Validation of a noninvasive, next-generation sequencing-based cell-free DNA test for fetal RHD, which could help diagnose and treat hemolytic disease of the fetus and newborn (HDFN), demonstrated remarkable accuracy in a large U.S. cohort, according to results from a study published recently in Obstetrics and Gynecology.
This test, with 100% sensitivity and 99.3% specificity, provided a reliable method for identifying fetal RHD genotype in RhD-negative pregnancies starting at nine weeks of gestation. Its implementation could transform the management of RhD alloimmunization, benefiting both patients and clinicians by conserving resources and personalizing care.
“Adoption of prenatal cell-free DNA screening for fetal RHD in the United States has been slow and until recently was not supported by national clinical practice guidelines,” explained the study’s authors.
The study involved 655 RhD-negative pregnant patients, representing a diverse racial and ethnic demographic reflective of the U.S. population. Among these, the test correctly identified all 356 RhD-positive fetuses and 295 out of 297 RhD-negative fetuses. This high degree of accuracy extended to identifying fetal RHD pseudogene (RHDΨ) genotypes in three cases. Only two samples failed to yield results, but the test maintained its performance metrics even under worst-case assumptions.
“This study demonstrates that a commercially available noninvasive prenatal cell-free DNA screening test has high sensitivity and specificity in a diverse U.S. population and has the potential to transform the approach to management of Rh-negative pregnant patients in the United States,” the authors wrote.
This testing method used cell-free DNA extracted from maternal blood, analyzed through advanced sequencing techniques. The median gestational age at testing was 12 weeks, with a fetal fraction as low as 2.8%. Unlike invasive procedures, this approach posed no risk to the fetus and provided early and reliable information about RhD status, enabling timely interventions.
Read more about HDFN causes and risk factors
The clinical implications are significant, as this test could reduce unnecessary administration of RhD immune globulin in up to 40% of RhD-negative pregnancies. Currently, RhD immune globulin is given routinely to RhD-negative pregnant women to prevent sensitization and Rh disease. With the precision of this test, such treatment could be reserved for pregnancies where the fetus is RhD-positive, conserving resources and reducing exposure to unnecessary blood products.
Compared to previous studies, this validation demonstrated the highest levels of sensitivity and specificity in a much larger sample size, ensuring confidence in its clinical utility. Earlier studies using different methods reported slightly lower performance metrics, underscoring the advancements made with this next-generation sequencing-based approach.
