Maternal & Newborn Atlas
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NEXT study (cell-free DNA for trisomy screening)

A large study at 35 centres in which pregnant women had both standard first-trimester screening and a cell-free DNA blood test, with the DNA result kept hidden. The DNA test found trisomy 21 more reliably and gave far fewer false alarms. The test maker paid for the study.

  • Study
  • In this atlas

Overview

Design
Prospective, multicentre, blinded study at 35 international centres. Pregnant women presenting for aneuploidy screening at 10 to 14 weeks of gestation had both standard screening (nuchal translucency and biochemical analytes) and cfDNA testing; participants received only the standard results. Birth outcome was determined by diagnostic genetic testing or newborn examination.
Phase
Not reported
Enrolled
  • 18,955 women (registry enrollment, type ACTUAL) (enrolled count) (Non-invasive Chromosomal Examination of Trisomy Study, retrieved )
  • 18,955 women (enrolled count) (Cell-free DNA analysis for noninvasive examination of trisomy, retrieved )
  • 15,841 women (results available for analysis) (analyzed count) (Cell-free DNA analysis for noninvasive examination of trisomy, retrieved )
Sponsor
Not recorded
Funder
Not recorded
Registry
  • NCT NCT01511458
Started
(Non-invasive Chromosomal Examination of Trisomy Study, retrieved )
Primary completion
(actual) (Non-invasive Chromosomal Examination of Trisomy Study, retrieved )
Completion
(actual) (Non-invasive Chromosomal Examination of Trisomy Study, retrieved )
Countries
United States, Belgium, Canada, Italy, Netherlands, Sweden (Non-invasive Chromosomal Examination of Trisomy Study, retrieved )
Care setting
Not reported
Registry status
  • “COMPLETED” (U.S. National Library of Medicine (ClinicalTrials.gov), retrieved )

Technical summary

Prospective, multicentre, blinded comparison (NEJM 2015; ClinicalTrials.gov NCT01511458, observational, completed). 18,955 women were enrolled and 15,841 analysed. Primary outcome: area under the ROC curve for trisomy 21, 0.999 for cfDNA testing against 0.958 for standard screening. Funded by Ariosa Diagnostics and the Perinatal Quality Foundation; the registry lists Roche Sequencing Solutions (industry) as lead sponsor. Primary comparator and test: the Ariosa Harmony Prenatal Test and combined first-trimester screening, per the registry.

Arms

Not reported

Findings

No findings are published for this study.

Claims and evidence

Context Fetuses of pregnant women having first-trimester aneuploidy screening at 35 centres (NEXT)

Recipient
Fetal
Population
Fetuses of 15,841 pregnant women (of 18,955 enrolled) presenting for aneuploidy screening at 10 to 14 weeks of gestation, whose results were available for analysis. Mean maternal age was 30.7 years and the mean gestational age at testing was 12.5 weeks. The women gave the blood sample; the chromosome status of the fetus is what was tested.
Care setting
35 international centres
Geography
Six countries in the registry record: United States, Belgium, Canada, Italy, the Netherlands and Sweden
Life stage
Pregnancy, 10 to 14 weeks of gestation at testing
Gestational age
10 weeks 0 days (70 days) to 14 weeks 2 days (100 days), measured at the time of measurement
Postnatal age
Not reported
Follow-up
Birth outcome by diagnostic genetic testing or newborn examination
Eligibility: 1 inclusion criterion; 1 exclusion criterion
Included
  • Pregnant women presenting for aneuploidy screening at 10 to 14 weeks of gestation
Excluded
  • Not stated in the parts of the source that were read.

  • Description Observational Certainty not assessed

    NEXT was a prospective, multicentre, blinded study at 35 international centres in which pregnant women presenting for aneuploidy screening at 10 to 14 weeks had both standard first-trimester screening (nuchal translucency and biochemical analytes) and cell-free DNA testing. Women received only the standard screening results; the cfDNA results were blinded. Of 18,955 women enrolled, results from 15,841 were analysed. For trisomy 21 the area under the ROC curve was 0.999 for cfDNA testing and 0.958 for standard screening (P=0.001). Trisomy 21 was detected in 38 of 38 women (100%; 95% CI 90.7 to 100) with cfDNA testing and 30 of 38 (78.9%; 95% CI 62.7 to 90.4) with standard screening. False positive rates were 0.06% (95% CI 0.03 to 0.11) with cfDNA and 5.4% (95% CI 5.1 to 5.8) with standard screening. The positive predictive value was 80.9% (95% CI 66.7 to 90.9) for cfDNA testing and 3.4% (95% CI 2.3 to 4.8) for standard screening.

    Applies to Fetal
    • Fetuses of 15,841 pregnant women (of 18,955 enrolled) presenting for aneuploidy screening at 10 to 14 weeks of gestation, whose results were available for analysis. Mean maternal age was 30.7 years and the mean gestational age at testing was 12.5 weeks. The women gave the blood sample; the chromosome status of the fetus is what was tested.
    • 35 international centres
    • Six countries in the registry record: United States, Belgium, Canada, Italy, the Netherlands and Sweden
    • Pregnancy, 10 to 14 weeks of gestation at testing
    • Gestational age 10 weeks 0 days to 14 weeks 2 days, measured at the time of measurement
    • Postnatal age Not reported
    Follow-up Birth outcome by diagnostic genetic testing or newborn examination
    Certainty method
    Not assessed
    Limitations
    This is a screening comparison, not a diagnosis: a cfDNA result needs confirmation by other tests, and a positive predictive value of 80.9% means a positive cfDNA result was not always correct. Only 38 pregnancies had trisomy 21, so the intervals are wide. The registry names one test, the Ariosa Harmony Prenatal Test, so the results do not describe every cfDNA test. The study was funded by Ariosa Diagnostics, which made the test studied, and by the Perinatal Quality Foundation; the registry lists Roche Sequencing Solutions, an industry sponsor. The abstract also evaluates trisomies 18 and 13 but the parts read give no numbers for them. The registry's eligibility text gives a gestational age of 10 weeks 0 days to 14 weeks 2 days at blood collection, slightly wider than the abstract's 10 to 14 weeks. Only the abstract and the registry record were read.
    Last checked
    2026-10-14
    Next evidence check due
    Not scheduled
    Sources and citations (20)

    1. Supports Cell-free DNA analysis for noninvasive examination of trisomy

      Publication · The New England journal of medicine · Edition PubMed record (abstract and bibliographic data) from NCBI E-utilities, retrieved 2026-10-14. The full text and the version of record were not read. · Published 2015-04-23 · DOI: 10.1056/NEJMoa1407349 · PMID: 25830321

      Locator
      Abstract, METHODS, sentence 1, fragment 1 of 2
      How it applies
      PubMed abstract.
      Retrieved
      Source effective date
      Not reported
      Source state
      Current
      Snapshot hash
      0044c214d8a4eb6ef93b5aead13513e02785b1baf07c54a0c9ef844bb1ff0e0d
      Reuse basis
      PubMed record fetched through NCBI E-utilities. Only the hash of the bytes is kept, because publisher copyright may apply to the abstract (https://pubmed.ncbi.nlm.nih.gov/disclaimer/). Short factual quotations under 25 words, with the citation.

    2. Supports Cell-free DNA analysis for noninvasive examination of trisomy

      Publication · The New England journal of medicine · Edition PubMed record (abstract and bibliographic data) from NCBI E-utilities, retrieved 2026-10-14. The full text and the version of record were not read. · Published 2015-04-23 · DOI: 10.1056/NEJMoa1407349 · PMID: 25830321

      Locator
      Abstract, METHODS, sentence 1, fragment 2 of 2
      How it applies
      PubMed abstract.
      Retrieved
      Source effective date
      Not reported
      Source state
      Current
      Snapshot hash
      0044c214d8a4eb6ef93b5aead13513e02785b1baf07c54a0c9ef844bb1ff0e0d
      Reuse basis
      PubMed record fetched through NCBI E-utilities. Only the hash of the bytes is kept, because publisher copyright may apply to the abstract (https://pubmed.ncbi.nlm.nih.gov/disclaimer/). Short factual quotations under 25 words, with the citation.

    3. Supports Cell-free DNA analysis for noninvasive examination of trisomy

      Publication · The New England journal of medicine · Edition PubMed record (abstract and bibliographic data) from NCBI E-utilities, retrieved 2026-10-14. The full text and the version of record were not read. · Published 2015-04-23 · DOI: 10.1056/NEJMoa1407349 · PMID: 25830321

      Locator
      Abstract, METHODS, sentence 2
      How it applies
      PubMed abstract.
      Retrieved
      Source effective date
      Not reported
      Source state
      Current
      Snapshot hash
      0044c214d8a4eb6ef93b5aead13513e02785b1baf07c54a0c9ef844bb1ff0e0d
      Reuse basis
      PubMed record fetched through NCBI E-utilities. Only the hash of the bytes is kept, because publisher copyright may apply to the abstract (https://pubmed.ncbi.nlm.nih.gov/disclaimer/). Short factual quotations under 25 words, with the citation.

    4. Supports Cell-free DNA analysis for noninvasive examination of trisomy

      Publication · The New England journal of medicine · Edition PubMed record (abstract and bibliographic data) from NCBI E-utilities, retrieved 2026-10-14. The full text and the version of record were not read. · Published 2015-04-23 · DOI: 10.1056/NEJMoa1407349 · PMID: 25830321

      Locator
      Abstract, METHODS, sentence 4
      How it applies
      PubMed abstract.
      Retrieved
      Source effective date
      Not reported
      Source state
      Current
      Snapshot hash
      0044c214d8a4eb6ef93b5aead13513e02785b1baf07c54a0c9ef844bb1ff0e0d
      Reuse basis
      PubMed record fetched through NCBI E-utilities. Only the hash of the bytes is kept, because publisher copyright may apply to the abstract (https://pubmed.ncbi.nlm.nih.gov/disclaimer/). Short factual quotations under 25 words, with the citation.

    5. Supports Cell-free DNA analysis for noninvasive examination of trisomy

      Publication · The New England journal of medicine · Edition PubMed record (abstract and bibliographic data) from NCBI E-utilities, retrieved 2026-10-14. The full text and the version of record were not read. · Published 2015-04-23 · DOI: 10.1056/NEJMoa1407349 · PMID: 25830321

      Locator
      Abstract, RESULTS, sentence 1
      How it applies
      PubMed abstract.
      Retrieved
      Source effective date
      Not reported
      Source state
      Current
      Snapshot hash
      0044c214d8a4eb6ef93b5aead13513e02785b1baf07c54a0c9ef844bb1ff0e0d
      Reuse basis
      PubMed record fetched through NCBI E-utilities. Only the hash of the bytes is kept, because publisher copyright may apply to the abstract (https://pubmed.ncbi.nlm.nih.gov/disclaimer/). Short factual quotations under 25 words, with the citation.

    6. Supports Cell-free DNA analysis for noninvasive examination of trisomy

      Publication · The New England journal of medicine · Edition PubMed record (abstract and bibliographic data) from NCBI E-utilities, retrieved 2026-10-14. The full text and the version of record were not read. · Published 2015-04-23 · DOI: 10.1056/NEJMoa1407349 · PMID: 25830321

      Locator
      Abstract, RESULTS, sentence 3
      How it applies
      PubMed abstract.
      Retrieved
      Source effective date
      Not reported
      Source state
      Current
      Snapshot hash
      0044c214d8a4eb6ef93b5aead13513e02785b1baf07c54a0c9ef844bb1ff0e0d
      Reuse basis
      PubMed record fetched through NCBI E-utilities. Only the hash of the bytes is kept, because publisher copyright may apply to the abstract (https://pubmed.ncbi.nlm.nih.gov/disclaimer/). Short factual quotations under 25 words, with the citation.

    7. Supports Cell-free DNA analysis for noninvasive examination of trisomy

      Publication · The New England journal of medicine · Edition PubMed record (abstract and bibliographic data) from NCBI E-utilities, retrieved 2026-10-14. The full text and the version of record were not read. · Published 2015-04-23 · DOI: 10.1056/NEJMoa1407349 · PMID: 25830321

      Locator
      Abstract, RESULTS, sentence 4, fragment 1 of 2
      How it applies
      PubMed abstract.
      Retrieved
      Source effective date
      Not reported
      Source state
      Current
      Snapshot hash
      0044c214d8a4eb6ef93b5aead13513e02785b1baf07c54a0c9ef844bb1ff0e0d
      Reuse basis
      PubMed record fetched through NCBI E-utilities. Only the hash of the bytes is kept, because publisher copyright may apply to the abstract (https://pubmed.ncbi.nlm.nih.gov/disclaimer/). Short factual quotations under 25 words, with the citation.

    8. Supports Cell-free DNA analysis for noninvasive examination of trisomy

      Publication · The New England journal of medicine · Edition PubMed record (abstract and bibliographic data) from NCBI E-utilities, retrieved 2026-10-14. The full text and the version of record were not read. · Published 2015-04-23 · DOI: 10.1056/NEJMoa1407349 · PMID: 25830321

      Locator
      Abstract, RESULTS, sentence 4, fragment 2 of 2
      How it applies
      PubMed abstract.
      Retrieved
      Source effective date
      Not reported
      Source state
      Current
      Snapshot hash
      0044c214d8a4eb6ef93b5aead13513e02785b1baf07c54a0c9ef844bb1ff0e0d
      Reuse basis
      PubMed record fetched through NCBI E-utilities. Only the hash of the bytes is kept, because publisher copyright may apply to the abstract (https://pubmed.ncbi.nlm.nih.gov/disclaimer/). Short factual quotations under 25 words, with the citation.

    9. Supports Cell-free DNA analysis for noninvasive examination of trisomy

      Publication · The New England journal of medicine · Edition PubMed record (abstract and bibliographic data) from NCBI E-utilities, retrieved 2026-10-14. The full text and the version of record were not read. · Published 2015-04-23 · DOI: 10.1056/NEJMoa1407349 · PMID: 25830321

      Locator
      Abstract, RESULTS, sentence 5, fragment 1 of 2
      How it applies
      PubMed abstract.
      Retrieved
      Source effective date
      Not reported
      Source state
      Current
      Snapshot hash
      0044c214d8a4eb6ef93b5aead13513e02785b1baf07c54a0c9ef844bb1ff0e0d
      Reuse basis
      PubMed record fetched through NCBI E-utilities. Only the hash of the bytes is kept, because publisher copyright may apply to the abstract (https://pubmed.ncbi.nlm.nih.gov/disclaimer/). Short factual quotations under 25 words, with the citation.

    10. Supports Cell-free DNA analysis for noninvasive examination of trisomy

      Publication · The New England journal of medicine · Edition PubMed record (abstract and bibliographic data) from NCBI E-utilities, retrieved 2026-10-14. The full text and the version of record were not read. · Published 2015-04-23 · DOI: 10.1056/NEJMoa1407349 · PMID: 25830321

      Locator
      Abstract, RESULTS, sentence 5, fragment 2 of 2
      How it applies
      PubMed abstract.
      Retrieved
      Source effective date
      Not reported
      Source state
      Current
      Snapshot hash
      0044c214d8a4eb6ef93b5aead13513e02785b1baf07c54a0c9ef844bb1ff0e0d
      Reuse basis
      PubMed record fetched through NCBI E-utilities. Only the hash of the bytes is kept, because publisher copyright may apply to the abstract (https://pubmed.ncbi.nlm.nih.gov/disclaimer/). Short factual quotations under 25 words, with the citation.

    11. Supports Cell-free DNA analysis for noninvasive examination of trisomy

      Publication · The New England journal of medicine · Edition PubMed record (abstract and bibliographic data) from NCBI E-utilities, retrieved 2026-10-14. The full text and the version of record were not read. · Published 2015-04-23 · DOI: 10.1056/NEJMoa1407349 · PMID: 25830321

      Locator
      Abstract, RESULTS, sentence 6, fragment 1 of 2
      How it applies
      PubMed abstract.
      Retrieved
      Source effective date
      Not reported
      Source state
      Current
      Snapshot hash
      0044c214d8a4eb6ef93b5aead13513e02785b1baf07c54a0c9ef844bb1ff0e0d
      Reuse basis
      PubMed record fetched through NCBI E-utilities. Only the hash of the bytes is kept, because publisher copyright may apply to the abstract (https://pubmed.ncbi.nlm.nih.gov/disclaimer/). Short factual quotations under 25 words, with the citation.

    12. Supports Cell-free DNA analysis for noninvasive examination of trisomy

      Publication · The New England journal of medicine · Edition PubMed record (abstract and bibliographic data) from NCBI E-utilities, retrieved 2026-10-14. The full text and the version of record were not read. · Published 2015-04-23 · DOI: 10.1056/NEJMoa1407349 · PMID: 25830321

      Locator
      Abstract, RESULTS, sentence 6, fragment 2 of 2
      How it applies
      PubMed abstract.
      Retrieved
      Source effective date
      Not reported
      Source state
      Current
      Snapshot hash
      0044c214d8a4eb6ef93b5aead13513e02785b1baf07c54a0c9ef844bb1ff0e0d
      Reuse basis
      PubMed record fetched through NCBI E-utilities. Only the hash of the bytes is kept, because publisher copyright may apply to the abstract (https://pubmed.ncbi.nlm.nih.gov/disclaimer/). Short factual quotations under 25 words, with the citation.

    13. Supports Cell-free DNA analysis for noninvasive examination of trisomy

      Publication · The New England journal of medicine · Edition PubMed record (abstract and bibliographic data) from NCBI E-utilities, retrieved 2026-10-14. The full text and the version of record were not read. · Published 2015-04-23 · DOI: 10.1056/NEJMoa1407349 · PMID: 25830321

      Locator
      Abstract, CONCLUSIONS, sentence 1, fragment 1 of 2
      How it applies
      PubMed abstract.
      Retrieved
      Source effective date
      Not reported
      Source state
      Current
      Snapshot hash
      0044c214d8a4eb6ef93b5aead13513e02785b1baf07c54a0c9ef844bb1ff0e0d
      Reuse basis
      PubMed record fetched through NCBI E-utilities. Only the hash of the bytes is kept, because publisher copyright may apply to the abstract (https://pubmed.ncbi.nlm.nih.gov/disclaimer/). Short factual quotations under 25 words, with the citation.

    14. Supports Cell-free DNA analysis for noninvasive examination of trisomy

      Publication · The New England journal of medicine · Edition PubMed record (abstract and bibliographic data) from NCBI E-utilities, retrieved 2026-10-14. The full text and the version of record were not read. · Published 2015-04-23 · DOI: 10.1056/NEJMoa1407349 · PMID: 25830321

      Locator
      Abstract, CONCLUSIONS, sentence 1, fragment 2 of 2
      How it applies
      PubMed abstract.
      Retrieved
      Source effective date
      Not reported
      Source state
      Current
      Snapshot hash
      0044c214d8a4eb6ef93b5aead13513e02785b1baf07c54a0c9ef844bb1ff0e0d
      Reuse basis
      PubMed record fetched through NCBI E-utilities. Only the hash of the bytes is kept, because publisher copyright may apply to the abstract (https://pubmed.ncbi.nlm.nih.gov/disclaimer/). Short factual quotations under 25 words, with the citation.

    15. Supports Cell-free DNA analysis for noninvasive examination of trisomy

      Publication · The New England journal of medicine · Edition PubMed record (abstract and bibliographic data) from NCBI E-utilities, retrieved 2026-10-14. The full text and the version of record were not read. · Published 2015-04-23 · DOI: 10.1056/NEJMoa1407349 · PMID: 25830321

      Locator
      Abstract, CONCLUSIONS, sentence 2
      How it applies
      PubMed abstract.
      Retrieved
      Source effective date
      Not reported
      Source state
      Current
      Snapshot hash
      0044c214d8a4eb6ef93b5aead13513e02785b1baf07c54a0c9ef844bb1ff0e0d
      Reuse basis
      PubMed record fetched through NCBI E-utilities. Only the hash of the bytes is kept, because publisher copyright may apply to the abstract (https://pubmed.ncbi.nlm.nih.gov/disclaimer/). Short factual quotations under 25 words, with the citation.

    16. Supports Non-invasive Chromosomal Examination of Trisomy Study

      Registry · U.S. National Library of Medicine (ClinicalTrials.gov) · Edition ClinicalTrials.gov API v2 record, last update posted 2014-07-14. · NCT: NCT01511458

      Locator
      protocolSection.outcomesModule.primaryOutcomes[0].measure
      How it applies
      ClinicalTrials.gov registry record (API JSON).
      Retrieved
      Source effective date
      2014-07-14
      Source state
      Current
      Snapshot hash
      58dc555c775cab23bc257288c10762a7f2b5a46d3dd5c63a3ac0aeac039e3026
      Reuse basis
      Registry record. The raw API JSON is committed. The ClinicalTrials.gov terms page is rendered by JavaScript and its text was not read by a script, so the redistribution basis is unverified; any quotation stays short. The raw file is committed at research/snapshots/mf-ctgov-NCT01511458.json.

    17. Supports Non-invasive Chromosomal Examination of Trisomy Study

      Registry · U.S. National Library of Medicine (ClinicalTrials.gov) · Edition ClinicalTrials.gov API v2 record, last update posted 2014-07-14. · NCT: NCT01511458

      Locator
      protocolSection.sponsorCollaboratorsModule.leadSponsor.name
      How it applies
      ClinicalTrials.gov registry record (API JSON).
      Retrieved
      Source effective date
      2014-07-14
      Source state
      Current
      Snapshot hash
      58dc555c775cab23bc257288c10762a7f2b5a46d3dd5c63a3ac0aeac039e3026
      Reuse basis
      Registry record. The raw API JSON is committed. The ClinicalTrials.gov terms page is rendered by JavaScript and its text was not read by a script, so the redistribution basis is unverified; any quotation stays short. The raw file is committed at research/snapshots/mf-ctgov-NCT01511458.json.

    18. Supports Non-invasive Chromosomal Examination of Trisomy Study

      Registry · U.S. National Library of Medicine (ClinicalTrials.gov) · Edition ClinicalTrials.gov API v2 record, last update posted 2014-07-14. · NCT: NCT01511458

      Locator
      protocolSection.sponsorCollaboratorsModule.leadSponsor.class
      How it applies
      ClinicalTrials.gov registry record (API JSON).
      Retrieved
      Source effective date
      2014-07-14
      Source state
      Current
      Snapshot hash
      58dc555c775cab23bc257288c10762a7f2b5a46d3dd5c63a3ac0aeac039e3026
      Reuse basis
      Registry record. The raw API JSON is committed. The ClinicalTrials.gov terms page is rendered by JavaScript and its text was not read by a script, so the redistribution basis is unverified; any quotation stays short. The raw file is committed at research/snapshots/mf-ctgov-NCT01511458.json.

    19. Supports Prenatal Testing (MedlinePlus health topic)

      Webpage · National Library of Medicine (MedlinePlus) · Edition The page as fetched on 2026-10-14.

      Locator
      What are the two types of prenatal tests?, bullet 1, sentences 1 and 2
      How it applies
      MedlinePlus (NLM) page.
      Retrieved
      Source effective date
      Not reported
      Source state
      Current
      Snapshot hash
      cd92cfdc10fb5a4f8184743c506b21c55b8196861259fdf72eb1e52e126a32dd
      Reuse basis
      MedlinePlus says works produced by the federal government are not copyrighted, and that summaries on health topic pages and medical test information are in the public domain (page fetched as mf-medlineplus-usingcontent.html, sha256 31267ce9db016893b80c5665312d92ffc8c34ec86916f84708c353936ba52228). The page bytes are not committed; short quotations only.

    20. Supports Prenatal Cell-Free DNA Screening (MedlinePlus medical test)

      Webpage · National Library of Medicine (MedlinePlus) · Edition The page as fetched on 2026-10-14.

      Locator
      What is a prenatal cell-free DNA (cfDNA) screening?, paragraph 7, sentence 2
      How it applies
      MedlinePlus (NLM) page.
      Retrieved
      Source effective date
      Not reported
      Source state
      Current
      Snapshot hash
      1d8edfa55c68d9c79091abbb854d2791e3ad5b52885f8871d21ca95389b4baaa
      Reuse basis
      MedlinePlus says works produced by the federal government are not copyrighted, and that summaries on health topic pages and medical test information are in the public domain (page fetched as mf-medlineplus-usingcontent.html, sha256 31267ce9db016893b80c5665312d92ffc8c34ec86916f84708c353936ba52228). The page bytes are not committed; short quotations only.

Record details

Record id
maternal:next-study
Content hash
6f2a1bb5140422fd26f7aae6fa0721f2632dd524f1206f9c6ebce66250bd4560