Screening Strategies For Down Syndrome Research Articles

Health economic evaluation of four prenatal screening strategies for Down syndrome in Changsha, China

To compare the clinical application and health economic values of non-invasive prenatal testing (NIPT) and second trimester serum screening (STSS). A retrospective analysis was carried out on 54 026 singleton pregnant women undergoing NIPT and STSS from March 1, 2018 to December 31, 2019 in Changsha Maternal and Child Health Care Hospital. For pregnant women with high-risk results of NIPT, prenatal diagnosis and follow-up of pregnancy outcomes were conducted. The data was grouped to 4 screening models, and their cost-benefit was analyzed. The sensitivity, specificity and positive predictive value of NIPT were all higher than STSS. Screening models 1 to 4 have prevented the birth of 71, 29, 52 and 54 patients with Down syndrome, respectively. The safety index of screening models 1 to 4 were 0.0036, 0.3944, 02215 and 0.1281, respectively. When the price of NIPT was decreased to 600 RMB, the cost-benefit of the screening models 1 to 4 was 0.46, 0.65, 0.44 and 0.40 million RMB, respectively. NIPT has a better detection performance than STSS. When the price of NIPT is 600 RMB, screening model 1 has the best screening effect and the highest accuracy, safety index and health economical value.

OP354 Cost-Effectiveness Analysis Of Different Prenatal Screening Strategies For Down Syndrome In China: Data From Shandong Province

IntroductionThere are large differences between the prenatal screening strategies for Down Syndrome (DS) in different provinces in China. In Henan province there is a serological triple screening in the second trimester (STS) strategy, while in Shandong province contingent non-invasive prenatal testing (NIPT) screening strategy (NIPT delivered to older pregnant women) is used, and there is a universal NIPT screening strategy in Anhui province. Moreover, many factors varied widely in different regions, such as the proportion of older pregnant woman and the ability of people to pay. This study aimed to determine the cost-effectiveness of current strategy in Shandong compared with strategies in other provinces.MethodsA decision tree model was developed according to the screening strategies in different provinces. Four screening strategies were involved, universal STS strategy, contingent STS strategy, contingent NIPT strategy, and universal NIPT strategy. Cost-effectiveness analysis was conducted from a societal perspective in a simulated cohort of 100,000 pregnant women. The data of costs and epidemiologic parameters were collected from field surveys in Shangdong and a literature review.ResultsThe universal STS strategy, contingent STS strategy, contingent NIPT strategy, and universal NIPT strategy could prevent 17.0, 40.0, 46.2, and 53.6 DS births, respectively. There was no strategy dominated by others. The universal NIPT strategy and contingent NIPT strategy would decrease invasive procedures for prenatal diagnosis, resulting in fewer procedure-related miscarriages. The sensitivity analysis showed that the effectiveness of the screening strategy is significantly influenced by the resident's acceptance of NIPT.ConclusionsFrom the perspective of maximizing the effect, the universal NIPT strategy is the optimal strategy. But taking into account the resident's and government's ability to pay, contingent NIPT Strategy may be appropriate for the current situation in Shandong. To ensure a better cost-effective advantage in the universal NIPT strategy, the government should provide health education to increase the acceptance of NIPT while controlling the price of NIPT.

DEPIST 21: Information and knowledge of pregnant women about screening strategies including non-invasive prenatal testing for Down syndrome

ObjectiveTo evaluate the knowledge of pregnant women and provide information about Down syndrome (DS) screening, including non-invasive prenatal testing (NIPT). Materials and methodsA prospective unicenter study of pregnant women recruited during their first trimester foetal ultrasound was carried out. Single pregnancies from 11 to 17 + 6 weeks of amenorrhoea (SA) without a history of DS were included. “Pre” and “post” questionnaire were fulfilled before and after the consultation. Patient characteristics, prior information, information provided during the consultation, and patient satisfaction were also analysed. ResultsA total of 273 were included in the study, and 147 completed surveys (pre and post) were examined. In pre-consultation, 82 % of women know that integrated screening includes maternal serum markers and nuchal translucency (n = 103). Concerning NIPT for DS, 8% (n = 11) of women declare having been informed before the ultrasound. A minority of patients know modalities of reimbursement (n = 33, 26 %) and invasive sampling is mandatory for diagnosis when NIPT is positive (n = 37, 28 %). Significant improvement in right answers was obtained for three questions: “nuchal translucency is included in the combined screening test for DS” (p = 0,007); “blood serum markers is included in the combined screening for DS” (p = 0,009) and advanced maternal age increases risk for DS” (p = 0,004). Total score in the post questionnaire was significantly higher than the “pre” consultation questionnaire (14,7 ± 2.8 versus 14,1 ± 2.9; p = 0.01). ConclusionPatients show a high level of knowledge on screening strategies for DS in pre-consultation. They benefit from the consultation on global knowledge, NIPT, and ultrasound notions.

Health economic evaluation of five prenatal screening strategies for Down's syndrome

Objective To investigate the cost-effectiveness and cost-benefit of five screening strategies for Down syndrome (DS) to optimize prenatal screening strategy. Methods A retrospective analysis was conducted in 26 803 gravidas, who underwent the second trimester maternal serum screening ( maternal serum α-fetoprotein and β-human chorionic gonadotropin) from 2002 to 2003, whom were classified into three groups according to the results of serum DS screening: high risk group (≥1/270), borderline risk group (≥1/1 000-<1/270) and elderly gravida group (age at expected date of confinement≥35 years old). TreeAge Pro 2011 sofware was used to set up the decision tree model for cost-effectiveness and cost-benefit analysis. Strategy 1: Maternal serum screening was carried out on all gravidas, and then prenatal diagnosis was performed for women in high risk group. Strategy 2: Non-invasive prenatal testing (NIPT) was carried out on all gravidas, and then prenatal diagnosis was offered for women with positive or suspected results. Strategy 3: NIPT was only carried out on gravidas of advanced maternal age and maternal serum screening was performed on the rest population. Gravidas with positive or suspected positive results in NIPT or classified into the high risk group underwent prenatal diagnosis. Strategy 4: Maternal serum screening was carried out on all gravidas. Those at high risk received prenatal diagnosis, while those at borderline risk underwent NIPT first and followed by prenatal diagnosis if positive or suspected positive NIPT results were identified. Strategy 5: Maternal serum screening was carried out on all gravidas. Those at high or borderline risk would undergo NIPT followed by prenatal diagnosis if they were positive or suspected positive for NIPT. Results (1) Among 26 803 gravidas, 1 244 were at high risk group (4.64%) with five having trisomy 21; 3 925 were at bordelrine risk (14.64%) with four having trisomy 21; 300 women were of advanced age (1.12%) with one having trisomy 21. (2) Cost-effectiveness analysis: the incremental cost-effectiveness ratios of strategy 3 and 4 were negative and that of strategy 1 was 0 with a cost-effectiveness ratio of 15 833 764.53. The incremental cost-effectiveness ratio of strategy 2 was 49 865 746.10, which was far greater than that of strategy 5 (63 049.56). The cost-effectiveness ratio of strategy 4 is 586 703.63, which was less than those of strategy 1,2 and 3 but higher than that of strategy 5. The average cost-effectiveness ratio of strategy 5 was the lowest (508 431.20) among these five strategies, which meant that for every diagnosis of DS, strategy 5 had the lowest cost (508 400 yuan). (3) Cost-benefit analysis: The benefits of strategy 4 and 5 were greater than their costs. Strategy 5 had the highest benefit-cost ratio, followed by strategy 4, 2, 3 and 1. (4) When other factors remained unchanged and only the acceptance rate of prenatal diagnosis was adjusted from 50% to 100%, strategy 1 had the least cost expectation, followed by strategy 3, 5, 4 and 2. When the cost of NIPT was below 82.4 yuan, the cost expectation of strategy 2 that performed on all gravidas was the lowest, while when it was between 82.4 and 1 827.2 yuan, the screening cost of strategy 5 was the lowest. Conclusions Strategy 5 has the best cost-effectiveness and cost-benefit. It would be the best screening strategy for DS, if the cost of NIPT is between 82.4-1 827.2 yuan. Key words: Down syndrome; Neonatal screening; Prenatal diagnosis; Costs and cost analysis; Cost-benefit analysis; High-throughput nucleotide sequencing

Economic analysis of prenatal screening strategies for Down syndrome in singleton pregnancies in Turkey

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

Likelihood Ratios to Apply for Nasal Bone, Ductus Venosus and Tricuspid Flow at the 11-13 Weeks' Scan in Down Syndrome Screening

Objective: To assess the feasibility of nasal bone (NB), ductus venosus (DV) and tricuspid flow (TF) at the 11-13 weeks' scan, calculate likelihood ratios for each of the markers and evaluate their efficacy in expanded and contingent screening strategies for Down syndrome. Material and Methods: NB, DV and TF were assessed in 11,261 singleton fetuses undergoing first trimester combined screening. For each marker, Down syndrome detection rate (DR), false positive rate (FPR), positive, negative and isolated likelihood ratios (PLR, NLR and iLR) were calculated. Likelihood ratios were multiplied to the combined test risk either to the entire population or to the intermediate risk group (expanded and sequential strategies, respectively). Results: Down syndrome was diagnosed in 101 pregnancies. Feasibility for marker assessment ranged from 71 to 97%, DRs for isolated markers from 20 to 54% and FPRs from 1.3 to 5.3%. PLR ranged from 10 to 15, NLR from 0.5 to 0.8 and iLR from 3.9 to 5.6. When ultrasound markers were added to both strategies, a significant FPR reduction was observed. Conclusion: The application of NB, DV and TF likelihood ratios to the combined test risk, either in an expanded or contingent strategy, result in a FPR reduction.

Contingent screening for Down syndrome completed in the first trimester: a multicenter study

To assess a new contingent screening strategy for Down syndrome completed in the first trimester. First-trimester screening combining nuchal translucency thickness measurement and assessment of serum analytes (combined test) was offered to pregnant women who presented for prenatal care during the first trimester to nine health centers and community hospitals in the area served by the Catalan Public Health Service. If an intermediate risk (1/101-1/1000) for Down syndrome was identified, women were referred to the Hospital Clinic Barcelona for risk reassessment that included the use of secondary ultrasound markers (nasal bone, ductus venosus blood flow and tricuspid flow). Intermediate-risk women were divided into two subgroups for further analysis: high-intermediate risk (1/101-1/250) and low-intermediate risk (1/251-1/1000). We compared feasibility and efficacy of both combined and contingent screening strategies. The combined test, the first screening stage, was performed in 16 001 pregnant women, of whom 1617 (10.1%) were found to have an intermediate risk. Further division of this group showed that 1.8% (n = 289) of women were at high-intermediate risk and 8.3% (n = 1328) at low-intermediate risk. The contingent screening strategy significantly reduced the false-positive rate, from 3.0% to 1.3-1.8% (P < 0.001), without affecting the detection rate (which was 75-79% and 76%, with and without the contingent screening strategy, respectively). However, only 45% of intermediate-risk patients underwent the second screening step due to a preference among high-intermediate-risk (1/101-1/250) women for invasive testing and to low uptake among low-intermediate-risk (1/251-1/1000) women. The proposed first-trimester contingent strategy reduces the screen false-positive rate without impacting on the detection rate of Down syndrome. The low compliance observed in our study may prevent its use in certain populations.

Antenatal Screening Strategies for Down Syndrome: Analysis of Existing Protocols and Implications in the Kingdom of Saudi Arabia

Antenatal Screening Strategies for Down Syndrome: Analysis of Existing Protocols and Implications in the Kingdom of Saudi Arabia

Antenatal Screening Strategies for Down Syndrome: Analysis of Existing Protocols and Implications in the Kingdom of Saudi Arabia

Background: Syndrome (DS) is the most frequent chromosomal abnormality in live births with an incidence of 1 to 1.7 per 1,000 births and a variable physical expression. syndrome screening has been an integral part of routine prenatal care in recent decades. Currently, there is no established DS screening program in the Kingdom of Saudi Arabia. Objective: The total number of DS pregnancies is increasing, probably due mainly to the increasing proportion of older mothers. Live birth with DS increased also so, there is an expected increase in long term survivors. There is a need for a well structured system for prenatal diagnosis and follow up program and an extra health care resource. Design: A systematic literature search for various prenatal screening tests for DS were explored regarding the time of screening during pregnancy, detection rate, false positive rate, advantages and disadvantages. Various search engines like Pub med, Medline, Index Medicus were used to review the published literature using the key words Down syndrome, antenatal screening, and “Chromosomal Results: Different screening strategies for DS are applied worldwide. In the United Kingdom, the combined test, the integrated test or the serum integrated test is offered for women who present in the first trimester, and the quadruple test for those who present in the second trimester. In the United States, Canada, and Australia the combined test is recommended for the first trimester and the quadruple test for the second trimester. Conclusion: The Quadruple test should be offered to all pregnant women in the second trimester, in addition all women should be offered a second –trimester ultrasound scan to identify major and minor fetal abnormalities. Extensive research is needed to establish accurate incidence of DS in the Kingdom of Saudi Arabia and its relation to maternal age and parity. Review Article

Prospective experience with contingent screening strategy for Down syndrome in Estonia

The purpose of this study was to establish the first-trimester screening for Down syndrome (DS) in Estonia and to evaluate the potential of a contingent screening in the population of pregnant women. A prospective cohort study included non-selected pregnancies during the programme of first-trimester screening for DS in a 4-year period at a single centre. The following screening tests were evaluated: measurement of nuchal translucency (NT) and serum screening [pregnancy-associated plasma protein A and free beta subunit of human chorionic gonadotropin (fβ-HCG)]; results were given as combined screening. After first-trimester screening, contingent screening protocol was used, and women were divided into three groups: high risk, low risk and an intermediate risk group. In the last group, a second-trimester triple test (AFP; total HCG and uE3) was also performed. The study group consisted of 3,194 non-selected pregnancies. In 1,387 (43.4%) women, first-trimester serum screening showed low risk (risk ≤ 1:5,000), and no future testing was performed, in 30 (0.9%) women screening test showed high risk (risk ≥ 1:50) and a diagnostic test was offered, and in 1,777 (55.7%) women repeated risk calculation in the second trimester was done. During the study period, there were 17 cases of trisomy 21, of which 15 (88.3%) were detected with the described screening programme. In conclusion, two-step contingent sequential screening is a better choice for Down syndrome screening in Estonia instead of previously used second-trimester screening, and it offers the advantage of earlier diagnosis.

Comparison of first‐trimester contingent screening strategies for Down syndrome

To assess the relative performance of a multi-stage first-trimester screening protocol for fetal Down syndrome. Data from 10,767 women who underwent combined ultrasound and biochemistry (BC) screening in the first trimester were reanalyzed using a contingent model approach. Amongst the 10,854 fetuses with known outcome, 32 had Down syndrome, 232 had other abnormalities and 10,590 were unaffected. Nuchal translucency (NT), BC and combined (NT-BC) gestational age-specific risks were calculated for each individual using The Fetal Medicine Foundation risk calculation algorithms (Mixture Model and Biochemistry). Individual patients were categorized as at low, high or intermediate risk according to one of the following three strategies. In 'Strategy-NT-BC' initial screening was performed using both NT and BC. In 'Strategy-BC' initial screening was undertaken using maternal serum markers followed by NT assessment in those with an intermediate risk (1 : 51 < risk <or= 1:1000) while in 'Strategy-NT' initial screening was undertaken using NT followed by serum marker assessment in those with an intermediate risk (1 : 51 < risk <or= 1:1000). The nasal bone was assessed in those with an intermediate risk as the final stage in each of the three strategies. Those with an adjusted risk of 1 in 100 or higher after nasal bone assessment were reclassified as high risk. Detection and false-positive rates were compared between differing strategies in our local population, and this analysis was also performed with the maternal age for our population standardized to the distribution found in England and Wales. In our local population the detection rate for a 5% false-positive rate using a combined screening policy (NT-BC) was 88% (95% CI, 75.3-98.9%), and 2.3% had an absent nasal bone. The respective detection rate and false-positive rate of the three multi-stage screening strategies were: Strategy-NT-BC: 87.5 and 2.5%; Strategy-BC: 87.5 and 5%; Strategy-NT: 84.4 and 2.9%. In the contingent Strategy-BC only 29% of those initially screened using serum markers required an NT scan. If the model were applied to a hypothetical obstetric population standardized to the maternal age distribution in England and Wales, the detection and false-positive rates of the same three screening strategies would be: Strategy-NT-BC: 86.2 and 1.9%; Strategy-BC: 82.8 and 4%; Strategy-NT: 75.8 and 2.3%, respectively. First-trimester contingent screening provides detection and false-positive rates comparable to those achieved using combined screening, but could be used to significantly reduce the number of scans performed.

P11.18: Impact of ductus venosus assessment in screening Down syndrome protocols

Screening by combination of nuchal translucency (NT) and maternal serum free beta-human chorionic gonadotropin (beta hCG) and pregnancy-associated plasma protein-A (PAPP-A) is an effective strategy to detect Down syndrome. Our objective is to estimate the improvement in screening efficiency when ductus venosus (DV) Doppler studies are added to existing Down syndrome (DS) screening protocols. First-trimester combined screening for DS was prospectively carried out, from February 2007 to January 2009, in 4408 singleton pregnancies at 11 + 0 to 13 + 6 gestational weeks, including maternal age, biochemistry (beta hCG and PAPP-A) and nuchal translucency. Ductus venosus pulsatility index for veins was calculated at the same time. The maternal serum biochemistry was measured using the Kryptor analyzer (Brahms Diagnostica) in a two-step strategy. The detection rate (DR) and false-positive rates (FPR) for standard screening strategy (maternal age, NT and biochemistry) and the same strategy but including DV assessment were calculated. The mean maternal age was 33 (range 18–46) years. The mean gestation age at blood test was 71 (+/− 10) days. The mean gestation age at scan was 12,6 (range 10,5–13.6) weeks. The population included 35,8% over 35 years. Down syndrome was identified in 16 pregnancies. At a fixed 1% FPR, the DR for trisomy 21 at screening time was 68,8% for standard screening strategy and 81,3% when including DV assessment, respectively. Compared to the standard DS screening strategies, DV assessment can improve screening efficiency by significantly reducing the false-positive rate. Early evaluation of DV can be introduced to standard DS screening strategies in experienced centers as a first level screening test to reduce invasive test rate derived from the extended existing DS screening protocols.

Impact of Ductus Venosus Assessment in Screening Down Syndrome Protocols: An Improved Strategy in a Fetal Medicine Unit

ABSTRACT Objective To estimate the improvement in screening efficiency when ductus venosus (DV) Doppler studies are added to existing Down syndrome (DS) screening protocols. Methods First-trimester combined screening for trisomy 21 was prospectively carried out, from October 2003 to March 2008, in 8842 consecutive singleton pregnancies attended in our tertiary reference center. The nuchal translucency (NT) and the pulsatility index for veins for DV were calculated. The maternal serum biochemistry was measured using the Kryptor analyzer, at the same time of the scan (one step strategy) or before it (two step strategy). The detection rate (DR) and false-positive rates for standard screening strategy (maternal age, NT and biochemistry) and the same strategy but including DV assessment were calculated. Results Successful DV assessment was possible in the 95.3% of cases, representing a total of 8426 cases. Down syndrome was identified in 34 pregnancies (prevalence of DS 1:250). For a fixed screen positive rate of 5%, the addition of the DV assessment improves the DR from 85 to 94% and, for a fixed DR of 85%, it reduces the number of unnecessary invasive tests from 3.7 to 3.2%. Conclusion Early evaluation of DV can be introduced to standard DS screening strategies in experienced centers as a first level test to reduce invasive test rate derived from the existing protocols.

588: Down syndrome screening strategies utilized by United States Maternal-Fetal Medicine specialists in 2007

MATERNAL-FETAL MEDICINE SPECIALISTS IN 2007 YU MING VICTOR FANG, PETER BENN, KATHERINE TRIBULATO, CONNOR FITZPATRICK, JAY BOLNICK, JAMES EGAN, University of Connecticut, Obstetrics and Gynecology, Farmington, Connecticut, University of Connecticut, Department of Pediatrics, Farmington, Connecticut, University of Nebraska, Omaha, Nebraska, Boston College, Boston, Massachusetts OBJECTIVE: Ball and colleagues suggested a cohesive national strategy regarding prenatal diagnosis and screening for Down syndrome (DS). (Obstet Gynecol 2007;110: 10-17) We determined the most common DS screening strategies currently utilized by Maternal-Fetal Medicine specialists (SMFM) in the United States (US). STUDY DESIGN: SMFM members in the US were surveyed in April 2007 regarding screening patterns for fetal aneuploidy. They were asked which of the following first trimester (trim) DS screening strategies they offered: combined screening (1st trim NT, PAPP-A, B-hCG. No 2nd trim screen), integrated screening (single risk given after 1st and 2nd trim tests are completed), stepwise sequential screening (results given after each trim, final risk is calculated from 1st and 2nd trim tests), contingency screening (use specific cut-offs to offer either invasive testing, no further testing, or 2nd trim screen), independent screening (1st and 2nd trim results are evaluated independently and not combined), or other. They could choose more than one strategy. Descriptive statistics are reported. RESULTS: There were 448/1756 (26%) responses of which 30.4% offered more than one screening strategy. The frequencies of the strategies offered by respondents are presented in the graph.

An update on antenatal screening for Down’s syndrome and specific implications for assisted reproduction pregnancies

Since the introduction of antenatal serum screening for Down's syndrome (DS) more than two decades ago, several screening approaches have been utilized in routine clinical practice. The current DS screening strategies involve mid-trimester serum biochemistry tests, first trimester tests combining sonographic markers and serum biochemistry and integration of first and second trimester markers. In this review, we evaluate the performance of DS screening strategies according to the Serum, Urine and Ultrasound Screening Study (SURUSS), the First and Second Trimester Evaluation of Risks (FASTER) Trial and the Serum Biochemistry and Fetal Nuchal Translucency Screening (BUN) Study. We also evaluate the performance of first trimester screening in studies and meta-analyses by other groups. Specific issues related to assisted reproduction technology (ART) pregnancies are also addressed in this review.

A Cost-Effectiveness Analysis of Prenatal Screening Strategies for Down Syndrome

To evaluate which Down syndrome screening strategy is the most cost-effective. Using decision-analysis modeling, we compared the cost-effectiveness of 9 screening strategies for Down syndrome: 1) no screening, 2) first-trimester nuchal translucency (NT) only, 3) first-trimester combined NT and serum screen, 4) first-trimester serum only, 5) quadruple screen, 6) integrated screening, 7) sequential screening, 8) integrated serum only, or 9) maternal age. Costs included cost of tests and resources used for raising a child with Down syndrome. One-way and multiway sensitivity analyses were performed for all model variables. The main outcome measures were cost per Down syndrome case detected, rate of delivering a liveborn neonate with Down syndrome, and rate of diagnostic procedure-related pregnancy loss for each strategy. Sequential screening detected more Down syndrome cases compared with the other strategies, but it had a higher procedure-related loss rate. Integrated serum screening was the most cost-effective strategy. Sensitivity analyses revealed the model to be robust over a wide range of values for the variables. The addition of the cost of genetic sonogram to the second-trimester strategies resulted in first-trimester combined screening becoming the most cost-effective strategy. Within our baseline assumptions, integrated serum screening was the most cost-effective screening strategy for Down syndrome. If the cost of nuchal translucency is less than dollars 57 or when genetic sonogram is included in the second-trimester strategies, first-trimester combined screening became the most cost-effective strategy. III.

Improved first‐trimester Down syndrome screening performance by lowering the false‐positive rate: a prospective study of 9941 low‐risk women

To determine the performance of screening for Down syndrome (DS) and other major chromosomal abnormalities using nuchal translucency (NT), free beta-human chorionic gonadotropin (beta-hCG) and pregnancy-associated plasma protein-A (PAPP-A) in a prospective study of a non-selected population. Of 9941 women with an early ultrasound examination, NT was measured in 8622 singleton pregnancies with a gestational age between 10 + 3 and 13 + 6 weeks. beta-hCG and PAPP-A were analyzed in 6441 cases. Detection rates (DR) and false-positive rates (FPR) for the NT screening, the double test (beta-hCG and PAPP-A) and the combined test (NT and the double test) were calculated using a 1 : 250 cut-off. NT could be measured in 97.5% of cases. The DR for DS with NT screening alone was 75% with a FPR of only 1.8%. The double test detected 73% and the combined test 91%, for FPRs of 8.8% and 2.1%, respectively. We detected 80% of fetuses with other major chromosomal abnormalities with a combination of NT screening and other ultrasound findings. Low beta-hCG and PAPP-A values (below 0.4 MoM) were observed in 0.5% of the women including all cases of triploidy and trisomy 18 and 13. The performance of a screening strategy for DS using a combination of NT and the double test was superior to that using either NT or the double test alone due to a very low FPR and a higher DR.

Changing demographics of advanced maternal age (AMA) and the impact on the predicted incidence of Down syndrome in the United States: Implications for prenatal screening and genetic counseling

This study documents the changes in the percentages of advanced maternal age (AMA) pregnancies in the United States and in Washington State, underlying demographic factors, the impact on the predicted incidence of Down syndrome, and its impact on Down syndrome screening. Data on births in the United States from 1933 to 2002 were obtained from publications and the website of the National Center for Health Statistics. Data for Washington State were obtained from the website of the Washington State Department of Health. Information on births at Swedish Medical Center was obtained from hospital records. The percentage of AMA pregnancies in the US was about 14% before World War II, dropped steadily to about 5% in the 1970s and rose since the 1980s to about 14% in 2002. AMA Fractions are greatest among non-Hispanic Caucasians and Asian/Pacific Islanders, women who have college education and beyond, and are married. However, since 1980, the AMA Fractions have increased across all racial/ethnic groups, educational levels, and married and unmarried women. In Washington State in 2001, the overall AMA Fraction was about 14%, but there was considerable variation in the AMA Fraction across counties. In 1980, AMA pregnancies accounted for about 25% of pregnancies with Down syndrome in the United States. In 2002, AMA pregnancies accounted for more than 50% of Down syndrome pregnancies. Given the current AMA Fraction, offering amniocentesis to women of age 35 and above would result in one in seven pregnant women undergoing amniocentesis. Based on likelihood ratios, AMA as a screening strategy for Down syndrome is significantly inferior to combined serum and sonographic screening.

A cost-effectiveness analysis of screening strategies for down syndrome (DS)

A cost-effectiveness analysis of screening strategies for down syndrome (DS)

Optimising the timing for nuchal translucency measurement.

It appears from current evidence that the most effective screening strategy for Down syndrome will involve a combination of first trimester nuchal translucency and serum biochemistry, whether performed in the first or second trimester. The aim of this study was to determine the optimum gestation based upon menstrual dates at which to schedule nuchal translucency (NT) measurement for the evaluation of fetal Down syndrome risk. Five thousand eight hundred and thirty-five pregnancies had an ultrasound scan scheduled between 11 and 14 completed weeks of gestation based upon either the last menstrual period (n = 3199) or a prior ultrasound scan (n = 2636). For last menstrual period-based ultrasound scans, with advancing gestation the frequency of missed miscarriage significantly decreased (p = 0.009, chi squared test), as did the need to reschedule a further scan because the gestation of the scheduled scan was too early to measure NT (p < 0.0001, Chi-squared test). In contrast, with advancing gestation the rate of unsuccessful NT measurement because the crown-rump length (CRL) was greater than 84 mm significantly increased (p < 0.0001, Chi-squared test). Of the women who had had an earlier ultrasound, 42 (1.6%) had a missed miscarriage and 9 (0.3%) were over gestation at the time of the NT scan. These data suggest that when only the last menstrual period is known the optimum time to schedule a nuchal translucency measurement is at 12 to 13 weeks' gestation.