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This article is an ethical evaluation of two familiar views in the debate on foetal diagnosis; one being the mainstream view in medical texts emphasizing early detection of foetuses with Down´s syndrome so they may be aborted, and the other coming from Down´s syndrome activists claiming that such screening is never acceptable. The core question asked is: What ethical weaknesses in modern medical practice does this discussion reveal? I argue that the marketization of noninvasive prenatal testing (NIPT) and the mainstream discussion in the health sector on its application shows two trends undermining the traditional ethos of medicine. Firstly, that doctors are, in their work, concentrating on diseases as isolated entities, whereas the patient and her life remains in the shadow. Secondly, the emphasis has been on the scientific foundation of medicine where the clinical evaluation of these scientific facts has not received due attention. This article is about how we can evaluate ethically two different views on tests done on foetuses. It describes how some medical texts talk about tests done on foetuses to see if they have Down's syndrome; and secondly, how some people with Down´s syndrome and their families talk about such tests. The medical view is criticized for failing to understand the importance of the lives of people with Down´s syndrome and for not taking their views of the value of their lives seriously. The medical texts focus on diseases instead of patients. Thus they tend to ignore the life and value of the person having the disease. The medical view is mainly about science and facts. It ignores the question of whether and how these facts matter for the patient. People with Down´s syndrome and their families have criticized this medical approach. Their criticism is very important. [ABSTRACT FROM AUTHOR]

The article focuses on prenatal diagnosis of trisomy 21. It mentions the caregiver must give clear and objective information to pregnant women and couples, that can serve as a support for dialogue between the carer and the pregnant woman, between the carer and the couple and allow future parents to discuss and decide whether to commit or not in the screening process.

The article focuses on study of financial analysis is carried out to assess costs and benefits of providing cell-free DNA screening in Finland, using different strategies. Topics discussed include considering the place of cell-free DNA screening it is important to make explicit the additional and marginal costs of different screening strategies and the associated benefits; and most assumptions the balance is favorable for Contingent screening.

Background: We developed a decision aid (DA) to help pregnant women and their partners make informed decisions about prenatal screening for trisomy. We aimed to determine its usefulness for preparing for decision-making and its acceptability among end-users.Methods: In this mixed-methods pilot study, we recruited participants in three prenatal care settings in Quebec City. Eligible women were over 18 and more than 16 weeks pregnant or had given birth recently. We asked them about the usefulness of the DA using an interview grid based on the Technology Acceptance Model. We performed descriptive statistics and deductive analysis.Results: Thirty-nine dyads or individuals participated in the study. Mean usefulness score was 86.2 ± 13. Most participants found the amount of information in the DA just right (79.5%), balanced (89.7%), and very useful (61.5%). They were less satisfied with the presentation and the values worksheet and suggested different values clarification methods.Conclusion: Rigorous pilot tests of DAs with patients are an important stage in their development before the more formal assessments that precede scaling up the DA in clinical practice.Practice Implications: The next version of the DA will integrate the suggestions of end-users for better decision-making processes about prenatal screening for trisomy. [ABSTRACT FROM AUTHOR]

Objective: To determine whether the improved precision of nuchal translucency (NT) measurement used in antenatal screening for Down's syndrome observed over time as evidenced by a decrease in the multiple of the median (MoM) standard deviation requires a modification to the NT MoM truncation limits to maintain accurate risk estimation. Methods: Probability plots were derived from the measurements of NT MoM values used in a 2018 audit of 22,362 unaffected pregnancies. The plots were used to determine whether the NT MoM upper truncation limit should be lowered. Validation plots were used to assess the screening accuracy of Down's syndrome risk estimates calculated from observed NT MoM values in the 22,362 unaffected pregnancies and 69 Down's syndrome pregnancies for original and revised NT MoM truncation limits. Results: Probability plots indicated that with improved precision of NT measurements, there was deviation from a Gaussian distribution at less high MoM values than with less precise measurements. Validation plots showed that using the current NT MoM upper truncation limit of 2.5 MoM with improved precision NT measurements overestimates the Down's syndrome risk (median risk in highest risk category expressed as an odds was 53.3:1 and observed prevalence was 1:1.1). The large discrepancy was corrected by changing the NTupper truncation limit to 2.0 MoM (median risk in highest risk category expressed as an odds was 1:1.78 and observed prevalence 1:2.7). Conclusion: The NT MoM upper truncation limit should be reduced from 2.5 to 2.0 MoM. [ABSTRACT FROM AUTHOR]

Aim: Analyze if the evaluation of aberrant right subclavian artery in the prenatal echography has improved the detection of chromosomal, genetic and/or morphological abnormalities in our population. Methods: Descriptive, observational, cross‐sectional study of the cases of aberrant right subclavian artery diagnosed in our Prenatal Diagnosis Unit between January of 2011 and December of 2018. Results: Two hundred and fifty‐seven cases of aberrant right subclavian artery were diagnosed and among them, 179 were considered isolated cases and thus were confirmed after birth. The detection of aberrant right subclavian artery did not improve itself neither the diagnosis of trisomy 21 in the second trimester of pregnancy nor other chromosomal or genetic abnormalities, including the not isolated cases. There were two cases of trisomy 21 diagnosed in the second trimester that presented major sonographic disorders and an inadequate examination during the first trimester. When aberrant right subclavian artery was associated with soft markers of aneuploidy in the second trimester, any case was a trisomy 21. Aberrant right subclavian artery seems to be associated with some minor and major heart defects, especially ventriculoseptal defect and aneurismatic ductus, and in some cases, also with clubfeet. Conclusion: When an adequate screening of aneuploidies and a thorough ultrasound have been performed during the first trimester, aberrant right subclavian artery hardly helps to perform other diagnosis in the second trimester. [ABSTRACT FROM AUTHOR]

Down syndrome screening has been available within clinical practice for over 50 years within which time significant innovation and exciting new advances have improved the accuracy, safety, and choice for women who are considering antenatal screening for Down syndrome. The UK National Screening Committee is responsible for setting the national standards regarding screening and it has steadily and consistently directed and facilitated an increase in the detection rate whilst minimising the screen positive rate. This has reduced the number of false positive results and consequently the number of invasive diagnostic procedures and their related miscarriages. Non-invasive pre-natal testing (NIPT) using cell free DNA is a rapidly evolving field and it will soon be incorporated into the existing NHS antenatal screening programme for aneuploidy. It will be offered to women who receive a 'high risk' result following current screening methods (combined test or quadruple test), and will further reduce the number of invasive tests performed, whilst maintaining current detection rates. [ABSTRACT FROM AUTHOR]

To discuss combinations of traditional screening and noninvasive prenatal screening (NIPS) and to compare which traditional screening is the most suitable first-line screening approach to NIPS, pregnant women were recruited in this retrospective observational study. Pregnant women underwent one of four traditional screening tests. The 9 contingent models were combined by high risk cut-offs of 1:50, 1:100, 1:270 and intermediate risk cut-offs of 1:1000, 1:1500, 1:2000. We analyzed cost and performance of various screening models with contingent screening of different risk cut-offs. Compared with other screening tests, combined first-trimester screening (CFTS) had the lowest proportion of high risk (≥1:270) with the highest detection rate (DR) (78.79%) and the lowest proportion of intermediate risk (1:271~1:1000). When intermediate risk was 1:51 ~1:1500, CFTS as first-line screening had the lowest cost with DR of 93.94%. Other screening tests as the first-line screening with intermediate risk of 1:51~1:1000 had the lowest cost, there DR were 90.91%, 84.62%, 91.67%, respectively. Our study demonstrated if only one traditional screening was allowed to screen pregnant women, CFTS was recommended as the first choice. According to local health and economic conditions, adopting appropriate traditional screening with suitable cut-offs as first-line screening will contributed to a cost-effective screening model. [ABSTRACT FROM AUTHOR]

This is the fourth in a series of papers. The previous papers inform midwifery practice by providing insight into whether, to what extent and how cognitive status influences understanding of Down syndrome screening information, the importance of tailoring information, and highlighting areas of communication that are effective in facilitating understanding. These findings led to the development of recommendations to inform a 'best practice' model for midwifery communication of screening information within a conceptual framework that recognises the importance of accurate facts, empathic communication and support for decision-making in a woman-centred approach. These recommendations may have wider relevance beyond midwife communication of Down syndrome screening and may impact upon the communication of other screening information provided within antenatal and neonatal screening. It is important that screening information is communicated effectively in light of changes to screening programmes, such as the introduction of non-invasive prenatal testing. [ABSTRACT FROM AUTHOR]

Objective: To report on the routine clinical implementation of cell-free DNA (cfDNA) analysis of maternal blood for trisomies 21, 18 and 13, contingent on the results of the first-trimester combined test in twin pregnancy.Methods: Screening for trisomies 21, 18 and 13 was carried out in 959 twin pregnancies by assessment of a combination of maternal age, fetal nuchal translucency thickness, and serum free β-human chorionic gonadotropin and pregnancy-associated plasma protein-A at 11-13 weeks' gestation in two UK NHS hospitals. Women in the high-risk group (risk ≥ 1 in 100) were offered the option of invasive testing, cfDNA testing or no further testing, and those in the intermediate-risk group (risk 1 in 101 to 1 in 2500 in the first phase of the study and 1 in 101 to 1 in 500 in the second phase) were offered cfDNA or no further testing. The trisomic status of the pregnancies was determined by prenatal or postnatal karyotyping or examination of the neonates.Results: In 42 (4.4%) of the 959 pregnancies, there was termination, miscarriage or stillbirth with no known karyotype or there was loss to follow-up. The 917 pregnancies with known trisomic status of both twins included six that were discordant for trisomy 21, four that were discordant for trisomy 18 and 907 with no trisomy 21, 18 or 13. Following combined screening, 47 (5.1%), 203 (22.1%) and 667 (72.7%) of the pregnancies were classified as high risk, intermediate risk and low risk, respectively. The high-risk group included five (83.3%) cases of trisomy 21 and three (75.0%) of trisomy 18. The cfDNA test was carried out in 224 pregnancies and results were provided in 214 (95.5%); this group included six pregnancies with trisomy 21, three with trisomy 18 and 206 with no trisomy 21, 18 or 13. The cfDNA test classified correctly as screen positive all six cases of trisomy 21 and two of the three with trisomy 18, and as screen negative for each of the trisomies all 206 unaffected pregnancies. Contingent screening led to prenatal detection of all cases of trisomy 21 and three of four with trisomy 18.Conclusion: This study has demonstrated the feasibility of introducing cfDNA testing, contingent on the results of the first-trimester combined test for major trisomies, in a routine population of twin pregnancies. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Objectives: The objective of this study is to identify the optimal cut-off points of contingent serum screening excluding nuchal translucency (NT) measurement, to categorize the risk level in the first trimester.Methods: A prospective database of women undergoing contingent serum screening, without NT measurement, was reviewed. In conventional categorization, the results of first-trimester screening were categorized into high risk (>1:30) (invasive diagnosis was offered); intermediate risk (1:30-1:1500) (second-trimester screening was needed); and low risk (<1:1500) (no further test). We recategorized the risk levels using various upper and lower cut-offs and compared detection rates, false-positive rates, and rates of intermediate risk.Results: Among 24,874 women, the prevalence of Down syndrome was 1:691. The previously agreed cut-offs had a detection rate of 88.9% and a false-positive rate of 8.5% with high rate of intermediate risk (38.2%). Re-categorization provided the optimal lower and upper cut-offs 1/900 and 1/50, respectively, giving a detection rate of 86.1%, a false-positive rate of 8.1%, and a rate of intermediate risk of 24.8%.Conclusions: This is the first study on contingent serum screening without NT measurement which shows a high detection rate with an acceptable false-positive rate. The optimal cut-offs to categorize the risk levels of the upper and the lower cut-off was 1:30-1:50 and 1:900, respectively. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the performance of high-resolution chromosomal microarray (CMA) as the standard diagnostic approach for genomic imbalances in pregnancies with increased risk based on combined first-trimester screening (cFTS).Methods: This was a retrospective study of genomic findings in a cohort of 575 consecutive pregnancies undergoing invasive testing because of a cFTS risk ≥ 1:300 on a publicly funded population-based screening program in the Central and Northern Regions of Denmark, between September 2015 and September 2016. Women with fetal nuchal translucency thickness ≥ 3.5 mm or opting for non-invasive prenatal testing (NIPT) were excluded. Comparative genomic hybridization was performed using a 180-K oligonucleotide array on DNA extracted directly from chorionic villus/amniocentesis samples. Genomic outcomes were reported in relation to cFTS findings.Results: Of the 575 pregnancies that underwent invasive testing, CMA detected 22 (3.8% (95% CI, 2.5-5.7%)) cases of trisomies 21, 18 and 13, 14 (2.4% (95% CI, 1.4-4.0%)) cases of other types of aneuploidy and 15 (2.6% (95% CI, 1.5-4.3%)) cases with a pathogenic or probably pathogenic copy number variant (CNV). Of the 15 CNVs, three were > 10 Mb and would probably have been detected by chromosomal analysis, but the other 12 would most probably not have been detected using conventional cytogenetic techniques; therefore, the overall detection rate of CMA (8.9% (95% CI, 6.8-11.5%)) was significantly higher than that estimated for conventional cytogenetic analysis (6.8% (95% CI, 5.0-9.1%)) (P = 0.0049). Reducing the cFTS risk threshold for invasive diagnostic testing to 1 in 100 or 1 in 50 would have led, respectively, to 60% or 100% of the pathogenic CNVs being missed.Conclusions: CMA is a valuable diagnostic technique that can identify an increased number of genomic aberrations in pregnancies at increased risk on cFTS. Limiting diagnostic testing to pregnancies with a risk above 1 in 100 or 1 in 50, as proposed in contingent NIPT/invasive testing models, would lead to a significant proportion of pathogenic CNVs being missed at first-trimester screening. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Objectives: To examine the costs and outcomes of different screening strategies for Down Syndrome (DS) in singleton pregnancies.Study Design: A decision-analytic model was developed to compare the costs and the outcomes of different prenatal screening strategies. Five strategies were compared for women under 35-year of age: 1A) triple test (TT), 2A); combined test (CT), 3A) Non-invasive Prenatal Screening Test by using cell free fetal DNA (NIPT), 4A) and 5A) NIPT as a second-step screening for high-risk patients detected by either TT, or CT respectively. For women ≥35-year of age, 1B) implementing invasive test (amniocentesis -AC) and 2B) NIPT for all women were compared. Data was analyzed to obtain the outcomes, total costs, the cost per women and the incremental cost-effectiveness ratios (ICERs) for screening strategies.Results: Among the current strategies for women under 35 years old, CT is clearly dominated to TT, as it is more effective and less costly. Although, the current routine practice (2A) is the least-costly strategy, implementing NIPT as a second step screening to high-risk women identified by CT (5A) would be more effective than 2A; leading to a 10.2% increase in the number of detected DS cases and a 96.3% reduction in procedural related losses (PRL). However, its cost to the Social Security Institution that is a public entity would be 17 times higher and increase screening costs by 1.5 times. Strategy 5A would result in an incremental cost effectiveness of 6,873,082 (PPP) US$ when compared to the current one (2A). Strategy 1B-for offering AC to all women ≥35-year of age is dominated over NIPT (2B), as it would detect more DS cases and would be less costly. On the other hand, there would be 206 PRL associated with AC, but NIPT provides clear clinical benefits as there would be no PRL with NIPT.Conclusions: NIPT leads to very high costs despite its high effectiveness in terms of detecting DS cases and avoiding PRL. The cost of NIPT should be decreased, otherwise, only individuals who can afford to pay from out-of-pocket could benefit. We believe that reliable cost-effective prenatal screening policies are essential in countries with low and smiddle income and high birth rates as well. [ABSTRACT FROM AUTHOR]

Down screening has been available within clinical practice for over 50 years during which time significant innovation and exciting new advances have improved the accuracy and safety of screening, and improved choice for women who are considering antenatal screening for Down syndrome. The UK National Screening Committee is responsible for setting the national standards regarding screening and it has steadily and consistently directed and facilitated an increase in the detection rate whilst minimising the screen positive rate of Down syndrome screening. This has reduced the number of false positive results and consequently the number of invasive diagnostic procedures and their related miscarriages. Non-invasive pre-natal testing (NIPT) using cell free DNA is a rapidly evolving field and it will soon be incorporated into the existing NHS antenatal screening programme for aneuploidy. It will be offered to women who receive a ‘high risk’ result following current screening methods (combined test or quadruple test), and will further reduce the number of invasive tests performed, whilst maintaining current detection rates. [ABSTRACT FROM AUTHOR]

Background Contingent screening for trisomy 21 using non-invasive prenatal testing has the potential to reduce invasive diagnostic testing and increase the detection of trisomy 21. Aim To describe the diagnostic and economic performance of prenatal screening models for trisomy 21 that use non-invasive prenatal testing as a contingent screen across a range of combined first trimester screening risk cut-offs from a public health system perspective. Methods Using a hypothetical cohort of 300 000 pregnancies, we modelled the outcomes of 25 contingent non-invasive prenatal testing screening models and compared these to conventional screening, offering women with a high-risk (1 > 300) combined first trimester screening result an invasive test. The 25 models used a range of risk cut-offs. High-risk women were offered invasive testing. Intermediate-risk women were offered non-invasive prenatal testing. We report the cost of each model, detection rate, costs per diagnosis, invasive tests per diagnosis and the number of fetal losses per diagnosis. Results The cost per prenatal diagnosis of trisomy 21 using the conventional model was $51 876 compared to the contingent models which varied from $49 309-66 686. The number of diagnoses and cost per diagnosis increased as the intermediate-risk threshold was lowered. Results were sensitive to trisomy 21 incidence, uptake of testing and cost of non-invasive prenatal testing. Conclusion Contingent non-invasive prenatal testing models using more sensitive combined first trimester screening risk cut-offs than conventional screening improved the detection rate of trisomy 21, reduced procedure-related fetal loss and could potentially be provided at a lower cost per diagnosis than conventional screening. [ABSTRACT FROM AUTHOR]

Objective: Prenatal screening with cell-free DNA (cfDNA) offers improved detection of Down syndrome (T21) compared to conventional screening. These tests are expensive and have fewer detectable anomalies. Our objective was to investigate potential costs and test performance of screening algorithms when accounting for detectable aneuploidies.Methods: This is a cost analysis for a large military treatment facility. Using a theoretical delivery cohort and published performance data, universal screening with cfDNA was compared to sequential screening, comparing T21 to all detectable aneuploidies. Predicted test performance and costs were calculated.Results: A cohort of 3000 deliveries was used. For T21, universal cfDNA is more expensive ($1,346,064) than sequential screening ($244,885), but has a lower false positive rate and avoids 101 invasive diagnostic tests. An additional case of T21 is detected with a marginal cost of $1,101,179. For all detectable aneuploidies, cfDNA is more expensive ($1,353,660) than sequential screening ($239,189), and 59 invasive diagnostic tests are avoided. Sequential screening detects an additional case of aneuploidy, with a cost savings of $1,114,471.Conclusions: Although cfDNA is superior in detecting T21 cases, sequential screening is superior when considering all aneuploidies detectable. The cost increase with universal cfDNA is significant, and is not justified with small improvements in the performance. [ABSTRACT FROM AUTHOR]

Objective: To evaluate first-trimester screening protocols for detecting trisomy 21 in an Indian population.Methods: The present prospective study collected data from women with singleton pregnancies and a crown-to-rump length of 45-84 mm who presented at the fetal medicine unit of a tertiary care center in North India between June 1, 2006, and December 31, 2015, for combined first-trimester screening. Maternal age, nuchal translucency, nasal bone, and maternal serum levels of free beta human chorionic gonadotropin and pregnancy-associated plasma protein A were assessed for calculating the risk of trisomy 21. Tricuspid regurgitation and qualitative analysis of ductus venosus data were available from June 2010, and were included where available. Trisomy-21 detection rates were calculated for various screening protocols and were compared.Results: There were 4523 women screened and 24 records of trisomy 21. Combined screening with maternal age, nuchal translucency, nasal bone, tricuspid regurgitation, and ductus venosus demonstrated optimal detection and false-positive rates of 93.8% and 1.9%, respectively. Screening using only maternal age yielded a detection rate of 37.5%; using fixed nuchal translucency cut-off values of 2.5 and 3 mm resulted in detection rates of 66.7% and 37.5%, respectively.Conclusion: Combined first-trimester screening performed well in an Indian population; combining maternal age, nuchal translucency, nasal bone, ductus venosus, and tricuspid regurgitation yielded the most accurate screening. [ABSTRACT FROM AUTHOR]

Background: Health professionals are expected to engage pregnant women in shared decision making to help them make informed values-based decisions about prenatal screening. Patient decision aids (PtDAs) foster shared decision-making, but are rarely used in this context. Our objective was to identify factors that could influence health professionals to use a PtDA for decisions about prenatal screening for Down syndrome during a clinical pregnancy follow-up.Methods: We planned to recruit a purposive sample of 45 health professionals (obstetrician-gynecologists, family physicians and midwives) involved in the care of pregnant women in three clinical sites (15 per site). Participating health professionals first watched a video showing two simulated consecutive prenatal follow-up consultations during which a pregnant woman, her partner and a health professional used a PtDA about Down syndrome prenatal screening. Participants were then interviewed about factors that would influence their use of the PtDA. Questions were based on the Theoretical Domains Framework. We performed content analyses of transcribed verbatim interviews.Results: Out of 42 eligible health professionals approached, 36 agreed to be interviewed (86 % response rate). Of these, 27 were female (75 %), nine were obstetrician-gynecologists (25 %), 15 were family physicians (42 %), and 12 were midwives (33 %), with a mean age of 42.1 ± 11.6 years old. We identified 35 distinct factors reported by 20 % or more participants that were mapped onto 10 of the 12 of the Theoretical Domains Framework domains. The six most frequently mentioned factors influencing use of the PtDA were: 1) a positive appraisal (n = 29, 81 %, beliefs about consequences domain); 2) its availability in the office (n = 27, 75 %, environmental context and resources domain); 3) colleagues' approval (n = 27, 75 %, social influences domain); 4) time constraints (n = 26, 72 %, environmental context and resources domain); 5) finding it a relevant source of information (n = 24, 67 %, motivation and goals domain); and 6) not knowing any PtDAs (n = 23, 64 %, knowledge domain).Conclusions: Appraisal, PtDA availability, peer approval, time concerns, evidence and PtDA awareness all affect whether health professionals are likely to use a PtDA to help pregnant women make informed decision about Down syndrome screening. Implementation strategies will need to address these factors. [ABSTRACT FROM AUTHOR]

Supporting pregnant women to make informed choices about Down syndrome screening is widely endorsed. We reviewed the literature on: (a) the association between socioeconomic position and informed choices and decision-making about Down syndrome screening, and (b) the possible mediating variables (e.g., health literacy, numeracy skills, behavioral and communication variables) that might explain the relationship. EMBASE, MEDLINE, PubMed, CINAHL, and PsycINFO were searched from January 1999 to September 2014. The methodological quality of studies was determined by predefined criteria regarding the research aims, study design, study population and setting, measurement tools, and statistical analysis. A total of 33 studies met the inclusion criteria. Women from lower socioeconomic groups experience greater difficulties making informed choices about Down syndrome screening compared to women from higher socioeconomic groups. Most studies focus on individual dimensions of informed decision-making rather than assessing elements in conjunction with one another. Few studies have explored why there are socioeconomic differences in women’s ability to make informed screening decisions. Future work is needed to identify mediating variables in this pathway. Systematic evidence-based intervention development to improve communication, understanding, and decision-making about Down syndrome screening is needed to ensure that women have an equal opportunity to make an informed choice about screening regardless of their socioeconomic position. [ABSTRACT FROM PUBLISHER]

Objectives: Cell-free DNA (cfDNA) analysis of maternal blood for detection of trisomies 21, 18 and 13 is superior to other methods of screening but is expensive. One strategy to maximize performance at reduced cost is to offer cfDNA testing contingent on the results of the first-trimester combined test that is used currently. The objectives of this study were to report the feasibility of implementing such screening, to examine the factors affecting patient decisions concerning their options for screening and decisions on the management of affected pregnancies and to report the prenatal diagnosis of fetal trisomies and outcome of affected pregnancies following the introduction of contingent screening.Methods: We examined routine clinical implementation of contingent screening in 11,692 singleton pregnancies in two National Health Service (NHS) hospitals in the UK. Women with a risk ≥ 1 in 100 (high-risk group) were offered options of invasive testing, cfDNA testing or no further testing, and those with a risk between 1 in 101 and 1 in 2500 (intermediate-risk group) were offered cfDNA testing or no further testing. The trisomic status of the pregnancies was determined by prenatal or postnatal karyotyping or by examination of the neonates.Results: In the study population of 11,692 pregnancies, there were 47 cases of trisomy 21 and 28 of trisomies 18 or 13. Screening with the combined test followed by invasive testing for all patients in the high-risk group potentially could have detected 87% of trisomy 21 and 93% of trisomies 18 or 13, at a false-positive rate of 3.4%; the respective values for cfDNA testing in the high- and intermediate-risk groups were 98%, 82% and 0.25%. However, in the high-risk group, 38% of women chose invasive testing and 60% chose cfDNA testing; in the intermediate-risk group 92% opted for cfDNA testing. A prenatal diagnosis was made in 43 (91.5%) pregnancies with trisomy 21 and all pregnancies with trisomies 18 or 13. In many affected pregnancies the parents chose to avoid testing or termination and 32% of pregnancies with trisomy 21 resulted in live births.Conclusions: Screening for fetal trisomies by cfDNA analysis of maternal blood, contingent on the results of the combined test, can be implemented easily in routine clinical practice. In the high-risk group from the combined test, most but not all women chose cfDNA testing rather than invasive testing. Performance of screening for trisomy 21 was superior by the cfDNA test than by the combined test. However, prenatal detection of trisomies and pregnancy outcome depend not only on performance of screening tests but also on parental choice. [ABSTRACT FROM AUTHOR]

Objective: To analyse population-based trends over the entire history of prenatal testing for aneuploidy.Design: Retrospective analysis of state-wide data sets.Setting: Australian state of Victoria with ~70 000 annual births.Population: All pregnant women undergoing invasive prenatal testing at <25 weeks' gestation from 1976 to 2013.Methods: Analysis of three state-wide data sets: (1) Prenatal diagnosis data set of 119 404 amniocenteses and chorionic villus samplings from 1976 to 2013; (2) central serum screening laboratory data set from 1996 to 2013; (3) government birth statistics from 1976 to 2013.Main Outcome Measures: Annual numbers and uptake rates of invasive prenatal tests and serum screening, indications for invasive prenatal testing, prenatal diagnoses of aneuploidy, diagnostic yield of invasive tests.Results: Annual numbers of invasive prenatal tests climbed steadily from 1976, then declined from 2000. In 2013, the number of invasive prenatal tests was the lowest in 25 years, while the number of trisomy 21 diagnoses was the highest ever recorded. Annual uptake of serum screening climbed from 1.6 to 83% over 1996-2013. Results from 2013 showed a high diagnostic yield (15.8%) for a low rate of invasive testing (3.4% of births). Over four decades, the number of invasive procedures performed for each diagnosis of major chromosome abnormality declined from 100 to six.Conclusions: This study demonstrates historic reductions in the proportion of women undergoing invasive testing and dramatic improvements in diagnostic yield. Monitoring the impact of new prenatal technologies on this progress remains an important research priority.Tweetable Abstract: Invasive prenatal testing has reached historic lows due to dramatic improvements in Down syndrome screening. [ABSTRACT FROM AUTHOR]

Objective: To assess how prenatal screening and diagnostic testing have impacted the diagnosis, termination and birth prevalence of Down syndrome in Western Australia (1980-2013).Method: We analysed trends in termination rates and birth prevalence of Down syndrome using aggregated data (1980-2013). We modelled the expected live-birth rate and prevalence of Down syndrome and compared different eras of screening and diagnosis with respect to the impact on live-birth rate and prevalence of Down syndrome.Results: Between 1980 and 2013, the rate of Down syndrome pregnancies increased, corresponding to a greater proportion of babies born to older women. Following the introduction of screening in 1994, the rate of live-born infants with Down syndrome reduced significantly (p = 0.001). The rate of terminations of pregnancy for Down syndrome remained stable over this period. In the absence of termination, the Down syndrome live-birth rate would have risen from 1.1 per 1000 to 2.17 per 1000 between 1980 and 2013.Conclusion: Prenatal testing in Western Australia has reduced the birth prevalence of Down syndrome despite an increased rate of Down syndrome pregnancies. Most women for whom a prenatal diagnosis of fetal Down syndrome is made, chose to terminate the pregnancy (93%), and this proportion has not changed over the study period. [ABSTRACT FROM AUTHOR]

Objective: To investigate midwives' knowledge of prenatal diagnosis especially Down syndrome, information given by midwives to parents, expectant parents' requests for information and how midwives perceive their own competence to give information.Method: A cross-sectional, prospective study with a questionnaire was completed by 64 out of 70 midwives working in the outpatient antenatal care in Uppsala County, Sweden.Results: The midwives had varying and in some areas low levels of knowledge about Down syndrome. Information about Down syndrome was most often given only when asked for or when there was an increased probability of a Down syndrome pregnancy. The most common questions from expectant parents concerned test methods and risk assessments while questions regarding symptoms of Down syndrome and consequences of having a child with Down syndrome were uncommon. The majority (83-89%) had insufficient or no education regarding different prenatal tests. Only two midwives (3%) had received education about Down syndrome, and 9% felt they had sufficient knowledge to inform about the syndrome. More education about prenatal tests and Down syndrome was desired by 94%.Conclusion: It is important to ensure that midwives in antenatal care have sufficient knowledge to inform expectant parents about the conditions screened for. © 2015 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Study Question: How does a national prenatal screening program for Down syndrome (DS) perform in detecting sex chromosome abnormalities (SCAs)-Turner syndrome (TS), Klinefelter syndrome, 47,XXX and 47,XYY syndromes.Summary Answer: The SCA detection rate resulting from DS screening was below 50% for all four groups of SCAs.What Is Known Already: The detection rates of SCAs are higher in countries with DS screening. TS is associated with greater nuchal translucency (NT) and lower pregnancy-associated plasma protein-A (PAPP-A). However, specific detection rates of SCAs using prenatal DS screening have not been determined. No clear trend in PAPP-A, free beta human chorionic gonadotropin (β-hCG) and NT has been found in the remaining SCAs. Several lines of inquiry suggest that it would be advantageous for individuals with SCA to be detected early in life, leading to prevention or treatment of accompanying conditions. There is limited information about pre- and perinatal status that distinguishes SCA embryogenesis from normal fetal development.Study Design, Size, Duration: A register-based case-control study from the Danish Central Cytogenetic Register (DCCR), cross-linked with the Danish Fetal Medicine Database (DFMD), was performed from 2008 to 2012. Groups of SCAs were compared with DS and then matched with non-SCA controls to assess differences between these groups in prenatal markers and birth outcomes.Participants/materials, Setting, Methods: We included cases with prenatal and post-natal SCA karyotypes (n = 213), DS (n = 802) and 168 056 controls. We screened 275 037 individuals examined prenatally. We retrieved information regarding maternal age, NT, β-hCG and PAPP-A, as well as details regarding maternal and newborn characteristics.Main Results and the Role Of Chance: The DS screening procedure detected 87 per 100 000 TS (42% of expected), 19 per 100 000 Klinefelter syndrome (13% of expected), 16 per 100 000 47,XXX (16% of cases) and 5 per 100 000 47,XYY (5% of expected) SCAs, with an overall detection rate of 27%. Compared with controls, all four SCA groups showed significantly higher NT and lower PAPP-A compared with controls (all P < 0.01) and similar to DS. The legal abortion rate was high for all four syndromes (47,XXX: 24%; 47,XYY: 29%; Klinefelter syndrome: 48%, TS: 84%). For SCA fetuses carried to term, only TS fetuses had consistently lower birthweights and placenta weights than non-SCA controls (both P = 0.0001). A few SCA cases localized in DCCR could not be found in DFMD (n = 16).Limitations, Reason For Caution: Controls were matched on sex of the fetus of cases, meaning that all electively aborted fetuses (before week 12) were excluded, possibly reducing the diversity in the control group. We were not able to localize all diagnosed cases of SCA and DS in DFMD. Although these cases were present in DCCR, we were not able to account for the discrepancy. In addition, we suspect that several SCA children have not been diagnosed yet and future post-natal diagnosis of these cases would reduce the diagnostic yield reported here even further.Wider Implications Of the Findings: The prenatal detection rate is below 50% for all SCAs. The approach used for detecting DS cannot be extended to also include SCAs. In addition, all SCAs have low PAPP-A and increased NT, thus probably reflecting an abnormal embryogenesis. Growth retardation of TS fetuses is if anything more pronounced than previously reported, both when evaluating fetus and placenta.Study Funding/competing Interests: This study received support from Aarhus University and the Novo Nordisk Foundation. The authors have no competing interests that may be relevant to the study. [ABSTRACT FROM AUTHOR]

Prenatal screening tests can help to estimate the possibility of a pregnant woman having a baby with trisomy 21 ( Down syndrome). As these tests are optional, it is essential that women are provided with appropriate verbal and written information to enable them to make an informed choice. In this study, we assessed the content and quality of Down syndrome screening information leaflets used by health professionals to provide information to pregnant women in the UK (26 leaflets) and Thailand (11 leaflets). We collected leaflets from health institutions and the Internet, and compared the topics covered in each one against recommendations for patient information on this topic. We also assessed the quality of each leaflet using the DISCERN Genetics tool. While the quality-rating score of the UK leaflets was significantly higher than the Thai leaflets, none of the leaflets included all the recommended topics; some contained erroneous material. In both countries, the quality of information can be improved to provide accurate information to women and their partners, which is essential to ensure prospective parents can make informed choices during pregnancy. [ABSTRACT FROM AUTHOR]

Background: Previous studies showed disparities in prenatal screening for Down syndrome according to socio-economic status and maternal place of birth. Thus, it remains uncertain that those disparities are related to access difficulties or lack of information offered to women. Our objective was to assess the opportunity for informed choice regarding Down syndrome screening according to maternal place of birth. Methods: Data were based on French national perinatal surveys of 2010 and 2016. These surveys include several questions relative to Down syndrome screening, such as measurement of nuchal translucency and realization of maternal serum screening. We considered that women had the opportunity for choice in case of realization or refusal of prenatal screening, or realization of amniocentesis or chorionic villous sampling. We considered that women had no opportunity for choice in case of ignorance of the realization of the tests, or if the screening has not been performed because not proposed, late prenatal follow-up, or another reason or unknown reason. We used multinomial logistic regression models to assess the association between the use of the tests and women country of birth. Results: The proportion of women undergoing measurement of nuchal translucency or maternal serum screening was higher in women born in France than women born in another country After adjustment on the year of the survey, maternal age, parity, education level and type of maternity, and after exclusion of women without adequate prenatal follow-up, the opportunity for making an informed choice for Down syndrome screening was higher for women born in France than women born in another European country (ORa 2.36; 95%CI,1.8-3.0), in Maghreb (ORa 4.01; 95%CI,3.4-4.8) or in another African country (ORa 3.52(2.8-4.3). Conclusions: Disparities in the use of Down syndrome screening according to women place of birth are almost partly related to differences in the opportunity of an informed choice. [ABSTRACT FROM AUTHOR]

The article presents the public health and ethics the case of prenatal screening and Down's syndrome. Topics include the societal attitudes to disability in the Great Britain however remain problematic, with increased reports of hate crime, the United Nations identifies a wide range of improvements needed to improve people's lives, and the medical profession has in a number of cases lagged in recognizing the value of those with disability, suffering, and disease with respect to Down's syndrome.

We evaluated the use of multiplex antibody array methodology for simultaneous measurement of serum protein markers for first trimester screening of Down Syndrome (DS) and other pregnancy outcomes such as preeclampsia. For this purpose, we constructed an antibody array for indirect (“sandwich”) measurement of seven serum proteins: pregnancy-associated plasma protein-A (PAPP-A), free beta subunit of human chorionic gonadotropin (fβ-hCG), alpha-fetoprotein (AFP), angiopoietin-like 3 (ANGPTL3), epidermal growth factor (EGF), insulin-like growth factor 2 (IGFII), and superoxide dismutase 1 (SOD1). This array was tested using 170 DS cases and 510 matched controls drawn during the 8th–13th weeks of pregnancy. Data were used for prediction modelling and compared to previously obtained AutoDELFIA immunoassay data for PAPP-A and fβ-hCG. PAPP-A and fβ-hCG serum concentrations obtained using antibody arrays were highly correlated with AutoDELFIA data. Moreover, DS prediction modeling using (log-MoMmed) antibody array and AutoDELFIA data gave comparable results. Of the other markers, AFP and IGFII showed significant changes in concentration, although adding these markers to a prediction model based on prior risk, PAPP-A and fβ-hCG did not improve the predictive performance. We conclude that implementation of antibody arrays in a prenatal screening setting is feasible but will require additional first trimester screening markers. [ABSTRACT FROM AUTHOR]

Background: Non-invasive prenatal testing (NIPT) for Down’s syndrome (DS) using cell free fetal DNA in maternal blood has the potential to dramatically alter the way prenatal screening and diagnosis is delivered. Before NIPT can be implemented into routine practice, information is required on its costs and benefits. We investigated the costs and outcomes of NIPT for DS as contingent testing and as first-line testing compared with the current DS screening programme in the UK National Health Service. Methods: We used a pre-existing model to evaluate the costs and outcomes associated with NIPT compared with the current DS screening programme. The analysis was based on a hypothetical screening population of 10,000 pregnant women. Model inputs were taken from published sources. The main outcome measures were number of DS cases detected, number of procedure-related miscarriages and total cost. Results: At a screening risk cut-off of 1∶150 NIPT as contingent testing detects slightly fewer DS cases, has fewer procedure-related miscarriages, and costs the same as current DS screening (around UK£280,000) at a cost of £500 per NIPT. As first-line testing NIPT detects more DS cases, has fewer procedure-related miscarriages, and is more expensive than current screening at a cost of £50 per NIPT. When NIPT uptake increases, NIPT detects more DS cases with a small increase in procedure-related miscarriages and costs. Conclusions: NIPT is currently available in the private sector in the UK at a price of £400-£900. If the NHS cost was at the lower end of this range then at a screening risk cut-off of 1∶150 NIPT as contingent testing would be cost neutral or cost saving compared with current DS screening. As first-line testing NIPT is likely to produce more favourable outcomes but at greater cost. Further research is needed to evaluate NIPT under real world conditions. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the performance of noninvasive prenatal testing for all fetal chromosomal aneuploidies in an extremely high-risk group undergoing first trimester combined Down syndrome screening. Method: A multicenter cohort prospective study in Taiwan was performed between June and December 2012. Maternal plasma was collected and shotgun massive parallel sequencing was performed on each fetal chromosome. 201 Taiwanese pregnant women at >12 weeks' gestation from 11 medical centers were enrolled in this trial. The extremely high-risk group was defined as a Down syndrome risk cutoff >1:30 or nuchal translucency >3.0 mm (n = 100), while the low-risk group was defined as a Down syndrome cutoff <1:1,500 (n = 101). Amniocentesis confirmation was performed and birth outcome was also recorded. Results: There were 11 cases of trisomy 21, 8 cases of trisomy 18, 3 cases of trisomy 13, 1 case of trisomy 16, 3 cases of 45,X, and 1 case of 47,XYY detected prenatally in 100 extremely high-risk gravidas [n = 27/100 (27%)]. The overall autosomal or sex chromosome aneuploidy detection rate was 96% (27/28) because of an insufficient amount maternal plasma for one fetus with Turner syndrome. In the low-risk group, no chromosomal abnormalities were detected (specificity = 100%). There were no false-positive cases in this study. Conclusions: This first trial in Taiwan shows that noninvasive prenatal testing for whole chromosome aneuploidies can be efficiently applied in extremely high- and low-risk populations. © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Aims and objectives To determine awareness, use and attitudes of Turkish women towards prenatal screening tests ( PST) for Down syndrome ( DS). Background The technology of screening and diagnosing congenital diseases and abnormalities of foetuses has rapidly developed in the past few decades and prenatal screening for DS in early pregnancy is a valued component representing a cost-effective public health intervention in modern developed countries. Design Cross-sectional and descriptive study. Methods The study was carried out in 518 women in the early postpartum period at the Maternity and Children's Hospital between 1 September 2010 and 1 March 2011 using a questionnaire developed by the researchers. Results Awareness about the first- and second-trimester PST [nuchal translucency ( NT), triple test] was 21·6 and 59·7%, whereas use of them was 13·7 and 44·8%, respectively. Women who had lower education, were unemployed, had a patriarchal family type, had a low income status, were unmarried, had consanguineous marriage and did not have a private doctor were less aware and had less use of NT and/or triple test. Women who did not have a genetic disease in their family, were multiparous, had an unplanned pregnancy and did not receive antenatal care were less aware and had less use of the triple test. In case, the foetus was diagnosed as DS, women made the following decisions: continuing the pregnancy, terminating the pregnancy, leaving the decision to the doctor and being not sure 34·9, 12·0, 29·9 and 23·2%, respectively. Conclusion Women's knowledge about and attitudes towards PST are important. This study shows that Turkish women have limited knowledge about and use of PST. Therefore, health professionals play a significant role in improving patients' information about PST. They should dedicate more time to discussions with women, provide appropriate and understandable information tailored to women's socio-economical level and should emphasise the indications, purposes and limitations of PST. Relevance to clinical practice Discovering women's opinions and knowledge about PST will help healthcare providers determine their information needs. [ABSTRACT FROM AUTHOR]

The article reports development of prenatal tests for women and recommends that all pregnant women must be offered this examination before 20 weeks' gestation. The currently available test uses plasma to discover any anomalies namely, Trisomy 21, 13, and 13 related to fetal chromosome by means of parallel sequencing. With the aim of having a highly sensitive noninvasive diagnostic test for fetal aneuploidy, the test delivers favorable results.

In the Netherlands, both the LifeCycle Elipse (LC) and the Astraia software package are used to calculate the risk of having a child with Down syndrome. Therefore, pregnant women can be presented with dissimilar risks. In this study the conformity between these risks before and after harmonization of the screening program and its influence on the performance indicators of the first trimester screening were evaluated. The agreement between combined risks (based on the biochemical parameters PAPP-A and fβ-hCG and a nuchal translucency measurement) was expressed as intraclass correlation coefficient (ICC)=0.99. Conformity between combined risks was better after harmonization (Cohen's κ=0.75) than before harmonization (Cohen's κ=0.63). For both risk calculation software packages the area under the ROC-curve was 0.84. The database contained 42 Down syndrome cases; based on the odds of being affected given a positive result (OAPR), LC performed slightly better than Astraia before harmonization (17.9 vs. 21.5, respectively). It has been acknowledged that using different software packages could lead to dissimilar risk calculations. In this study the screening performance indicators of two software packages were quite similar. The agreement of the screening performance after harmonization remains to be seen, but is expected to be even higher. [ABSTRACT FROM AUTHOR]

The aim of this article is to give an overview of current status of worldwide discussion of effectivness of Down's syndrome screeening programs. This article explaines structure of basic screening strategies and review of their published evidence. In this article screening tests of the first trimester (combined test with or without new sonographic markers), the second trimester (quadruple, triple and double test) and tests which combine markes of the first trimester with markers of the second trimester (integrated test, sequential test and contingent tests) are discussed. Arguments supporting current trend to perform screening in the first trimester with combination ultrasound and biochemical markers of the first trimester are discussed. [ABSTRACT FROM AUTHOR]

Objective: To describe any trends in the uptake of antenatal screening for Down's syndrome since the addition of the earlier first trimester combined test. Study Design: All antenatal screening tests for Down's syndrome were carried out and their results were recorded by the Clinical Biochemistry Department at the Hull Royal Infirmary (HRI) and reviewed against the antenatal booking data held at the Women and Children's Hospital at HRI. The uptake of antenatal Down's syndrome screening for 5 different age groups of women across a four-year-period from 2007 to 2010 was analysed. Results: There was a significant increase in uptake of antenatal screening for Down's syndrome from 43.9% to 56.5% after the introduction of the combined test in 2010. This increase was apparent in all age groups. There was no change in the proportion of women opting for an invasive test following a positive screening test. Conclusion: Addition of the earlier first trimester combined test has increased uptake of antenatal screening for Down's syndrome in women of all ages. This is most likely due to the advantages this test gives women such as earlier decision making, earlier further invasive diagnostic testing and earlier termination, if necessary. [ABSTRACT FROM AUTHOR]

Abstract: In the past two decades second-trimester maternal serum screening for Down syndrome has been the most common strategy for prenatal diagnosis of chromosomal aneuploidies. More recently, screening for and diagnosis of chromosomal abnormalities have increasingly been performed in the first trimester. With improvements and technological advances in ultrasound, it is now possible to identify many fetal anomalies at 11–13weeks of gestation. During the same period biochemical markers in maternal serum (PAPP-A and hCGβ) combined with sonographic measurement of nuchal translucency achieve a Down syndrome detection rate of 85% with a 5% false-positive rate. We describe here the potential of first-trimester markers to screen for Down syndrome as well as other adverse outcomes such as fetal loss, pre-eclampsia, intrauterine growth retardation, and preterm delivery. This early consultation may be the opportunity to help counsel patients and to screen for other adverse complications during pregnancy, such as pre-eclampsia, and to manage potential adverse pregnancy outcomes. [Copyright &y& Elsevier]

Objective: To report the strategy of first-trimester aneuploidy screening in pregnancies at risk for homozygous α(0)-thalassemian.Methods: Women at risk of homozygous α(0)-thalassemia were given an ultrasound examination at 11-14 weeks' gestation to exclude an affected pregnancy. Fetal cardiothoracic ratio (CTR) and nuchal translucence (NT) were measured. If cardiomegaly was found, chorionic villus sampling (CVS) was offered for α-thalassemia; otherwise the first-trimester combined screening test was performed on the pregnancy. The invasive testing for karyotyping was only followed in those cases with a positive aneuploidy screening test.Results: In total, 69 of 288 pregnancies were found to be affected by homozygous α(0)-thalassemia using ultrasound, and the findings were confirmed by invasive testing. In the remaining 219 pregnancies, invasive testing was not performed for α-thalassemia because of a normal fetal CTR, and the women received the first-trimester combined screening. Nine CVS procedures were performed for karyotyping because of a positive aneuploidy screening. Totally three pregnancies with aneuploidy were diagnosed and terminated.Conclusions: Our strategy can selectively detect aneuploidy pregnancies not affected by homozygous α-thalassemia, and, meanwhile, save on the cost of unnecessary aneuploidy screening or karyotyping in pregnancies with an affected fetus of homozygous α(0)-thalassemia. [ABSTRACT FROM AUTHOR]

We sought to update the value of the 11- to 13 +6-week ultrasound evaluation for prenatal screening of trisomy 21. An English literature search was conducted for pertinent original research articles, review articles, and websites related to the 11- to 13 +6-week ultrasound evaluation. Reports from prenatal diagnostic units published since 1990 that included two- and three-dimensional ultrasound and Doppler hemodynamic evaluations for prenatal screening of trisomy 21 between weeks 10 and 13 +6of gestation were selected. Alternative screening methods were identified, and clinical information concerning each of them was extracted, integrated into tables, and then synthesized to provide meaningful clinical interpretations. Finally, mechanisms that could lead to improvements in the efficiency of these screening tests are discussed. Two-dimensional measurements of the fetal nuchal translucency play a key role in screening for trisomy 21. Evaluations of the nasal bone, ductus venosus, tricuspid valve function, frontomaxillary facial angle, hyperechogenic bowel, intracardiac echogenic focus, and renal pelvis fullness can become part of the 11- to 13 +6-week screening test if the imaging protocols are standardized. The role of 3-D ultrasound during the 11- to 13 +6-week ultrasound evaluations is under investigation. [ABSTRACT FROM AUTHOR]

The article offers tips for selecting laboratory for Cell-free DNA (cfDNA) testing. Suggestions include looking for a laboratory that have publicly available validation data and significant existing experience; clear description of test methodology; and availability of laboratories screening for trisomy 21, trisomy 18 and trisomy 13. It also mentions two different methods of cfDNA testing including massively parallel shotgun sequencing (MPSS) and chromosome-selective sequence analysis. [ABSTRACT FROM AUTHOR]

Objective: To assess the usefulness of triple-marker screening for Down syndrome in Venezuela.Method: Maternal serum concentrations of alpha fetoprotein (AFP), beta human chorionic gonadotropin (beta-hCG), and unconjugated estriol (uE3) were measured weekly in 3895 women from the 15th to the 20th week of pregnancy. Population-specific likelihood ratios were determined and used to calculate the risk of fetal Down syndrome for each pregnancy.Results: The median multiple of the median values for AFP, beta-hCG, and uE3 concentrations were 0.69, 2.10, and 0.67 for the affected pregnancies. The likelihood ratio for a positive result was 1:19. The detection and false-positive rates were 69.23% and 5.8%.Conclusion: These findings were consistent with reported data and therefore confirmed triple-marker serum screening as effective and suitable for prenatal care in Venezuela. Latin American governments and Health Agencies should recommend offering this screening method to all pregnant women. [ABSTRACT FROM AUTHOR]

Policies and practices around antenatal screening services have long been the subject of debate in a sociological context. However, existing research has largely overlooked the way in which the policies and practices that underpin antenatal screening services are enacted through talk between pregnant women and their health professionals. This paper focuses on one such policy, that of informed choice. It uses data from 14 tape-recorded pre-screening consultations with community midwives, forming part of a newly introduced nuchal translucency screening programme, to examine how the issue of choice is topicalised and discussed. It concludes that, whilst there is clear evidence that midwives are at pains to explicitly invoke the issue of decision making, there are other more subtle factors in the interactional presentation of screening tests that serve to undermine whether and how a recognition of choice is received by pregnant women. [ABSTRACT FROM AUTHOR]

The article discusses various prenatal screening options for Down syndrome and other fetal abnormalities. Down syndrome is the most common genetic cause of mental retardation. Screening options include second trimester quad, first trimester combined, serum integrated, full integrated and sequential integrated.

Objective: To validate empirically the accuracy of antenatal Down's syndrome screening using the Integrated test, to compare this with other screening tests (including the Integrated test with the addition of cross trimester [CT] marker ratios) and to suggest how such validation analyses should be presented and interpreted. Methods: Using data from 7809 unaffected and 27 Down's syndrome pregnancies that had had an Integrated test, risk estimates for various screening tests (maternal age, Double, Triple, Quadruple, Combined, Integrated and serum Integrated tests) that use Integrated test markers were categorized according to quintile categories of risk estimates of the 27 affected pregnancies. For each screening test, the median risk estimate for each category was plotted against the observed prevalence within each category. Such validation plots were also produced for the Integrated test with CT marker ratios by measuring the level of the serum markers in the trimester of pregnancy not already measured in stored samples of all affected and a one-in-five sample of unaffected pregnancies. The robustness of the method was assessed by repeating the analysis for the Integrated test after re-classifying affected pregnancies with low risk estimates as unaffected, simulating the underascertainment of cases. Results: The validation plots (i) confirmed the accuracy of risk estimation for the different tests (by how close the points lay to the line of identity between predicted risk and observed prevalence), (ii) demonstrated the differences in screening performance of the different tests (by the range of risk spanned by the points and, in particular, the separation between the points representing the lowest risk and the next point), and (iii) are robust to underascertainment of affected pregnancies (by having little influence on the closeness of the points to the line of identity). Conclusion: The validation plot is a useful, simple and robust way to assess the validity of new screening methods, to assess the accuracy of risk estimation and to audit the performance of screening programmes. [ABSTRACT FROM AUTHOR]

Pregnancy-associated plasma protein A (PAPP-A) is a maternal serum marker of fetal chromosomal disease and a risk marker for adverse outcome. PAPP-A in the circulation exists both as a 2:2 complex (PAPP-A/proMBP) with the proform of eosinophil major basic protein (proMBP) and as dimeric PAPP-A. Non-PAPP-A containing proMBP complexes constitute the bulk of proMBP in maternal serum. We developed and characterized a sandwich enzyme immunoassay for PAPP-A using a polyclonal rabbit anti-PAPP-A/proMBP antibody (SSI 6823) and a monoclonal murine anti-PAPP-A/proMBP antibody (HYB 234-3), reactive with the PAPP-A part of PAPP-A/proMBP. The assay range was 2 mIU/L-500 mIU/L, intra- and inter-assay coefficients of variation <10%. The immunoreactivity eluted ahead of thyroglobulin, Mr 669 kDa, in gel filtration and bound to a heparin column. Serum concentrations of PAPP-A were determined in gestational weeks 5-13 in 167 pregnant women with normal fetuses and 39 women with Down's syndrome (DS) fetuses. The median PAPP-A MoM (multiples of the median in normal controls) in DS pregnancies was 0.30 (quartile range: 0.17-0.54). The PAPP-A logMoMs in DS pregnancies were normally distributed with a mean of -0.5927 and SD of 0.3639. When simulating the performance of PAPP-A and age as markers for DS in population screening a detection rate (DR) of 62% was found for a screen positive rate (SPR) of 5%. Together with beta-HCG and nuchal translucency, two other first trimester markers for fetal DS, a DR 90% could be obtained for an SPR of 5%. [ABSTRACT FROM AUTHOR]

An editorial is presented which explores the comparison of different screening methods to keep the specific test performance, both the detection rate and false-positive rate, distinct from the uptake of further testing.

Objectives We evaluated the performance of first trimester screening for Down syndrome in women less than 35 years of age (study group) and in women aged 35 years or more (control group) in an unselected low-risk population. Methods The study group comprised a total of 63 945 women who participated in the first trimester combined screening in public health care in Finland during the study period of 1 May 2002 to 31 December 2008. Women at the age of 35 or more ( n = 13 004) were controls. Prevalence of Down syndrome, detection rate, false positive rate and number of invasive procedures needed to detect a single case of Down syndrome were analyzed in both groups. Results The overall prevalence of Down syndrome ( n = 73) in the study group was 1:876. The number of detected cases was 54. The detection rate was 74.0% with a false positive rate of 2.8%. Number of invasive procedures needed to detect a single case of Down syndrome was 33. In the control group, the detection rate was 87.0% with a false positive rate of 11.9%. The number of invasive procedures needed to detect a single case of Down syndrome was 15. The differences in detection rate and false positive rate were significant, P < 0.012, P < 0.001, respectively. Conclusion The overall detection rate given for the entire population is an overestimate for a woman younger than the age of 35, which should be taken into consideration when counselling women of that age. [ABSTRACT FROM AUTHOR]

The author comments on the method of test interpretation for suboptimal Down's syndrome screening. He wrote a paper urging the combination of biochemical and ultrasound screening for Down's syndrome into a single late first-trimester test. At that time, the method of test interpretation hinders rapprochement. He suggests three principles of screening needed in evaluating the optimal way to allow for gestation and calculate risks.

Among patients with pregnancies considered at‐risk for Down syndrome undergoing non‐invasive prenatal testing, preferring extended reports was associated with greater education and knowledge of testing. [ABSTRACT FROM AUTHOR]

The article offers information on the cell-free fetal DNA (cffDNA) screening and its increasing use in Australia. Topics discussed include a study in Denmark which reported a 50% reduction in live-born prevalence of Down syndrome and 50% reduction in invasive testing following the introduction of combined first tri-mester screening, and another study in Victoria which found a high positive predictive value for cffDNA.