Society for Maternal-Fetal Medicine Statement: Evaluation and management of cell-free DNA screening for fetal red cell antigen genotype in alloimmunized and non-alloimmunized pregnancies

SMFM, BD Rink, JA Kuller, TN Sparks, M Prabhu, AH Mardy, L Dugoff, JR Biggio, SMFM Publications Committee2026

A substantial portion of RhD-negative pregnant patients carry an RhD-negative fetus and are not at risk of RhD alloimmunization. Knowing the fetal RhD genotype allows such patients to avoid unnecessary monitoring or treatment. The use of cell-free DNA (cfDNA) to detect the fetal RhD genotype from maternal blood has been proposed to identify pregnancies in alloimmunized patients at risk for hemolytic disease of the fetus and newborn and to decrease the antenatal use of Rho(D) immune globulin (RhIg) in patients not at risk. However, a number of factors limit the utility of cfDNA for RhD genotyping, including a lack of data that adequately reflect US populations or US laboratory testing approaches and a lack of data or research from independent sources. This document describes considerations and offers guidance on cfDNA screening for red blood cell antigen genotypes in three scenarios: RhD in a non-alloimmunized patient, RhD in a non-alloimmunized patient in the setting of an RhIg shortage, and any fetal red cell antigen genotype in an alloimmunized obstetrical patient.

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red cell alloimmunization, screening
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SMFM Statement