Effect of High Throughput RHD Typing of Fetal DNA in Maternal Plasma on Use of Anti-RhD Immunoglobulin in RhD Negative Pregnant Women: Prospective Feasibility Study

摘要

Alloimmunization against the RhD red cell surface antigen remains the commonest cause of hemolytic disease in the fetus and newborn infant. Mass antenatal testing for fetal blood group, done by analyzing fetal DNA in maternal plasma, would be expected to substantially reduce the use of anti-RhD immunoglobulin, an expensive product in short supply. In addition, women with a RhD-negative fetus would avoid unnecessary exposure to the immunoglobulin with its attendant discomfort and risk of contamination by a virus or prion. This study prospectively compared fetal RHD genotypes determined from fetal DNA in maternal plasma with the serologically determined fetal RhD phenotype from cord blood. Samples were taken from 1997 women at or before the 28-week antenatal visit. An automatic robotic technique was used in a high throughput method to predict the fetal RhD phenotype. The RhD phenotype was determined serologically in 1869 cord blood samples. In 95.7% of instances the correct fetal RhD phenotype was predicted by genotyping. In 3.4% of cases, results either could not be obtained or were inconclusive. In many of these cases the sample was more than 2 weeks old and had excessively high levels of maternal DNA, probably from the breakdown of maternal leukocytes. The rate of false-positive results was 0.8%; these results probably reflected unexpressed or weakly expressed fetal RHD genes. Only 3 results (0.2%) were falsely negative. Had these results served as a guide to treatment, only 2% of women would have received anti-RhD unnecessarily, compared with 38% without genotyping. These results suggest that fetal genotyping and withholding of antenatal anti-RhD prophylaxis when an RhD-negative fetus is identified would preclude the need for exposure to anti-RhD immunoglobulin in RhD-negative women with an RhD-negative fetus.