# NEXT study (cell-free DNA for trisomy screening) Study · id `maternal:next-study` · Maternal & Newborn Atlas · release `c7fb95f1d15a7d13` (public) > General information from published sources, not medical advice, and not reviewed by clinicians. Check the cited source before relying on anything here. The atlas's own text and curation may be reused under Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0, https://creativecommons.org/licenses/by-nc/4.0/): credit the atlas, and do not use it commercially. See the atlas About page. Text quoted from a source stays under that source's own terms, given as the source's reuse\_basis. The atlas's reuse terms do not cover it. The downloads list each quotation with its source in third\_party\_quotations. Browse, life stage: Pregnancy Browse, care area: The baby before birth ## In plain language 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. ## 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. ## Key facts - 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: 18955 women (registry enrollment, type ACTUAL) (enrolled count; Non-invasive Chromosomal Examination of Trisomy Study, snapshot `maternal:ctgov-nct01511458-2026-10-14`, retrieved 2026-10-14); 18955 women (enrolled count; Cell-free DNA analysis for noninvasive examination of trisomy, snapshot `maternal:pubmed-25830321-2026-10-14`, retrieved 2026-10-14); 15841 women (results available for analysis) (analyzed count; Cell-free DNA analysis for noninvasive examination of trisomy, snapshot `maternal:pubmed-25830321-2026-10-14`, retrieved 2026-10-14) - Started: 2012-03 (Non-invasive Chromosomal Examination of Trisomy Study, snapshot `maternal:ctgov-nct01511458-2026-10-14`, retrieved 2026-10-14) - Primary completion: 2013-11 (actual) (Non-invasive Chromosomal Examination of Trisomy Study, snapshot `maternal:ctgov-nct01511458-2026-10-14`, retrieved 2026-10-14) - Completion: 2014-05 (actual) (Non-invasive Chromosomal Examination of Trisomy Study, snapshot `maternal:ctgov-nct01511458-2026-10-14`, retrieved 2026-10-14) - Countries: United States; Belgium; Canada; Italy; Netherlands; Sweden (Non-invasive Chromosomal Examination of Trisomy Study, snapshot `maternal:ctgov-nct01511458-2026-10-14`, retrieved 2026-10-14) - Care setting: Not reported - Registry status: "COMPLETED" (U.S. National Library of Medicine (ClinicalTrials.gov), snapshot `maternal:ctgov-nct01511458-2026-10-14`, retrieved 2026-10-14) ## Claims, with the population each applies to ## 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 ### 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. - Category: Description - Evidence stage: Observational - Certainty: Certainty not assessed - Applies to: 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 - 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 - Sources: 1. Supports: Cell-free DNA analysis for noninvasive examination of trisomy (Publication, 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.) Locator: Abstract, METHODS, sentence 1, fragment 1 of 2. Retrieved 2026-10-14T18:18:28Z. Source state: Current. Snapshot hash: 0044c214d8a4eb6ef93b5aead13513e02785b1baf07c54a0c9ef844bb1ff0e0d. How it applies: PubMed abstract. 2. Supports: Cell-free DNA analysis for noninvasive examination of trisomy (Publication, 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.) Locator: Abstract, METHODS, sentence 1, fragment 2 of 2. Retrieved 2026-10-14T18:18:28Z. Source state: Current. Snapshot hash: 0044c214d8a4eb6ef93b5aead13513e02785b1baf07c54a0c9ef844bb1ff0e0d. How it applies: PubMed abstract. 3. Supports: Cell-free DNA analysis for noninvasive examination of trisomy (Publication, 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.) Locator: Abstract, METHODS, sentence 2. Retrieved 2026-10-14T18:18:28Z. Source state: Current. Snapshot hash: 0044c214d8a4eb6ef93b5aead13513e02785b1baf07c54a0c9ef844bb1ff0e0d. How it applies: PubMed abstract. 4. Supports: Cell-free DNA analysis for noninvasive examination of trisomy (Publication, 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.) Locator: Abstract, METHODS, sentence 4. Retrieved 2026-10-14T18:18:28Z. Source state: Current. Snapshot hash: 0044c214d8a4eb6ef93b5aead13513e02785b1baf07c54a0c9ef844bb1ff0e0d. How it applies: PubMed abstract. 5. Supports: Cell-free DNA analysis for noninvasive examination of trisomy (Publication, 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.) Locator: Abstract, RESULTS, sentence 1. Retrieved 2026-10-14T18:18:28Z. Source state: Current. Snapshot hash: 0044c214d8a4eb6ef93b5aead13513e02785b1baf07c54a0c9ef844bb1ff0e0d. How it applies: PubMed abstract. 6. Supports: Cell-free DNA analysis for noninvasive examination of trisomy (Publication, 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.) Locator: Abstract, RESULTS, sentence 3. Retrieved 2026-10-14T18:18:28Z. Source state: Current. Snapshot hash: 0044c214d8a4eb6ef93b5aead13513e02785b1baf07c54a0c9ef844bb1ff0e0d. How it applies: PubMed abstract. 7. Supports: Cell-free DNA analysis for noninvasive examination of trisomy (Publication, 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.) Locator: Abstract, RESULTS, sentence 4, fragment 1 of 2. Retrieved 2026-10-14T18:18:28Z. Source state: Current. Snapshot hash: 0044c214d8a4eb6ef93b5aead13513e02785b1baf07c54a0c9ef844bb1ff0e0d. How it applies: PubMed abstract. 8. Supports: Cell-free DNA analysis for noninvasive examination of trisomy (Publication, 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.) Locator: Abstract, RESULTS, sentence 4, fragment 2 of 2. Retrieved 2026-10-14T18:18:28Z. Source state: Current. Snapshot hash: 0044c214d8a4eb6ef93b5aead13513e02785b1baf07c54a0c9ef844bb1ff0e0d. How it applies: PubMed abstract. 9. Supports: Cell-free DNA analysis for noninvasive examination of trisomy (Publication, 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.) Locator: Abstract, RESULTS, sentence 5, fragment 1 of 2. Retrieved 2026-10-14T18:18:28Z. Source state: Current. Snapshot hash: 0044c214d8a4eb6ef93b5aead13513e02785b1baf07c54a0c9ef844bb1ff0e0d. How it applies: PubMed abstract. 10. Supports: Cell-free DNA analysis for noninvasive examination of trisomy (Publication, 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.) Locator: Abstract, RESULTS, sentence 5, fragment 2 of 2. Retrieved 2026-10-14T18:18:28Z. Source state: Current. Snapshot hash: 0044c214d8a4eb6ef93b5aead13513e02785b1baf07c54a0c9ef844bb1ff0e0d. How it applies: PubMed abstract. 11. Supports: Cell-free DNA analysis for noninvasive examination of trisomy (Publication, 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.) Locator: Abstract, RESULTS, sentence 6, fragment 1 of 2. Retrieved 2026-10-14T18:18:28Z. Source state: Current. Snapshot hash: 0044c214d8a4eb6ef93b5aead13513e02785b1baf07c54a0c9ef844bb1ff0e0d. How it applies: PubMed abstract. 12. Supports: Cell-free DNA analysis for noninvasive examination of trisomy (Publication, 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.) Locator: Abstract, RESULTS, sentence 6, fragment 2 of 2. Retrieved 2026-10-14T18:18:28Z. Source state: Current. Snapshot hash: 0044c214d8a4eb6ef93b5aead13513e02785b1baf07c54a0c9ef844bb1ff0e0d. How it applies: PubMed abstract. 13. Supports: Cell-free DNA analysis for noninvasive examination of trisomy (Publication, 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.) Locator: Abstract, CONCLUSIONS, sentence 1, fragment 1 of 2. Retrieved 2026-10-14T18:18:28Z. Source state: Current. Snapshot hash: 0044c214d8a4eb6ef93b5aead13513e02785b1baf07c54a0c9ef844bb1ff0e0d. How it applies: PubMed abstract. 14. Supports: Cell-free DNA analysis for noninvasive examination of trisomy (Publication, 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.) Locator: Abstract, CONCLUSIONS, sentence 1, fragment 2 of 2. Retrieved 2026-10-14T18:18:28Z. Source state: Current. Snapshot hash: 0044c214d8a4eb6ef93b5aead13513e02785b1baf07c54a0c9ef844bb1ff0e0d. How it applies: PubMed abstract. 15. Supports: Cell-free DNA analysis for noninvasive examination of trisomy (Publication, 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.) Locator: Abstract, CONCLUSIONS, sentence 2. Retrieved 2026-10-14T18:18:28Z. Source state: Current. Snapshot hash: 0044c214d8a4eb6ef93b5aead13513e02785b1baf07c54a0c9ef844bb1ff0e0d. How it applies: PubMed abstract. 16. Supports: Non-invasive Chromosomal Examination of Trisomy Study (Registry, edition ClinicalTrials.gov API v2 record, last update posted 2014-07-14.) Locator: protocolSection.outcomesModule.primaryOutcomes\[0\].measure. Retrieved 2026-10-14T18:20:44Z. Source state: Current. Snapshot hash: 58dc555c775cab23bc257288c10762a7f2b5a46d3dd5c63a3ac0aeac039e3026. How it applies: ClinicalTrials.gov registry record (API JSON). 17. Supports: Non-invasive Chromosomal Examination of Trisomy Study (Registry, edition ClinicalTrials.gov API v2 record, last update posted 2014-07-14.) Locator: protocolSection.sponsorCollaboratorsModule.leadSponsor.name. Retrieved 2026-10-14T18:20:44Z. Source state: Current. Snapshot hash: 58dc555c775cab23bc257288c10762a7f2b5a46d3dd5c63a3ac0aeac039e3026. How it applies: ClinicalTrials.gov registry record (API JSON). 18. Supports: Non-invasive Chromosomal Examination of Trisomy Study (Registry, edition ClinicalTrials.gov API v2 record, last update posted 2014-07-14.) Locator: protocolSection.sponsorCollaboratorsModule.leadSponsor.class. Retrieved 2026-10-14T18:20:44Z. Source state: Current. Snapshot hash: 58dc555c775cab23bc257288c10762a7f2b5a46d3dd5c63a3ac0aeac039e3026. How it applies: ClinicalTrials.gov registry record (API JSON). 19. Supports: Prenatal Testing (MedlinePlus health topic) (Webpage, edition The page as fetched on 2026-10-14.) Locator: What are the two types of prenatal tests?, bullet 1, sentences 1 and 2. Retrieved 2026-10-14T18:25:54Z. Source state: Current. Snapshot hash: cd92cfdc10fb5a4f8184743c506b21c55b8196861259fdf72eb1e52e126a32dd. How it applies: MedlinePlus (NLM) page. 20. Supports: Prenatal Cell-Free DNA Screening (MedlinePlus medical test) (Webpage, edition The page as fetched on 2026-10-14.) Locator: What is a prenatal cell-free DNA (cfDNA) screening?, paragraph 7, sentence 2. Retrieved 2026-10-14T18:34:50Z. Source state: Current. Snapshot hash: 1d8edfa55c68d9c79091abbb854d2791e3ad5b52885f8871d21ca95389b4baaa. How it applies: MedlinePlus (NLM) page. ## Connected pages - Compares cell-free DNA testing with standard screening: Cell-free DNA screening for fetal chromosome conditions (`maternal:cell-free-dna-screening`) ## Provenance Content hash: 6f2a1bb5140422fd26f7aae6fa0721f2632dd524f1206f9c6ebce66250bd4560 Last substantive edit: 2026-10-14 Evidence last checked: 2026-10-14