Preventing hemolytic disease of the fetus and newborn (HDFN) depends on accurately identifying fetomaternal hemorrhage, according to a review published recently in Frontiers in Physiology.
HDFN stems from blood type incompatibility and can be life-threatening to the infant if not managed early. Timely and reliable testing of fetal red blood cells in maternal blood enables clinicians to administer proper immunoglobulin treatment to protect the baby and may lead to earlier detection, targeted treatment and healthier outcomes for mothers and their babies.
Currently, two main diagnostic methods—the rosette screen test and the Kleihauer-Betke (K-B) acid elution test—are most commonly used to detect fetomaternal hemorrhage. The rosette test is FDA-approved and relatively easy to perform but is limited to detecting RhD-positive fetal cells and can return false results if the mother or fetus has a weak D antigen. The K-B test is more broadly applicable but is highly subjective, labor-intensive, and prone to human error. It requires manually counting thousands of cells within a short timeframe, often amid distracting artifacts on the test slide.
“At present, flow cytometry is a dependable detection technology,” explained the authors of this overview. They continued, “Nevertheless, certain municipal or county hospitals are unable to perform the procedure due to the instrument’s extremely high power consumption. A small instrument is anticipated to be created in order to detect fluorescent markers in subsequent experiments, rather than relying on flow cytometry.”
Read more about HDFN testing and diagnosis
To improve diagnostic accuracy and efficiency, newer technologies are gaining attention. Flow cytometry, for example, can rapidly analyze up to 50,000 red blood cells using anti-fetal hemoglobin antibodies, offering significantly better accuracy and reproducibility than the K-B test. A commercial FDA-approved kit based on this technology is currently in use, providing hope for wider clinical adoption.
Other promising techniques include fluorescence microscopy, which enhances accuracy but remains costly and equipment-intensive, and the microcolumn gel method, which offers semi-quantitative results but with lower sensitivity for detecting small hemorrhages. Gene typing also plays a crucial role by distinguishing between different weak D phenotypes, helping determine whether a pregnant woman should be treated as RhD positive or negative.
Emerging research includes silk membrane-based enzyme-linked immunosorbent assays, which show potential for low-cost, user-friendly, and safe detection. This method uses natural silk’s porous structure to capture fetal red blood cells and could eventually replace manual processes with automated interpretation.
These advances are critical for pregnant patients at risk for HDFN. Better tools mean earlier detection, targeted treatment, and healthier outcomes for mothers and their babies.
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