Detection of trisomy 18 and trisomy 13 using first and second trimester Down's syndrome screening markers

Abstract

Objective To estimate the detection rates (DRs) and false-positive rates (FPRs) in the incidental identification of trisomy 18 (T18) and trisomy 13 (T13) as part of antenatal screening for Down's syndrome (DS) using the Combined, Quadruple and Integrated test markers. Methods Screening marker levels on 224 T18 and 67 T13 pregnancies screened for DS were evaluated. Estimated means, standard deviations and correlation coefficients were used with published estimates for unaffected pregnancies to derive detection algorithms for the two disorders. DRs and FPRs of the algorithms were estimated using Monte Carlo simulation. Results In T18 and T13 pregnancies first trimester nuchal translucency was raised, free β-human chorionic gonadotrophin (hCG) and pregnancy associated plasma protein-A reduced. In T18 pregnancies second trimester alphafetoprotein, unconjugated oestriol and free β-hCG were reduced. In T13 pregnancies second trimester inhibin-A was raised. These markers specified T18 and T13 algorithms. The DS Combined test algorithm detected 42% of T18 and 59% of T13 (2.00% FPR); 88% and 74% by adding the T18 Combined test algorithm (2.17% FPR) and 89% and 75% by further adding the T13 Combined test algorithm (2.19% FPR). The corresponding detection rates for the Quadruple test were: 2% and 17% (2.00% FPR), 55% and 17% (2.16% FPR) and 55% and 19% (2.28% FPR), and for the Integrated test were: 40% and 64% (2.00% FPR), 92% and 65% (2.12% FPR) and 92% and 72% (2.18% FPR). Conclusions Antenatal screening for DS detects about 40% of T18 and about 60% of T13 pregnancies. The addition of a T18 algorithm substantially increases the detection of both trisomies with a small increase in the FPR. The further addition of a T13 algorithm results in a small increase in the detection of T13.