohort study.
OBJECTIVE
To determine the critical maternal antibody threshold for specialist referral in cases of RhD alloimmunization.


METHODS
This was a retrospective cohort study, covering a 16-year period at the national tertiary fetal medicine center for management of alloimmunization. Data concerning RhD alloimmunized pregnant women were extracted from an institutional database and maternal anti-D antibody levels were cross-checked with the national reference laboratory. Fetal hemoglobin (Hb) levels were determined only at the first intrauterine transfusion (IUT) and were compared with the pretransfusion maternal anti-D antibody level (IU/mL). Sensitivity, specificity and positive and negative predictive values of maternal antibody thresholds for detecting moderate to severe (Hb ≤ 0.64MoM) fetal anemia were calculated.


RESULTS
Between 1996 and 2011, 66 women underwent a first IUT for RhD alloimmunization at our institution. The highest serum anti-D antibody level was extracted for 208 RhD alloimmunized women who did not require IUT during the last 10 years of the study period. The traditional maternal antibody threshold of > 15 IU/mL failed to detect 20% of cases of moderate to severe fetal anemia. The ≥ 4 IU/mL threshold had 100% sensitivity but a 45% false-positive rate. The optimal anti-D antibody threshold for specialist referral in our population was ≥ 6 IU/mL; at this level, no case of moderate to severe anemia was missed and specificity was 61%. Use of this threshold would have eliminated 10% of referrals to our fetal medicine unit without compromising fetal outcomes.


CONCLUSIONS
Setting the critical maternal RhD antibody level at >15 IU/mL does not provide sufficient sensitivity. The lower threshold of ≥ 4 IU/mL, though sensitive, is associated with a 45% false-positive rate. In our population, a threshold of ≥ 6 IU/mL minimizes false-positive referrals while maintaining 100% sensitivity for moderate to severe fetal anemia.
Fetal Medicine Unit, National Maternity Hospital, Dublin, Ireland.
C A
CA
Walsh
B
B
Doyle
J
J
Quigley
F M
FM
McAuliffe
J
J
Fitzgerald
R
R
Mahony
S
S
Higgins
S
S
Carroll
P
P
McParland
D000328:Adult; D000740:Anemia / Q000276:immunology*; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D005260:Female; D005315:Fetal Diseases / Q000175:diagnosis* / Q000276:immunology; D006801:Humans; D007518:Isoantibodies / Q000097:blood*; D011237:Predictive Value of Tests; D011247:Pregnancy; D012189:Retrospective Studies; D012203:Rh Isoimmunization / Q000276:immunology*; D018029:Rho(D) Immune Globulin; D012680:Sensitivity and Specificity
D015415:Biomarkers; D007518:Isoantibodies; C061961:RHO(D) antibody; D018029:Rho(D) Immune Globulin
RhD; alloimmunization; antibody; transfusion