Prenatal Screening For Down Syndrome Research Articles

Trisomy 21 Testing in Second Trimester: Reliability Comparison of Triple and Quadruple Testing in Pakistan

Objectives: Down syndrome is a disorder that affects one in every 700 babies born, and it is one of the most frequent causes of developmental delay (DS). In Pakistan, prenatal screening for Down syndrome is not being practised according to any approved protocol. The biochemical screening that takes place during the second trimester is still carried out using the triple test. Although the quadruple test has a better sensitivity and specificity than other diagnostic methods, its usage in routine medical settings is not advised. The purpose of this study was to explore the second trimester screening for trisomy 21 (quadruple test with genetic sonogram) in order to determine its sensitivity and accuracy in comparison to biochemical testing. Place of Study: District Headquarters Hospital, Gujranwala Duration of Study: January 2021 to December 2021 Methods: This retrospective observational study was carried out in a Fetal Medicine Centre with the purpose of analysing the odds of being affected with Down syndrome, given a positive risk (OAPR) upon screening in the quadruple test; triple test and quadruple test plus a genetic sonogram for highrisk singleton pregnancies (in view of advanced maternal age; an anomaly scan showing some abnormality, etc.). Given the presence of a positive risk factor, the goal of this study was to ascertain the likelihood of having a child impacted by Down syndrome. Practical Implication: To explore the second trimester screening for trisomy 21 (quadruple test with genetic sonogram) in order to determine its sensitivity and accuracy in comparison to biochemical testing. Results: The discovery of trisomies was made after an investigation into 3,042 highrisk pregnancies with a singleton baby. 327 pregnant women who have received positive findings from a triple test, quadruple test, or quadruple test in addition to a genetic ultrasonography opt to have an amniocentesis. This decision was made after the ladies learned that their unborn child may have a genetic disorder. It was discovered that 20 of the developing babies were affected by Down syndrome. The OAPR for the quadruple test was demonstrated to be significantly higher when compared to the OAPR for the triple test (1:29.1 as compared to 1:39.2). It was found that the combination of the triple test and the genetic sonogram had the highest OAPR of 1:7. Conclusions: The triple test combined with a genetic sonogram is the most effective tool for screening for trisomy 21, and it has the potential to cut down on the number of unnecessary amniocentesis operations carried out in high-risk populations. Keywords: Down syndrome, genetic, quadruples test, second trimester screening, triple test,ultrasound

Neonatal mortality and morbidity in Down syndrome in the time of prenatal aneuploidy testing: a retrospective cohort study

The total uptake of prenatal aneuploidy screening for Down syndrome (DS) is increasing worldwide. As a result of increasing prenatal diagnosis of DS and subsequent termination of pregnancy, livebirth prevalence of DS is decreasing. The aim of this study is to explore the impact of an increasing uptake of prenatal aneuploidy screening on the neonatal mortality and morbidity in DS. This is a retrospective cohort study of 253 neonates with DS born between 2012 and 2018 that were seen at the outpatient clinic of five hospitals in the Netherlands. The medical files were reviewed for maternal and neonatal characteristics and neonatal morbidities. The Dutch national birth registry (Perined) provided mortality numbers of neonates with DS. The results were interpreted in the context of other published studies. Neonatal mortality in DS remained stable, ranging from 1.4 to 3.6%. A congenital heart defect (CHD) was found in 138 of the 251 neonates (55.0%) with atrial septal defect, atrioventricular septal defect, and ventricular septal defect being the most common. The type of CHD in DS did not change over time. Gastro-intestinal defects were present in 22 of the 252 neonates with DS (8.7%), with duodenal atresia as the most reported anomaly. Persistent pulmonary hypertension of the neonate (PPHN) was found in 31 of the 251 infants (12.4%). Conclusions: Although uptake of prenatal aneuploidy screening increased, neonatal mortality and morbidity in DS appears to be stable. An increased incidence of PPHN was found.What is Known:• The total uptake of prenatal aneuploidy screening for Down syndrome is increasing worldwide.• As a result of increasing prenatal diagnosis of Down syndrome and subsequent termination of pregnancy, the livebirth prevalence of Down syndrome is decreasing.What is New:• Although uptake of prenatal aneuploidy screening increased, neonatal mortality and morbidity in Down syndrome appears to be stable.• An increased incidence of persistent pulmonary hypertension of the neonate was found.

The anxiety caused by abnormal results of Down syndrome screening tests

The objective of our survey was to evaluate the anxiety experienced by women receiving abnormal results of prenatal Down syndrome screening by an electronic anonymous survey. Anxiety level was evaluated by a six-item Spielberger State-Trait Anxiety Inventory. Of 559 respondents, high anxiety scores were reported in the majority (86.0%). Higher anxiety scores were noted in women informed of the abnormal result by the caregiver vs. written answer. 59.1% of the respondents preferred the risk reported as percentage, while only 4.4% gave precedence to the current form (e.g. 1 in 100). The participants noted several factors which could relieve their anxiety, including an explanatory booklet (72.4%) or a website (77.9%). In conclusion, women receiving abnormal results of Down syndrome screening experience significant anxiety. Efforts should be made to relieve this distress, including changing the historical ratio risk format to percentage, adding a non-directive verbal annotation, an explanatory website and improving health professionals' understanding of the exact statistical meaning of the risk. Impact statement What is already known on this subject? Abnormal results of prenatal screening for Down syndrome might cause the women significant anxiety. Several simple methods are able to relieve this distress; however, they are frequently not implemented in the routine practice. What the results of this study add? We show that abnormal results of the screening tests are associated with high anxiety scores in the majority of women (86.0%). The majority of the respondents preferred the risk reported as percentage (vs. historical representation as a ratio). The participants noted several factors which could relieve their anxiety, including an explanatory booklet or a website. What the implications are of these findings for clinical practice and/or further research? Based on the results, we discuss the numerous ways able to available alleviate the distress.

Prediction of Pregnancy Complications With Maternal Biochemical Markers Used in Down Syndrome Screening.

Objective: To determine whether first- and second-trimester maternal serum biomarkers are useful for the prediction of pregnancy complications like preterm birth, intrauterine growth restriction (IUGR), and macrosomia.Methods: We conducted a retrospective analysis of 353 women having first- or second-trimester combined test for Down syndrome screening who delivered at our institution between January 2018 and December 2020. Associations between first- and second-trimester serum markers and adverse pregnancy outcomes among those who underwent prenatal screening for Down syndrome in our clinic were studied. The adverse pregnancy outcomes, serum levels of pregnancy-associated plasma protein-A (PAPP-A), β-human chorionic gonadotropin (β-hCG), and maternal serum alpha-fetoprotein (ms-AFP) were recorded and analyzed. Correlation analyses of PAPP-A, free βhCG, and ms-AFP with pregnancy outcomes were studied. We sought to predict the risks of preterm delivery (PTD, <37 weeks gestational age), low birth weight (LBW, <2500 grams) and macrosomia (>4000 grams).Results: A total of 353 women who had first- and second-trimester screening test for Down syndrome were included. Two hundred fifty (70.08%) of them had first-trimester and 103 (41.2%) had second-trimester test. Mean age of the patients who underwent screening test for Down syndrome was 29.3±5.9, mean maternal weight was 67.3±13.6, mean gestational weeks at birth was 38.6±2.1 weeks and mean birth weight was 3260.9±511.1, preterm birth rate was 40/353 (11.3%), IUGR rate was 21/353 (5.9%), macrosomia rate was 17/353 (4.8%), stillbirth rate was 3/353 (0.8%). When laboratory and clinical parameters affecting birth weight and birth weeks were analysed in correlation analysis, both birth week and birth weight were found to be positively correlated with maternal weight. Of first-trimester markers Papp-A MoM (Multiples of Median) was found to be positively correlated with fetal birth weight (p = 0.044). Of second-trimester biochemical parameters ms-AFP was found to be negatively correlated with fetal birth weight (p = 0.039).Conclusion: The study concluded that there is a relationship between serum markers and adverse pregnancy outcomes. Significant associations were found between the levels of first- and second-trimester serum markers PAPP-A, AFP and IUGR, macromia and additionally significant association was found between maternal weight and both delivery week and fetal weight. These results can highlight the pregnancies at risk and follow-up intervals may be arranged according to risk scala which may help at antenatal follow-up of high-risk patients.

Second-tier non-invasive prenatal screening for Down syndrome in a public obstetric unit: the first 12 months

Second-tier non-invasive prenatal screening for Down syndrome in a public obstetric unit: the first 12 months

Web-Based Training for Nurses on Using a Decision Aid to Support Shared Decision-making About Prenatal Screening: Parallel Controlled Trial.

BackgroundNurses play an important role in supporting pregnant women making decisions about prenatal screening for Down syndrome. We developed a web-based shared decision-making (SDM) training program for health professionals focusing on Down syndrome screening decisions.ObjectiveIn this study, we aim to assess the impact of an SDM training program on nurses’ intention to use a decision aid with pregnant women deciding on prenatal screening for Down syndrome.MethodsIn this 2-arm, parallel controlled trial, French-speaking nurses working with pregnant women in the province of Quebec were recruited by a private survey firm. They were allocated by convenience either to the intervention group (web-based SDM course that included prenatal screening) or to the control group (web-based course focusing on prenatal screening alone, with no SDM content). The primary outcome was the intention to use a decision aid. Secondary outcomes were psychosocial variables of intention, knowledge, satisfaction, acceptability, perceived usefulness, and reaction to the pedagogical approach. All outcomes were self-assessed through web-based questionnaires, including the space for written comments. We used 2-tailed Student t test and Fisher exact test to compare continuous and categorical variables between groups, respectively.ResultsOf the 57 participants assessed for eligibility, 40 (70%) were allocated to the intervention (n=20) or control group (n=20) and 36 (n=18 in each) completed the courses. The mean age of the participants was 41 (SD 9) years. Most were women (39/40, 98%), White (38/40, 95%), clinical nurses (28/40, 70%), and had completed at least a bachelor’s degree (30/40, 75%). After the intervention, the mean score of intention was 6.3 (SD 0.8; 95% CI 5.9-6.7) for the intervention group and 6.0 (SD 1.2; 95% CI 5.42-6.64) for the control group (scale 1-7). The differences in intention and other psychosocial variable scores between the groups were not statistically significant. Knowledge scores for SDM were significantly higher in the intervention group (79%, 95% CI 70-89 vs 64%, 95% CI 57-71; P=.009). The intervention was significantly more acceptable in the intervention group (4.6, 95% CI 4.4-4.8 vs 4.3, 95% CI 4.1-4.5; P=.02), and reaction to the pedagogical approach was also significantly more positive in the intervention group (4.7, 95% CI 4.5-4.8 vs 4.4, 95% CI 4.2-4.5; P=.02). There was no significant difference in overall satisfaction (or in perceived usefulness). Furthermore, 17 participants (9 in the intervention group and 8 in the control group) provided written comments on the intervention.ConclusionsThis study focuses on web-based nursing education and its potential to support pregnant women’s decision-making needs. It shows that nurses’ intention to use a decision aid to enhance SDM in prenatal care is high, with or without training, but that their knowledge about SDM can be improved with web-based training.International Registered Report Identifier (IRRID)RR2-10.2196/17878

Racial implicit bias among obstetricians and midwives, and information on Down syndrome screening

Abstract Background and objectives Previous studies showed disparities in prenatal screening for Down syndrome according to the maternal place of birth. Among the factors that might be involved in these differences, social cognition offers the concept of implicit bias (IB) used to describe the fact of having attitudes towards people or associating stereotypes with them without necessarily conscious knowledge. In line with theoretical and empirical contributions in social psychology that postulate and demonstrate the role of automatic processes in determining behavior, IBs often predict how individuals behave more accurately than conscious values. The existence of IB among health professionals has been demonstrated in emergency care or pain management. To our knowledge, no study of IB has been conducted in Europe, nor in the field of perinatal care. Thus, our objectives were to test for IBs towards African women in terms of evaluation (negative bias) and strength (positive bias) among perinatal health professionals and test whether these IBs predicted treatment recommendations toward African vs. French patients. Methods Through online data collection, 887 perinatal care practicians (obstetrician-gynecologists, midwives) answered a series of case vignettes depicting African vs. French patients, with one specific to a Down syndrome screening situation. Then, participants completed two Implicit Association Tests to assess valence and strength IBs toward African vs. French women. Results 81.3% of the sample showed an implicit evaluative preference for French over African women, and 60.2% had an implicit perception of African women as stronger than French. However, decision toward Down syndrome screening were not influenced by the patient's origin nor by the healthcare professional implicit bias. Conclusions Perinatal practicians seem to have implicit biases toward African women, but the way they provide information regarding Down Syndrome screening is not affected.

Evidence for differential care in Down syndrome screening based on maternal origin: a population based survey in France

Abstract 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.

Novel Approaches to an Integrated Route for Trisomy 21 Evaluation.

Trisomy 21 (T21) is one of the most commonly occurring genetic disorders, caused by the partial or complete triplication of chromosome 21. Despite the significant progress in the diagnostic tools applied for prenatal screening, commonly used methods are still imprecise and involve invasive diagnostic procedures that are related to a maternal risk of miscarriage. In this case, novel prenatal biomarkers are still being evaluated using highly specialized techniques, which could increase the diagnostic usefulness of biochemical prenatal screening for T21. From the other hand, the T21′s pathogenesis, caused by the improper division of genetic material, disrupting many metabolic pathways, could be further evaluated with the use of omics methods, which could result in bringing relevant insights for the evaluation of potential medical targets. Accordingly, a literature search was undertaken to collect novel information about prenatal screening for Down syndrome with the use of advanced technology, with a particular emphasis on the evaluation of novel screening biomarkers and the discovery of potential medical targets. These meta-analyses are focused on novel approaches designed with the use of omics techniques, representing the most rapidly developing and promising field in research today. Considering the limitations and progress of these methods, the use of omics techniques in evaluating T21 pathogenesis could bring beneficial results in prenatal screening, simultaneously uncovering novel potential medical targets.

Does women\u2019s place of birth affect their opportunity for an informed choice about Down syndrome screening? A population-based study in France

BackgroundTo examine disparities by maternal place of birth in the opportunity to make an informed choice about Down syndrome screening, in France, where the national guidelines recommend that physicians offer it to all pregnant women.MethodsWe used population-based data from the nationally representative French Perinatal Surveys in 2010 and 2016 (N=24,644 women) to analyze the opportunity for an informed choice for prenatal screening, measured by a composite indicator.ResultsAmong the 24 644 women in the study, 20 612 (83.6%) were born in France, 861 (3.5%) elsewhere in Europe, 1550 (6.3%) in North Africa, and 960 (3.9%) in sub-Saharan Africa. The probability of screening was lower for women born outside France. After adjustment for survey year, maternal age, parity, education level, and the maternity unit’s level of perinatal care, women born outside France had the opportunity to make an informed choice less often than women born in France. This association remained essentially the same even after excluding women without adequate prenatal care.ConclusionsWomen born outside France, including those with adequate prenatal care, had less opportunity than women born in France to make an informed choice about prenatal screening for Down syndrome.

Prenatal serum screening for Down syndrome and neural tube defects in the United States: Changes in utilization patterns from 2012 to 2020.

To compile current usage of serum-based prenatal screening for Down syndrome in the United States and compare it with results from a similar 2011/2012 survey. The College of American Pathologists maternal screening proficiency testing survey includes a supplemental question on the first of three yearly distributions. Information regarding tests offered and the monthly number of pregnancies tested for US-based laboratories were reviewed. Results were stratified by size of laboratory, tests offered, and pregnancies tested. Findings were compared to an earlier survey. Fifty-six laboratories reported they will have screened 1,131,336 pregnancies in 2020. Of these, 36% are screened by stand-alone first trimester testing, 48% by stand-alone second trimester testing, and 16% using tests that integrate results from both trimesters. Eighty percent of all serum screens were provided by the five laboratories that performed the most screens (at least 50,000). These five performed similar proportions of first or second trimester screens (42.2% and 41.8%, respectively). Compared to eight years earlier, there are now 54% fewer laboratories. Pregnancies screened using the first trimester, second trimester, and integrated protocols were lower by 27%, 69%, and 72%, respectively. The serum screening activity in the US showed a 62% decrease from 2012 levels. During 2012-2020, the number of cell-free DNA tests increased from negligible to 1,492,332. Maternal serum screening for common aneuploidies has changed significantly in eight years with fewer laboratories, a shift toward larger laboratories and a 2.5-fold reduction in pregnancies tested, likely due to the introduction of cell-free DNA screening.

Amniotic fluid and urine metabolomic alterations associated with pregnant women with Down syndrome fetuses

Background Down syndrome (DS) is a chromosomal disorder caused by a third copy of all or part of chromosome 21. Clinical observations and preclinical studies both suggest that DS may be associated with significant metabolic and bioenergetic alterations. But the metabolic alterations in pregnant women carrying DS fetuses still remains unclear. In this study, we investigated the characteristic metabolomics and lipidomics changes during fetal development of DS. Methods The AF and random urine specimens were selected from 20 pregnant women carrying DS fetuses and 20 pregnant women carrying healthy fetuses. The diagnosis of DS was screened according to chromosome karyotype analysis, and untargeted metabolomic and lipidomic analyses were performed. Results Through the analyses of AF, 308 differential metabolites were selected between DS and controls. The metabolites with significant changes mainly involved lipid molecules, organic acids, nucleotides and carbon. Further analysis of lipidomics showed 64 differential metabolites, mainly involving glycerides, sphingolipids and glycerolipids. As for urine metabolomic and lipidomic analyses, there existed consistent metabolites with AF, but the number was much less. Conclusions Compared with the controls, carbon metabolism, amino acid metabolism, glyceride metabolism, sphingolipid metabolism and glycerophospholipid metabolism were significantly changed in DS cases. In addition, characterized biomarkers in AF and urine were screened for DS diagnosis, and these metabolites were mainly involved in energy metabolism and liver dysfunction. This finding may help improve the efficiency of prenatal screening for DS.

Prenatal screening for Down syndrome: popularity, perceptions and factors associated with acceptance or refusal of testing

Background Prenatal screening tests for aneuploidies have become increasingly used in maternal and fetal medicine. Given that all pregnancies associate a potential risk of Down syndrome, adequate knowledge of the tests, and their characteristics as well as facilitating decision-making autonomy are fundamental rights that must be respected. Objectives Identification of the popularity of the tests, their perception and the factors associated with the acceptance or refusal to perform them. Methods A cross-sectional study was carried out in the South-East region of Romania, between April and September 2016. The data were collected from 275 postpartum women. The instrument used was a self-administered questionnaire and the data obtained were processed using the IBM SPSS 20.0 statistical software (IBM Corp., Armonk, NY, USA). The normality of the distribution was analyzed with Chi-square, Kolmogorov–Smirnov and Shapiro–Wilk tests. Factorial Analysis was carried out for the Principal Components of the scales for the reasons for performing and not performing. Results The 2nd Trimester Morphology had the popularity as well as the highest rate of accomplishment (98.2% respectively 67.6%) among the investigated women. It is also the preferred recommendation of the specialists (81.1%). The least popular test was the TPNI, only 13.1% of the participants heard about it, as it was recommended in only 2% of the situations. Most of the participants perceived the screening tests as essential and useful, but 43.3% considered that they become mandatory if the doctor recommends them. The acceptance of the child with DS and the misperception of the risk were the main factors associated with the refusal of the test and the compliance with the recommendation of the specialist (system confidence), and social influence (non-acceptance of the Down syndrome by the society) were the main factors associated with the acceptance. Conclusions The number of women who made the decision to accept the test was greater than the ones who refused. The amendment is that acceptance was based on the custom of socio-economic-medical compliance and responsibility. For many women, the motivation of acceptance meant alignment with the normality directed by the society and the system. Even the popularity of the tests carries the imprint of the beliefs and values of the system and the specialists involved. For an adequate perception and an autonomous and informed choice of women, the screening program must include adequate information and communication services by involving specialists responsible for multidisciplinary competencies. The percentage of completion and the type of test performed almost perfectly align with the recommendations received.

Impact of prenatal screening on congenital heart defects in neonates with Down syndrome in the US.

Non-invasive prenatal screening (NIPS) has fundamentally changed thescreening processfor Down syndrome (DS). Rates of complex congenital heart defects (CHD) have decreased in international studies but whether these shifts exist in the US is unknown. Encounters for neonates with DS from 2007 to 2018 were obtained from the Pediatric Health Information System database. CHD were categorized as complexCHD, atrioventricular septal defects (AVSD), ventricular septal defects (VSD), and tetralogy of Fallot (TOF). Comparisons were made between pre-NIPS era (2007-2010) vs. post-NIPS era (2014-2018) and between states with low vs. high access to pregnancy termination as described by the Guttmacher Institute. Among 9122 patients, 6% had complex CHD, 22% had an AVSD, 22% had a VSD, and 4% had TOF. No difference in proportions of CHD was seen between eras. A small difference was observed in the proportion of AVSD between states with low vs. high access to pregnancy termination (23 vs. 17%, p < 0.001). The proportion of CHD in patients with DS appears to be stable despite widespread adoption of NIPS in the US. Variations were observed between states with low vs. high access to pregnancy termination. Population based studies are needed to fully evaluate the current epidemiology of CHD in DS. Through investigation of the Pediatric Health Information System database, this study assesses contemporary epidemiology of congenital heart disease among patients with Down syndrome. It has been suggested that improved prenatal screening for Down syndrome has altered the cardiac phenotype in international populations. Whether a similar shift also exists in the United States is unknown. In a contemporary United States cohort, a shift in the proportion or type of heart defects over the past decade was not observed. Regional differences in the proportion of heart defects were seen and may be due to differential access to prenatal care.

Analysis of External Quality Assessment of Maternal Serum Prenatal Screening for Down Syndrome in the First Trimester in China.

We analyzed the 2019 external quality assessment (EQA) results to evaluate the analytical performance of maternal serum prenatal screening for Down Syndrome (DS) in the first trimester in China. In each round, five lyophilized EQA samples with detailed clinical information were distributed to participants and used to test the concentration of human chorionic gonadotropin free beta subunits (free β-HCG) and pregnancy-associated plasma protein-A (PAPP-A) to calculate the risk value of DS. The robust coefficient of variability (CV) was calculated or test results for free β-HCG and PAPP-A using analytes and major measurement platforms. For DS risk values, the robust CV was calculated using a professional calculation platform. Failed EQA results were analyzed using serum marker testing results and DS risk values. EQA results were collected from 242 laboratories in round 1 and 239 laboratories in round 2. Total acceptable rates of testing results for free β-HCG and PAPP-A ranged from 95.04% to 97.91%. Overall acceptable rates of DS risk values ranged from 97.52% to 97.90%. The proportion of laboratories exhibiting satisfactory performance was higher in round 2 than in round 1 for serum marker testing results and DS risk values. The robust CV for risk values for each sample were significantly higher than those of serum markers. Three EQA result failure types were found, including result reporting errors, serum marker concentration testing errors, and DS risk calculation errors. The analytical performance of maternal serum prenatal screening for DS in the first trimester in China can be improved further.

Performance of second-trimester maternal biochemistry screening (quadruple test vs. triple test) for trisomy 21: An Indian experience.

Background & objectives:Down syndrome (DS) is one of the most common causes of developmental delay. In India, there is no protocol for prenatal screening of DS. Second-trimester biochemical screening is still being done by triple test. Quadruple test is with better sensitivity and specificity but is not advised routinely. So, the objective of this study was to evaluate the sensitivity and accuracy of the second-trimester screening (quadruple test with genetic sonogram) for trisomy 21 as compared to biochemical testing.Methods:This retrospective observational study was carried out in a Fetal Medicine Centre to analyze the odds of being affected with DS, given a positive risk (OAPR) upon screening in the quadruple test; triple test and quadruple test plus a genetic sonogram for high-risk singleton pregnancies (in view of advanced maternal age; an anomaly scan showing some abnormality, etc).Results:3175 high-risk singleton pregnancies were screened for trisomy 21. 394 women underwent amniocentesis on the basis of triple test, quadruple test or quadruple plus genetic sonogram positive. 17 foetuses were diagnosed to have DS. The quadruple test was found to have a higher OAPR as compared to the triple test (1:30.1 as compared to 1: 40.2). Quadruple test plus the genetic sonogram was found to have the highest OAPR of 1:6.Interpretation & conclusions:Best screening for trisomy 21 is provided with quadruple test with genetic sonogram which can lower the rates of unnecessary amniocentesis in high-risk population.

The Significance of Apolipoprotein E Measurement in the Screening of Fetal Down Syndrome.

Prenatal screening for Down syndrome (DS) is based on both noninvasive and invasive methods. Noninvasive, cell-free fetal DNA genetic tests are expensive, whereas biochemical methods remain imprecise. Amniocentesis is the most frequently used invasive diagnosis procedure, characterized by 99.8% diagnostic efficiency and less than 1% risk of miscarriage. The aim of this study was to evaluate the screening value of apolipoprotein E (ApoE) as a potential noninvasive biomarker for prenatal DS assessment. This study was conducted on a group of female patients who decided to undergo routine amniocentesis between the 15th and 18th week of pregnancy at the Department of Reproduction and Gynecological Endocrinology of the Medical University of Bialystok, Poland. For the purpose of this study, 20 women with DS fetuses were selected as the study group, and 20 healthy pregnant women with euploid fetus karyotypes as the control group. The plasma levels of ApoE were significantly higher in the study group compared to healthy subjects (p < 0.05). The area under the receiver operating characteristic (ROC) curve was 0.978 (p < 0.001), with the cut-off set to 1.37 mg/mL, which was characterized by 80% of sensitivity and 100% of specificity. The high sensitivity and specificity demonstrate the screening utility of maternal ApoE concentration in prenatal fetal DS screening.

Introducing cell-free DNA noninvasive testing in a Down syndrome public health screening program: a budget impact analysis

BackgroundNon-invasive prenatal testing (NIPT) using cell-free fetal DNA in maternal plasma is a high accurate test for prenatal screening for Down syndrome. Although it has been reported to be cost effective as a contingent test, evidence about its budget impact is lacking.ObjectiveTo evaluate, using computer simulations, the budget impact of implementing NIPT as a contingent test in the Quebec Program of screening for Trisomy 21.MethodsA semi-Markov analytic model built to simulate the budget impact of implementing NIPT into the current Quebec Trisomy 21 public Prenatal Screening, Serum Integrated prenatal screening (SIPS). Comparisons were made for a virtual population similar to that of expected Quebec pregnant women in 2015 in terms of size and age. Data input parameters were retrieved from a thorough literature search and in government databases, especially data from Quebec Program of screening for Trisomy 21. The 2015–2016 fiscal year budget impact was estimated from the Quebec healthcare system perspective and was expressed as the difference in the overall costs between the two alternatives (SIPS minus SPS + NIPT).ResultsOur study found that, at a baseline cost for NIPT of CAD$ 795, NIPT as a second-tier test offered to high-risk women identified by current screening program (SIPS + NIPT) may be affordable for Quebec health care system. Compared to the current screening program, it would be implemented at a neutral cost, considering a modest annual savings of $ 80,432 (95% CI $ 79, $ 874–$ 81,462). Results were sensitive to the NIPT costs and the uptake-rate of invasive diagnostic tests.ConclusionIntroducing NIPT as a contingent test in the Quebec Trisomy 21 screening program is an affordable strategy compared to the current practice. Further research is needed to confirm if our results can be reproduced in other healthcare jurisdictions.

Web-Based Training for Nurses on Shared Decision Making and Prenatal Screening for Down Syndrome: Protocol for a Randomized Controlled Trial.

BackgroundPregnant women often find it difficult to choose from among the wide variety of available prenatal screening options. To help pregnant women and their partners make informed decisions based on their values, needs, and preferences, a decision aid and a web-based shared decision making (SDM) training program for health professionals have been developed. In Canada, nurses provide maternity care and thus can train as decision coaches for prenatal screening. However, there is a knowledge gap about the effectiveness of SDM interventions in maternity care in nursing practice.ObjectiveThis study aims to assess the impact of an SDM training program on nurses’ intentions to use a decision aid for prenatal screening and on their knowledge and to assess their overall impressions of the training.MethodsThis is a 2-arm parallel randomized trial. French-speaking nurses working with pregnant women in the province of Quebec were recruited online by a private survey firm. They were randomly allocated (1:1 ratio) to either an experimental group, which completed a web-based SDM training program that included prenatal screening, or a control group, which completed a web-based training program focusing on prenatal screening alone. The experimental intervention consisted of a 3-hour web-based training hosted on the Université Laval platform with 4 modules: (1) SDM; (2) Down syndrome prenatal screening; (3) decision aids; and (4) communication between health care professionals and the patient. For the control group, the topic of SDM in Module 1 was replaced with “Context and history of prenatal screening,” and the topic of decision aids in Module 3 was replaced with “Consent in prenatal screening.” Participants completed a self-administered sociodemographic questionnaire with close-ended questions. We also assessed the participants' (1) intention to use a decision aid in prenatal screening clinical practice, (2) knowledge, (3) satisfaction with the training, (4) acceptability, and (5) perceived usefulness of the training. The randomization was done using a predetermined sequence and included 40 nurses. Participants and researchers were blinded. Intention to use a decision aid will be assessed by a t test. Bivariate and multivariate analysis will be performed to assess knowledge and overall impressions of the training.ResultsThis study was funded in 2017 and approved by Genome Canada. Data were collected from September 2019 to late January 2020. This paper was initially submitted before data analysis began. Results are expected to be published in winter 2020.ConclusionsStudy results will inform us on the impact of an SDM training program on nurses’ intention to use and knowledge of decision aids for prenatal screening and their overall impressions of the training. Participant feedback will also inform an upgrade of the program, if needed.Trial RegistrationClinicalTrials.gov NCT04162288; https://clinicaltrials.gov/ct2/show/NCT04162288International Registered Report Identifier (IRRID)DERR1-10.2196/17878

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.