Rapid and Non Invasive Prenatal Diagnosis

Prenatal screening and diagnosis are routinely offered at antenatal care clinic visits, and are important in decision making about the continuation of pregnancies affected by genetic conditions for which there are no cures, and prevention through therapeutic abortion is a reasonable option. Prenatal screening is offered to all pregnant women and include fetal ultrasonography and maternal serum biochemistry to select the pregnancies at-risk for chromosomal abnormalities. However, these methods have limited sensitivities (60.0-75.0%) and specificities (false positive rate of 5.0%). Even when used in combination and taking into account maternal age, the identification rate of affected fetuses does not exceed 90.0% [one]. Prenatal diagnosis is usually preformed for detection of chromosomal aneuploidies or monogenic diseases in “high risk” pregnancies. Diagnostic testing currently requires a sample of fetal cells obtained either by chorionic villus sampling (CVS) between 10 and 14 weeks gestation or by amniocentesis after 15 weeks of gestation. However, these invasive procedures carry a risk of miscarriage of around 1.0% [2]. Prenatal Diagnosis of Chromosomal Abnormalities. Chromosomal abnormalities (numerical or structural) occur in 1 of 160 live births, with extra copies of chromosomes 21, 18, and 13 accounting for the majority of numerical alterations that are not related to sex chromosomes. The prevalence of trisomies is highest in the first trimester because of subsequent miscarriage and demise of aneuploid conceptuses during pregnancy [3]. Conventional cytogenetic techniques (karyotyping) are usually used to detect aneuploidies and large (510 Mb) rearrangements in fetal cells (amniocytes, trophoblasts), however, these are time-consuming (2-3 weeks), subjective (small rearrangements) and expensive. The development of molecular methods for the rapid, targeted detection of aneuploidies of chromosomes 13, 18, 21 and the sex chromosomes by quantitative fluorescent polymerase chain reaction (QF-PCR) [4,5] using fetal DNA, do not provide a genome-wide screen for unexpected imbalances, but are rapid (24-48 hours), accurate and inexpensive. Multiplex ligation probe amplification (MLPA) is a recent technique for relative quantitaRAPID AND NON INVASIVE PRENATAL DIAGNOSIS