Prenatal Screening For Down Syndrome Research Articles

GC–MS analysis of seven metabolites for the screening of pregnant women with Down Syndrome fetuses

Down Syndrome is a genetic disorder caused by the presence of all or part of a third copy of chromosome 21. Metabolomics is identification and quantification of small-molecule metabolites (molecular weight <1000 Da) in tissues, cells and physiological fluids within a certain period time. Metabolites are intermediate products of various types of biochemical reactions that participate in bonding metabolic pathways. In this study, metabolites such as 2-Hydroxybutyric acid, 3-Hydroxybutyric acid, β-Hydroxyisovaleric acid, Uracil, Glutamic acid, Maltose and Melezitose were chosen as the possible determinants/markers for the prenatal screening of Down Syndrome. Quantitative analysis of the metabolites conducted by GCMS method using 5 % phenyl / 95 % dimethylpolysiloxane (30 m ×0.25 mm, 0.25 μm film thickness) capillary column. The oven temperature was held constant at 60 °C for 1 min and ramped at 10 °C /min to 200 °C then ramped at 30 °C/min to 320 °C and hold for 6 min before cool-down, as helium mobile phase and flow rate of 2.8 mL/min and adding Myristic acid-d27 as an internal standard. Our method was validated by parameters of system suitability, stability, linearity, sensitivity, accuracy, precision, selectivity, robustness and ruggedness. The developed and validated method was applied to plasma samples taken from pregnant women with Down Syndrome (study group) and euploid fetuses (healthy group). The levels of these seven metabolites are statistically different (p < 0.05 for all) between the groups. It can be concluded that these relevant metabolites might be used for the prenatal screening of Down Syndrome.

First-trimester screening versus non-invasive prenatal testing for Down syndrome at high-risk pregnant women in Hanoi Obstetrics and Gynecology Hospital, Vietnam: A cost-utility analysis

ABSTRACT Background: Non-invasive prenatal testing (NIPT) is a relatively new technology for diagnosis of fetal aneuploidies in the context of a developing country like Vietnam. Currently, first-trimester screening (FTS) is more conventional in Vietnam. NIPT is assumed to be more accurate than other maternal screening but is also more costly. The purpose of the study was to perform a cost-utility analysis comparing the FTS and NIPT for Down syndrome for high-risk pregnant women (over 35-year-old) in Vietnam. Methods: Decision tree model and probabilistic sensitivity analysis were used. Results: With the modelling population of 27,232 over 35 years of age pregnant women, FTS helps detect 218.5 cases of the fetus with Down syndrome compared with 247.2 cases when screening with NIPT. In addition, NIPT reduced 1384 false-positive cases compared to FTS. From a societal perspective, NIPT-dominated FTS. Compared to FTS, adopting an NIPT would cost an additional of USD 3,800 for each additional quality-adjusted life-year gained. Conclusions: NIPT is a cost-effective alternative to FTS for prenatal screening for Down syndrome with high-risk pregnant women. This is a very first attempt on cost-utility analysis of prenatal screening methods for Down syndrome in Vietnam and recommendations are made for future research to determine the most cost-effectiveness methods.

Missed Down Syndrome Cases after First Trimester False-Negative Screening-Lessons to be Learned.

Background and Objectives: Here, we performed a descriptive analysis of Down syndrome (DS) cases that were misdiagnosed and/or false-negative diagnosed after first trimester traditional screening via risk evaluation using ultrasound, biochemical markers, and different software programs. Our objective was to demonstrate the clear need to improve the application of prenatal DS screening programs using standardized ultrasound measurements, accurate pregnancy dating, analytical immunoassay performance, and properly selected medians. Materials and Methods: We performed a database search for the period 2010–2015 to analyze DS cases that were false-negative diagnosed after the first trimester of pregnancy, before the introduction of cell free fetal DNA-based tests by Romanian laboratories in 2015. First-trimester screening was performed using two software programs for prenatal DS risk calculation: Astraia and Prisca. The rationale for using both software programs was to assess the full risk using the maternal age combined test (based on nuchal translucency thickness, nasal bone, ductus venosus flow, tricuspid flow, free beta-human chorionic gonadotropin level, and serum pregnancy-associated plasma protein-A) and, in some cases, the triple test. Results: We identified seven DS cases that exhibited low risk for trisomy 21, and 6540 cases with a low risk for trisomy 21 and euploid fetus in the first trimester. Using Astraia software, 14 cases were diagnosed, and three cases were missed after risk calculation. Using Prisca software, four cases were missed. Additionally, one neonate had a missed prenatal diagnosis of atrio-ventricular canal defect. Conclusion: In Romania, the evaluation of DS risk depends on patient choice (without knowing the accuracy of the utilized tests) and on the operators’ skills. Both Astraia and Prisca software were developed by experts, who can prove their performance in DS screening. However, even in an ideal situation, false-negative results are possible. The application of first and second-trimester combined screening based on biochemical markers could be improved by the implementation of standardized protocols, professional guidelines for test application, and audit control.

Evolution of Down Syndrome Prenatal Screening Clinical Practices in Québec.

Prenatal screening for Down syndrome (DS) has evolved greatly over the last decades with the improvement of first- and second-trimester serum screening and the introduction of cell-free fetal DNA. This study aimed to estimate the impact of such changes on practices. This retrospective cohort study included fetuses and newborns diagnosed with DS between 2005-2007 and 2015-2017 in the single obstetrical care centre in Québec City. Data were collected on the prenatal screening method, diagnosis, and delivery. The median was compared between the study periods. Complete clinical data were available for only 78 (66%) of 119 cases of DS. Significant changes were observed in screening methods, including an increase in the use of first-trimester serum, ultrasound, and cell-free fetal DNA. No significant changes were noted in terms of gestational age at diagnosis (median [interquartile range; IQR]: 17.0 [16.0-20.9] weeks in 2005-2007 vs. 17.9 [16.3-22.5] weeks in 2015-2017; P = 0.49) and delivery or termination of pregnancy (median 20.9 [IQR 18.0-23.3] weeks in 2005-2007 vs. 21.3 [18.4-23.4] weeks in 2015-2017; P = 0.46). The methods of diagnosis did not change significantly over the decade, with amniocentesis used 85% and 79% of the time, respectively (P = 0.19). The increased use of first-trimester screening and cell-free fetal DNA tests was not associated with earlier diagnosis of DS or earlier delivery or termination of pregnancy. The use of chorionic villus sampling should be encouraged for DS diagnosis when indicated because it could reduce the gestational age at diagnosis and termination if requested.

Receiving the news of Down syndrome in the era of prenatal testing.

To explore the prenatal trajectory and the experiences of mothers of a child with Down syndrome (DS) at the time of receiving information or test results when participating in a nationwide prenatal screening program. An online questionnaire study was completed by mothers of children with DS born between January 1, 2010 and February 28, 2016 (n = 212). Data were collected between February 15 and 28, 2016. Most of the live born children with DS were diagnosed postnatally. The majority of their mothers had explicitly chosen not to have prenatal DS screening. Of the 39 mothers prenatally informed their child might have DS, only 49% were completely or mostly satisfied about the information provided by their clinical providers at that time. About 16% of women (of the 38 that answered this question) recall some perceived emphasis on the option of terminating pregnancy as the first choice. Mothers who had received a postnatal diagnosis rated the experience as more positive than their counterparts who received prenatal diagnoses. With recent developments in screening, more parents are expected to receive a DS diagnosis before birth. Meeting the parents' individual counseling needs at the time of prenatal diagnosis requires careful exploration of their personal values and preferences.

Inhibin as a reproductive biomarker part 2. Clinical significance of inhibins in reproductive medicine

In the early 2000s, the determination of inhibin levels was used actively for the diagnosis of ovarian tumors, as a diagnostic marker for prenatal screening of Down syndrome, as well as a prognostic marker for ovarian reserve when conducting assisted reproductive technologies. However, to date, inhibin is rarely used as a marker for reproductive function. At the same time, numerous studies of recent years indicate the crucial role of inhibin in folliculogenesis and spermatogenesis, as well as in implantation and placentation. This allows to significantly expand the diagnostic spectrum of inhibin levels in various disorders of the reproductive system of both women and men.

Cost-effectiveness of prenatal screening and diagnostic strategies for Down syndrome: A microsimulation modeling analysis

ObjectivesDown syndrome (DS) is the most frequently occurring fetal chromosomal abnormality and different prenatal screening strategies are used for determining risk of DS worldwide. New non-invasive prenatal testing (NIPT), which uses cell-free fetal DNA in maternal blood can provide benefits due to its higher sensitivity and specificity in comparison to conventional screening tests. This study aimed to assess the cost-effectiveness of using population-level NIPT in fetal aneuploidy screening for DS.MethodsWe developed a microsimulation decision-analytic model to perform a probabilistic cost-effectiveness analysis (CEA) of prenatal screening and diagnostic strategies for DS. The model followed individual simulated pregnant women through the pregnancy pathway. The comparators were serum-only screening, contingent NIPT (i.e., NIPT as a second-tier screening test) and universal NIPT (i.e., NIPT as a first-tier screening test). To address uncertainty around the model parameters, the expected values of costs and quality-adjusted life-years (QALYs) in the base case and all scenario analyses were obtained through probabilistic analysis from a Monte Carlo simulation.ResultsBase case and scenario analyses were conducted by repeating the micro-simulation 1,000 times for a sample of 45,605 pregnant women per the population of British Columbia, Canada (N = 4.8 million). Preliminary results of the sequential CEAs showed that contingent NIPT was a dominant strategy compared to serum-only screening. Compared with contingent NIPT, universal NIPT at the current test price was not cost-effective with an incremental cost-effectiveness ratio over $100,000/QALY. Contingent NIPT also had the lowest cost per DS case detected among these three strategies.ConclusionIncluding NIPT in existing prenatal screening for DS is shown to be beneficial over conventional testing. However, at current prices, implementation of NIPT as a second-tier screening test is more cost-effective than deploying it as a universal test.

Budget impact of incorporating non-invasive prenatal testing in prenatal screening for Down syndrome in Turkey

ObjectivesTo provide information to the government about the budget impact of implementing non-invasive prenatal testing (NIPT) into prenatal screening strategies to detect Down syndrome (DS) in singleton pregnancies in Turkey; the likely costs or savings associated with NIPT in comparison to the current practice were calculated. MethodsA decision-analytic model was developed to calculate the cost estimates for 1,309,771 women who gave birth in 2016; 84.8% of whom were <35-years-of-age. The superior combined test (CT) among current strategies is compared with contingent NIPT for women < 35-years-of-age; and usual practice of amniocentesis (AC) for women ≥ 35 years-of-age was replaced with universal NIPT. ResultsWhen the market price of NIPT (1,077 PPPUS$) is used, contingent NIPT offered to high-risk women < 35-years-of-age adds 34,907,225 PPPUS$; and for women-35 ≥ years-of-age the universal NIPT leads to 142,785,818 PPPUS$ more cost to the government compared to current strategies. The additional costs with NIPT are partially compensated by the cost-savings due to reduction of the number of invasive tests and procedure related losses (17,826,476 PPPUS$ for women < 35-years-of-age and 37,070 PPPUS$ for women ≥ 35-years-of-age). Results are sensitive to the NIPT costs; with a lower cost of NIPT, a total saving would be 33,116,046 PPPUS$ with new strategies. ConclusionsNIPT might be the choice of prenatal screening strategies if its price is lowered to economically acceptable levels. Until that time, currently accepted protocols seem to be more realistic. On the other hand, decision makers should also consider possible savings and the women's quality of life that can be improved with the new technology.

Down Syndrome Prediction Using a Cascaded Machine Learning Framework Designed for Imbalanced and Feature-correlated Data

Down syndrome (DS) caused by the presence of part or all of a third copy of chromosome 21 is the most common form of aneuploidy. The prenatal screening for DS is a key component of antenatal care and is recommended to be universally offered to women irrespective of age or background. The objective of this paper is to introduce a noninvasive and accurate diagnosis procedure for DS and to minimize social and financial cost of prenatal diagnosis. Recently, machine learning has received considerable attention in predictive analytics for medical problems. However, there is few its applications on DS prediction reported due to the difficulty of dealing with highly imbalanced and feature-correlated screening data. In this paper, we propose a cascaded machine learning framework designed for DS prediction based on three complementary stages: 1) pre-judgment with isolation forest technique, 2) model ensemble by voting strategy, and 3) final judgment using logistic regression approach. The experimental results show that the performance of this framework on maternal serum screening data set, when evaluated with different evaluation parameters, is superior to those of some machine learning methods. The best suggested combination of input features for DS screening is the group of alpha-fetoprotein, human chorionic gonadotropin, unconjugated estriol, and maternal age. In addition, our method has the potential to generate further accurate prediction for imbalanced and feature-correlated data, thereby providing a novel and effective approach for certain diseases analysis.

Down to Counsel: Towards A Transdisciplinary Toolbox for Non-directive Counseling in Prenatal Screening for Down Syndrome

Abstract Since the introduction of non-invasive prenatal testing (NIPT) in Belgium in 2013, expectant parents have had access to a new efficient and reliable test for genetic abnormalities, including trisomy 13, 18 and 21. In 2017, the Belgian government decided to cover over 95% of the cost for all women who choose to take this test. In this context, a diagnosis of trisomy 21 (Down syndrome) presents an especially challenging decision for parents: it is impossible to tell the severity of impairment prenatally, and although several medical risks are involved in the condition, many individuals with Down syndrome live a long, happy, and relatively independent life (Shakespeare, 1998; Scott et. al., 2014). Expectant parents face a very difficult situation: how to decide whether or not to terminate a pregnancy? It appears that termination is becoming the routinized outcome of the clinical encounter during which a diagnosis is delivered.The intricacy of the matter, and the fact that many actors are involved, lead to the necessity of a transdisciplinary methodology when scrutinizing the future of prenatal counseling. However, medical professionals tend to approach Down syndrome from an exclusively medical perspective (Skirton and Barr, 2010), leaving aside the economic, social and psychological dimensions of living with Down syndrome. This may result in unbalanced information; some (perhaps precipitously) refer to this phenomenon as ‘nudging practices’ (Hippman et. al., 2012; Reid et. al., 2009). In order to address this imbalance, we adopt a stakeholder approach in this project: we consulted &lt;target target-type="page-num" id="p-39"/&gt;experts with diverse backgrounds and fields of expertise. Through this transdisciplinary approach, we hope to bring about a more transdisciplinary perspective directly within the offices of gynecologists and GPs. More specifically, we aim to find ways to provide GPs and gynecologists with direct access to information about the aforementioned dimensions of Down syndrome.The next step is to define a strategy to achieve this goal. Given the fact that medical professionals often lack both time and easy access to concise information about Down syndrome to present a nuanced perspective (Ahmed et. al., 2007), but are still the first in the prenatal screening process, the output of this project is the idea of an online tool in a succinct Q&amp;A format. The goal of such a website would be to provide up-to-date, easily accessible and balanced information for general practitioners and gynecologists on multiple aspects of Down syndrome. This way, in anticipation of and directing explicitly towards further counseling by a multidisciplinary team, physicians can provide expectant parents with a more balanced, transdisciplinary view of Down syndrome, thereby enhancing their capability to make informed, autonomous and hence sustainable decisions about their pregnancies.

Prenatal screening for Down syndrome in twin pregnancies: Estimates of screening performance based on 61 affected and 7302 unaffected twin pregnancies.

The aims of this study were to determine whether assumptions used in prenatal screening for Down syndrome in twin pregnancies are valid and derive estimates of risk and screening performance in twin pregnancies using observed data. Data were collected on nuchal translucency, chorionicity, pregnancy associated plasma protein-A (PAPP-A), and free ß human chorionic gonadotrophin (free ß-hCG) from 61 twin pregnancies with Down syndrome and 7302 unaffected twin pregnancies. Distribution parameters were determined and used to estimate screening performance. The assumption that proportional differences in serum marker levels in affected and unaffected singleton pregnancies apply to twin pregnancies was not confirmed. Median free β-hCG value in monochorionic affected twin pregnancies (2.63 multiples of the median [MoM]; 95% CI, 1.79-3.22 MoM) was lower than that assuming proportionality (3.76 MoM), and the median PAPP-A value in dichorionic affected twin pregnancies (1.88 MoM; 95% CI, 1.60-2.17 MoM) was higher than that based on proportionality (1.33 MoM). The detection rate was 87% for a 3% false-positive rate in monochorionic twin pregnancies and 74% in dichorionic twin pregnancies compared with 86% in singleton pregnancies. Estimates of screening performance in Down syndrome twin pregnancies do not need to rely on assumptions and can take account of chorionicity and gestational age.

Noninvasive Approaches to Prenatal Diagnosis: Historical Perspective and Future Directions.

The field of prenatal screening and diagnosis has undergone enormous progress over the past four decades. Most of this period has been characterized by gradual improvements in the technical and public health aspects of prenatal screening for Down syndrome. Compared to the direct analysis of fetal cells from amniocentesis or chorionic villus sampling, noninvasive approaches using maternal blood or ultrasound have the great advantage of posing no risk of miscarriage to the pregnancy. Recent advances in molecular genetics and DNA sequencing have revolutionized both the accuracy and the range of noninvasive testing for genetic abnormalities using cell-free DNA in maternal plasma. Many of these advances have already been incorporated into clinical care, including diagnosis of fetal blood group and aneuploidy screening. The accelerated pace of these recent developments is creating not just technical and logistical challenges, but is also magnifying the ethical and public policy issues traditionally associated with this field.

Verification of foetal Down syndrome biomarker proteins in maternal plasma and applications in prenatal screening for Down syndrome

BackgroundDown Syndrome (DS) has a very high morbidity, according to statistics, the incidence rate of DS is as high as 1:700 among the new born babies. At present, there are still no effective prevention or treatment methods for the disease. We used a Western Blot technique to validate differentially expressed proteins between DS foetal umbilical cord blood plasma and healthy foetal peripheral blood plasma from pregnant women to identify new prenatal diagnostic biomarkers for down syndrome (DS) and establish a new non-invasive prenatal diagnosis method.MethodsWe collected maternal peripheral blood (8 with foetal DS and 8 from normal foetuses) from April 2013 to January 2014, and separated the plasma. We combined the clinical characteristics and clinical differentially expressed proteins between DS foetal umbilical cord blood plasma and healthy foetal umbilical cord blood plasma to identify specific protein marker candidates and prepared monoclonal antibodies, which were then used for Western Blot technique to analyse the candidate markers.ResultsIn the DS foetal maternal plasma, serum amyloid P-component, Apolipoprotein E, Nucleosome assembly protein 1-like 1, Complement factor B,ERO1-like protein alpha, 2-oxoglutarate dehydrogenase-like, and Thymosin beta 10 were up-regulated proteins compared to the healthy control group, and the DS group showed higher expression, which agreed with the results from the DS foetal umbilical cord blood plasma.ConclusionThe up-regulated amyloid P-component, Apolipoprotein E, Nucleosome assembly protein 1-like 1, Complement factor B, ERO1-like protein alpha, 2-oxoglutarate dehydrogenase-like, Thymosin beta 10 all are up-regulation, all of them have potential to be prenatal diagnosis biomarkers for DS, and these biomarkers can further reveal the pathogenesis of DS.

Attitude, knowledge and informed choice towards prenatal screening for Down Syndrome: a cross-sectional study

BackgroundDown Syndrome screening test is a bridge between knowledge and uncertainty, safety and risk, unpredictability and desire to know in order to gain control. It may be accepted either not to have a baby with Down syndrome, or to prepare to have a baby with this condition. Every woman should understand that it is an option and should be encouraged to make their own decisions based on information and personal values. The implications and possible subsequent scenarios differentiate this type of test from the common biochemical tests performed during pregnancy, of paramount importance being the right to make informed choices. The aim of this study was to investigate the knowledge and attitude towards prenatal Down syndrome screening in order to asses to what extent the Romanian women make informed choices in this area.MethodsA cross-sectional study was carried out that included 530 postpartum women, clients of Romania’ south-east region maternities, during April–September 2016. The level of knowledge and the attitude concerning the Down syndrome screening were evaluated using a questionnaire. Data were analyzed using SPSS version 20.0.Results48.1% of the women have never heard about any tests for Down Syndrome and from those 51.9% who have heard, only 14.2% made an informed choice, 78.9% had a positive attitude for screening, 88% were classified as having insufficient knowledge and 68.3% made a value-consistent decision to accept or decline prenatal screening. A higher knowledge level was associated with a higher education level and the urban residence. The information satisfaction and confidence in the overall value of screening were predictive factors of positive attitude. More informed choices were made by women monitored by an obstetrician in a private practice.ConclusionsThe prenatal screening tests for Down Syndrome were mostly unknown and the women who accepted or not to perform a test were insufficiently knowledgeable that means that the ethical concept of the informed choice wasn’t followed. In our opinion the Romanian Health System needs to improve the antenatal policy by developing an adequate information strategy at the reproductive population level based on a network of trained specialists.

Danish Sonographers' Experiences of the Introduction of "Moderate Risk" in Prenatal Screening for Down Syndrome.

Objective The aim of the study was to determine sonographers' experiences with the introduction of an offer of noninvasive prenatal testing (NIPT) to a new moderate-risk (MR) group at the combined first-trimester prenatal screening (cFTS). Study Design A qualitative approach consisting of seven semistructured interviews with five sonographers (midwives and nurses). Data was analyzed using thematic analysis. Main Outcome Measures Sonographers' perception of offering NIPT to women in MR. Results The sonographers understood NIPT as a positive development in prenatal screening due to a safe procedure and high detection rates for trisomies 13, 18, and 21. Prior to the introduction of MR, the sonographers were concerned about inducing worry in pregnant women in this new risk group. However, the pregnant women responded very positively, which the sonographers attributed to several factors such as the women's overall reason for participating in prenatal screening, the simplicity of the NIPT procedure, and the communicative strategies used by the sonographers. The strategies included all sonographers using the same words and explanations, emphasizing that statistics were in the women's favor, initiating the presentation of MR with a positive message, and downplaying the MR category. Conclusion Sonographers' communicative strategies succeeded in limiting worry in pregnant women in MR. As such, the findings are valuable for health professionals, who are responsible for communicating about prenatal screening results and diagnostic options.

Psychosocial Factors of Health Professionals' Intention to Use a Decision Aid for Down Syndrome Screening: Cross-Sectional Quantitative Study.

BackgroundDecisions about prenatal screening for Down syndrome are difficult for women, as they entail risk, potential loss, and regret. Shared decision making increases women’s knowledge of their choices and better aligns decisions with their values. Patient decision aids foster shared decision making but are rarely used in this context.ObjectiveOne of the most promising strategies for implementing shared decision making is distribution of decision aids by health professionals. We aimed to identify factors influencing their intention to use a DA during prenatal visit for decisions about Down syndrome screening.MethodsWe conducted a cross-sectional quantitative study. Using a Web panel, we conducted a theory-based survey of health professionals in Quebec province (Canada). Eligibility criteria were as follows: (1) family physicians, midwives, obstetrician-gynecologists, or trainees in these professions; (2) involved in prenatal care; and (3) working in Quebec province. Participants watched a video depicting a health professional using a decision aid during a prenatal consultation with a woman and her partner, and then answered a questionnaire based on an extended version of the theory of planned behavior, including some of the constructs of the theoretical domains framework. The questionnaire assessed 8 psychosocial constructs (attitude, anticipated regret, subjective norm, self-identity, moral norm, descriptive norm, self-efficacy, and perceived control), 7 related sets of behavioral beliefs (advantages, disadvantages, emotions, sources of encouragement or discouragement, incentives, facilitators, and barriers), and sociodemographic data. We performed descriptive, bivariate, and multiple linear regression analyses to identify factors influencing health professionals’ intention to use a decision aid.ResultsAmong 330 health professionals who completed the survey, 310 met the inclusion criteria: family physicians, 55.2% (171/310); obstetrician-gynecologists, 33.8% (105/310); and midwives, 11.0% (34/310). Of these, 80.9% were female (251/310). Mean age was 39.6 (SD 11.5) years. Less than half were aware of any decision aids at all. In decreasing order of importance, factors influencing their intention to use a decision aid for Down syndrome prenatal screening were as follows: self-identity (beta=.325, P<.001), attitude (beta=.297, P<.001), moral norm (beta=.288, P<.001), descriptive norm (beta=.166, P<.001), and anticipated regret (beta=.099, P=.003). Underlying behavioral beliefs significantly related to intention were that the use of a decision aid would promote decision making (beta=.117, 95% CI 0.043-0.190), would reassure health professionals (beta=.100, 95% CI 0.024-0.175), and might require more time than planned for the consultation (beta=−.077, 95% CI −0.124 to −0.031).ConclusionsWe identified psychosocial factors that could influence health professionals’ intention to use a decision aid about Down syndrome screening. Strategies should remind them of the following: (1) using a decision aid for this purpose should be a common practice, (2) it would be expected of someone in their societal role, (3) the experience of using it will be satisfying and reassuring, and (4) it is likely to be compatible with their moral values.

Application of droplet digital PCR for prenatal screening of Down syndrome

Background: This study was proposed to explore the feasibility of droplet digital PCR (ddPCR) analysis for non-invasive prenatal diagnosis of Down syndrome. Materials and Methods: The authors studied maternal plasma samples from 465 pregnant women carrying euploid and trisomy 21 (T21) fetuses. A methylation-sensitive restriction endonuclease, BstUI, was used to digest the hypomethylated holocarboxylase synthetase (HLCS) gene. The authors quantified digestion-resistant HLCS gene on chromosome 21 and fetal-specific rs6636 SNP allele on chromosome 14 by droplet digital PCR analysis. Maternal plasma DNA analysis was performed by comparing the ratio of hypermethylated HLCS to fetal-specific rs6636 SNP allele between two groups. Results: Using a rs6636 SNP allele on chromosome 14 as the reference marker, the authors analyzed 78 euploid and 28 T21 plasma samples. The ratios of the numbers of positive hypermethylated HLCS and the fetal-specific C allele in the euploid and T21 samples were significantly different ( p p Conclusions: The study demonstrated that ddPCR approach can be applied for prenatal screening of trisomy 21.

Significance of data analysis in the quality control of prenatal screening for Down syndrome.

Dual detection of α-fetoprotein (AFP) and free β-human chorionic gonadotropin (β-HCG) is a common screening method for Down syndrome in the second trimester and its efficacy is assessed by false-positive rate (FPR). The present study aimed to investigate the effects of the bias in median multiple of the median (mMoM) values of AFP and free β-HCG on FPR. The bias in mMoM values of AFP and free β-HCG and the bias in mMoM values under different gestational ages and weight groups were analyzed. Median equations were adjusted, and medians in LifeCycle software were replaced by local medians. Following two adjustments of the median equations, all indices including FPR, mMoM values of markers and mMoM values under different gestational ages and weight groups generally reached an ideal state. In conclusion, abnormal bias in mMoM values may prompt aberrant application of median equations, and regular monitoring of these indicators may be important for quality control in prenatal screening.

Informed Decision‐Making in the Context of Prenatal Chromosomal Microarray

The introduction of chromosomal microarray (CMA) into the prenatal setting has involved considerable deliberation due to the wide range of possible outcomes (e.g., copy number variants of uncertain clinical significance). Such issues are typically discussed in pre-test counseling for pregnant women to support informed decision-making regarding prenatal testing options. This research study aimed to assess the level of informed decision-making with respect to prenatal CMA and the factor(s) influencing decision-making to accept CMA for the selected prenatal testing procedure (i.e., chorionic villus sampling or amniocentesis). We employed a questionnaire that was adapted from a three-dimensional measure previously used to assess informed decision-making with respect to prenatal screening for Down syndrome and neural tube defects. This measure classifies an informed decision as one that is knowledgeable, value-consistent, and deliberated. Our questionnaire also included an optional open-ended question, soliciting factors that may have influenced the participants' decision to accept prenatal CMA; these responses were analyzed qualitatively. Data analysis on 106 participants indicated that 49% made an informed decision (i.e., meeting all three criteria of knowledgeable, deliberated, and value-consistent). Analysis of 59 responses to the open-ended question showed that "the more information the better" emerged as the dominant factor influencing both informed and uninformed participants' decisions to accept prenatal CMA. Despite learning about the key issues in pre-test genetic counseling, our study classified a significant portion of women as making uninformed decisions due to insufficient knowledge, lack of deliberation, value-inconsistency, or a combination of these three measures. Future efforts should focus on developing educational approaches and counseling strategies to effectively increase the rate of informed decision-making among women offered prenatal CMA.

Prenatal diagnosis and socioeconomic status in the non-invasive prenatal testing era: A population-based study.

Advances in technology can bring great benefits to human health, but their implementation may be influenced by socioeconomic factors, particularly in the field of prenatal screening for Down syndrome. To analyse screening test indications for, and diagnostic yield of, invasive prenatal diagnostic testing (PNDx) according to socioeconomic status. Retrospective analysis of population-based data on PNDx and karyotype results for 2014-2015 in the Australian state of Victoria. Women having PNDx<25weeks due to combined first trimester screening (CFTS), second trimester serum screening (STSS), or noninvasive prenatal testing (NIPT) results were included. PNDx data were analysed by indication and maternal Index of Relative Socio-economic Advantage and Disadvantage (IRSAD), the latter determined by postcode. There were 145206 births in 2014-2015; 1906 women underwent PNDx for the indication of CFTS (70.1%), NIPT (17.8%) or STSS (12.0%). Covariates positively associated with NIPT-indicated PNDx, compared with CFTS-indicated testing, were residence in a region of socioeconomic advantage, metropolitan status and maternal age. Women from the most advantaged regions had higher adjusted odds ratios (aOR) of NIPT-indicated testing compared with women from disadvantaged regions (aOR 5.72, 95% CI: 2.95-11.09). The diagnostic yield of PNDx increased with socioeconomic region, from 14% in the lowest IRSAD quintile to 31.2% in the highest (P<0.0001). Population-based data reveal significant disparities in screening indications for PNDx and hence, in diagnostic yield, according to socioeconomic region. This finding may have ethical and policy implications for prenatal screening in Australia.