Prenatal blood test increases accuracy - reduces risk

A simple, accurate and low risk blood test can now detect the fetal blood group, sex, and genetic conditions of an unborn baby more accurately and with less risk than ever before.

The new test can be carried out on mothers at risk for X-linked genetic recessive diseases including haemophilia and Duchenne muscular dystrophy; also, for a special group of mothers at risk of having an immune response (Haemolytic Disease of the Newborn - HDN) to their own fetus or new-born.

Hemolytic disease of the fetus or newborn is a condition which develops when IgG molecules produced by the mother pass through the placenta and attack and destroy red blood cells in the fetus or newborn. This disease ranges from mild to severe, fetal death can occur.

With the new test, blood taken from the mother at her first appointment and early in pregnancy — can detect potentially damaging and even life threatening disorders before damage occurs.

The research represents a collaboration between Plymouth Hospitals National Health Service Trust and Plymouth University, United Kingdom. The DNA test is non-invasive - as opposed to traditional amniocentesis - involving only a needle stick. The research is published in the international scientific journal, Clinical Chemistry.

"Although fetal blood grouping and sexing using maternal blood has been done for over a decade, this research proves a much more accurate and sensitive method of detecting fetal DNA. This offers great opportunities to detect other conditions using this technique, but is much cheaper than current non-invasive methods. The end is now in sight for the invasive techniques of amniocentesis and chorionic villus sampling."

"It is important to emphasise that the objective of such a test is to contribute to clinical management - in such testing strategies termination never a consideration."

Neil Avent PhD, Professor, Plymouth University School of Biomedical and Healthcare Sciences, United Kingdom; lead corresponding author of the study.

Dr Ross Welch, a consultant in fetomaternal medicine at Plymouth Hospitals NHS Trust added: "Doing a test is an option for people continuing with a pregnancy as they have the right to know what is ahead. It is of course correct that the test should not only be effective but also delivered at low risk to the health of both mother and child."

Abstract
Background: Noninvasive genotyping of fetal RHD (Rh blood group, D antigen) can prevent the unnecessary administration of prophylactic anti-D to women carrying RHD-negative fetuses. We evaluated laboratory methods for such genotyping.

Methods: Blood samples were collected in EDTA tubes and Streck® Cell-Free DNA™ blood collection tubes (Streck BCTs) from RHD-negative women (n = 46). Using Y-specific and RHD-specific targets, we investigated variation in the cell-free fetal DNA (cffDNA) fraction and determined the sensitivity achieved for optimal and suboptimal samples with a novel Droplet Digital™ PCR (dPCR) platform compared with real-time quantitative PCR (qPCR).

Results: The cffDNA fraction was significantly larger for samples collected in Streck BCTs compared with samples collected in EDTA tubes (P < 0.001). In samples expressing optimal cffDNA fractions (≥4%), both qPCR and digital PCR (dPCR) showed 100% sensitivity for the TSPY1 (testis-specific protein, Y-linked 1) and RHD7 assays. Although dPCR also had 100% sensitivity for RHD5, qPCR had reduced sensitivity (83%) for this target. For samples expressing suboptimal cffDNA fractions (<2%), dPCR achieved 100% sensitivity for all assays, whereas qPCR achieved 100% sensitivity only for the TSPY1 (multicopy target) assay.

Conclusions: qPCR was not found to be an effective tool for RHD genotyping in suboptimal samples (<2% cffDNA). However, when testing the same suboptimal samples on the same day by dPCR, 100% sensitivity was achieved for both fetal sex determination and RHD genotyping. Use of dPCR for identification of fetal specific markers can reduce the occurrence of false-negative and inconclusive results, particularly when samples express high levels of background maternal cell-free DNA.

The study was sponsored by the Trust and organisations involved were Plymouth University School of Biomedical and Healthcare Science; Plymouth University Peninsula Schools of Medicine and Dentistry and the Department of Fetal Medicine, Plymouth Hospital NHS Trust.

'Fetal sex and RHD genotyping using droplet digital PCR demonstrates greater sensitivity compared to real-time PCR'
Clinical Chemistry
DOI: 10.1373/clinchem.2015.239137

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Nov 12, 2015   Fetal Timeline   Maternal Timeline   News   News Archive   

Pregnancies at risk of HDN are those in which an Rh D-negative mother becomes pregnant with an RhD-positive child (the child having inherited the D antigen from the father). But HDN can also be caused by an incompatibility of the ABO blood group. It arises when a mother with blood type O becomes pregnant with a fetus with a different blood type (type A, B, or AB).

Image Credit from video: Hemolytic disease of the newborn