Hemolytic disease of the fetus and newborn in the molecular era

SummaryMaternal–fetal red cell antigen incompatibility can lead to alloimmunization, maternal immunoglobulin transplacental transfer, and hemolytic disease of the fetus and newborn (HDFN). The use of routine antenatal anti-D prophylaxis (RAADP) has sharply decreased the incidence of and mortality from HDFN due to RhD allosensitization. The ability to identify pregnancies/fetuses at risk of HDFN has significantly improved due to paternal molecular RHD zygosity testing, and non-invasive fetal molecular diagnostics for detecting putative antigen(s) (notably RhD) in fetuses utilizing cff-DNA in maternal plasma. Fetal RHD genotyping using cff-DNA has become increasingly accurate for fetal RHD detection, prompting some countries to implement targeted RAADP through mass screening programs of RhD-negative pregnant women. Along with middle cerebral artery Doppler ultrasonography for predicting fetal anemia, non-invasive fetal molecular diagnostics have greatly decreased the need for invasive diagnostic procedures in pregnancies at risk for severe HDFN. This review highlights these molecular advancements in HDFN-related prenatal diagnostics.