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

doi:10.1136/bmj.39518.463206.25

BMJ, doi: 10.1136/bmj.39518.463206.25, (Published 3 April 2008)

Research

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

Kirstin Finning, clinical scientist¹, Pete Martin, clinical scientist¹, Joanna Summers, biomedical scientist¹, Edwin Massey, consultant haematologist¹, Geoff Poole, head of red cell immunohaematology², Geoff Daniels, head of molecular diagnostics¹

¹ International Blood Group Reference Laboratory, NHS Blood and Transplant, Bristol BS10 5ND, ² NHS Blood and Transplant, Bristol

Correspondence to: G Daniels geoff.daniels{at}nbs.nhs.uk

Objectives To assess the feasibility of applying a high throughputmethod, with an automated robotic technique, for predictingfetal RhD phenotype from fetal DNA in the plasma of RhD negativepregnant women to avoid unnecessary treatment with anti-RhDimmunoglobulin.

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

Setting Antenatal clinics and antenatal testing laboratoriesin the Midlands and north of England and an international bloodgroup reference laboratory.

Participants Pregnant women of known gestation identified asRhD negative by an antenatal testing laboratory. Samples from1997 women were taken at or before the 28 week antenatal visit.

Main outcome measures Detection rate of fetal RhD from maternalplasma, error rate, false positive rate, and the odds of beingaffected given a positive result.

Results Serologically determined RhD phenotypes were obtainedfrom 1869 cord blood samples. In 95.7% (n=1788) the correctfetal RhD phenotype was predicted by the genotyping tests. In3.4% (n=64) results were either unobtainable or inconclusive.A false positive result was obtained in 0.8% (14 samples), probablybecause 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, only2% of the women would have received anti-RhD unnecessarily,compared with 38% without the genotyping.

Conclusions High throughput RHD genotyping of fetuses in allRhD negative women is feasible and would substantially reduceunnecessary administration of anti-RhD immunoglobulin to RhDnegative pregnant women with an RhD negative fetus.

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Rapid Responses:

Read all Rapid Responses

Universal Fetal Genotyping of RHD Negative Pregnancies� How Cost-Effective?: Ala Szczepura, et al.
bmj.com, 17 Apr 2008 [Full text]
Universal Fetal RHD Genotyping of RhD-negative Pregnancies � How Cost Effective?: Geoff Daniels, et al.
bmj.com, 27 Apr 2008 [Full text]