Current Prenatal Screening Research Articles

Clinical strategy study on prenatal screening and diagnostic model for Down syndrome

Exploring efficient and easily implementable prenatal screening strategies aims at birth defect prevention and control. However, there have been limited economic evaluations of non-invasive prenatal screening (NIPS) strategies in China. Furthermore, these studies were predominantly confined to local or geographically proximate provinces and lacked universality and representativeness. This study assesses the health economics of current prenatal screening strategies and NIPS as first-line screening programs, analyzing their efficacy to determine an optimal strategy. From the perspective of health economics, cost-effectiveness, cost-benefit, and single-factor sensitivity were conducted for five different screening strategies using a decision tree model. Among pregnant women aged < 35 years who underwent only one screening for foetal Down syndrome (DS), the detection rate, false positive rate and positive predictive value of NIPS for foetuses with DS were superior to those of the other four serological screening methods. Although applying NIPS as first-line screening method yields the highest efficacy and benefits, it currently lacks cost-effectiveness when compared to serological screening and sequential NIPS screening strategies.

Automatic segmentation of 15 critical anatomical labels and measurements of cardiac axis and cardiothoracic ratio in fetal four chambers using nnU-NetV2

BackgroundAccurate segmentation of critical anatomical structures in fetal four-chamber view images is essential for the early detection of congenital heart defects. Current prenatal screening methods rely on manual measurements, which are time-consuming and prone to inter-observer variability. This study develops an AI-based model using the state-of-the-art nnU-NetV2 architecture for automatic segmentation and measurement of key anatomical structures in fetal four-chamber view images.MethodsA dataset, consisting of 1,083 high-quality fetal four-chamber view images, was annotated with 15 critical anatomical labels and divided into training/validation (867 images) and test (216 images) sets. An AI-based model using the nnU-NetV2 architecture was trained on the annotated images and evaluated using the mean Dice coefficient (mDice) and mean intersection over union (mIoU) metrics. The model’s performance in automatically computing the cardiac axis (CAx) and cardiothoracic ratio (CTR) was compared with measurements from sonographers with varying levels of experience.ResultsThe AI-based model achieved a mDice coefficient of 87.11% and an mIoU of 77.68% for the segmentation of critical anatomical structures. The model’s automated CAx and CTR measurements showed strong agreement with those of experienced sonographers, with respective intraclass correlation coefficients (ICCs) of 0.83 and 0.81. Bland–Altman analysis further confirmed the high agreement between the model and experienced sonographers.ConclusionWe developed an AI-based model using the nnU-NetV2 architecture for accurate segmentation and automated measurement of critical anatomical structures in fetal four-chamber view images. Our model demonstrated high segmentation accuracy and strong agreement with experienced sonographers in computing clinically relevant parameters. This approach has the potential to improve the efficiency and reliability of prenatal cardiac screening, ultimately contributing to the early detection of congenital heart defects.

Indigenization of the median of markers for Down syndrome screening based on statistical analysis of medical big data

ObjectiveTo indigenize the median of Down syndrome (DS) screening markers for first and second trimester, and compare the impact of the indigenized and built-in median data on the efficiency of DS screening. Materials and MethodsData derived from first and Second-trimester screening (FTS and STS) for DS, composed of selected pregnancies deemed to be normal, were examined in a retrospective study. Indigenization regression analysis was calculated by using five models to fit statistical the raw data. Multiple of median (MoM) values estimated by using indigenized medians were compared with those calculated by using built-in. ResultsThis study established a regression equation which is more suitable for the median of each screening marker in the local pregnant women. The changes of median MoM of screening markers were statistically significant after indigenization. For FTS, the detection rate was 100% when the false positive rate was 5%, and the cut-off value was 1/262. On the other hand, for STS, the detection rate of the model with indigenized parameters was 77.42%, which is 16.13% higher than that of built-in parameters. ConclusionFor the individual specific risk of pregnancy, when the indigenized parameters was used to calculate, is more accurately and screening effectiveness has been improved. This is a great reference significance for the current prenatal screening whether indigenized data should be used.

A Novel Conception Towards Effect of Preconception Hypothyroidism and First Diagnosed Hypothyroidism During Pregnancy on Offspring's Neurocognitive Function: Evidence from a Prospective, Cohort Study in China

Background: Hypothyroidism during pregnancy is associated with offspring’s neurodevelopment. Current prenatal screening is not effective, and hypothyroidism screening before conception is expected to be beneficial for improving offspring’s neurocognitive development. This study was to evaluate offspring’s neurocognitive development and pregnancy outcomes among women with hypothyroidism before conception and firstly diagnosed in early pregnancy. Method: In this prospective cohort study, women with hypothyroidism before 14 gestational week were recruited in Obstetrics and Gynecology Hospital of Fudan University. They were assigned into preconception controlled hypothyroidism, preconception uncontrolled hypothyroidism and hypothyroidism firstly diagnosed in early pregnancy based on their history of hypothyroidism before pregnancy and thyroid stimulating hormone (TSH) at first antenatal visit. Their general characteristics and pregnancy outcome were recorded. Gesell development diagnosis scale (GDDS) was applied for the evaluation of offspring’s neurocognitive function at six-month and one-year old. Results: During January 2012-December 2013, 295 women were firstly diagnosed during pregnancy (TSH≥3.61mIU/L), and 78 women with hypothyroidism controlled (TSH<2.5mIU/L) and 107 with uncontrolled thyroid function (TSH≥2.5mIU/L). Full-scale quotation of Gesell scale in clinical hypothyroidism group was of no statistical difference compared to that of subclinical hypothyroidism (P=0.309). In offspring’s Gesell assessment at six-month old, children in controlled hypothyroidism group performed a better adaptive ability compared to those firstly diagnosed during pregnancy (104.45±13.93 vs 99.38±17.71, P=0.022). At one-year old, children in preconception uncontrolled group performed inferior to those those firstly diagnosed during pregnancy, in the GDDS full-scale DQ (100.61±5.96 vs 105.14±7.40, P=0.001), and fine motor, adaptability, language and social emotional response category. Conclusions: Maternal hypothyroidism before conception and during pregnancy possibly shares different effect on offspring’s neurodevelopment. Impaired offspring’s neurocognitive function suggested the necessity of preconception hypothyroidism screening and close follow up of offspring’s neurodevelopment in early infancy. Trial Registration: The registered ClinicalTrials ID was NCT01744743. Funding Statement: This study was funded by the grants from Health industry special funds for Public Benefit Research Foundation from the Ministry of Health, People's Republic of China (201002013), the National Science Fund of China (81270712), National Science Foundation for Young Scholars of China (81200449), National Science Foundation for Young Scholars of China (81300506), National Key Basic Research Plan of China (973 Plan) (2010CB529500), National Science Foundation for Young Scholars of Shanghai (13ZR1452000), the Shanghai Key Laboratory of Female Reproductive Endocrine-Related Diseases, and the Key Specialty Project of the Ministry of Health, People's Republic of China. Declaration of Interests: The authors report no conflict of interest. Ethics Approval Statement: The study was reviewed and approved by the Ethics and Research Committee of Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China. All the women have signed the consent.

Stimulating Informed Decisions in Prenatal Screening: Exploring Initiatives to Aid Parental Decision-Making

Abstract Informed decisions concerning non-invasive prenatal testing (NIPT) seem contingent on health professionals and expectant parents (1) having access to multifaceted information about the procedure of NIPT and the subsequent choices; and (2) actively reflecting about what prenatal screening means beyond the medical level (including personal values and beliefs). International studies show that many pregnant women do not make informed decisions about prenatal testing (Beulen et al. 2016). Interviews we conducted with various stakeholders in Belgium show similar tendencies.Based on transdisciplinary research (Dehens et al. 2017)—which included stakeholder interviews, and a review of academic literature, current prenatal screening guidelines, and good practices—we propose three initiatives that can help stimulate informed choices. The initiatives are: (1) a decision aid that encourages expectant parents to think about NIPT, its possible outcomes, and the conditions NIPT screens for (see e.g. Smith et al. 2018; Carslon et al. 2019); (2) the creation of a nation-wide protocol (draaiboek) for prenatal screening outlining what information should be provided at what point during a pregnancy, in what way, and by whom (see for instance the Draaiboek Prenatale screening down-, edwards- en patausyndroom en structureel echoscopisch onderzoek versie 9.0 in the Netherlands); and (3) an online platform featuring a balanced representation of testimonials about various experiences with the main conditions NIPT screens for taking Braverman (2008) as a starting point. These initiatives were discussed (conceptually) at a round table discussion with a broad range of stakeholders (May 8, 2019). A concluding poll showed &lt;target target-type="page-num" id="p-20"/&gt;a strong consensus concerning the need to develop a prenatal screening protocol and a decision aid in order to help health professionals and expectant parents, navigate through prenatal screening programs in Belgium. Anticipating the widening scope of genetic tests, a general plan of action is necessary to ensure counseling possibilities and informed decisions.

HIV Status and Other Risk Factors for Prevalent and Incident Sexually Transmitted Infection during Pregnancy (2000-2014).

Background Sexually transmitted infections (STIs) are associated with adverse birth outcomes. Current prenatal STI screening guidelines define “risk” without explicit consideration of HIV status. Our objective was to test the hypothesis that HIV status is associated with bacterial STI in pregnant women. Methods We designed a retrospective cohort study to identify pregnant women with HIV who delivered at our facility during 2000-2014. HIV+ women were compared to HIV- women with matching by year of delivery. Logistic regression was used to model adjusted odds of prevalent and incident STI. Prevalent STI was defined as chlamydia (CT), gonorrhea (GC), syphilis, or trichomoniasis detected on an initial prenatal screening test and incident STI as a newly positive result following a negative prenatal test. Results The cohort included 432 women, 210 HIV+ and 222 HIV-. Most pregnant women were screened for STI (92% of HIV+ women and 74% of HIV- women). STI rates were high and particularly elevated in HIV+ women: 29% vs 18% (p=0.02), for prevalent STI and 11% vs 2% (p<0.001) for incident STI. Risk factors for prevalent STI were as follows: HIV status (aOR 3.0, CI: 1.4-6.4), Black race (aOR 2.7, 95% CI: 1.1-6.6), and more recent delivery (2007-2014 compared to 2000-2006) (aOR 2.3, CI: 1.1-4.7). HIV status was an independent risk factor for incident STI (aOR 7.2, CI: 2.1-25.0). Conclusion Pregnant women who delivered in our center had high STI rates. Since HIV infection was independently associated with prevalent and incident STI, prenatal screening guidelines may need to incorporate HIV status as a high-risk group for repeat testing.

Rationale and Design of the FREQUENCY Study: The Fetal Cardiac Registry of Québec to Improve Resource Utilization in Fetal Cardiology.

Prenatal detection of congenital heart diseases (CHD) decreases morbidity and cost. To improve detections rates, most physicians refer pregnant women with high-risk pregnancies to fetal cardiologists even when there is no suspicion of CHD at the second trimester screening. This paper presents the rationale and detailed method of the Fetal Cardiac Registry of Québec to Improve Resource Utilization in Fetal Cardiology (FREQUENCY) study. The overall objective is to assess the impact of second trimester ultrasound screening (U/S) and referral pattern in fetal cardiology on detection rates, health care costs, and resource utilization, as well as perinatal morbidity and mortality. This multicentre retrospective population-based cohort study will link fetal echocardiography data from all centres performing fetal echocardiography in Québec with administrative health care data. This data linking will allow the determination of a true denominator (all women in Québec who underwent second trimester U/S) with complete follow-up of up to 2 years for offspring. This protocol meets Canadian Task Force Classification II-2. The study investigators have collected and cleaned fetal echocardiography data for 24259 eligible pregnancies referred to fetal cardiology. These data will be matched to approximately 860000 pregnancies between 2007 and 2015. The results of the FREQUENCY study will shed light on the impact of the current prenatal CHD screening strategy in Canada.

884: Need to know: A pilot study to evaluate informed consent of current prenatal aneuploidy screening

884: Need to know: A pilot study to evaluate informed consent of current prenatal aneuploidy screening

Attitudes Toward and Uptake of Prenatal Genetic Screening and Testing in Twin Pregnancies

The rate of twinning is rising and since the introduction of non-invasive prenatal testing, interest in and uptake of genetic screening and testing in twin pregnancies has not been investigated. This study aimed to explore the attitudes toward and uptake of current prenatal genetic screening and diagnostic testing options for fetal aneuploidy in twin pregnancies. Women being seen for genetic counseling with twin gestations were recruited for participation in a descriptive study with questionnaire (n = 42) and semi-structured phone interview (n = 15). Women were significantly more in favor of screening than diagnostic testing (p = 0.049). Sixty-nine (n = 25) percent elected screening, while one participant had a diagnostic procedure. Women were interested in screening for preparation or reassurance despite having concerns about accuracy and uncertainty. Most women (86%) felt they would make the same decision in a singleton pregnancy. Despite this, 48% cited twin pregnancy as influential to some degree. Information learned from providers, past experiences, and family and friends were also cited as influencing and anchoring factors, suggesting that tailoring prenatal genetic counseling sessions for twins might parallel that of singletons. No significant differences between natural and assisted conception patients were found. Although it did not alter patient decisions, genetic counseling was used as a platform to raise concerns and gather information.

Prenatal maternal plasma DNA screening for cystic fibrosis: A computer modelling study of screening performance

Background: Prenatal cystic fibrosis (CF) screening is currently based on determining the carrier status of both parents. We propose a new method based only on the analysis of DNA in maternal plasma. Methods: The method relies on the quantitative amplification of the CF gene to determine the percentage of DNA fragments in maternal plasma at targeted CF mutation sites that carry a CF mutation. Computer modelling was carried out to estimate the distributions of these percentages in pregnancies with and without a fetus affected with CF. This was done according to the number of DNA fragments counted and fetal fraction, using the 23 CF mutations recommended by the American College of Medical Genetics for parental carrier testing. Results: The estimated detection rate (sensitivity) is 70% (100% of those detected using the 23 mutations), the false-positive rate 0.002%, and the odds of being affected given a positive screening result 14:1, compared with 70%, 0.12%, and 1:3, respectively, with current prenatal screening based on parental carrier testing. Conclusions: Compared with current screening practice based on parental carrier testing, the proposed method would substantially reduce the number of invasive diagnostic procedures (amniocentesis or chorionic villus sampling) without reducing the CF detection rate. The expected advantages of the proposed method justify carrying out the necessary test development for use in a clinical validation study.

Prenatal maternal plasma DNA screening for cystic fibrosis: A computer modelling study of screening performance.

Background: Prenatal cystic fibrosis (CF) screening is currently based on determining the carrier status of both parents. We propose a new method based only on the analysis of DNA in maternal plasma. Methods: The method relies on the quantitative amplification of the CF gene to determine the percentage of DNA fragments in maternal plasma at targeted CF mutation sites that carry a CF mutation. Computer modelling was carried out to estimate the distributions of these percentages in pregnancies with and without a fetus affected with CF. This was done according to the number of DNA fragments counted and fetal fraction, using the 23 CF mutations recommended by the American College of Medical Genetics for parental carrier testing. Results: The estimated detection rate (sensitivity) is 70% (100% of those detected using the 23 mutations), the false-positive rate 0.002%, and the odds of being affected given a positive screening result 14:1, compared with 70%, 0.12%, and 1:3, respectively, with current prenatal screening based on parental carrier testing. Conclusions: Compared with current screening practice based on parental carrier testing, the proposed method would substantially reduce the number of invasive diagnostic procedures (amniocentesis or chorionic villus sampling) without reducing the CF detection rate. The expected advantages of the proposed method justify carrying out the necessary test development for use in a clinical validation study.

EP06.18: Current prenatal screening efficacy of Trisomy 21, 18 13 in the Taiwan: a 6‐year national registry study

To evaluate of the prenatal screening efficacy of Trisomy 21, 18 13 in the Taiwan. This was a national registry-based cohort study, the total 1,218,851 baby births since January 2010 to December 2015. The current prenatal screening methods including the first trimester combined test, the secondary trimester quadruple and double serum test in Taiwan. The indication of prenatal cytogenetic diagnosis including: advanced maternal age (35 years and older at expected time of delivery), abnormal first trimester combined or second trimester serum screening risk higher than 1/270 on the basis both of tests, ultrasound scan abnormalities suggestive of a chromosomal abnormality, neural tube defect or elevated MS-AFP, parents with chromosomal balanced rearrangements, previous baby with chromosomal or congenital abnormality, have family history of DNA abnormality or metabolic disorder, and miscellaneous. Personal registration numbers of women having had an amniocentesis or a CVS were retrieved from the Taiwan Central Cytogenetic Registry, and cross-linked with the National Registry of Patients to determine the outcome of each pregnancy. We estimated the total invasive prenatal diagnosis was 299,917 (amniocentesis n=298,063; chorionic villus sampling n=1,604; cordocentesis n=238), and the overall invasive procedure rate was 24.59%. The population prevalence in Trisomy 21, 18, and 13 is one in 624, 2232, and 8055 respectively. The prenatal detection Trisomy 21, 18, and 13 had 1794, 534, and 145 cases and had 156, 11, and 6 cases live born respectively. The overall detection rate was one in 92.0%, 98.0%, and 96.0% respectively. The overall detection rate is high than 92%, which is related too high invasive procedure rate. It may adjust the indications strategy to reduce the invasive prenatal diagnosis rate to prevent collateral damage.

Twin Anemia Polycythemia Sequence: A Complication of Monochorionic Diamniotic Twin Gestation [16P

INTRODUCTION: Twin anemia polycythemia sequence (TAPS) is an important prenatal complication of monochorionic twin gestations due to abnormal placental vascular anastomosis. Prenatal ultrasound is the only screening modality. Our objective was to evaluate the prediction potential of current prenatal ultrasound screening in diagnosing TAPS in monochorionic diamniotic twin gestations. METHODS: Maternal and neonatal medical records were reviewed for women with monochorionic diamniotic twins who delivered at Beaumont Hospital System (Royal Oak and Troy) from 2009-2014. Available prenatal ultrasound findings were compared with the neonatal outcomes. Postnatal TAPS diagnosis was confirmed with neonatal peripheral blood hemoglobin values. RESULTS: A total of 132 maternal charts were reviewed and 102 were used in data collection. The median maternal age was 31 years (19-45) with a median parity of 1 (0-3). Among these women 10% (n=10) had assisted reproductive technology. Median gestational age at time of delivery was 35.4 weeks (20.7-39). Median NICU stay for twin A and twin B were 9 (0-264) and 8.5 days, (0-103), respectively. Among 132 prenatal ultrasound screenings, 26% (n=32) were reported as abnormal. Thirty-three percent (n=34) of the neonates were diagnosed with anemia and polycythemia; of these neonates 29% (n=30) had anemia, 4% (n=4) had polycythemia. The sensitivity and specificity of prenatal ultrasound in the prediction of TAPS was 26% (95% CI: 13-44) and 77% (95% CI: 65-87), respectively. CONCLUSION: Current prenatal ultrasound screening guidelines have low sensitivity and specificity in predicting TAPS in monochorionic diamniotic twin gestations. New and updated prenatal screening methods may improve TAPS prediction.

VP36 Cost-Effectiveness Of Non-Invasive Prenatal Testing For Down Syndrome

INTRODUCTION:The analysis of cell-free fetal DNA in maternal blood, also called Non-Invasive Prenatal Testing (NIPT), represents an emerging technology and a possible alternative/complement to current prenatal screening based on biochemical and sonographic markers for Down Syndrome (DS) detection.The aim of the study was to compare the application of NIPT with the prenatal diagnosis/screening procedures currently applied in the Basque Country.METHODS:An analytical decision model was developed to assess the costs and consequences, comparing current prenatal screening, NIPT as a contingency test in high-risk cases and NIPT as a first-line screening test. An economic analysis was conducted to determine which strategy was more cost-effective. Sensitivity analyses were performed (1).RESULTS:For a population of 97,074 pregnant women in gestational week 14 and a cut-off point of 1:270, NIPT as a contingent test was not cost-effective, detecting two cases less of DS and causing a lower number of miscarriages related to invasive-testing (4 versus 23) at a slightly lower cost (EUR8,111,351 versus EUR8,901,872).For risk cut-off points of 1:500 or 1:1000 for contingent NIPT, the number of DS cases detected increased, as did the cost. It could be cost-effective compared with current prenatal screening, (EUR61,763 or EUR256,123 per extra DS case detected, respectively).Using the NIPT as a primary test detected more DS cases (296 versus 271) and caused less miscarriages (5 versus 23), at a substantially higher cost (EUR41,395,645 versus EUR8,901,872). Cost-effectiveness analysis indicated that it was more expensive and more effective.Univariant sensitivity-analysis showed that when the price of the NIPT as primary test was EUR76, it was dominant compared with current prenatal screening. It was also cost-effective compared with the NIPT as a contingent test (EUR9,869 per extra DS case detected).CONCLUSIONS:The study shows that NIPT had higher detection rates for DS in different scenarios, but the cost constitutes a limiting factor for implementation in the Basque Health System.

Overview of the impact of noninvasive prenatal testing on diagnostic procedures.

Noninvasive prenatal testing (NIPT) has had a profound influence in the field of prenatal diagnosis since the 1997 discovery of cell-free fetal DNA in maternal blood. Research has progressed rapidly, with clinical data supporting laboratory studies showing that NIPT is highly sensitive and specific for fetal aneuploidy, resulting in marked uptake in the high-risk patient population. The superior accuracy of NIPT compared with conventional screening methods has led to significant decreases in the number of invasive diagnostic procedures, in addition to a concomitant decrease in the number of procedure-related fetal losses. Yet, NIPT has been described as a 'disruptive innovation' due to the considerable changes the technology has commanded on current prenatal screening and diagnostic practices. This review summarizes both institutional and global experience with NIPT uptake, its effect on reducing diagnostic invasive procedures, and the unique challenges that reduced procedural volume may have on physician and trainee proficiency, cytogenetic laboratories, and neonatal outcome.

Lessons Learned from Two Missed Prenatal Cases of Hemoglobin Bart’s Hydrops Fetalis Until Second Trimester Despite a Nationwide Screening Program

Hemoglobin (Hb) Bart’s hydrops fetalis is the most severe form of alpha-thalassemia and has high mortality. It is caused by deletion of all four α-globin genes leading to a severe deficiency in α-globin and to the production of γ-globin tetramers, resulting in ineffective tissue oxygen delivery. Current preconceptional or prenatal screening policies for this disorder are comprehensive, but not all pregnancies with Hb Bart’s disease can be detected early before hydrops become apparent. We report here two cases with Hb Bart’s disease that escaped being detected until second trimester after hydrops fetalis occurred. These cases remind the clinicians that the importance of this well-characterized condition (alpha-thalassemia) should be reasserted despite a nationwide screening program is available. We also review the current status of prenatal screening and diagnosis of alpha-thalassemia.

Current controversies in prenatal diagnosis 4: pre-conception expanded carrier screening should replace all current prenatal screening for specific single gene disorders.

Current controversies in prenatal diagnosis 4: pre-conception expanded carrier screening should replace all current prenatal screening for specific single gene disorders.

Attitudes of pregnant women and male partners towards non-invasive prenatal testing and widening the scope of prenatal screening

Non-invasive prenatal testing (NIPT) and its potential to test for multiple disorders has received much attention. This study explores attitudes of women and men towards NIPT, and their views on widening the scope of prenatal testing in a country with a low uptake of prenatal screening (The Netherlands). Five focus groups with low-risk pregnant women (n=28), three focus groups with men (n=19) and 13 interviews with high- and low-risk pregnant women were conducted. Participants felt that current prenatal screening has great disadvantages such as uncertain results and risk of miscarriage from follow-up diagnostics. Characteristics of NIPT (accurate, safe and early testing) could therefore diminish these disadvantages of prenatal screening and help lower the barrier for participation. This suggests that NIPT might allow couples to decide about prenatal testing based mostly on their will to test or not, rather than largely based on fear of miscarriage risk or the uncertainty of results. The lower barrier for participation was also seen as a downside that could lead to uncritical use or pressure to test. Widening the scope of prenatal testing was seen as beneficial for severe disorders, although it was perceived difficult to determine where to draw the line. Participants argued that there should be a limit to the scope of NIPT, avoiding testing for minor abnormalities. The findings suggest that NIPT could enable more meaningful decision-making for prenatal screening. However, to ensure voluntary participation, especially when testing for multiple disorders, safeguards on the basis of informed decision-making will be of utmost importance.

5: Rare chromosome abnormalities detected by current prenatal screening compared to expected performance using non-invasive prenatal testing (NIPT)

To determine the range and number of chromosome abnormalities detected in a large statewide prenatal screening program and to assess how many of these would be identified if current screening and invasive diagnostic testing strategies were replaced by noninvasive prenatal testing (NIPT).

Incorporating DNA Sequencing into Current Prenatal Screening Practice for Down's Syndrome

BackgroundPrenatal screening for Down's syndrome is performed using biochemical and ultrasound markers measured in early pregnancy such as the Integrated test using first and second trimester markers. Recently, DNA sequencing methods have been introduced on free DNA in maternal plasma, yielding a high screening performance. These methods are expensive and there is a test failure rate. We determined the screening performance of merging the Integrated test with the newer DNA techniques in a protocol that substantially reduces the cost compared with universal DNA testing and still achieves high screening performance with no test failures.MethodsPublished data were used to model screening performance of a protocol in which all women receive the first stage of the Integrated test at about 11 weeks of pregnancy. On the basis of this higher risk women have reflex DNA testing and lower risk women as well as those with a failed DNA test complete the Integrated test at about 15 weeks.ResultsThe overall detection rate was 95% with a 0.1% false-positive rate if 20% of women were selected to receive DNA testing. If all women had DNA testing the detection rate would be 3 to 4 percentage points higher with a false-positive rate 30 times greater if women with failed tests were treated as positive and offered a diagnostic amniocentesis, or 3 times greater if they had a second trimester screening test (Quadruple test) and treated as positive only if this were positive. The cost per women screened would be about one-fifth, compared with universal DNA testing, if the DNA test were 20 times the cost of the Integrated test.ConclusionThe proposed screening protocol achieves a high screening performance without programme test failures and at a substantially lower cost than offering all women DNA testing.