Expanded fetal RhD testing could improve safety for patients

Improved testing accuracy lowers the chance of missed RhD incompatibility, protecting families from severe fetal anemia and emergency interventions.

Pregnancy care improves when fetal RhD genotyping is accurate because it directly affects the risk of hemolytic disease of the fetus and newborn (HDFN), a condition that can cause mild to life-threatening anemia in an RhD positive fetus, according to a review published recently in Transfusion and Apheresis Science.

The testing helps determine which RhD negative pregnant women are actually carrying RhD positive fetuses and therefore need careful monitoring or preventive treatment. Patients benefit through fewer unnecessary procedures, earlier identification of serious complications and more personalized care throughout pregnancy.

“Fetal RHD genotyping, as an integrated part of maternity care for non-alloimmunized RhD negative pregnant women, is implemented nationwide in several countries,” explained this review’s author.

This approach supports targeted routine antenatal anti-D prophylaxis, in which anti-D immunoglobulin is given only to those carrying an RhD positive fetus. 

When paired with postpartum prophylaxis, this strategy has cut the rate of D-alloimmunization in half. Still, some RhD negative pregnant women form immune anti-D despite these programs, so accurate genotyping remains essential.

Read more about testing and diagnosis for HDFN

For women who already have alloanti-D, accurate fetal RhD genotyping is equally critical. If the fetus is RhD positive, the pregnancy requires close oversight to prevent HDFN. Without early detection and tight monitoring, severe fetal anemia can occur and may become fatal if untreated. 

These patients undergo blood testing in specialized immunohematology or transfusion medicine laboratories and receive frequent evaluations by obstetricians or fetal medicine experts. Doppler ultrasound is used to detect fluid buildup or signs of anemia by measuring blood flow in the middle cerebral artery.

Health assessments and cost-effectiveness studies show that fetal RHD genotyping benefits both non-alloimmunized and D-alloimmunized RhD negative women. When the fetus is RhD negative, families can avoid unnecessary worry, testing and treatment. When the fetus is RhD positive, early and accurate results support safer and more focused monitoring.

Most laboratories performing this testing rely on the same assays used for routine screening, although about 21 percent include a fetal marker. Because false negatives could place an RhD positive fetus at risk of severe HDFN, some experts argue that fetal markers should become standard. Their use may further lower the chance of missing a pregnancy that needs heightened surveillance.

In one validated approach, testing begins at 18 weeks of pregnancy with repeat testing at 24 weeks if the first result is negative. This process helps rule out technical issues or low cell-free fetal DNA levels. As evidence grows, laboratories and clinicians continue to refine these methods to protect mothers and newborns and provide the safest path through pregnancy.

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