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Background: Cell-free DNA (cfDNA) analysis in maternal blood for the detection of fetal Down syndrome is gradually replacing first trimester screening. We present here a large clinical series of 10,000 consecutive pregnancies. Objectives: To study the reliability of cell-free DNA (cfDNA) analysis in maternal blood for the detection of fetal trisomy 21, 18 and 13 in a clinical setting in 10,000 consecutive pregnancies with variable risk. cfDNA testing has been evaluated in an increasing number of pregnancies mainly at high risk for fetal trisomy, and some studies have suggested that its positive predictive value (PPV) might be lower in low-risk populations. Study design: CfDNA testing using the Harmony™ Prenatal Test was performed in 10,000 consecutive pregnancies with high or low a-priori risk for fetal trisomy 21, 18 and 13. Results: In 147 (1.47%) of the 10,000 pregnancies a high-risk cfDNA testing result indicated trisomy 21 (n=121), trisomy 18 (n=15) or trisomy 13 (n=11). It failed to detect 5 trisomies (2 trisomies 21, 2 trisomies 18, and 1 trisomy 13). Five false-positive results were recorded (4 in the high and 1 in the low risk population). The overall positive predictive value (PPV) was 96%, with a PPV of 96% in the high-risk (>1/200) population and 97% in the low risk (

The aim of the study was to evaluate thyroid-stimulating hormone (TSH) concentration in a reference group and to compare it with the TSH in subjects with high probability of thyroid dysfunction. The study population consisted of 852 subjects. The reference group consisting of 316 subjects was obtained by the exclusion of the subjects having thyroid disease, taking thyroid influencing drugs, having increased thyroid peroxidase (TPO) antibodies, or having abnormal thyroid ultrasound. 42 high probability of thyroid dysfunction subjects were defined by the association of increased TPO antibody concentration, changed echogenicity, and changed echosonographic structure of thyroid parenchyma. In the reference group TSH reference range was 0.45 mU/l (95% CI 0.39-0.56 mU/l) to 3.43 mU/l (95% CI 3.10-4.22 mU/l). To distinguish reference and high probability of thyroid dysfunction group a TSH threshold was calculated. At a threshold value of 3.09 mU/l (95% CI 2.93-3.38 mU/l), specificity was 95% and sensitivity 38.1%. Using 2 different approaches to find upper limit of the TSH reference range we obtained similar results. Using reference group only a value of 3.43 mU/l was obtained. Using both reference group and subjects with the high probability of thyroid dysfunction we obtained 95% CI for the upper reference limit between 2.93 and 3.38 mU/l. Based on these premises, it could be argued that conservative estimate of the TSH upper reference range should be 3.4 mU/l for both sexes.