Researchers in China have adapted a noninvasive prenatal blood test to more accurately predict a baby’s RhD blood type in Chinese and other East Asian populations, according to a study recently published in BMC Medical Genomics.
This is an advance aimed at improving prevention of hemolytic disease of the fetus and newborn (HDFN).
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For years, RhD-negative mothers routinely received preventive injections of a medication called anti-D immunoglobulinIntravenous immunoglobulin A therapy made from donated antibodies that may help reduce the mother’s immune response and protect the fetus. as a safeguard. The ability to determine the baby’s blood type from a sample of the mother’s blood during pregnancy changed that, allowing doctors to skip the injection when the baby is also RhD-negative and it serves no purpose.
The researchers noted that this widely used test performs less reliably in East Asian patients and proposes a way to address that gap. The test reads cell-free DNA, tiny fragments of the baby’s DNA that circulate in the mother’s blood. Its design is better suited to people of European descent, in whom RhD-negative status almost always has the same genetic cause: the RHD gene is completely deleted from the chromosome. With no gene present in the mother, any RHD signal in her blood must come from the baby—a clean read.
Chinese and other East Asian populations more often carry variants in which the gene is not fully gone. In these cases, the gene may be present but inactive, or largely intact while producing only trace amounts of the RhD protein. Because the gene is still detectable, a standard test can mistake the mother’s own DNA for the baby’s, producing a false positive.
Read more about HDFN causes and risk factors
To evaluate their refined version, the team used residual blood from pregnant women who had undergone routine prenatal screening at 12 weeks or later. They extracted DNA from four donors carrying the key variants and cut it into fragments the size of naturally circulating cell-free DNA. They then blended in small, set amounts of fetal-type DNA — 5%, 20% and 40% of the mixture — to recreate the blend of maternal and fetal DNA found in a real pregnancy sample and to test the method’s accuracy under a range of conditions.
Across every simulated maternal background, the adapted test correctly identified the baby’s RhD status, even when fetal DNA made up as little as 5% of the sample.
The researchers concluded that reading several regions of the RHD gene lets the test work reliably “without reliance on prior maternal RHD genotyping” — meaning it can assess the baby’s blood type without first mapping the mother’s genes. They noted, however, that this was a small study, and described it as a foundation for future large-scale clinical validation.
