The determination of the fetal D status from maternal plasma for decision making on Rh prophylaxis is feasible

Transfusion. 2008 Nov;48(11):2292-301. doi: 10.1111/j.1537-2995.2008.01843.x. Epub 2008 Aug 7.

Abstract

Background: Noninvasive fetal RHD genotyping might become a valuable tool in decision making on antenatal Rh prophylaxis, which is currently in routine practice for all D- pregnancies in several countries. This study provides a large-scale validation study of this technology to address questions concerning feasibility and applicability of its introduction into clinical routine.

Study design and methods: Real-time polymerase chain reaction (PCR) targeting RHD Exons 5 and 7 was applied for the detection of fetal-specific RHD sequences in maternal plasma. A total of 1113 women in 6 to 32 weeks (median, Week 25) of pregnancy were recruited. All of them were serologically typed as D- according to current German guidelines. DNA was extracted via a spin-column method and a novel automated approach using magnetic tips. Real-time PCR results were compared with postnatal serology and discrepancies further elucidated by DNA sequencing from a newborn's buccal swab.

Results: Sensitivities of fetal RHD genotyping were 99.7 percent (spin columns) and 99.8 percent (magnetic tips), thus comparable with serology (99.5%). The detection of weak D variants was more reliable by real-time PCR. Specificities of fetal RHD genotyping were 99.2 percent (spin columns) and 98.1 percent (magnetic tips), which is lower than serology (>99.7%). Automation achieved significantly higher yields of cell-free fetal DNA.

Conclusion: This prospective clinical trial revealed that routine determination of the fetal D status from maternal plasma is feasible. Noninvasive fetal RHD genotyping can be considered as sensitive as the traditional postnatal serologic assay.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Adult
  • Blood Grouping and Crossmatching / methods*
  • Computer Systems
  • DNA / blood
  • DNA / isolation & purification
  • Decision Making
  • Erythroblastosis, Fetal / prevention & control
  • Female
  • Fetal Blood / immunology*
  • Fetomaternal Transfusion*
  • Genotype
  • Humans
  • Infant, Newborn
  • Isoantibodies
  • Polymerase Chain Reaction / methods
  • Pregnancy
  • Prenatal Diagnosis / methods*
  • Prospective Studies
  • Rh-Hr Blood-Group System / analysis*
  • Rh-Hr Blood-Group System / genetics
  • Rho(D) Immune Globulin
  • Sensitivity and Specificity
  • Unnecessary Procedures

Substances

  • Isoantibodies
  • RHO(D) antibody
  • Rh-Hr Blood-Group System
  • Rho(D) Immune Globulin
  • Rho(D) antigen
  • DNA