Screening Test For Down Syndrome Research Articles

Public Health England and Co-Production with the Fetal Anomaly Screening Programme

As the new Cell-free DNA (Cf-DNA) prenatal screening test for Down syndrome was being introduced into the UK’s fetal anomaly screening program, Down syndrome charities had an opportunity to participate. An experience of co-production where we were the minority voice then followed. This paper explores that process and our experience as a charity. Institutional and societal structures meant that it was difficult to be heard and a significant amount of bias was noted within the program. Consequently, our viewpoints were often considered and then dismissed. However, at times we were listened to, and feel that there were some valuable changes made resulting from our involvement. The end product was far from reflective of all that we stand for, and there are still lessons to be learned in England about the need to place a higher value on minority voices of lived experience in a co-production exercise.

Analysis of the Effectiveness of First Trimester Nucal Translucence, Free Beta-Human Chorionic Gonadotropin, and Pregnancy-Related Plasma Protein-A in Prediction of Pregnancy Complications

In this study, we aimed to investigate whether there was an association between fetal nuchal translucency (NT) and the serum markers plasma protein-A (PAPP-A) and free beta-human chorionic gonadotropin (β-hCG) measured by the first-trimester screening test, as well as birth weight and hypertension. 454 pregnant women who had undergone the first-trimester screening test for Down syndrome were included in the study. All measurements and values of NT, PAPP-A and β-hCG levels were performed between gestational weeks 11-14. Values of PAPP-A and β-hCG converted to multiples of the corrected median (MoM) were obtained using the PRISCA software package. Regarding the prediction of SGA infants, when the PAPP-A value < was 0.99MoM as a threshold, and when the free β-hCG value < was 0.69 MoM, SGA cases could be detected with a sensitivity of 83% and a specificity of 71.9%. Regarding the prediction of hypertension, at a threshold PAPP-A value of

Health Supervision for Children and Adolescents With Down Syndrome.

Health Supervision for Children and Adolescents With Down Syndrome.

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.

Ethnicity-Specific Normative Models of Quadruple Test as a Screening Test for Down Syndrome.

Background and Objectives: To establish normative models for median levels of serum biomarkers of the second trimester quad test (alpha-fetoprotein: AFP; free beta-human gonadotropins: hCG; inhibin-A; and unconjugated estriol: uE3) specific to Thai women and to compare multiples of the median (MoMs) derived from ethnicity-specific models and those derived from Caucasian models with ethnic correction. Materials and Methods: A cross-sectional study was undertaken in a tertiary, medical teaching center among low-risk pregnant Thai women between 14 and 21 weeks of gestation to measure the levels of the four serum biomarkers. The measured values of each biomarker were analyzed using the multivariable factorial polynomial technique for quantile regression as a function of gestational age and maternal weight. Results: The Thai-specific normative models for the four biomarkers were generated and available for use. The MoMs of all individuals generated from our models were significantly different from conventional (Caucasian) models with ethnic correction (Wilcoxon signed-rank test; p < 0.0001 for all biomarkers). The MoMs of AFP and hCG from both methods were in agreement, but those from Thai-specific models were significantly higher. However, those of inhibin-A and uE3 were markedly different and ethnic correction was unlikely to be useful. Conclusions: The Thai-specific normative models of the quad test as a function of gestational age and maternal weight were constructed using multivariable factorial polynomial models, better than simple quantile regression or log-linear regression used in earlier decades. The analysis of MoMs supports the use of ethnicity-specific models instead of Caucasian models with ethnic correction.

Non-invasive prenatal testing: clinical utility and ethical concerns about recent advances.

The combined first trimester screening test for Down syndrome, involving a nuchal translucency scan and biochemistry at 11–13 weeks, improved detection rates to 90% when compared with the sensitivity of screening by age-related a priori risk of around 30% for a false positive rate of 5%. The advent of non-invasive prenatal testing (NIPT) in 2010 as a screening test for the common trisomies was revolutionary, with sensitivity, specificity and detection rates unmatched by the combined first trimester screening programs. NIPT was found to achieve a detection rate for Down syndrome of 99.7%, with a false positive rate of 0.04%. However, some NIPT providers now additionally offer extended panels and low resolution whole genome sequencing (WGS) including sex chromosome aneuploidies, rare autosomal aneuploidies, and subchromosomal deletions, duplications and recurrent microdeletions. This comes at a cost of a higher false positive rate and lower positive predictive value. Moreover, the expanded panels and WGS NIPT raise issues of clinical utility and ethical concerns.

Bulgarian Down Syndrome Prenatal Testing

With the emergence of non-invasive prenatal testing, Down syndrome screening and diagnosis technologies have advanced quickly in recent years. Not all of the women, however, are aware of the additional test alternatives. As a result, the purpose of our study is to look at women's awareness of prenatal Down syndrome tests in Bulgaria. The survey's findings reveal a lack of understanding of the available screening and diagnostic tests for Down syndrome, particularly NIPT. Women should be better educated and counselled throughout their pregnancy appointments. According to the most recent EUROCAT study, Down syndrome, also known as Trisomy 21, is the most prevalent chromosomal anomaly, with a frequency of 23.02 per 10000. Intellectual handicap, characteristic facial traits, heart abnormalities, and other clinical indications are well-known.

The effects of exogenous oral micronized progesterone on first trimester aneuploidy screening markers in women with threatened miscarriage: a matched case control study

Objectives To evaluate the effect of using progesterone due to early vaginal bleeding on aneuploidy screening markers in the first trimester. Material and methods This case control study includes the pregnant women who applied to our clinic in order to have a screening test for Down syndrome in the weeks of 11°/7−136/7. The patients were divided into three groups. Self reported vaginal bleeding with progesterone therapy (Bl+, Prg+, n:70), Self reported vaginal bleeding without progesterone therapy (Bl+, Prg−, n:70) and as a control group pregnant women who had no vaginal bleeding. (NoBl, NoPrg, n:70). In all patients, free beta-human chorionic gonadotrophin (β-hCG), pregnancy associated plasma protein-A (PAPP-A) levels and nuchal translucency (NT) thickness were analyzed. Mean MoMs of the markers were compared between three groups. Results In the two groups with vaginal bleeding (Bl+, Prg + and Bl+, Prg−) the free β-Hcg MoM values were statistically higher (1.22 ± 0.72, 0.98 ± 0.45, respectively) compared to the No Bleeding/No Progesterone group (0.81 ± 0.52) (p ≤ 0.001, p ≤ .01, respectively). However, no significant difference was found between the free β-hCG MoM value of women with Bl+, Prg + group (1.22 ± 0.72) and Bl+, Prg − group (0.98 ± 0.45). (p: .053, significance level limitation with Bonferroni correction p: .017). PAPP-A and NT thickness did not differ significantly between the groups. Conclusion Our data did not find an association between the use of oral progesterone and any alternations in first trimester screening parameters. Regardless of the progesterone usage, vaginal bleeding in the first trimester pregnancies increased the free β-hCG MoM values compared to pregnancies without vaginal bleeding during pregnancy.

The importance of gestational age in first trimester, maternal urine MALDI-Tof MS screening tests for Down Syndrome

The importance of gestational age in first trimester, maternal urine MALDI-Tof MS screening tests for Down Syndrome

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.

Aiding risk information learning through simulated experience (ARISE): Using simulated outcomes to improve understanding of conditional probabilities in prenatal Down syndrome screening

ObjectiveTo determine whether the use of visually-presented simulated experiences to communicate statistical information can improve an individual’s understanding of conditional probabilities—specifically the positive predictive value (PPV) of prenatal screening tests for Down syndrome. MethodsIn Experiment 1 (N=64) and Experiment 2 (N=180) participants were asked to estimate the PPV of a prenatal screening test for Down syndrome based on either (1) explicit statistics regarding the prevalence of Down syndrome and the sensitivity and specificity of a prenatal screening test for Down syndrome, or (2) experiencing up to 5000 simulated test results over a short time. ResultsParticipants’ estimates of the PPV were more accurate when they had learned via simulated experiences (79% accuracy) compared with estimates based on explicitly described statistics (14%). Participants in the simulated experience condition also reported decreased interest in screening and decreased concern with a positive test result. ConclusionA visual paradigm presenting simulated experiences improves PPV estimates, compared to estimates derived from explicitly provided statistics, while also shifting attitudes away from screening. Practice implicationsThe use of simulated experiences may prove to be simple but powerful tool to communicate complex statistical information to patients in medical decision making situations.

The mid-gestation triple test profile among women diagnosed with vasa previa

Purpose: To assess the mid-trimester triple test biomarkers among women diagnosed with vasa previa (VP).Methods: The study included 43 singleton pregnancies diagnosed with vasa previa between the years 1988 and 2011. The mid-gestation screening test for Down syndrome was calculated from the combination of triple serum markers and maternal age, and expressed as a multiple of the gestation specific normal mean (MoM). Reference MoM values were calculated from the local population. The levels of mid-gestation maternal serum alpha-fetoprotein (AFP), human chorionic gonadotropin (hCG), and unconjugated estriol (uE3) of patients with VP were compared with control reference group.Results: The mean hCG and αFP levels of women diagnosed with VP was significantly higher compared to control reference group (1.42 versus 0.99 MoM; p < .002 and 1.24 versus1.01 MoM; p < .001, respectively). In contrast, there was no significant difference in uE3 levels between these two groups (0.99 versus 0.98 MoM; p = .71).Conclusions: Our findings suggest that increased mid-gestation hCG and AFP were found among pregnancies complicated with VP. Clinicians should consider targeted scanning of pregnant women with risk factors for VP, including unexplained high maternal levels of hCG and αFP of the triple test, while conducting mid-gestation anomaly scan.

Cost Benefit Analysis of Prenatal Screening Test with Thai NIPT (Thai Non- Invasive Prenatal Test) for Down Syndrome in Developing Countries

Objective: The purpose of this study was to assess cost benefits of prenatal screening test for Down syndrome in developing countries (like Thailand) in order to inform OB/GYN clinical practice and medical/public health policy). Methods: A decision tree model was developed to analyze cost-benefits of the two screening modalities versus conventional screening test as base case. The first screening modality was universal Thai NIPT (Thai Non-invasive Prenatal Test) and the second was contingent Thai NIPT. Input parameters related to clinical values and costs were obtained from both primary and secondary sources for Thai population. One-way analysis and probabilistic sensitivity analysis were performed to evaluate uncertainty surrounding model parameters. Results: Based on the societal perspective, performing universal Thai NIPT and contingent Thai NIPT yielded differences of incremental benefit to incremental cost of -4,472 to -3,784 Thai Baht (-127.77 to -108.11 US$) and 396 to 1,085 (11.31 to 31.00 US$) when each was compared to conventional tests. The ratio of incremental benefit to incremental cost was 0.03 to 0.14 for universal Thai NIPT, respectively and thus cost was saved for contingent Thai NIPT. Conclusion: Applying Thai NIPT as the first line of screening for Down syndrome might be cost beneficial if the price was around 4,047 to 4,795 Thai Baht or US$ 115.63 to 137.00 per test. The contingent Down syndrome screening tests by offering the conventional tests first, then followed by Thai NIPT before performing the invasive screening test which seems to be a cost beneficial alternative approach.

Influence of Behçet's disease on first and second trimester serum screening markers.

Behçet's disease (BD) is a rare and multisystemic vasculitis disease. In this study, we investigated whether BD had any effect on the biochemical components of first and second trimester aneuploidy screening tests. A case-control retrospective study was conducted with 32 pregnant women with BD and 60 healthy pregnant women as controls. All pregnant womens' first trimester maternal serum pregnancy-associated plasma protein-A, free β-human chorionic gonadotropin and second trimester serum alpha-fetoprotein, unconjugated estriol and total human chorionic gonadotropin levels were examined from medical records. First and second serum screening markers were compared between pregnancies with BD and without. There was no difference in age, body mass index and obstetric history between the groups. No significant difference was observed between the groups in terms of first and second trimester serum screening test results in the absence of aneuploidy or neural tube defect. Gestational age at birth, birth weight and neonatal intensive care admission rate were also similar between the groups. Both first and second serum screening tests for Down syndrome may be recommended to pregnant women with BD without the need to readjust these markers. Pregnancy with BD was not associated with adverse perinatal outcome with respect to gestational age at birth or birth weight.

Uptake, Outcomes, and Costs of Implementing Non-invasive Prenatal Testing for Down Syndrome Into NHS Maternity Care: Prospective Cohort Study in Eight Diverse Maternity Units

(Abstracted from BMJ 2016;354:i3426) Noninvasive prenatal testing, also known as cell-free DNA (cfDNA) screening, is an efficient screening test for Down syndrome with roughly 99% sensitivity and false-positive rates of less than 0.1% in both high-risk and general populations. This study aimed to examine the potential costs and consequences of introducing cfDNA screening in the public sector Down syndrome screening pathway as an additional screening test dependent on the risk generated by current screening.

Decision aids that support decisions about prenatal testing for Down syndrome: an environmental scan.

BackgroundPrenatal screening tests for Down syndrome (DS) are routine in many developed countries and new tests are rapidly becoming available. Decisions about prenatal screening are increasingly complex with each successive test, and pregnant women need information about risks and benefits as well as clarity about their values. Decision aids (DAs) can help healthcare providers support women in this decision. Using an environmental scan, we aimed to identify publicly available DAs focusing on prenatal screening/diagnosis for Down syndrome that provide effective support for decision making.MethodsData sources searched were the Decision Aids Library Inventory (DALI) of the Ottawa Patient Decision Aids Research Group at the Ottawa Health Research Institute; Google searches on the internet; professional organizations, academic institutions and other experts in the field; and references in existing systematic reviews on DAs. Eligible DAs targeted pregnant women, focused on prenatal screening and/or diagnosis, applied to tests for fetal abnormalities or aneuploidies, and were in French, English, Spanish or Portuguese. Pairs of reviewers independently identified eligible DAs and extracted characteristics including the presence of practical decision support tools and features to aid comprehension. They then performed quality assessment using the 16 minimum standards established by the International Patient Decision Aids Standards (IPDASi v4.0).ResultsOf 543 potentially eligible DAs (512 in DALI, 27 from experts, and four on the internet), 23 were eligible and 20 were available for data extraction. DAs were developed from 1996 to 2013 in six countries (UK, USA, Canada, Australia, Sweden, and France). Five DAs were for prenatal screening, three for prenatal diagnosis and 12 for both). Eight contained values clarification methods (personal worksheets). The 20 DAs scored a median of 10/16 (range 6–15) on the 16 IPDAS minimum standards.DiscussionNone of the 20 included DAs met all 16 IPDAS minimum standards, and few included practical decision support tools or aids to comprehension.ConclusionsOur results indicate there is a need for DAs that effectively support decision making regarding prenatal testing for Down syndrome, especially in light of the recently available non-invasive prenatal screening tests.Electronic supplementary materialThe online version of this article (doi:10.1186/s12911-015-0199-6) contains supplementary material, which is available to authorized users.

Advantages and Disadvantages of Different Implementation Strategies of Non-Invasive Prenatal Testing in Down Syndrome Screening Programmes

Background: Implementation of non-invasive prenatal testing (NIPT) in Down syndrome screening programmes requires health policy decisions about its combination with other tests and its timing in pregnancy. Aim: Our aim was to aid health policy decision makers by conducting a quantitative analysis of different NIPT implementation strategies. Methods: Decision trees were created to illustrate all plausible alternatives in a theoretical cohort of 100,000 pregnant women in five screening programmes: classical screening by the first-trimester combined test (FCT), pre-selection of high-risk women prior to NIPT by the FCT, NIPT as the first screening test at 10 weeks and at 13 weeks, and the simultaneous conductance of NIPT and the FCT. Results: Pre-selection by FCT prior to NIPT reduces the number of amniocenteses to a minimum because of a reduction of false-positive NIPT results. If NIPT is the first screening test, it detects almost all fetal Down syndrome cases. NIPT at 10 weeks reassures women early in pregnancy, while NIPT at 13 weeks prevents unnecessary tests due to spontaneous miscarriages and allows for immediate confirmation by amniocentesis. Conclusion: Every implementation strategy has its advantages and disadvantages. The most favourable implementation strategy may be NIPT as the first screening test at 13 weeks, offering the most accurate screening test for Down syndrome, when the risk for spontaneous miscarriage has declined remarkably and timely confirmation by amniocentesis can be performed.

Current controversies in prenatal diagnosis 1: NIPT for chromosome abnormalities should be offered to women with low a priori risk.

In its successful annual cycle of controversies and debates, the International Society of Prenatal Diagnosis and Therapy once again addressed non-invasive prenatal testing (NIPT) by following up on the 2013 controversy, 'Should non-invasive DNA testing be the standard screening test for Down syndrome in all pregnant women'? with the proposition, 'NIPT for chromosomel abnormalities should be offered to women with low a priori risk'.

Israeli Society of Medical Genetics NIPT Committee Opinion 072013: Non-Invasive Prenatal Testing of Cell-Free DNA in Maternal Plasma for Detection of Fetal Aneuploidy

Non-invasive prenatal testing (NIPT) of cell-free fetal DNA in maternal plasma is a novel approach, designed for detecting common aneuploidies in the fetus. The Israeli Society of Medical Geneticists (ISMG) supports its use according to the guidelines stated herein. The clinical data collected thus far indicate that NIPT is highly sensitive in detecting trisomies 21 and 18, and fairly sensitive in detecting trisomy 13 and sex chromosome aneuploidies. Because false-positive results may occur, an abnormal result must be validated by invasive prenatal testing. At this juncture, NIPT does not replace existing prenatal screening tests for Down syndrome, as these are relatively inexpensive and cost-effective. Nonetheless, NIPT may be offered to women considered to be at high risk for fetal chromosomal abnormalities as early as 10 weeks of gestation. The ISMG states that NIPT should be an informed patient choice, and that pretest counseling regarding the limitations of NIPT is warranted. Women at high risk for genetic disorders not detected by NIPT should be referred for genetic counseling. A normal test result may be conveyed by a relevant healthcare provider, while an abnormal result should be discussed during a formal genetic consultation session.

Association between altered placental human chorionic gonadotrophin (hCG) production and the occurrence of cryptorchidism: a retrospective study.

BackgroundAn increase in cryptorchidism has been reported in many countries. One mechanism could be low fetal testosterone production possibly secondary to altered placental human chorionic gonadotrophin (hCG) release. Our Objective was to compare hCG values from maternal blood between boys with cryptorchidism and normal boys.MethodsTotal hCG and α-fetoprotein (AFP) values [12–16 weeks of gestation; from the double test for Down syndrome screening) were compared between cases of cryptorchidism and normal control boys who were matched for maternal age, maternal smoking, gestational age at time of hCG measurement (±1 day), birth weight and birth term. Measurements were performed in a single laboratory; values were expressed as absolute values (KU/L) and multiples of the median (MoM). Boys whose mothers had had a complicated pregnancy were excluded. Groups were compared using the Student’s t test. Log transformation was used to normalize hCG, MoM hCG, AFP and MoM AFP distribution, and values were expressed as geometric means (-1, + 1 tolerance factor).ResultsTotal hCG and MoM hCG levels were significantly lower in the 51 boys with cryptorchidism compared to 306 controls (21.4 (12.3; 37) KU/L vs 27.7 (15.9; 47.9) KU/L and 0.8 (0.5; 1.2) MoM vs 1.0 (0.6; 1.6) MoM, respectively, p < 0.01). By contrast, AFP and MoM AFP levels were similar between groups.ConclusionThis study showed a link between low maternal serum hCG levels and cryptorchidism in boys from uncomplicated pregnancy, while normal AFP levels indicated a normal fetoplacental unit. Whether these abnormalities were due to endogenous or exogenous factors remains to be determined.