Prenatal and Pregnancy Loss Evaluation by Noninvasive Screening and Diagnostic Genetic Testing

Noninvasive prenatal testing (NIPT) utilizing cell-free fetal DNA (cffDNA) in the maternal blood is the screening test of choice for physicians today. NIPT depends on the amount of cffDNA in the maternal blood, called the fetal fraction (FF). Researchers are investigating the implications of the FF value in reference to multiple variables in pregnancy outcome, including the risk for aneuploidy and maternal factors that influence the FF. Diagnostic techniques utilized in patient care include cytogenetics, fluorescence in-situ hybridization (FISH), and microarray. Diagnostic testing is critical to confirm or rule out genetic abnormalities among women with abnormal screening results, those with high-risk pregnancies, or in situations of an adverse pregnancy outcome and to define the recurrence risk. Genetic testing has also been commonly utilized to assist in finding reasons for pregnancy loss and support future pregnancy planning. A retrospective analysis of cases with NIPT results, diagnostic procedures in prenatal testing, and the diagnostic genetic testing for pregnancy loss were reviewed. A comprehensive single-institution study demonstrated the pros and cons of the most widely used genetic screening methods. The present study determined that low FF is associated with an adverse pregnancy outcome, the maternal factors associated with low FF, and emphasized the need to redefine the algorithm for the diagnostic testing that must follow the screen in select prenatal cases. We also identified the discrepancies in screening and diagnostic procedures currently used for the various abnormalities. Our data delineated the accurate procedures to determine various abnormalities, identified the genetic abnormalities that are most misdiagnosed by screening, and provided information to facilitate the risk determination in future pregnancies. Further, this study demonstrated the benefit of microarray in pregnancy loss investigations. Together, these studies redefined the need for appropriate diagnostic studies in prenatal and pregnancy loss cases and demonstrated its utilization in risk determination and genetic counseling