Researchers have developed a new method to identify pregnancies at risk of fetal and neonatal alloimmune thrombocytopenia (FNAIT) by simultaneously determining fetal human platelet antigen status and markers of fetal DNA. Findings were recently published in Blood Transfusion.
What is FNAIT?
Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a rare but serious condition that affects 0.1% of pregnancies in which a pregnant mother’s immune system produces antibodies against the platelets of her fetus. This occurs when a fetus inherits platelet antigens from the father that are not compatible with the mother, typically involving a protein called human platelet antigen (HPA). The mother’s immune system recognizes the fetal platelets as foreign, attacking and destroying them, leading to low platelet levels (thrombocytopenia) in the fetus or newborn.
A variety of tests are available to ascertain fetal human platelet antigen (HPA) genotype from maternal blood samples, which can be used to identify mismatches that could lead to FNAIT. With these tools, only one marker is typically used to identify the presence of fetal DNA. Additionally, these methods carry limitations that can make them both time- and cost-intensive.
In their study, the authors sought to use an advanced form of genetic testing to detect a variety of genetic signals, called single-nucleotide variants (SNVs), to more accurately quantify the presence of fetal DNA. At the same time, the method was able to determine the type of HPA present in the fetus.
Read more about FNAIT testing and diagnosis
The tool could detect eight different HPA systems, including HPA-1, -2, -3, -4, -5, -6, -9 and 15, as well as 48 unique SNVs.
A total of 81 blood samples were collected from 67 pregnant women between 10 and 40 weeks gestation. In order to evaluate the accuracy of their technique, the authors also collected samples from the infants after birth to confirm HPA genotype.
The SNV panel proved useful for determining the amount of fetal DNA present in each sample. The percentage ranged from 1.1% to 16.1%, and generally increased with gestational age.
“In our hands, the technical time — for 1 to 16 samples in the same assay — is about 10 hours, including DNA extraction, preparation of the library, sequencing and analysis,” the authors added.
The method was not only quick, but also accurate: of the 81 samples, fetal HPA genotype was correctly determined in 80 cases. The remaining sample had a low percentage of fetal DNA, as shown by SNV marker analysis, which resulted in a false negative.
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