Novel perspectives in fetal biomarker implementation for the noninvasive prenatal testing

Abstract

Noninvasive prenatal testing (NIPT) utilizes cell-free fetal DNA (cffDNA) present in maternal peripheral blood to detect chromosomal abnormalities. The detection of 21-trisomy, 18-trisomy, and 13-trisomy in the fetus has become a common screening method during pregnancy and has been widely applied in routine clinical testing because of its analytical and clinical validity. Currently, noninvasive prenatal testing involving copy number variations (CNVs) and other frequent single-gene disorders is being widely studied, and it plays an important and indispensable role in prenatal detection. The multiple approaches that have been reported and validated by various laboratories have different merits and limitations. Their clinical validity, utility, and application vary with different diseases. This review summarizes the principles, methods, advantages, and limitations of noninvasive prenatal testing for the detection of aneuploidy, CNVs and single-gene disorders. Before implementation of NIPT into clinical practice, a list of criteria that the application must meet is crucial. Essential parameters such as clinical sensitivity, clinical specificity, positive predictive value (PPV) and negative predictive value (NPV) are required to properly evaluate the clinical validity and utility of NIPT. We then discuss and analyze these clinical parameters and clinical application guidelines, providing physicians and scientists with feasible strategies and the latest research information.

Keywords:

• cffDNA
• noninvasive prenatal testing
• aneuploidy
• copy number variation
• single-gene disorder

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by grants from National Natural Science Foundation of China (Grant 81871721), the Nonprofit Central Research Institute Fund of Chinese Academy of Medical Sciences (2018RC320014), the Ten-Thousand Talents Program of China, and the Seed Fund for Jinqiao project from Beijing Association for Science and Technology (JQ18039).