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

BMJ. 2008 Apr 12;336(7648):816-8. doi: 10.1136/bmj.39518.463206.25. Epub 2008 Apr 3.


Objectives: To assess the feasibility of applying a high throughput method, with an automated robotic technique, for predicting fetal RhD phenotype from fetal DNA in the plasma of RhD negative pregnant women to avoid unnecessary treatment with anti-RhD immunoglobulin.

Design: Prospective comparison of fetal RHD genotype determined from fetal DNA in maternal plasma with the serologically determined fetal RhD phenotype from cord blood.

Setting: Antenatal clinics and antenatal testing laboratories in the Midlands and north of England and an international blood group reference laboratory.

Participants: Pregnant women of known gestation identified as RhD negative by an antenatal testing laboratory. Samples from 1997 women were taken at or before the 28 week antenatal visit.

Main outcome measures: Detection rate of fetal RhD from maternal plasma, error rate, false positive rate, and the odds of being affected given a positive result.

Results: Serologically determined RhD phenotypes were obtained from 1869 cord blood samples. In 95.7% (n=1788) the correct fetal RhD phenotype was predicted by the genotyping tests. In 3.4% (n=64) results were either unobtainable or inconclusive. A false positive result was obtained in 0.8% (14 samples), probably because of unexpressed or weakly expressed fetal RHD genes. In only three samples (0.2%) were false negative results obtained. If these results had been applied as a guide to treatment, only 2% of the women would have received anti-RhD unnecessarily, compared with 38% without the genotyping.

Conclusions: High throughput RHD genotyping of fetuses in all RhD negative women is feasible and would substantially reduce unnecessary administration of anti-RhD immunoglobulin to RhD negative pregnant women with an RhD negative fetus.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • DNA / analysis*
  • Feasibility Studies
  • Female
  • Fetal Blood / chemistry
  • Fetal Diseases / genetics*
  • Genetic Techniques / standards
  • Genotype
  • Gestational Age
  • Humans
  • Phenotype
  • Pregnancy
  • Prospective Studies
  • Rh Isoimmunization / genetics*
  • Rho(D) Immune Globulin / genetics*
  • Sensitivity and Specificity
  • Unnecessary Procedures


  • Rho(D) Immune Globulin
  • DNA