, Volume 287, Issue 3, pp 413-420
Date: 19 Oct 2012

Analysis of the impact of PAPP-A, free β-hCG and nuchal translucency thickness on the advanced first trimester screening

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The intention of this study is to analyze the impact of the single parameters NT, PAPP-A and free β-hCG used in combined first trimester screening and to determine their contribution in the risk assessment.


A retrospective risk assessment on the advanced first trimester screening (AFS) algorithm was made to determine the effect of a particular parameter while the remaining ones were fixed for calculation. Afterward data were recalculated by the AFS module. Test performance was measured by receiver operating characteristics (ROC) curves and their area under curve (AUC).


Among the 14,862 cases are 14,748 healthy fetuses, 86 with trisomy 21, 22 with trisomy 18 and 6 with trisomy 13. Some settings obtain at default cut-off a very high sensitivity. However, a lack of specificity, as a high false-positive rate, too. The ROC analysis was best for NT, followed by PAPP-A. Free β-hCG showed the lowest AUC. Combining PAPP-A and free β-hCG offered a better AUC than each parameter alone. Best test performance was obtained by including all three parameters.


A detection rate of 69 % for testing NT discretely is in order with present study data. PAPP-A is following and free β-hCG is not useful with a test positive rate of about a third. The detection rate of the biochemical parameters combined is higher than for NT alone, but results in a five times higher punctuation rate. All parameters together in the AFS provide the best test performance. The impact of each parameter NT, PAPP-A and free-β-hCG in a combined test strategy is nearly a third. Thus, every single parameter is needed to provide a high detection rate for all of the trisomies and minimize the number of unnecessary invasive diagnostics.

An erratum to this article can be found at http://dx.doi.org/10.1007/s00404-013-2907-8.