Noninvasive Fetal RhD Blood Group Genotyping: A Systematic Review of Economic Evaluations

J Obstet Gynaecol Can. 2021 Dec;43(12):1416-1425.e5. doi: 10.1016/j.jogc.2021.07.014. Epub 2021 Aug 11.


Objective: Noninvasive fetal rhesus D (RhD) blood group genotyping may prevent unnecessary use of anti-D immunoglobulin (RhIG) in non-alloimmunized RhD-negative pregnancies and can guide management of alloimmunized pregnancies. We conducted a systematic review of the economic literature to determine the cost-effectiveness of this intervention over usual care.

Data sources: Systematic literature searches of bibliographic databases (Ovid MEDLINE, Embase, and Cochrane) until February 26, 2019, and auto-alerts until October 30, 2020, and of grey literature sources were performed to retrieve all English-language studies.

Study selection: We included studies done in serologically confirmed non-alloimmunized or alloimmunized RhD-negative pregnancies, comparing costs and effectiveness of the intervention versus usual care.

Data extraction and synthesis: Two reviewers extracted data from the eligible studies and assessed their methodological quality (risk of bias) using the Quality of Health Economic Studies (QHES) and Drummond tools. We narratively synthesized findings. Our review included 8 economic studies that evaluated non-invasive fetal RhD genotyping followed by targeted RhIG prophylaxis in non-alloimmunized pregnancies. Five studies further considered a subsequent alloimmunized pregnancy. The cost-effectiveness of the intervention versus usual care (e.g., universal RhIG or prophylaxis conditional on results of paternal testing) for non-alloiummunized pregnancies was inconsistent. Two studies indicated greater benefits and lower costs for the intervention, and another 2 suggested a trade-off. In 4 studies, the intervention was less effective and costlier than alternatives. Three studies were determined to be of high quality by both tools. Two of these studies favoured the intervention, and one assessed benefits in quality-adjusted life-years. No study clearly examined the cost-effectiveness of repetitive use of fetal genotyping in multiple non-alloimmunized or alloimmunized pregnancies. The cost of genotyping was the most influential parameter.

Conclusion: The cost-effectiveness of noninvasive fetal RhD genotyping for non-alloimmunized pregnancies varies between studies. Potential savings from targeted management of alloimmunized pregnancies requires further research.

Keywords: Rh isoimmunization; Rh-Hr blood-group system; blood group incompatibility; cost-benefit analysis; genetic testing; noninvasive prenatal testing; systematic review.

Publication types

  • Review
  • Systematic Review

MeSH terms

  • Cost-Benefit Analysis
  • Female
  • Fetal Blood
  • Genotype
  • Humans
  • Pregnancy
  • Prenatal Diagnosis
  • Rh Isoimmunization* / prevention & control
  • Rh-Hr Blood-Group System / genetics


  • Rh-Hr Blood-Group System