Antenatal Screening For Down's Syndrome Research Articles

Direct and rapid mass spectral fingerprinting of maternal urine for the detection of Down syndrome pregnancy.

BackgroundThe established methods of antenatal screening for Down syndrome are based on immunoassay for a panel of maternal serum biomarkers together with ultrasound measures. Recently, genetic analysis of maternal plasma cell free (cf) DNA has begun to be used but has a number of limitations including excessive turn-around time and cost. We aimed to develop an alternative method based on urinalysis that is simple, affordable and accurate.Method101 maternal urine samples sampled at 12–17 weeks gestation were taken from an archival collection of 2567 spot urines collected from women attending a prenatal screening clinic. 18 pregnancies in this set subsequently proved to be Down pregnancies. Samples were either neat urine or diluted between 10 to 1000 fold in dH2O and subjected to matrix assisted laser desorption ionization (MALDI), time of flight (ToF) mass spectrometry (MS). Data profiles were examined in the region 6,000 to 14,000 m/z. Spectral data was normalised and quantitative characteristics of the profile were compared between Down and controls.ResultsIn Down cases there were additional spectral profile peaks at 11,000-12,000 m/z and a corresponding reduction in intensity at 6,000-8,000 m/z. The ratio of the normalised values at these two ranges completely separated the 8 Down syndrome from the 39 controls at 12–14 weeks. Discrimination was poorer at 15–17 weeks where 3 of the 10 Down syndrome cases had values within the normal range.ConclusionsDirect MALDI ToF mass spectral profiling of maternal urinary has the potential for an affordable, simple, accurate and rapid alternative to current Down syndrome screening protocols.

Antenatal screening for Down syndrome: A quantitative demonstration of the improvements over the past 20 years

Pregnant women who receive a high screening risk result for Down, Edwards or Patau syndrome are offered diagnostic tests that carry a procedure-related risk of miscarriage. This study quantifies the improvement in the screening tests by calculating the number of women who had such tests per syndrome diagnosis from 1991 to 2010. Routinely stored data on prenatal chorionic villus sampling (CVS) and amniocentesis samples performed from 1991 to 2010 from the Wessex Regional Genetics Laboratory in England were extracted from the laboratory database. The numbers of diagnostic tests performed per Down, Edwards or Patau syndrome diagnosis were calculated according to the type of diagnostic test, and were adjusted for maternal age and gestational age at diagnosis. A total of 32,345 CVSs and amniocenteses identified 872 diagnoses of Down syndrome and 328 of Edwards and Patau syndrome. In 1991, there were 46 (95%CI: 16-111) CVSs per syndrome diagnosis compared with five (95%CI: 4-7) in 2010. For amniocenteses, the number fell from 53 (37-78) to 15 (11-22). This analysis demonstrates the improvements in antenatal screening for Down syndrome that have been made over the past 20 years, resulting in a reduction in the number of women tested and thus in the number of foetal deaths attributable to the testing procedure.

Role of second‐trimester ultrasound in screening for Down syndrome

Role of second‐trimester ultrasound in screening for Down syndrome

Informed decision making regarding antenatal screening for fetal abnormality in the United Kingdom: A qualitative study of parents and professionals

The aim of this study was to explore the views of parents and health professionals regarding informed decision making for antenatal screening for Down syndrome. This qualitative study was based on thematic analysis and conducted in England, where screening for Down syndrome is universally offered to all pregnant women. Four focus groups were held with pregnant women and/or their partners (n = 22), and another four groups were held with health professionals who offer antenatal screening (n = 22). Data were analyzed through coding of the transcribed focus group discussions and extraction of main themes. Extracted themes were: information overload, gaps in information, challenges in providing information and involvement of both parents in the decision. Parents and professionals believed that burdening parents with untimely information on a wide range of topics in the first trimester detracted from decision making about screening. Many parents also reported they were not sufficiently informed and wanted individualized discussion with a health professional. To ensure parents make informed decisions, information on screening should be provided at the appropriate time, with opportunity for personal discussion with a knowledgeable health professional.

Antenatal Screening for Down Syndrome Using Serum Placental Growth Factor with the Combined, Quadruple, Serum Integrated and Integrated Tests

ObjectiveTo estimate the value of first or second trimester placental growth factor (PlGF) as an additional antenatal screening marker for Down syndrome.DesignNested case-control study.SettingAntenatal screening service.Population or Sample532 Down syndrome pregnancies and 1,155 matched unaffected pregnancies.MethodsStored maternal serum samples (−40°C) were assayed for PlGF. Monte Carlo simulation was used to estimate the screening performance of PlGF with the Combined, Quadruple, serum Integrated and Integrated tests.Main Outcome MeasuresMedian PlGF levels in affected and unaffected pregnancies and screening performance (detection rates [DR] for specified false-positive rates [FPR] and vice versa).ResultsFirst trimester median PlGF was 15%, 28% and 39% lower in Down syndrome than unaffected pregnancies at 11, 12 and 13 completed weeks’ gestation respectively (all p<0.001). Second trimester median PlGF was 31% lower at 14 weeks (p<0.001), and the difference decreased (6% lower at 17 weeks). At a 90% DR with first trimester markers measured at 13 weeks, adding PlGF decreased the FPR from 11.1 to 5.1% using the Combined test, 9.3% to 4.5% using the serum Integrated test, and 3.4% to 1.5% using the Integrated test (or 1.5 to 1.4% with first trimester markers measured at 11 weeks). Adding PlGF to the Quadruple test (measured at 15 weeks) decreased the FPR from 10.0% to 9.6% at a 90% DR.ConclusionsFirst trimester PlGF measurements improve the performance of antenatal screening for Down syndrome using the Combined, serum Integrated and Integrated tests. Second trimester PlGF measurements are of limited value.

A meta-synthesis of pregnant women's decision-making processes with regard to antenatal screening for Down syndrome

The diffusion of antenatal screening programmes for Down syndrome has triggered much discussion about their powerful potential to enhance pregnant women's autonomy and reproductive choices. Simultaneously, considerable debate has been engendered by concerns that such programmes may directly contribute to the emergence of new and complex ethical, legal and social dilemmas for women. Given such discussion and debate, an examination of women's decision-making within the context of antenatal screening for Down syndrome is timely. This paper aims to undertake a meta-synthesis of qualitative studies examining the factors influencing pregnant women's decisions to accept or decline antenatal screening for Down syndrome. The meta-synthesis aims to create more comprehensive understandings and to develop theory which might enable midwives and other healthcare professionals to better meet the needs of pregnant women as they make their screening decisions. Ten electronic health and social science databases were searched together with a hand-search of eleven journals for papers published in English between 1999 and 2008, using predefined search terms, inclusion and exclusion criteria, and a quality appraisal framework. Nine papers met the criteria for this meta-synthesis, providing an international perspective on pregnant women's decision-making. Twelve themes were identified by consensus and combined into five core concepts. These core concepts were: destination unknown; to choose or not to choose; risk is rarely pure and never simple; treading on dreams, and betwixt and between. A conceptual framework is proposed which incorporates these themes and core concepts, and provides a new insight into pregnant women's complex decision-making processes with regard to antenatal screening for Down syndrome. However, further research is necessary to determine whether or not the development of a model of decision-making may empower pregnant women in making choices about screening.

The validation and translation of Multidimensional Measure of Informed Choice in Greek

Objective to translate the original English version of the Multidimensional Measure of Informed Choice (MMIC) into Greek, to adapt it culturally to Greece, and to determine its psychometric properties for the assessment of informed choice in antenatal screening for Down syndrome. Design survey using self-administrated questionnaires. Setting public hospital in Athens, Greece. Participants 135 pregnant women with gestational age between 11th and 20th week just prior to having antenatal screening for Down syndrome. Findings 96% of women had a positive attitude towards screening and 45% had a good level of knowledge concerning the screening process for Down syndrome. Using a standard measure of informed choice, validated for use in Greek, it was found that 44% of women made an informed choice, and thus 56% of women made an uninformed choice. The internal consistency of the scales was good; Cronbach's alpha was found to be 0.76 for the attitude scale and 0.64 for the knowledge scale, suggesting that all items were appropriate to measure. The performed factor analysis of the attitude scale indicated three factors with an eigenvalue over 1.0. Those factors were responsible for 87% of the variance. Key conclusions this study indicates that the Greek version of the MMIC appears to be a reliable and valid tool for measuring informed choice in antenatal screening for Down syndrome. Due to its short length and consumption of time, it seems to be a practical instrument for use in Greek antenatal clinics.

Defining purpose: a key step in genetic test evaluation

The introduction of new genetic tests, like other medical innovations, can be conceptualized as a three-step process. Tests are proposed for use based on research findings and clinical reasoning; an evaluation occurs; and judgments are made about clinical use and reimbursement (Fig. 1). The evaluation may be informal, as when a clinician determines whether a new test will be helpful in a particular patient encounter, or formal, as when a practice guideline panel utilizes a defined methodology to assess a test or a health care funder utilizes a set of criteria to determine test coverage. Although genetic tests are often described in terms of technology, a full evaluation requires that the test be considered as a clinical process in which the laboratory assay, or other testing procedure, is done to acquire information about a particular health condition, in a defined population, for a specific clinical purpose.1 Genetic tests have a wide range of health care applications. They are used to confirm the presence of a genetic condition, identify reproductive risks, and select preventive therapy. Testing occurs in newborn screening programs and in primary, specialty, and prenatal care, and may be initiated on the basis of clinical symptoms, family history, or population demographics. Genetic tests also utilize a range of technologies, and vary considerably in their predictive value. This diversity poses a challenge for the evaluation process. Several groups have considered methods for genetic test evaluation,2–5 and model programs for systematic evaluation have been established in the United States (Evaluation of Genomic Applications in Practice and Prevention6) and the UK (the UK Genetic Testing Network7). To date, however, the evaluation process has not fully addressed the clinical diversity of genetic tests. The Evaluation of Genomic Applications in Practice and Prevention project has focused on genetic tests related to common disorders and drug therapy, whereas the United Kingdom Genetic Testing Network has primarily addressed tests for single gene disorders. An effort by the Secretary’s Advisory Committee on Genetic Testing to categorize genetic tests into those requiring higher versus lower levels of scrutiny was not successful.8 To address the challenge of genetic test diversity, we propose an outcome-orientated taxonomy for defining test purpose. A focus on health outcomes allows the definition of a small and informative set of purposes for genetic testing, despite the range of technologies and clinical settings in which testing occurs. Defining test purpose in turn clarifies the benefits to be expected from the testing process, and provides guidance to clinicians and policy makers concerning the evidence needed to support test use. Defining test purpose, therefore, is an important first step in genetic test evaluation.

Antenatal screening for Down syndrome in New Zealand: Time for a national screening policy?

Antenatal screening for Down syndrome in New Zealand: Time for a national screening policy?

Changes in maternal age in England and Wales - implications for Down syndrome

The risk of having a pregnancy with Down syndrome increases with maternal age. The percentage of all births in England and Wales to mothers aged 35 and over increased from 9% in 1989 to 19% in 2003. A 51% increase in the numbers of pregnancies with Down syndrome has been observed over the same time period (from 954 to 1440). Due to improvements in antenatal screening for Down syndrome and the subsequent termination of affected pregnancies, the total number of births with Down syndrome decreased from 770 in 1989 to 609 in 2003. However the number of births with Down syndrome to women aged 35 and over increased from 186 in 1989 to 310 in 2003 because of the increasing number of pregnancies amongst these women.

New developments in prenatal screening for Down syndrome.

Since the introduction of the triple screen, the emergence of additional analytes found to be associated with trisomy 21 pregnancies has challenged the clinical pathology and obstetric communities to determine which combination provides the best performance characteristics as a screening test. The cost, practicality, and psychosocial and ethical dimensions of different screening regimens further complicate the issue. This review attempts to give an overview of the various markers, current methods of screening, and most promising recent developments in antenatal screening for Down syndrome, with an emphasis on performance in prospective studies that have emerged during the last few years, rather than on estimates from statistical modeling.

Prenatal screening for Down syndrome in England and Wales and population-based birth outcomes

Objective Whether the introduction of antenatal screening for Down syndrome in England and Wales with serum biochemistry or ultrasound has led to improvements in patient outcomes is unknown. The purpose of this study was to relate pregnancy outcomes to the dominant method used for prenatal Down syndrome screening. Study design For the years 1989 through 1999, England and Wales were divided into geographically defined areas where specific hospitals, health authorities, and cytogenetic laboratories provided maternity care for well-defined populations. For each year from 1989 through 1999, the dominant Down syndrome screening method that was used in each area was determined. Outcomes for area-years that used serum biochemistry or ultrasound (first or second trimester) were compared with area-years that used advanced maternal age as the dominant screening method. The percent of Down syndrome cases that were diagnosed prenatally (effectiveness) and the number of invasive prenatal tests that were performed to diagnose each Down syndrome case prenatally (efficiency) were compared. Results There were 5,980,519 births and 335,184 referrals for prenatal karyotyping (amniocentesis and chorionic villus sampling) that occurred in the area-years studied, of which 12,047 pregnancies were diagnosed as Down syndrome; 5393 cases of Down syndrome (45%) were diagnosed prenatally. Invasive testing increased from 4.4% of pregnancies in 1989 to 6.4% in 1997 and declined slightly in 1999 (5.8%). Prenatal diagnosis of Down syndrome cases rose from 28% in 1989 to 53% in 1999, and the number of invasive tests that were performed to diagnose each Down syndrome case fell from 89.7 to 47.7 ( P [for trend]<.0001). Areas with serum or ultrasound as the dominant screening method detected 50% more Down syndrome cases in prenatally (52% and 53% vs 36%; P<.0001) and performed fewer invasive procedures to diagnose each Down syndrome case (60.7 and 52.0 vs 88.0; P<.0001) compared with areas in which advanced maternal age screening was dominant, despite serving populations with similar mean/median maternal ages. Conclusion In clinical practice, screening programs for Down syndrome that were based on maternal serum biochemistry or ultrasound were more effective and efficient than the screening programs that used advanced maternal age alone.

Advances in Prenatal Screening

After completing this article, readers should be able to: 1. Define the association between nuchal translucency and Down syndrome. 2. Describe the role of nuchal translucency-based ultrasonography in prenatal screening for Down syndrome in singleton and multiple gestations. 3. Characterize the criteria for good nuchal translucency ultrasonographic technique. 4. Identify the limitations of implementing first trimester screening in the general obstetric population. Prenatal screening for Down syndrome and other aneuploidies has advanced significantly since its advent in the 1980s. Antenatal screening for Down syndrome began by selecting women older than age 35 years as candidates for amniocentesis. Maternal serum screening for Down syndrome in the second trimester started in the mid-1980s, with low levels of the analyte alpha-fetoprotein (AFP) associated with an increased risk of fetal Down syndrome. The panel of serum analytes has expanded considerably and generally includes four markers, known as the “quad test,” comprised of AFP, human chorionic gonadotropin (hCG), unconjugated estriol, and most recently, inhibin-A. Second-trimester multiple-marker screening and maternal age remain the standard-of-care in prenatal screening for Down syndrome throughout the United States today, although they can detect only 55% (the double screen) to 76% (the quad test) of Down syndrome cases, with a 5% false-positive rate (FPR). Much emphasis in Down syndrome screening research has been placed on finding protocols that increase the detection rate and make screening available at an earlier time in pregnancy. The most significant advance in this front came in the early 1990s, with the ultrasonography marker nuchal translucency (NT) at 10 to 14 weeks’ gestation, in combination with maternal serum markers of free beta-hCG and pregnancy-associated plasma protein A (PAPP-A). This review focuses on ultrasonographic screening for Down syndrome in the first trimester. Fetal NT refers to the normal subcutaneous fluid-filled space between the back of the neck and the overlying skin (Fig. …

505 Antenatal screening for Down Syndrome in the U.S. in 2001: A survey of maternal-fetal medicine specialists

505 Antenatal screening for Down Syndrome in the U.S. in 2001: A survey of maternal-fetal medicine specialists

Nuchal translucency screening and antenatal maternal serum screening for Down syndrome: results of a project

Objectives: To asses the implementation of antenatal screening for Down syndrome using individual risk estimates based on maternal age, nuchal translucency and three serum markers; alpha fetoprotein, unconjugated estriol and human chorionic gonadotrophin (hCG) in maternal blood. Women with an estimated risk of 1 in 250 or greater were classified as screen positive and offered diagnostic amniocentesis.Subjects: A total of 1956 women of all ages with singleton pregnancies seen between June 1999 and March 2001.Results: The screening result of combination of first trimester ultrasonographic and serum screening was 85% Down syndrome detection and the false positive rate was 3%. The median gestational age of nuchal translucency was 11 weeks and the time of serum screening was 16 weeks.Conclusion: The combination of nuchal translucency and serum screening increases the Down syndrome detection and decreases the false positive rate. Is very important because the amniocentesis is associated with a risk of pregnancy loss from 0.5 to 1%. Besides, it is cost‐effective and performs better than the selection for amniocentesis on the basis of maternal age only, nuchal translucency only or serum screening.

Screening for Down syndrome using first-trimester ultrasound and second-trimester maternal serum markers in a low-risk population: a prospective longitudinal study.

To compare nuchal translucency and second-trimester maternal serum measurements as alternative methods of antenatal screening for Down syndrome in a low-risk population and to evaluate the consequence of combining the results in the estimation of risk. In a consecutive series of 4130 women aged less than 38 years with a singleton pregnancy, we examined both the detection rate of Down syndrome by nuchal translucency measurement at 10-14 weeks and maternal serum screening by human chorionic gonadotrophin and alpha-fetoprotein at 14-18 weeks. Women with a nuchal translucency measurement of > or = 3 mm and women with a maternal serum screening-derived risk > or = 1/250 were recommended to have amniocentesis. A second-trimester detailed ultrasound scan was also performed in all women. The outcome of all pregnancies was recorded prospectively and the detection rate and false-positive rate of different screening strategies were retrospectively analyzed. Out of the 4130 pregnancies that were followed (mean maternal age, 30.1 years), 12 cases of Down syndrome were observed (0.28%), all detected prenatally. Seven of 12 cases had a nuchal translucency measurement of > or = 3 mm (58%), and six out of 10 cases with available maternal serum screening had a calculated risk of > or = 1/250 (60%). Four of the five Down syndrome cases with a nuchal translucency measurement of < 3 mm were detected by subsequent maternal serum screening. At a threshold giving 5% of positive tests, the sensitivity of nuchal translucency, maternal serum screening and combined risk screening were 75%, 60% and 90%, respectively. In screening for Down syndrome, an approach which combines the results from first-trimester nuchal translucency and second-trimester biochemistry is effective and increases the detection rate compared to the use of any single test. However, this strategy is likely to raise the false-positive rate and the interpretation of maternal serum screening-derived risk should be combined with the first-trimester nuchal translucency measurement.

Repeat testing in antenatal screening for Down syndrome using dimeric inhibin-A in combination with other maternal serum markers

The effect on screening performance of collecting a second fresh blood sample in antenatal screening for Down syndrome has been previously reported for the commonly used double and triple tests. Recently, dimeric inhibin-A has been used with the triple test (together constituting the quadruple test) in several centres and here we assess the effect of repeat testing using inhibin-A. Routine repeat testing using the quadruple test did not yield a material increase in performance compared with having no repeat testing. For a 5% false-positive rate the increase in detection rate was only about 3-5 percentage points; a modest increase which is probably not worthwhile in the light of the extra cost and delay.

Knowledge of Down syndrome in pregnant women from different ethnic groups.

The uptake of any screening test is influenced by knowledge of the condition being screened for. In the present study, the knowledge and the source of knowledge of women offered antenatal screening for Down syndrome (DS) was assessed by means of a self-administered questionnaire. The questionnaire was administered to 300 consecutive women booking for antenatal care, of the 245 (82%) women who completed and returned the questionnaire, 117 (48%) were Caucasian, 85 (35%) were Asian born outside the UK, 32 (13%) were Asian born in the UK and ten (4%) belonged to other categories. Only 30% of the cohort had a good understanding of the condition. Racial groups other than Caucasian had a poorer understanding of DS. The factors which affected knowledge of DS included quality of spoken English, knowing an affected child, parity and religion. The most significant factor affecting acceptance of screening was the woman's knowledge of DS. The source of information for the condition varied widely: 42% from a general practitioners (GP), 24% from the hospital and 16% from midwives. The proportion with good knowledge was similar in those women whose source of information was the GP (45%) and the midwife (41%). These proportions were, however, higher (though not significantly) when the source of information was from magazines and newspapers (67%) and from friends (53%). Uptake of the screening test was best in those with good knowledge (53%) compared to those with poor knowledge (23%) (p<0.02). Between 28% and 66% (depending on the ethnic group) of women had a screening blood test "allegedly" without knowing why it had been performed. In order to improve uptake of the screening test for DS there is need for better education and counselling of women attending for antenatal care.

Repeat testing in antenatal screening for Down syndrome using dimeric inhibin‐A in combination with other maternal serum markers

Repeat testing in antenatal screening for Down syndrome using dimeric inhibin‐A in combination with other maternal serum markers

Advances in antenatal screening for Down Syndrome

Antenatal screening for Down Syndrome using maternal age alone is no longer an adequate standard of care. Screening in the early second trimester of pregnancy (between 15 and 20 weeks of pregnancy) using the quadruple test can identify 76% of affected pregnancies with a 5% false-positive rate. Screening in the first trimester of pregnancy (between 10 and 13 weeks of pregnancy) is possible using two biochemical markers (PAPP-A and free β-hCG) together with an ultrasound marker nuchal translucency measurement; using these three markers together with maternal age can identify 85% of affected pregnancies, with a 5% false-positive rate. While there is debate over issues involved in choosing between first and second trimester screening, the most effective screening test for Down Syndrome is the integrated test based on the integration of the first trimester and the second trimester markers. This has a 94% detection rate for a 5% false-positive rate. If the false-positive rate were set at 1%, the detection rate would be 85%. No other screening test for Down Syndrome can detect such a high proportion of affected pregnancies with such a low false-positive rate.