1 Department of Clinical Medicine - Department of clinical biochemistry, Department of Clinical Medicine, Health, Aarhus University2 Studienævnene på HE - Board of Studies, Health Science, Studienævnene på HE, Health, Aarhus University3 Department of Clinical Medicine - Department of clinical biochemistry, Department of Clinical Medicine, Health, Aarhus University
Background Screening for fetal trisomy 21 in the first trimester includes analysis of the serological markers pregnancy-associated plasma protein A (PAPP-A) and free beta human choriogonadotropin (free βhCG). With the recent launch of the PAPP-A free βhCG and assays on the Roche Cobas and Elecsys platforms, we investigated their clinical and analytical performance in samples from gestaional weeks 8+0 to 14+0. Methods. We conducted a multicenter study based on serum samples from 5397 pregnancies including 107 samples from cases of verified fetal trisomy 21 at 8 to 14 weeks of gestation. A technical validation of the Roche Elecsys® free βhCG and PAPP-A assays were performed, including method comparisons with the Brahms Kryptor, AutoDELFIA PerkinElmer and Siemens Immulite assays. Furthermore a clinical validation including genertion of assay specific medians for PAPP-A and free βhCG from gestational age 8+0 to 14+0 weeks, and clinical test performance of risk assesment was conducted. Results The in-between day imprecision of the Elecsys® free βhCG and PAPP-A assays were between 1.0 and 2.8%. Comparison (Passing/Bablok regression) of free βhCG and PAPP-A from Roche Elecsys® and the Brahms Kryptor assays showed slopes of 0.94 and 0.95 and Pearson’s correlation of r = 0.981 and r = 0.987 respectively. Similar comparison to AutoDELFIA PerkinElmer Perkin gave slopes of 0,83 (free βhCG) and 1.20 (PAPP-A). With a cut off at 1:300 the overall sensitivity of the first trimester screening including nuchal translucency reached 94% for a 3% false positive rate. Bloodsampling in gestational weeks 8 and 9 gave a sensitivity of 95% for a 2% false positive rate, and in gestational weeks 10 to14 the sensitivity was 94% for a 3% false positive rate. Conclusions The Roche Elecsys® free βhCG and PAPP-A assays apply with the standards for biochemical assays for prenatal screening set by the Fetal Medicine Foundation, with low assay imprecision, and a high clinical performance of prenatal screening for fetal trisomy in the first trimester.