Noninvasive single-exon fetal RHD determination in a routine screening program in early pregnancy

Obstet Gynecol. 2012 Aug;120(2 Pt 1):227-34. doi: 10.1097/AOG.0b013e31825d33d9.


Objective: To develop a simple and robust assay suitable for fetal RHD screening in first-trimester pregnancy and to estimate the sensitivity and specificity of the test after its implementation in an unselected pregnant population.

Methods: Pregnant women attending their first antenatal visit were included, and fetal RHD determination was performed for all women who typed RhD-negative by routine serology. DNA was extracted by an automated system and quantitative polymerase chain reaction was done by an assay based on exon 4. Reporting criteria were simple and strict.

Results: Four thousand one hundred eighteen pregnancies, with a median gestational age of 10 weeks, were included. After 211 (5.1%) reanalyses, fetal RHD was reported positive in 2,401 (58.3%), negative in 1,552 (37.7%), and inconclusive in 165 (4.0%) based on the first sample. After a second sample in 147 of 165, only 14 remained inconclusive, all resulting from a weak or silent maternal RHD gene. Using blood group serology of the newborns as the gold standard, the false-negative rate was 55 of 2,297 (2.4%) and the false-positive rate was 15 of 1,355 (1.1%). After exclusion of samples obtained before gestational week 8, the false-negative rate was 23 of 2,073 (1.1%) and the false-positive rate was 14 of 1,218 (1.1%). Both sensitivity and specificity were close to 99% provided samples were not collected before gestational week 8. From gestational week 22, sensitivity was 100%.

Conclusion: Fetal RHD detection in early pregnancy using a single-exon assay in a routine clinical setting is feasible and accurate.

Level of evidence: I.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Blood Group Incompatibility / diagnosis*
  • Exons
  • Female
  • Humans
  • Infant, Newborn
  • Mass Screening
  • Middle Aged
  • Pregnancy
  • Pregnancy Trimester, First
  • Prospective Studies
  • Rh-Hr Blood-Group System / genetics*
  • Young Adult


  • Rh-Hr Blood-Group System
  • Rho(D) antigen