Noninvasive Prenatal Testing Using Cell-free DNA in Maternal Circulation

Abstract

Noninvasive prenatal testing (NIPT) is revolutionizing prenatal screening and diagnosis. Through the analysis of cell free DNA in maternal plasma, it is possible to screen for trisomies 21, 18, and 13, sex chromosome aneuploidies, triploidy and some microdeletion syndromes. For aneuploidies the sensitivity and specificity approaches, but does not meet, that of diagnostic testing. It is estimated that the positive predictive value for NIPT for the identification of trisomy 21 is approximately 90 % compared to 4–6 % for conventional prenatal screening tests. Depending on the NIPT technology used, discordancy between NIPT and the true fetal karyotype can be due to low fetal DNA concentration, presence of a maternal chromosome abnormality, undetected vanishing twin, or mosaicism (including apparent confined placental mosaicism). NIPT can be expanded to include additional cytogenetic abnormalities such as other small copy number variations and will be increasingly used for monogenic disorders. The testing poses a number of ethical challenges including potentially increased pregnancy termination rates for affected pregnancies, the detection of milder or late onset disorders, and identification of fetal sex. Developing nations such as India have very high rates of birth defects and advanced molecular genetic technologies such as NIPT are needed to help reduce neonatal morbidity and mortality. It is important that the implementation of the Pre-Conception and Pre-Natal Diagnostic Techniques Act that prohibits disclosure of fetal sex does not prevent access to this extraordinarily powerful new technology that offers substantial benefits to the Indian population.

Keywords

Prenatal - Ultrasound - Screening - Diagnosis - Trisomy 21 - Aneuploidy

Publication History

Received: 30 October 2014

Accepted: 13 November 2014

Article published online:
08 May 2023