title: Diagnostic accuracy of routine antenatal determination of fetal RHD status across gestation: population based cohort study.
abstract: OBJECTIVE
  To assess the accuracy of fetal RHD genotyping using cell-free fetal DNA in maternal plasma at different gestational ages.
  
  
  METHODS
  A prospective multicentre cohort study.
  
  
  METHODS
  Seven maternity units in England.
  
  
  METHODS
  RhD negative pregnant women who booked for antenatal care before 24 weeks' gestation.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
authors.affiliation: UCL 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 l.chitty@ucl.ac.uk.
authors.forename: Lyn S
authors.initials: LS
authors.lastname: Chitty
authors.affiliation: International Blood Group Reference Laboratory, NHS Blood and Transplant, Bristol BS34 7QH, UK Kirstin Finning.
authors.forename: Kirstin
authors.initials: K
authors.lastname: Finning
authors.affiliation: Centre for Paediatric Epidemiology and Biostatistics, UCL Institute of Child Health, London WC1N 1EH, UK.
authors.forename: Angela
authors.initials: A
authors.lastname: Wade
authors.affiliation: Fetal Medicine Unit, St Michael's Hospital, Bristol BS2 8EG, UK.
authors.forename: Peter
authors.initials: P
authors.lastname: Soothill
authors.affiliation: Fetal Medicine Unit, Birmingham Women's NHS Foundation Trust, Birmingham B15 2TG, UK.
authors.forename: Bill
authors.initials: B
authors.lastname: Martin
authors.affiliation: Fetal Medicine Unit, University College London Hospitals NHS Foundation Trust, London NW1 2BU, UK.
authors.forename: Kerry
authors.initials: K
authors.lastname: Oxenford
authors.affiliation: International Blood Group Reference Laboratory, NHS Blood and Transplant, Bristol BS34 7QH, UK Kirstin Finning.
authors.forename: Geoff
authors.initials: G
authors.lastname: Daniels
authors.affiliation: International Blood Group Reference Laboratory, NHS Blood and Transplant, Bristol BS34 7QH, UK Kirstin Finning.
authors.forename: Edwin
authors.initials: E
authors.lastname: Massey
mesh_terms: D004247:DNA / Q000032:analysis* / Q000097:blood; D004899:Erythroblastosis, Fetal / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology; D005188:False Negative Reactions; D005189:False Positive Reactions; D005260:Female; D005312:Fetal Blood / Q000276:immunology*; D005838:Genotype; D005865:Gestational Age; D006801:Humans; D011247:Pregnancy; D011264:Pregnancy Trimesters; D011296:Prenatal Diagnosis; D011446:Prospective Studies; D012204:Rh-Hr Blood-Group System / Q000235:genetics*; D012680:Sensitivity and Specificity
chemical_list: D012204:Rh-Hr Blood-Group System; C026410:Rho(D) antigen; D004247:DNA