Analysis of cell‐free fetal DNA in maternal blood for detection of trisomy 21, 18 and 13 in a general pregnant population and in a high risk population – a systematic review and meta‐analysis

Erik Iwarsson, Bo Jacobsson, Jessica Dagerhamn, Thomas Davidson, Eduardo Bernabé, Marianne Heibert Arnlind

To review the performance of non-invasive prenatal testing (NIPT) for detection of trisomy 21, 18 and 13 (T21, T18 and T13) in a general pregnant population as well as to update the data on high-risk pregnancies. Systematic Review and Meta-Analysis. PubMed, Embase and the Cochrane Library were searched. Methodological quality was rated using QUADAS and scientific evidence using GRADE. Summary measures of diagnostic accuracy were calculated using a bivariate random-effects model. In a general pregnant population, there is moderate evidence that the pooled sensitivity is 0.993 (95% 0.955 to 0.999) and specificity was 0.999 (95% 0.998 to 0.999) for the analysis of T21. Pooled sensitivity and specificity for T13 and T18 was not calculated in this population due to the low number of studies. In a high-risk pregnant population, there is moderate evidence that the pooled sensitivities for T21 and T18 are 0.998 (95% CI 0.981 to 0.999) and 0.977 (95% CI 0.958 to 0.987) respectively, and low evidence that the pooled sensitivity for T13 is 0.975 (95% CI 0.819 to 0.997). The pooled specificity for all three trisomies is 0.999 (95% 0.998 to 0.999). This is the first meta-analysis using GRADE that shows that NIPT performs well as a screen for trisomy 21 in a general pregnant population. Although the false positive rate is low compared to First Trimester Combined Screening, women should still be advised to confirm a positive result by invasive testing if termination of pregnancy is under consideration. This article is protected by copyright. All rights reserved.