Reassessing critical maternal antibody threshold in RhD alloimmunization: a 16-year retrospective cohort study

Abstract

To determine the critical maternal antibody threshold for specialist referral in cases of RhD alloimmunization. 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. 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. 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.