still in use. the clinical significance of this highly immunizing d antigen (i.e., rh factor) was soon realized. some keystones were to recognize its importance for blood transfusion (including reliable diagnostic tests), hemolytic disease of the newborn (including exchange transfusion), and very importantly the prevention of it by screening and prophylaxis. the discovery of fetal cell-free dna in maternal circulation by holzgrieve et al. led to the noninvasive genotyping of fetal rh genes in many countries.