Transfusion Medicine Consultant, Medical Director Center for Regenerative Biotherapeutics Mayo Clinic Rochester, Minnesota, United States
Background/Case Studies: Historically, anti-M was generally described as benign in pregnancy and not associated with hemolytic disease of the fetus and newborn (HDFN). Recently, there has been a preponderance of severe HDFN cases reported in Asia. Because the M antigen is expressed on immature erythroid precursors, anti-M has been postulated to mediate severe HDFN by inhibiting erythropoiesis. However, this hypothesis does not explain the apparent propensity for severe disease in Asian patients. The objective of this study is to determine if there is a difference in anti-M HDFN severity among subjects who self-identify as Asian vs. non-Asian.
Study
Design/Methods: This is an interim analysis of an international, multi-center, retrospective study, where medical records were reviewed to determine if pregnancies with anti-M were affected by HDFN over 11 years (1/1/2012 to 12/31/2022, if available). Pregnancies affected by HDFN were classified as mild (phototherapy), moderate (simple transfusion to neonate, intravenous immunoglobulin to obstetric patient or neonate), or severe (intrauterine transfusion, neonatal exchange transfusion, maternal plasma exchange, hydrops fetalis, stillborn, fetal demise) based on the outcome of the pregnancy and/or the management of the fetus/neonate to treat immune-mediated hemolysis.
Results/Findings: Anti-M was identified during 500 pregnancies in 416 obstetric patients (n=322 non-Asian, n=51 Asian subjects, n=43 unknown) at 12 sites (United States n=6, Canada n=3, Scotland n=1, Saudi Arabia n=1, and Japan n=1). Cases were excluded from analysis for the following reasons: unknown ancestry of the obstetric patient (n=43), unavailable neonatal outcome (n=68), pregnancy did not result in live birth due to elective abortion or fetal demise not attributable to HDFN (n=18), and unknown ABO group of the neonate(n=135). As shown in Figure A, among 226 pregnancies included in the analysis, anti-M in isolation was detected in 134 pregnancies. In this group, the majority of pregnancies (94%, 126/134) were not affected by HDFN and 6% (8/134) were affected by HDFN. The percentage of affected cases is 10% (2/20) among Asian patients and 5.3% (6/114) among non-Asian patients. Among the 8 HDFN cases, 2 were severe and both occurred in patients who self-identified as Asian. One moderate and 5 mild cases were reported in non-Asian patients. The outcomes of pregnancies with anti-M and additional serologic findings, including alloantibodies (e.g., anti-D) and passive anti-D, are also presented in Figure A; all affected cases were mild. Conclusions: Data analyzed to date signal that the antenatal serologic finding of anti-M in isolation may be associated with severe HDFN in Asian patients and not in non-Asian patients. This study is limited by the relatively low number of Asian subjects. Four additional study sites have been recruited, and their data are pending analysis.
