Diagnostic accuracy of non-invasive fetal RhD genotyping using cell-free fetal DNA: a meta analysis

Abstract

Objective: To determine the diagnostic accuracy, validity, current limitations of, and possible solutions to, fetal RhD genotyping from maternal blood based on existing studies written in English.

Methods: A literature search was conducted that described fetal RhD determination from maternal blood. The number of samples tested, fetal RhD genotype, the source of cell-free fetal DNA, gestational age and fetal Rh type were examined in each study to calculate the accuracy, sensitivity and specificity of fetal RhD genotyping.

Results: Forty-one publications, which included 11?129 samples with non-invasive Rh genotyping of cell-free fetal DNA from maternal blood, were selected. After the exclusion of 352 inconclusive samples, the overall diagnostic accuracy was 98.5% (10?611/10?777), and sensitivity and specificity were 99% and 98%, respectively. First trimester diagnosis showed an accuracy of 99%, higher than second and third trimester diagnosis. Thirty studies reported a 100% diagnostic accuracy of fetal RhD genotyping.

Conclusion: Non-invasive fetal RhD genotyping from maternal blood has high accuracy, sensitivity and specificity. Methods reducing false results have been explored and applied in research. These achievements indicate that this technique will be widely used in routine clinical care.