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Introduction: Contingent cell-free (cf) DNA screening on the basis of the first-trimester combined test (FCT) results has emerged as a cost-effective strategy for screening of trisomy 21 (T21).Objectives: To assess performance, patients' uptake, and cost of contingent cfDNA screening and to compare them with those of the established FCT.Methods: This is a prospective cohort study including all singleton pregnancies attending to their FCT for screening of T21 at 2 university hospitals in South Spain. When the FCT risk was ≥1:50, there were major fetal malformations, or the nuchal translucency was ≥3.5 mm, women were recommended invasive testing (IT); if the risk was between 1:50 and 1:270, women were recommended cfDNA testing; and for risks bellow 1:270, no further testing was recommended. Detection rate (DR), false-positive rate (FPR), patients' uptake, and associated costs were evaluated.Results: We analyzed 10,541 women, including 46 T21 cases. DR of our contingent strategy was 89.1% (41/46) at 1.4% (146/10,541) FPR. Uptake of cfDNA testing was 91.2% (340/373), and overall IT rate was 2.0%. The total cost of our strategy was €1,462,895.7, similar to €1,446,525.7 had cfDNA testing not been available.Conclusions: Contingent cfDNA screening shows high DR, low IT rate, and high uptake at a similar cost than traditional screening. [ABSTRACT FROM AUTHOR]

Objective: To assess the sensitivity (Sen) and false positive ratio (FPR) of stepwise sequential screening [1st step: combined test (CT), 2nd step: modified genetic sonography (major malformation and nuchal fold, MGS)] as a screening method for Down's syndrome (DS) in the general population of pregnant women. Methods: Prospective study. During a 5-year study period (July 2005 to June 2010), 17,911 pregnant women were screened for DS using a stepwise sequential screening method (CT+MGS). We evaluated the Sen and FPR (95% CI) of the two chromosomal disorder screening methods for DS: CT and CT+MGS. Results: Seventeen thousand nine hundred and eleven cases were analysed, including 67 with chromosome abnormalities and 45 with DS. The Sen of CT for DS was 80% (95% CI; 68.3-91.7) (36/45) with a FPR of 4.2% (95% CI; 3.9-4.5) (752/17, 866). The Sen of CT+MSG for DS was 93.3 (95% CI; 85.9-99) (42/45) with a FPR of 4.8% (95% CI; 4.5-5.1) (860/17, 866). Conclusions: MGS coupled with CT increases the Sen of DS diagnosis by 13.3% (95% CI; 2.7-25.9), with an increase in FPR of 0.6% (95% CI; 0.5-0.7). [ABSTRACT FROM AUTHOR]

Objectives To assess the value of ductus venosus blood flow (expressed as pulsatility index, DVPI) in antenatal Down's syndrome screening when used with the Combined and Integrated tests. Methods DVPI measurements between 10 and 13 weeks' gestation in 66 Down's syndrome and 7184 unaffected pregnancies were collected from women attending the Hospital Clinic, Barcelona, for antenatal care from 1999 to 2007 and combined with the Serum Urine and Ultrasound Screening Study (SURUSS) data to model screening performance, safety and costeffectiveness of the screening tests with and without DVPI. Results The median DVPI multiple of the normal median in Down's syndrome pregnancies was 1.55 (95% CI 1.36-1.73). As a single screening marker without using maternal age, DVPI has a 62% detection rate for a 5% false-positive rate. At a 90% detection rate (first trimester measurements at 11 weeks' gestation) the addition of DVPI reduced the false-positive rate of the Combined test from 8.5% to 4.6% and the Integrated test from 2.0% to 1.1%, with a corresponding reduction in fetal losses from diagnostic procedures. There was no material loss of cost-effectiveness. Conclusion Addition of DVPI measurements to the Combined and Integrated tests substantially improves the efficacy and safety of antenatal Down's syndrome screening. [ABSTRACT FROM AUTHOR]

To date, studies assessing whether the information given to people about screening tests facilitates informed choices have focussed mainly on the UK, US and Australia. The extent to which written information given in other countries facilitates informed choices is not known. The aim of this study is to describe the presentation of choice and information about Down's syndrome in written information about prenatal screening given to pregnant women in five European and two Asian countries. Leaflets were obtained from clinicians in UK, Netherlands, Spain, Italy, Czech Republic, China and India. Two analyses were conducted. First, all relevant text relating to the choice about undergoing screening was extracted and described. Second, each separate piece of information or statement about the condition being screened for was extracted and then coded as either positive, negative or neutral. Only Down's syndrome was included in the analysis since there was relatively little information about other conditions. There was a strong emphasis on choice and the need for discussion about prenatal screening tests in the leaflets from the UK and Netherlands. The leaflet from the UK gave most information about Down's syndrome and the smallest proportion of negative information. By contrast, the Chinese leaflet did not mention choice and gave the most negative information about Down's syndrome. Leaflets from the other countries were more variable. This variation may reflect cultural differences in attitudes to informed choice or a failure to facilitate informed choice in practice. More detailed studies are needed to explore this further.European Journal of Human Genetics (2007) 15, 563–569. doi:10.1038/sj.ejhg.5201790; published online 21 February 2007 [ABSTRACT FROM AUTHOR]

Objectives. This paper presents the results of different screening policies for prenatal detection of Down syndrome that would allow decision makers to make informed choices. Methods. A decision analysis model was built to compare 8 screening policies with regard to a selected set of outcome measures. Probabilities used in the analysis were obtained from official administrative data reports in Spain and Catalonia and from data published in the medical literature. Sensitivity analyses were carried out to test the robustness of screening policies' results to changes in uptake rates, diagnostic accuracy, and resources consumed. Results. Selected screening policies posed major trades-offs regarding detection rates, false-positive results, fetal loss, and costs of the programs. All outcome measures considered were found quite robust to changes in uptake rates. Sensitivity and specificity rates of screening tests were shown to be the most influential factors in the outcome measures considered. Conclusions. The disclosed trade-offs emphasize the need to comprehensively inform decision makers about both positive and negative consequences of adopting one screening policy or another. [ABSTRACT FROM AUTHOR]

Background: DNA-based non-invasive prenatal testing (NIPT) using maternal blood constitutes an emerging technology for the detection of Down syndrome (DS). The aim of the study was to conduct a cost-effectiveness analysis to evaluate the economic costs and health implications of the introduction of NIPT based on cell-free foetal DNA analysis through different screening strategies for the detection of DS. Methods: An analytical short-term decision model was developed, from the payer´s perspective (Spanish National Health Service). The main outcome measure was the number of DS cases detected. Secondary measures included associated miscarriages, women undergoing current screening, women undergoing NIPT, positive NIPT and invasive procedures performed. The study setting was the Spanish National Health Service. Three strategies were compared: (a) first- and second-trimester screening (current screening); (b) NIPT as contingent testing; and (c) NIPT as first-line testing. Modelling was based on a hypothetical cohort of 100,000 Spanish pregnant women. Population data were obtained from the database of the Basque Antenatal Screening Programme. Deterministic sensitivity analyses were performed to assess variations in the cost of NIPT, screening risk cut-off, screening uptake-rate and rate of failure of NIPT. Results: NIPT as contingent testing (strategy b) led to fewer miscarriages following invasive procedures and a slight reduction in the number of DS cases detected compared to current screening. However, lowering the screening cut-off to ≥ 1:500 would improve the overall effectiveness of NIPT as contingent testing, increasing the number of DS cases detected and decreasing foetal losses as compared to the current screening, despite there would be an extra-cost of 3.5%. When NIPT was used as first-line testing (strategy c), the screening would be more effective but also more expensive, with incremental cost-effectiveness ratios (ICERs) per additional case of DS detected of €1,299,763 and €1,232,763, compared with strategies a and b, respectively. Results were sensitive to the different parameters considered in the analysis. Conclusions: Both, as first-line testing and as contingent testing when screening cut-off was lowered ≥ 1:500, NIPT would lead to more favourable outcomes as compared to the current screening (both in terms of DS cases detected and miscarriages avoided), but at a greater cost. [ABSTRACT FROM AUTHOR]