
UPDATED MODELING PARAMETERS FOR
DOWN’S SYNDROME SCREENING
Cuckle HS* *Corresponding Author: Professor Howard S. Cuckle, Reproductive Epidemiology, University of Leeds, 3 Gemini Park, Sheepscar Way, Leeds LS7 3JB, North Yorkshire, UK; Tel.: +44-113-284-9230; Fax: +44-113-262-1658; E-mail: h.s.cuckle@leeds.ac.uk page: 101
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INTRODUCTION
Routine antenatal screening for Down’s syndrome (DS) is now capable of detecting nine out of 10 cases. In order to achieve this level of performance, multiple maternal serum and ultrasound markers are determined. Multivariate Gaussian modeling techniques are used to convert information on the marker profile, maternal age and family history into a risk factor, and the result is considered positive if the risk exceeds a fixed cut-off. The precision and accuracy of the risk estimate is dependent on the modeling parameters: means, standard deviations (SD) and correlation coefficients (R-values).
Risk is most imprecise when the parameters are derived from a single series as the number of DS cases will be relatively small. And it is inaccurate when the there are local factors such as ethnic distribution, assay precision and gestational accuracy which differ from those in the population used to derive the parameters. The best approach is to use: 1) a meta-analysis of all the published results on DS pregnancies to estimate the DS means; 2) the local screened population to estimate the SDs and R-values in unaffected pregnancies, and 3) a meta-analysis to estimate the difference in variance and covariance between DS and unaffected pregnancies, which are added to the unaffected estimates to derive DS SDs and R-values. This has been done for first trimester maternal serum pregnancy associated plasma protein (PAPP)-A, free-β human chorionic gonadotrophin (hCG), β-fetoprotein (AFP) and unconjugated estriol (uE3) [1], and second trimester hCG, free-β hCG, AFP and uE3 [2]. In this paper the method is extended to second trimester inhibin, combining first trimester PAPP-A with second trimester markers, and ultrasound first trimester nuchal translucency (NT) and second trimester nuchal skin-fold (NF). The existing and updated meta-analysis parameters are used to predict screening performance for policies using inhibin, NT, NF or PAPP-A together with second trimester serum.
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