PMCID: PMC3604109This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

AB Sparks

B Zimmerman

Cees Oudejans

DW Bianchi

GE Palomaki

J Morris

JK Morris

Jonathan P. Bestwick

KH Nicolaides

Nicholas J. Wald

NJ Wald

RWK Chiu

S Dan

PLoS ONE

English

PubMed

Crossref

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

BACKGROUND: Prenatal 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. METHODS: Published 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. RESULTS: The 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. CONCLUSION: The proposed screening protocol achieves a high screening performance without programme test failures and at a substantially lower cost than offering all women DNA testing

Nicholas J Wald

Jonathan P Bestwick

Directory of Open Access Journals

Incorporating DNA sequencing into current prenatal screening practice for Down's syndrome.

Background: Prenatal 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. Methods: Published 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. Results: The 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 time

CiteSeerX

Incorporating DNA sequencing into current prenatal screening practice for Down’s syndrome

Wald, NJ

Bestwick, JP

Queen Mary Research Online

Birth Statistics. England and Wales;

Clinical application of massively parallel sequencing-based prenatal noninvasive fetal trisomy test for trisomies 21 and 18 in 11105 pregnancies with mixed risk factors. Prenat Diag 32:1225–1232.

Community Corner: Opening the Pandora’s box of prenatal genetic testing.

Comparisons of models of maternal age-specific risk for Down syndrome live births.

Corrections to maternal age-specific live birth prevalence of Down’s syndrome.

DNA sequencing of maternal plasma to detect Down syndrome: An international clinical validation study.

Fetal loss in Down syndrome pregnancies.

First and Second trimester Antenatal screening for Down’s syndrome: the results of the Serum, Urine and Ultrasound Screening Study (SURUSS).

Improvements in antenatal screening for Down’s syndrome.

Maternal Blood IS Source to Accurately diagnose fetal aneuploidy (MELISSA) Study Group. Genome-wide fetal aneuploidy detection by maternal plasma DNA sequencing. Obstet Gynecol 119:890–901.

Noninvasive prenatal aneuploidy testing of chromosomes 13, 18, 21, X and Y, using targeted sequencing of polymorphic loci.

Noninvasive prenatal assessment of trisomy 21 by multiplexed maternal plasma DNA sequencing: large scale validity study.

Noninvasive prenatal testing for fetal trisomies in a routinely screened first-trimester population.

Oliphant A

Revised estimates of the maternal age specific live birth prevalence of Down’s syndrome.

Prenatal 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.Published 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.The 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.The proposed screening protocol achieves a high screening performance without programme test failures and at a substantially lower cost than offering all women DNA testing

Wald Nicholas J.

Bestwick Jonathan P.

Public Library of Science (PLOS)

<div>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. </div

Nicholas J. Wald (130535)

Jonathan P. Bestwick (130538)

The Francis Crick Institute

http://dx.doi.org/10.1371/journal.pone.0058732

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

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