A new breakthrough study has reported the development of a simple, non-invasive, prenatal blood test based on the multiplex ligation-dependent probe amplification (MLPA) technique, which could help in the accurate detection of chromosomal aberrations in the developing fetus, and thereby avoid the risk of miscarriage associated with conventional invasive techniques such as chorionic villus sampling and amniocentesis. The findings of the study were also presented recently at the 26th annual meeting of the European Society of Human Reproduction and Embryology (ESHRE), held at Rome from 27th-30th June, 2010.
A kit based on the MLPA technique is currently employed for detecting chromosomal abnormalities in chorionic villi and amniotic fluid samples of pregnant women. The test being cheaper and faster, delivers results within 24-48 hours. However, the usefulness of the MLPA technique in detecting chromosomal abnormalities in the maternal blood samples containing cell-free fetal DNA was not known.
In the current study, Suzanna Frints, Clinical Geneticist, Maastricht University Medical Centre, Netherlands, and co-workers, evaluated the use of MLPA technique in detecting fetal DNA in the blood samples of women, pregnant for at least six to eight weeks. Subjects with a high abnormal pregnancy risk, undergoing prenatal screening and invasive diagnostic procedures were recruited and divided into four groups:
• Group A: Fourteen women who experienced pregnancy termination amid 14-22 gestation weeks due to trisomy 13, 18 or 21, as identified by invasive prenatal diagnosis
• Group B: Four women subjected to non-invasive prenatal screening at 12-14 weeks gestation
• Group C: Three women subjected to invasive prenatal diagnosis as they were of ≥36 years of age
• Group D: Nine non-pregnant women (control) with ≤3 children
The researchers compared MLPA test results with chorionic villus sampling, amniocentesis, and pregnancy outcome. It was noted that all the samples except one correlated with the non-invasive MLPA test results. The study was successfully used to detect the risk of inheriting X-linked disorders such as hemophilia and Duchenne’s muscular dystrophy by the identification of DNA from the Y chromosome. The researchers are hoping that the test could also aid in detecting trisomy 21 (Down’s syndrome), 18 (Patau syndrome), and 13 (Edward’s syndrome). The study concluded that the results were promising and the reliability of the test was approximately 80% owing to false negative results. Initiated in 2009, the trial is expected to extend to 2012 or further.
Conventional prenatal genetic screening procedures, such as amniocentesis, chorionic villus sampling, and umbilical blood sampling, being invasive, could pose a risk to the fetus or/and rarely the mother. The procedures are also reported to be associated with complications such as bleeding, infection, cramping, amniotic fluid leakage, apart from the risk of fetal loss. The research on the MLPA-based maternal blood test could result in a reliable, non-invasive prenatal genetic screening technique, and eliminate such risks associated with the conventional techniques.
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