Stepwise Sequential Screening Research Articles

A Multi-centre Experience of Trans-abdominal Chorionic Villus Sampling in Pakistan.

To determine the safety and outcomes of trans-abdominal chorionic villus sampling technique. Observational study. Departments of Obstetrics and Gynaecology, PNS Shifa Karachi, Pak-Emirates Military Hospital Rawalpindi and CMH Lahore, from 2005-2020. Methodology: A total of 1530 consecutive chorionic villus samplings (CVS) were performed on pregnant females between 10-20 weeks of gestation using the transabdominal approach. Patients were subjected to integrated, stepwise sequential screening. Analysis of data was based on demographic features, indications for sampling, gestational age, attempts of CVS, needle aspiration time, assessment, placental location, sample yield, complications, pain estimation by visual analogue scale (VAS), CVS culture results and pregnancy outcomes. The most common indication for CVS was couple having thalassemia traits and history of having a thalassemia major child previously (55.2%). Pain was the most common complication (64.1%). Procedure-related pregnancy loss (considered to be till 20 weeks of gestation) was observed in two cases (0.1%) only. The most common abnormal karyotype was found to be β-Thalassemia trait (23.6%) followed by β-Thalassemia major (22.1%) and Trisomy 21(16.8%). No abnormality was detected in 33.5% of the cases. Five hundred and eighty-nine (38.4%) interruptions of pregnancies were done on the basis of CVS results. CVS is a safe and useful technique for sampling in prenatal diagnosis of genetic disorders, markedly affecting the management. Chorionic villus sampling, Pre-natal diagnosis, Karyotype.

The utilization and choices of aneuploidy screening in a midwestern population.

The types, interpretation, and use of first- and second-trimester aneuploidy screening are often unclear for many women. This impairs appropriate decision making and understanding of the implications of prenatal genetic testing options. The purpose of this study was to examine the utilization of Stepwise Sequential screening in our Midwestern population, demographic factors associated with choice of screening and method of risk reporting and it’s potential impact on women’s choices. First trimester screening was performed for 2,634 women during the study period. Results were not reported or “framed” as “positive” or “negative”. Rather, the specific age-risk and screen-risk for T21 were relayed, along with options for follow-up Stepwise Sequential screening and invasive testing. Nearly 80 % of women declined Stepwise Sequential screening. Minorities and women of lower education were least likely to pursue further screening. Less than 4 % of the study population elected invasive testing. First trimester screening was associated with a 53 % reduction in amniocenteses and 20 % fewer CVS’s compared to pre-first trimester screening availability. Reporting age-and screen-risks for T21, rather than classifying results as “positive” or “negative” based on a pre-determined threshold, was associated with a low uptake of further testing.

Efficacy of the Genetic Sonogram in a Stepwise Sequential Protocol for Down Syndrome Screening

The purpose of this study was to evaluate the efficacy of the genetic sonogram in Down syndrome screening for women who have received the stepwise sequential test. This retrospective cohort study included women with singleton pregnancies who underwent stepwise sequential (first-trimester combined and second-trimester serum) screening and then had a genetic sonogram between March 2005 and January 2010. Stepwise sequential Down syndrome risks were multiplied by either a positive or negative likelihood ratio based on the second-trimester sonographic findings to determine the final Down syndrome risk. A final Down syndrome risk of 1:270 or higher was considered screen positive. A total of 6286 women fulfilled our criteria, including 17 with Down syndrome-affected fetuses. After stepwise sequential testing, the Down syndrome detection rate was 88.2% (15 of 17), and after the genetic sonogram, there was a non-significant reduction in detection to 82.4% (14 of 17; P > .05). For the 6269 unaffected pregnancies, the genetic sonogram converted 58 screen-negative results (1%) to positive and 183 screen-positive results (3.1%) to negative. The net effect was a change in the false-positive rate from 6.2% (390 of 6269) after stepwise sequential screening to 4.2% (266 of 6269) after the genetic sonogram. The genetic sonogram should be applied cautiously for women who have received prior prenatal screening tests. Women with screen-positive results need to be counseled that a negative sonographic result can be falsely reassuring. Conversely, for women with screen-negative results who have a risk close to the cutoff, a sonographic examination could assist in the decision of whether to accept or reject amniocentesis.

606: Who's coming back? Factors influencing compliance with a stepwise sequential screening process

606: Who's coming back? Factors influencing compliance with a stepwise sequential screening process

Stepwise sequential screening for Down’s syndrome (combined test associated with modified genetic sonography) in pregnant women with low risk for chromosomal disorders

To assess the sensitivity (Sen) and false positive ratio (FPR) of stepwise sequential screening [1st step: combined test (CT), 2nd step: modified genetic sonography (major malformation and nuchal fold, MGS)] as a screening method for Down's syndrome (DS) in the general population of pregnant women. Prospective study. During a 5-year study period (July 2005 to June 2010), 17,911 pregnant women were screened for DS using a stepwise sequential screening method (CT+MGS). We evaluated the Sen and FPR (95% CI) of the two chromosomal disorder screening methods for DS: CT and CT+MGS. Seventeen thousand nine hundred and eleven cases were analysed, including 67 with chromosome abnormalities and 45 with DS. The Sen of CT for DS was 80% (95% CI; 68.3-91.7) (36/45) with a FPR of 4.2% (95% CI; 3.9-4.5) (752/17, 866). The Sen of CT+MSG for DS was 93.3 (95% CI; 85.9-99) (42/45) with a FPR of 4.8% (95% CI; 4.5-5.1) (860/17, 866). MGS coupled with CT increases the Sen of DS diagnosis by 13.3% (95% CI; 2.7-25.9), with an increase in FPR of 0.6% (95% CI; 0.5-0.7).

Role of fetal echocardiography in stepwise sequential screening for chromosomal disorders (combined test associated with modified genetic sonography)

Objectives: To evaluate the contribution made by fetal echocardiography in identifying Down’s syndrome (DS) and other chromosomal disorders in a stepwise sequential screening method (first step: combined test (CT), second step: modified genetic sonography (MGS) (major malformation and nuchal fold)), for DS in the general population of pregnant women. Methods: Prospective study. During a 5-year study period (July 2005–June 2010) 17,911 pregnant women underwent CTs with MGS (with fetal cardiac morphological evaluation performed by obstetricians in a tertiary hospital) as a screening method for DS. We evaluated the sensitivity and false positive rate (FPR) (95% confidence interval (CI)) of three screening methods for DS and all chromosomal disorders: CT, CT + MGS, and CT + fetal echocardiography. Results: A total of 17,911 cases were analyzed with 67 chromosome disorders and 45 DS cases being found. For DS, the CT sensitivity was 80% (95% CI; 68.3–91.7) (36/45) and 79.1% (95% CI; 69.4–88.8) (53/67) for all chromosome disorders, with a FPR of 4.2% (95% CI; 3.9–4.5) (752/17,866) and 4.1% (95% CI; 3.8–4.4) (735/17,844), respectively. For CT + MSG and CT + fetal echocardiography, the sensitivity for DS was 93.3% (95% CI; 85.9–0.99) (42/45) and 95.5% (95% CI; 90.5–0.99) (64/67) for all chromosome disorders. The FPR for CT + MSG was 4.8% (95% CI; 4.5–5.1) (860/17,866) and 4.6% (95% CI; 4.3–4.9) (836/17,844), respectively. The FPR of CT + fetal echocardiography was 4.4% (95% CI; 4.1–4.7) (792/17,866) for DS screening and 4.3% (95% CI; 4–4.6) (770/17,844) for chromosome abnormality screening. Conclusions: Fetal echocardiography is highly capable of identifying DS and other chromosomal disorders as a part of genetic sonography in stepwise sequential screening.

Contribution of “modified genetic sonography” to the combined test as a screening method for chromosomal abnormalities

Objectives: We propose to assess the contribution of “modified genetic sonography” (MGS) to the combined test (CT) as a method of stepwise sequential screening (1st step: CT, 2nd step: MGS) for chromosome abnormalities in the general population of pregnant women. Methods: Prospective study. During a 4 year study period (July 2005–June 2009) 16,548 pregnancies underwent a CT combined with MGS (major malformation and nuchal fold) as a screening method for chromosome abnormalities. We assessed sensitivity and false positive rate (FPR) (95% CI). Results: We offered a chromosome abnormalities screening test to 96.6% of pregnancies (15,995 cases). 14,160 cases are analyzed (1st step: CT, 2nd step: MGS) including 49 chromosome abnormalities and 35 Down’s syndrome (DS). The sensitivity of CT for DS was 77.1% [95% CI, 63.2–91] (27/35) and 77.5% for all chromosome abnormalities [95% CI, 65.8–89.2] (38/49) with a FPR of 4.4% [95% CI, 4.1–4.7]. If MGS was combined with CT, the sensitivity for DS was 91.4% [95% CI, 82.1–99] (32/35) and 93.8% for all chromosome abnormalities [95% CI, 87–99] (46/49) for a FPR of 5.1% [95% CI, 4.7–5.5]. Conclusions: The addition of an MGS to combined first-trimester screening test for aneuploidy improved sensitivity by 14.3% while only increasing the FPR by 0.7%.

Stepwise sequential aneuploidy screening in clinical practice

To evaluate stepwise sequential screening (SSS) efficiency in clinical practice. All singletons undergoing SSS in a single practice by NTQR (Nuchal Translucency Quality Review Program)-credentialed providers in a 2-year period were included. Prenatal diagnosis was offered to all screen-positive women and those with a nuchal translucency ≥3.5 mm or cystic hygroma at the 11- to 14-week scan. Data were extracted from prospectively ascertained serum screening and genetics databases. A total of 2,726 patients were screened, with SSS detecting all eight cases of trisomy 21 and all seven cases of other aneuploidies at a 4.3% screen-positive rate. Stepwise sequential screening offers excellent aneuploidy screening efficiency when introduced into clinical practice.

Comparison of combined, stepwise sequential, contingent, and integrated screening in 7292 high‐risk pregnant women

To compare the efficacy of combined, stepwise sequential, and contingent screening versus the integrated test in detecting fetal aneuploidies. First trimester combined test, sequential second trimester, and contingent risks were retrospectively calculated for 7292 unselected pregnant women with singleton pregnancies who had received integrated screening. The first trimester testing was based on nuchal translucency, pregnancy-associated plasma protein-A, and free-beta-human chorionic gonadotrophin (free β-hCG) and the second trimester tests were alpha-fetoprotein, hCG, and unconjugated estriol. A second trimester risk of 1:250 defined a positive result for all protocols with the contingent protocol based on additional second trimester testing for those with risks between 1:30 and 1:1200. Among the population submitted for the integrated test, the detection rate was 19/21 (90%) for Down syndrome (DS) and 6/6 (100%) for Edwards syndrome (ES) and the DS false-positive rate (FPR) was 247/7271 (3.4%). Provision of the first trimester combined test alone would have resulted in a 17/21 (81%) detection rate for DS, that of 4/6 (67%) for ES and a DS FPR of 292/7271 (4.0%). The sequential and contingent approaches had the same final detection rates as the integrated test but potentially allowed a high proportion of the affected pregnancies to be detected in the first trimester. The lowest net DS FPR was seen with the contingent approach (2.6%) and using this protocol only 12.7% of women would have required second trimester testing. Integrated, sequential, and contingent screenings are all more efficacious than the combined test. Overall, the contingent approach was the most efficient with a high-detection rate, the lowest FPR, and the least amount of testing.

First‐trimester stepwise sequential prenatal screening for Down syndrome using NT and maternal age

The measurement of the fetal nuchal translucency thick-ness (NT) combined with maternal age and maternalblood biochemical markers [free beta human chorionicgonadotrophin (free βhCG) and pregnancy-associatedplasma protein A (PAPP-A)] is widely accepted and nowthe most commonly used method for screening Downsyndrome (DS) in the first trimester. Most often, mater-nal blood is taken during the NT visit, and it usuallyrequires a week or two to measure biochemistry andproduce a final report. A one-stop clinic assessment ofrisk model has been proposed, but most clinics do nothave sufficient clinical volume to afford it financially(Spencer

Stepwise sequential screening for trisomy 21 in assisted reproduction pregnancies

Stepwise sequential screening for trisomy 21 in assisted reproduction pregnancies

OP01.06: Stepwise sequential screening for Down syndrome at a referral centre in Prague, Czech Republic

To evaluate the efficiency of individual segments of the three part step-wise sequential screening for Down syndrome (DS) in an unselected population. We reviewed the cytogenetic results of 7434 pregnancies tested by sequential test at our center between October 2002 and December 2007. Test consisted of three parts: 1/combined test in the first trimester with DS risk cutoff 1/100 and CVS offer at positive cases 2/all first trimester negative continued without published DS risk and their results were integrated with the second trimester part (triple test) with risk cutoff 1/250 and AMC offer at positive cases. 3/All continuing mothers were scanned in the 20th week Pre and post natal cytogenetic results of this group were retrieved from our laboratory information system. The mean maternal age was 37.7 years with 20% mothers over 35 years. Crude detection rate was 50/52 (96%). 41/52 (8.8%) of all DS cases were detected by first trimester combined test. 6/52 (11.5%) of DS cases were detected by second trimester integrated test. 1/52(1.8%) integrated screen negative cases were indicated to invasive prenatal diagnosis by results of second trimester scan and 2/52 (3.8%) of maternat age. Also 2/52 (3.8%) DS cases were born all test negative. False positive rate (FPR) of combined and integrated tests was 1.43%, respective 3.8%. 26/52 (50%) prenatal diagnoses was made by CVS. Step-wise sequential test is highly efficient with detection rate over 90% and acceptable false positive rate 6.5%. All segments are important with priority of first trimester combined test.

Stepwise sequential screening for fetal aneuploidy

Stepwise sequential screening for fetal aneuploidy

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.

Stepwise sequential screening for fetal aneuploidy

The purpose of this study was to evaluate stepwise sequential screening for fetal aneuploidy. Women who received first-trimester screening were also offered second-trimester tests with second-trimester risks that were based on both sets of markers. Screen-positive rates, use of second-trimester testing and invasive testing, sensitivity, and changes in risks were evaluated. Of 1528 women who received first-trimester screening, 133 women (8.7%) had an indication for invasive testing that was based on first-trimester results alone; 1173 women (76.8%) received second-trimester tests, which reduced the net number of women with an indication for invasive testing to 105 (6.9%). In unaffected pregnancies, the addition of the second-trimester testing reduced the median Down syndrome risk from 1:2368 to 1:10,301. Six of 10 chromosome abnormalities (60%) were identified by first-trimester screening, and 9 of 10 chromosome abnormalities (90%) were identified by sequential screening. Sequential screening can be introduced successfully into clinical practice, is effective, and can reduce the number of invasive tests that are performed.

First-Trimester or Second-Trimester Screening, or Both, for Down???s Syndrome

Debate continues over whether to screen pregnant women for fetal Down syndrome in the first or the second trimester of pregnancy or in both trimesters. The First- and Second-Trimester Evaluation of Risk Factors (FASTER) Trial obtained direct comparative data on current screening methods from 38,167 women with singleton pregnancies who were cared for at 15 U.S. centers over approximately 3 years in 1999-2002. Down syndrome was found in 117 instances. Inclusion criteria included a maternal age of 16 or older and a fetal crown-rump length of 36 to 79 mm-consistent with a gestational age of 10 weeks 3 days through 13 weeks 6 days. First-trimester screening combined measurement of the nuchal translucency with maternal serum pregnancy-associated plasma protein A (PAPP-A) and free beta human chorionic gonadotropin (fβhCG) levels. Quadruple screening in the second trimester, from 15 to 18 weeks gestation, included alpha-fetoprotein, total hCG, unconjugated estriol, and inhibin. Stepwise sequential screening, in which the Down syndrome risk estimate was provided after each test, was compared with screening, which yielded only a single risk result after both the first- and second-trimester screening tests had been done. Although first-trimester serum screening and measurement of nuchal translucency gave similar results, the combination proved to be superior for detecting Down syndrome at 11 to 13 weeks gestation. When the false-positive rate was 5%, first-trimester combined screening at 11,12, and 13 weeks identified 87%, 85%, and 82% of Down syndrome cases, respectively. The detection rate for second-trimester quadruple screening was 81%. Quadruple screening outperformed triple screening, resulting in a higher detection rate at a lower false-positive rate. With fully integrated screening, in which the first-trimester studies were performed at 11 weeks gestation, 96% of cases were detected. For women younger than 35 years of age, first-trimester combined screening detected 75% of cases at a 5% false-positive rate, compared with 77% and 2.3%, respectively, for second-trimester quadruple screening and 77% and 0.4% for fully integrated screening. In women aged 35 and older, first-trimester combined screening detected 95% of cases with a false-positive rate of 22%. The respective figures for second-trimester quadruple screening were 92% and 13%, and for integrated screening with first-trimester markers measured at 11 weeks, 91% and 2%. In stepwise sequential screening, women have combined screening in the first trimester and results are provided immediately. Women with positive results are offered chorionic villus sampling. Women with negative results return at 15 weeks for quadruple testing, and a combined risk estimate is provided at that time. Using this approach and setting the false-positive rate for each component at 2.5%, 95% of cases were detected with a false-positive rate of 4.9%. For fully integrated screening, in which both first- and second-trimester tests are done but the woman gets only one risk estimate after the second-trimester tests are completed, setting the Down syndrome detection rate at 95% resulted in a false-positive rate of 4%. First-trimester combined screening is an effective means of detecting Down syndrome, assuming that there is adequate quality control for measuring nuchal translucency. Both stepwise sequential screening and fully integrated screening have high detection rates at acceptably low false-positive results. The lower false-positive rate must be weighed against the advantages of earlier diagnosis using sequential screening.