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  3. Diagnostic accuracy of routine antenatal determination of fetal RHD status across gestation: population based cohort study
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Research

Diagnostic accuracy of routine antenatal determination of fetal RHD status across gestation: population based cohort study

BMJ 2014; 349 doi: https://doi.org/10.1136/bmj.g5243 (Published 04 September 2014) Cite this as: BMJ 2014;349:g5243
  1. Lyn S Chitty, professor1,
  2. Kirstin Finning, clinical scientist2,
  3. Angela Wade, senior lecturer3,
  4. Peter Soothill, professor4,
  5. Bill Martin, consultant obstetrician5,
  6. Kerry Oxenford, research midwife6,
  7. Geoff Daniels, consultant clinical scientist 2,
  8. Edwin Massey, associate medical director2
  1. 1UCL Institute of Child Health, Great Ormond Street Hospital for Children NHS Foundation Trust and University College London Hospitals NHS Foundation Trust, London WC1N 3BH, UK
  2. 2International Blood Group Reference Laboratory, NHS Blood and Transplant, Bristol BS34 7QH, UK Kirstin Finning
  3. 3Centre for Paediatric Epidemiology and Biostatistics, UCL Institute of Child Health, London WC1N 1EH, UK
  4. 4Fetal Medicine Unit, St Michael’s Hospital, Bristol BS2 8EG, UK
  5. 5Fetal Medicine Unit, Birmingham Women’s NHS Foundation Trust, Birmingham B15 2TG, UK
  6. 6Fetal Medicine Unit, University College London Hospitals NHS Foundation Trust, London NW1 2BU, UK
  1. Correspondence to: L S Chitty l.chitty{at}ucl.ac.uk
  • Accepted 13 August 2014

Abstract

Objectives To assess the accuracy of fetal RHD genotyping using cell-free fetal DNA in maternal plasma at different gestational ages.

Design A prospective multicentre cohort study.

Setting Seven maternity units in England.

Participants RhD negative pregnant women who booked for antenatal care before 24 weeks’ gestation.

Interventions Women who gave consent for fetal RHD genotyping had blood taken at the time of booking for antenatal care and, when possible, at other routine visits such as for Down’s syndrome screening between 11 and 21 weeks’ gestation, at the anomaly scan at 18-21 weeks, and in the third trimester when blood was taken for the routine antibody check. The results of cord blood analysis, done routinely in RhD negative pregnancies, were also obtained to confirm the fetal RHD genotyping.

Main outcome measures The accuracy of fetal RHD genotyping compared with RhD status predicted by cord blood serology.

Results Up to four analyses per woman were performed in 2288 women, generating 4913 assessable fetal results. Sensitivity for detection of fetal RHD positivity was 96.85% (94.95% to 98.05%), 99.83% (99.06% to 99.97%), 99.67% (98.17% to 99.94%), 99.82% (98.96% to 99.97%), and 100% (99.59% to 100%) at <11, 11-13, 14-17, 18-23, and >23 completed weeks’ gestation, respectively. Before 11 weeks’ gestation 16/865 (1.85%) babies tested were falsely predicted as RHD negative.

Conclusions Mass throughput fetal RHD genotyping is sufficiently accurate for the prediction of RhD type if it is performed from 11 weeks’ gestation. Testing before this time could result in a small but significant number of babies being incorrectly classified as RHD negative. These mothers would not receive anti-RhD immunoglobulin, and there would be a risk of haemolytic disease of the newborn in subsequent pregnancies.

Footnotes

  • We acknowledge the assistance of Rekha Anand, NHS Blood and Transplant, Birmingham, UK; and the research midwives and medical and laboratory staff at Birmingham Women’s NHS Foundation Trust Hospital; St Michael’s Hospital Bristol, North Bristol Trust, Bristol; University College London Hospitals NHS Foundation Trust; Royal Victoria Hospital, Newcastle upon Tyne; and City Hospitals Sunderland NHS Foundation Trust.

  • Contributors: LSC, GD, KF, EM, AW, and PS designed the study; LSC, EM, and GD carried out the literature search; AW created the figures; KF, PS, BM, and KO collected the data; AW analysed the data; LSC, GD, KF, EM, and AW interpreted the data; LSC, EM, GD, and AW wrote the paper, which was revised by all authors. LSC is guarantor.

  • Funding: This study was funded by the National Institute for Health Research, Research for Patient Benefit Programme (PB-PG-0107-12005), and Howard Ostin Trust (Project No 011). LSC is partially funded by the Great Ormond Street Hospital Children’s Charity and the NIHR Biomedical Research Centre at Great Ormond Street Hospital. The funded research is independent and the views expressed in the paper are those of the authors and not necessarily those of the NHS, the NIHR, or the Department of Health.

  • Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.

  • Ethical approval: The study was approved by the joint UCL/UCLH committee on the ethics of human research (committee A) of the National Research Ethics Service (07/H0714/128).

  • Transparency: The lead author affirms that the manuscript is an honest, accurate, and transparent account of the study being reported and that no important aspects of the study have been omitted.

  • Data sharing: No additional data are available.

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 3.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/3.0/.

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