Rate of clinically significant red blood cell antibody seroconversion in pregnancy

To determine the rate of clinically significant red blood cell (RBC) antibody seroconversion in pregnancy and associated risk factors and neonatal outcomes.

This is a retrospective cohort study of all deliveries within a large multi-hospital system from July 2016 to March 2023. Deliveries with a missing RBC antibody screen on admission for delivery were excluded, as were deliveries with a positive antibody screen on admission for delivery without a record of antecedent type and screen (T&S) in that pregnancy. Deliveries were categorized as 1) not possessing clinically significant antibodies (which includes those with a negative antibody screen, evidence of passive immunity solely due to Rh(D) immune globulin (RhIG), or possessing only non-clinically significant RBC antibodies); 2) previously alloimmunized (i.e. pregnancies that demonstrated clinically significant antibodies on the first T&S, regardless if they accrued additional antibodies throughout the pregnancy); or 3) seroconverted (i.e. no clinically significant antibodies on the first T&S with subsequent development of alloimmunization with clinically significant antibodies). For neonates born to seroconverted patients with clinically significant antibodies, neonatal outcomes such as initial hemoglobin, need for transfusion, and neonatal intensive care unit (NICU) admission were ascertained via chart abstraction. All records were linked with an existing validated database, inclusive of maternal characteristics and pregnancy outcomes, and comparisons were made between three categories based on antibody status with a sub-analysis of two categories. Bivariate analysis was performed with Chi-square for categorical and Wilcoxon rank-sum or Kruskal-Wallis test for continuous variables.

There were 58,912 pregnant individuals with 71,384 eligible deliveries during the study period, with 67,570 deliveries remaining after data linkage. Of these, 67,209 (99.5%) deliveries had a negative or non-clinically significant antibody screen at delivery. Of the remaining 361 (0.53%) deliveries, 185 (0.27%) were previously alloimmunized and 176 (0.26%) seroconverted in pregnancy. Among pregnancies demonstrating seroconversion, the most common newly acquired antibodies were anti-E, anti-c, anti-JkA, anti-C, anti-D, anti-M, anti-K, and anti-S. Among the 176 pregnancies complicated by seroconversion, there were four unexplained fetal losses, none of which were attributable to HDFN. Among the 178 liveborn neonates born to the 176 pregnancies demonstrating seroconversion, three (1.7%) infants had initial hemoglobin <13.5 mg/dL, four (2.2%) required postnatal transfusion but all were unrelated to HDFN, and 34 (19.1%) required NICU admission. When comparing deliveries demonstrating seroconversion with those with a negative antibody screen at delivery, advanced maternal age and increasing gravidity and parity were most strongly associated with seroconversion.

Development of new clinically significant RBC antibodies in pregnancy occurred at a rate of 0.26% in this large cohort study with no cases of stillbirth or neonatal demise attributable to RBC alloimmunization among pregnancies demonstrating seroconversion. Advanced maternal age and increasing gravidity and parity were most strongly associated with seroconversion in pregnancy. Routine third trimester prenatal assessment of maternal antibody status may not be indicated due to low likelihood for clinically significant seroconversion.