The Accuracy of Fetal Cell Free DNA in the Assessment of Fetal Karyotype: A Systematic Review of Literature

Cristina Rossi1 and Vincenzo Berghella2

1Clinic of Obstetrics and Gynecology, University of Bari, Bari, Italy; 2Department of Maternal Fetal Medicine, Thomas Jefferson University, Philadelphia, PA, USA


Abstract: Objective: To review literature about the accuracy of non invasive prenatal testing by cell free fetal DNA (NIPT) to detect fetal trisomies (T).

Methods: A search in PubMed, EMBASE, Medline, reference lists was performed (January 2009 – December 2013). Inclusion criteria for study selection: fetal karyotype assessed at birth or by invasive procedures, report of true positive, false positive, true negative, and false negative rates of trisomy 21, 18, 13, and other aneuploidies, data reported as proportional rates. Exclusion criteria: articles aimed to describe genetic procedures, data reported in graphs or percentage. Data abstracted from each article were: sensitivity, specificity, failure rate, demographic characteristics. Pooled sensitivity and specificity and 95% Confidence Interval (95% CI) were calculated by using Der Simonian Laird methods.

Results: From 15 articles, 11,512 women were screened with cfDNA. Sensitivity was 99% (98-100%) for T21, 96% (92-98%) for T18, 86% (71-95%) for T13, and 90% (81-96%) for other aneuploidies. Failure rate of blood analysis was 12% with DANSR and 3% with MPSS technique. Sensitivity for T21 was 99% (98-100%) and 85% (69-94%) following MPSS and DANSR, respectively.

Conclusion: Paucity of data about gestational age at time of NIPT, placental mosaicism, direct comparison between techniques. Fetal cfDNA is an efficacious method to detect fetal T. Further studies are needed to standardize criteria for cfDNA isolation, select population and define the optimal time for NIPT assessment.

Keywords: Aneuploidy, non invasive prenatal testing, karyotype, prenatal diagnosis, prenatal screening, cell free DNA.