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Prenatal Cytogenetics and Cell-Free DNA Screening

Performance of non-invasive prenatal testing (cfDNA), invasive diagnostic testing, and detection rates of maternal and fetal chromosomal abnormalities in late maternal age pregnancies.

95 sources ↓Last researched 2026-10-17
Hierarchy:
Natural & Life SciencesMedicine, Health & LongevityReproductive Medicine & Human FertilityAdvanced Maternal Age & Pregnancy After 40Prenatal Cytogenetics and Cell-Free DNA ScreeningFetal Fraction Determinants and Test Failure DynamicsNon-Invasive Prenatal Testing and Cell-Free Fetal DNA DynamicsPrenatal Cytogenetic Techniques and Invasive Diagnostic ProtocolsSubchromosomal Structural Variations and Microdeletion Screening
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Clinical Efficacy & Obstetric Outcomes (intersects) Clinical Nutrition and Assisted Reproductive Technology Outcomes (intersects) Hyaluronan Biochemistry & Endometrial Adhesion Mechanisms (intersects) Impact on Endometrial Receptivity and Fecundity (intersects) Micronutrient Supplementation in Ovarian Aging (intersects) Reproductive Nutrition, Dietary Patterns & Ovulatory Function (intersects) Ovarian Refractoriness and Endocrine Environment (intersects) Ovarian Reserve and Primordial Follicle Activation (intersects) Patient Stratification & Indications (intersects) Perinatal Safety & Neonatal Outcomes (intersects) Perinatal Safety and Maternal Epigenetic Outcomes (intersects) Micronutrient, Antioxidant & Mitochondrial Fertility Supplementation (intersects)
State of the Field Monograph · AI Research Synthesis7 min read · 95 sources · 34 graded findingsPeak certainty: T1

State of the Field: Prenatal Cytogenetics and Cell-Free DNA Screening

Performance of non-invasive prenatal testing (cfDNA), invasive diagnostic testing, and detection rates of maternal and fetal chromosomal abnormalities in late maternal age pregnancies. Grounded synthesis across 95 primary sources and 34 graded findings within Reproductive Medicine & Human Fertility → Advanced Maternal Age & Pregnancy After 40.

Synopsis · Executive Overview

Non-invasive prenatal screening using cell-free DNA (cfDNA) demonstrates high analytical performance for common autosomal aneuploidies, with pooled detection rates of 99.2% for trisomy 21, 96.3% for trisomy 18, and 91.0% for trisomy 13, accompanied by false-positive rates below 0.25%. Because positive predictive value (PPV) is inherently prevalence-dependent, advancing maternal age substantially elevates PPV, exceeding 98% for common trisomies in women aged 45 and older, compared to significantly lower PPVs in younger cohorts or for sex chromosome aneuploidies and microdeletions (such as 22q11.2 deletion syndrome, where PPVs range from 15% to 24%). However, cfDNA remains an indirect screening modality assessing placental trophoblastic DNA rather than fetal tissue; discordant results arise from confined placental mosaicism (accounting for approximately one-third of false positives), vanishing twins, and occult maternal genomic alterations including copy number variants or malignancies. Consequently, diagnostic confirmation via invasive cytogenetics remains essential. Modern meta-analyses of controlled studies demonstrate that procedure-related pregnancy loss risks are modest (0.30% for amniocentesis and 0.20% for chorionic villus sampling), with amniocentesis specifically preferred over chorionic villus sampling when confirming discordant placental findings in the setting of normal fetal ultrasonography.

Section I · Primary Literature & Evidence Synthesis

What the Peer-Reviewed Record Establishes

The primary research record in Prenatal Cytogenetics and Cell-Free DNA Screening is stratified by study design so that meta-analyses and replicated randomised controlled trials (T1–T2) carry greater epistemic weight than observational cohorts (T3–T4) or preclinical laboratory work (T5). Leading graded findings establish the core empirical baseline: [T1] The 2019 Korean Society of Maternal-Fetal Medicine clinical practice guidelines recommend offering cell-free DNA screening for autosomal trisomies 21, 18, 13 and sex chromosome aneuploidies to all pregnant women at 10 weeks or beyond, but advise against screening for microdeletions or in multiple gestations. [37] [T1] Non-invasive prenatal testing provides high sensitivity and low false-positive rates for autosomal aneuploidies but remains a screening modality that requires genetic counseling and confirmatory invasive diagnostic cytogenetics for high-probability findings. [2][8]

Further clinical and mechanistic stratification across the literature demonstrates: [T1] The weighted procedure-related risk of pregnancy loss before 24 weeks is 0.30% (95% CI 0.11-0.49%) following amniocentesis and 0.20% (95% CI -0.13 to 0.52%) following chorionic villus sampling (CVS) in meta-analysis of controlled studies. [47] [T1] Maternal age and body mass index (BMI) are negatively correlated with fetal fraction in cell-free DNA (cfDNA) screening, potentially impacting test reliability. [24]

Section II · Mechanisms, Interventions & Subgroup Calibration

Comparative Evaluation of Levers & Theoretical Models

When evaluated as a quantitative decision and mechanism ledger, the best-supported interventions and frameworks in Prenatal Cytogenetics and Cell-Free DNA Screening are: Amniocentesis vs Chorionic Villus Sampling for cfDNA Confirmation (Guideline — Procedure-related loss 0.30% (amniocentesis) vs 0.20% (CVS); eliminates false-positive concordance from confined placental mosaicism present in up to 75.5% of monosomy X and 57.9% of rare trisomies; landmark evidence: Meta-analysis (Salomon et al., 2019; 64,207 procedures) and diagnostic consensus guidelines: Because cfDNA assays apoptosis-derived trophoblast fragments (the identical lineage sampled by CVS cytotrophoblast), CVS can duplicate placental mosaic false-positives. Amniocentesis interrogates true fetal amniocytes and is the definitive confirmation tool, especially with normal ultrasound.); Second-Tier High-Resolution Fetal Ultrasonography (Supported — Increases absolute PPV by up to 71% for trisomy 13, 40% for trisomy 18, and 12% for trisomy 21; landmark evidence: Prospective/retrospective clinical validation cohorts (2026): Normal ultrasound significantly lowers post-test probability of trisomies 18 and 13 but cannot rule out trisomy 21; an abnormal anatomical finding radically confirms clinical suspicion and dictates rapid invasive diagnostic pathway.); Subchromosomal Microdeletion and CNV cfDNA Panels (Targeted — Sensitivity 75.0% and PPV 23.7% for 22q11.2 deletion syndrome; PPVs as low as 6.45% for general CNV panels; landmark evidence: SMART Trial (Dar et al., 2022; n=18,289) and multi-center evaluations: Unlike common aneuploidies, microdeletions do not correlate with maternal age. Screening suffers from high false-alarm rates, maternal CNV confounding, and disproportionate diagnostic invasive follow-ups.).

Within the Tree of Knowledge, this field branches into 4 specialised sub-disciplines: Fetal Fraction Determinants and Test Failure Dynamics (Analyzes factors influencing circulating cell-free fetal DNA fraction, including maternal body mass index, gestational age, placental volume, and management of uninformative test results); Non-Invasive Prenatal Testing and Cell-Free Fetal DNA Dynamics (Evaluates the sensitivity, specificity, and positive predictive value of cell-free fetal DNA screening for autosomal trisomies and sex chromosome aneuploidies across maternal age cohorts); Prenatal Cytogenetic Techniques and Invasive Diagnostic Protocols (Examines performance, diagnostic yield, and safety profiles of invasive techniques including chorionic villus sampling, amniocentesis, karyotyping, and chromosomal microarray analysis); Subchromosomal Structural Variations and Microdeletion Screening (Assesses detection capabilities, positive predictive values, and screening limitations of genome-wide cfDNA for subchromosomal copy number variants and rare microdeletion syndromes).

Section III · Historical Trajectory & Contested Frontiers

Evolution of the Field, Open Debates & Active Trials

Chronologically, the field evolved through key inflection points: in 1997, Discovery of Cell-Free Fetal DNA in Maternal Plasma (Identification of circulating cell-free fetal DNA in maternal peripheral blood established the biological foundation for non-invasive prenatal screening); in 2011, Clinical introduction of non-invasive prenatal testing (Non-invasive prenatal testing (NIPT) using maternal plasma cell-free DNA is introduced into clinical practice for fetal aneuploidy screening); in 2017, Discovery of NIPT as a Maternal Cancer Screen (Large-scale study characterizes the incidental detection of maternal malignant neoplasms through abnormal cfDNA profiles originally intended for fetal screening); in 2019, First Korean Clinical Practice Guidelines for Prenatal Aneuploidy Screening (The Korean Society of Maternal-Fetal Medicine established the first national practice guidelines for maternal serum and cell-free DNA prenatal screening).

Active scientific debates and unresolved methodological tensions centre on: Controlled meta-analyses (Salomon et al. 2019) isolate a true procedure-attributable fetal loss rate of 0.2-0.3%, whereas older unselected national cohort registries (e.g., Danish registry 2009) reported background crude pregnancy loss rates of 1.4-1.9% post-procedure without controlling for underlying structural/chromosomal indications. (contradiction) Commercial and academic platforms contest whether SNP-based cfDNA inherently outperforms massively parallel shotgun sequencing (MPSS) across detection rate and false-positive rates, as comparative claims are largely vendor-sponsored and sensitive to fetal fraction thresholds. (contested) Claims asserting 100% sensitivity or reliable down-to-1 Mb CNV detection rely on single-center proof-of-concept cohorts or bioinformatic modeling that have not demonstrated analytical consistency in large prospective multi-center trials. (weak evidence)

Section IV · Evidentiary Gaps & Research Frontiers

Open Questions & Priorities for the Next Research Sweep

Methodological priorities and open empirical questions queued for the next research sweep across Prenatal Cytogenetics and Cell-Free DNA Screening focus on resolving subgroup effect sizes, causal mechanisms, and long-term outcomes:

  • Long-term diagnostic and pediatric health outcomes in discordant cfDNA cases attributed to low-level fetoplacental mosaicism.
  • Standardized clinical management and oncologic workup protocols for pregnant patients with unexplained atypical or multiple-chromosomal non-reportable cfDNA patterns.
  • Clinical utility and false-positive burden of routine genome-wide cfDNA screening for subchromosomal copy number variants and microdeletions in unselected late-maternal-age cohorts.
  • Comparative prospective head-to-head performance trials between single-nucleotide polymorphism (SNP)-based and massively parallel shotgun sequencing (MPSS) platforms under low fetal fraction conditions.
  • SMART 2 registry: Long-term pediatric neurodevelopmental confirmation of expanded microdeletion cfDNA screening
  • Clinical implementation trials evaluating cfDNA fragment-size selection and single-molecule sequencing without minimum fetal fraction thresholds

Evidence Hierarchy (Graded Claims)

  • T1Synthesis of trials
    6 (18%)
  • T2Randomised trial
    0 (0%)
  • T3Observational, large
    21 (62%)
  • T4Observational, small or case-based
    5 (15%)
  • T5Preclinical or mechanistic
    1 (3%)
  • T6Opinion, news or unverified
    1 (3%)
24 settled8 debated2 contested / frontier

Study Designs in Indexed Literature

  • Meta-analyses, Systematic Reviews & Guidelines11 (12%)
  • Randomised Controlled Trials (RCTs)2 (2%)
  • Prospective Cohorts & Clinical Registries27 (28%)
  • Observational & Clinical Case Series6 (6%)
  • Preclinical, Cellular & Computational Models5 (5%)
  • Primary Literature & Archive Records44 (46%)

Publication Timeline Velocity

Fig. 1 — Field Evidence Architecture & Publication Trajectory. Distribution of methodological study designs (95 indexed publications) and 34 extracted claims graded from T1 (meta-analyses and guidelines) to T6.

Epistemic Verdict Distribution Across Evaluated Levers & Mechanisms (4)

Guideline1 lever (25%)
Supported1 lever (25%)
Targeted1 lever (25%)
Case by case1 lever (25%)
Fig. 2 — Intervention & Mechanism Epistemic Calibration. Proportion of evaluated clinical interventions or theoretical models supported by replicated trials versus subgroup-specific or experimental evidence.
Primary Citations & Landmark Studies

Key Studies Anchoring This Monograph

Synthesis & Conclusions

State of the Field Conclusions

Taken together, the evidence record in Prenatal Cytogenetics and Cell-Free DNA Screening (95 primary sources, 34 graded claims, highest certainty T1 — Synthesis of trials) separates replicated high-tier findings from early-stage hypotheses. The most robust actionable levers supported by current evidence are Amniocentesis vs Chorionic Villus Sampling for cfDNA Confirmation (Procedure-related loss 0.30% (amniocentesis) vs 0.20% (CVS); eliminates false-positive concordance from confined placental mosaicism present in up to 75.5% of monosomy X and 57.9% of rare trisomies), Second-Tier High-Resolution Fetal Ultrasonography (Increases absolute PPV by up to 71% for trisomy 13, 40% for trisomy 18, and 12% for trisomy 21), Subchromosomal Microdeletion and CNV cfDNA Panels (Sensitivity 75.0% and PPV 23.7% for 22q11.2 deletion syndrome; PPVs as low as 6.45% for general CNV panels). The 8 open research priorities detailed above guide the next autonomous literature and clinical trial sweep.

Key Quantitative Takeaways

  • 98.8%: Combined cfDNA positive predictive value for common autosomal trisomies (21, 18, 13) in women aged 45 and older (Zheng et al., 2020 / PMC7816004).
  • 0.30%: Procedure-related excess fetal loss rate before 24 weeks gestation for amniocentesis in controlled meta-analysis (Salomon et al., 2019, Ultrasound Obstet Gynecol).
  • Amniocentesis vs Chorionic Villus Sampling for cfDNA Confirmation [Guideline]: Procedure-related loss 0.30% (amniocentesis) vs 0.20% (CVS); eliminates false-positive concordance from confined placental mosaicism present in up to 75.5% of monosomy X and 57.9% of rare trisomies — Because cfDNA assays apoptosis-derived trophoblast fragments (the identical lineage sampled by CVS cytotrophoblast), CVS can duplicate placental mosaic false-positives. Amniocentesis interrogates true fetal amniocytes and is the definitive confirmation tool, especially with normal ultrasound.
  • Second-Tier High-Resolution Fetal Ultrasonography [Supported]: Increases absolute PPV by up to 71% for trisomy 13, 40% for trisomy 18, and 12% for trisomy 21 — Normal ultrasound significantly lowers post-test probability of trisomies 18 and 13 but cannot rule out trisomy 21; an abnormal anatomical finding radically confirms clinical suspicion and dictates rapid invasive diagnostic pathway.
  • Open frontier in Prenatal Cytogenetics and Cell-Free DNA Screening: Long-term diagnostic and pediatric health outcomes in discordant cfDNA cases attributed to low-level fetoplacental mosaicism.
98.8%

Combined cfDNA positive predictive value for common autosomal trisomies (21, 18, 13) in women aged 45 and older

Zheng et al., 2020 / PMC7816004

0.30%

Procedure-related excess fetal loss rate before 24 weeks gestation for amniocentesis in controlled meta-analysis

Salomon et al., 2019, Ultrasound Obstet Gynecol

33.3%

Proportion of false-positive cfDNA results attributable to confined placental mosaicism

Clinical cytogenetics cohort, 2026 / PMC10928341

3.4%

First-trimester cfDNA test failure/non-reportable rate in singleton pregnancies

Kontovounisios et al., 2019 / PMC6858902

Where each lever applies

A graded decision ledger of interventions across clinical subgroups. Each row names its best landmark evidence, measured effect, clinical reading, and epistemic verdict.

Supported: RCT live-birth gainTargeted: specific subgroupGuideline: clinical consensusWeak: inconsistent/unproven gainNot supported: RCTs show no gainTrial: human trial in progressLab: preclinical / cell dish

Confirmatory Diagnostics

Lever & MechanismBest Landmark EvidenceMeasured Effect & Clinical ReadingVerdict
Amniocentesis vs Chorionic Villus Sampling for cfDNA Confirmation

Selection of invasive diagnostic modality following an abnormal cfDNA screening result in advanced maternal age pregnancies.

Meta-analysis (Salomon et al., 2019; 64,207 procedures) and diagnostic consensus guidelines

Effect: Procedure-related loss 0.30% (amniocentesis) vs 0.20% (CVS); eliminates false-positive concordance from confined placental mosaicism present in up to 75.5% of monosomy X and 57.9% of rare trisomies

Clinical reading: Because cfDNA assays apoptosis-derived trophoblast fragments (the identical lineage sampled by CVS cytotrophoblast), CVS can duplicate placental mosaic false-positives. Amniocentesis interrogates true fetal amniocytes and is the definitive confirmation tool, especially with normal ultrasound.

Guideline

Diagnostic Stratification

Lever & MechanismBest Landmark EvidenceMeasured Effect & Clinical ReadingVerdict
Second-Tier High-Resolution Fetal Ultrasonography

Immediate detailed anatomical and biometric sonography following positive or high-risk cfDNA screening.

Prospective/retrospective clinical validation cohorts (2026)

Effect: Increases absolute PPV by up to 71% for trisomy 13, 40% for trisomy 18, and 12% for trisomy 21

Clinical reading: Normal ultrasound significantly lowers post-test probability of trisomies 18 and 13 but cannot rule out trisomy 21; an abnormal anatomical finding radically confirms clinical suspicion and dictates rapid invasive diagnostic pathway.

Supported

Screening Expansion

Lever & MechanismBest Landmark EvidenceMeasured Effect & Clinical ReadingVerdict
Subchromosomal Microdeletion and CNV cfDNA Panels

Expanded non-invasive prenatal screening for subchromosomal microdeletions (e.g., 22q11.2, 1p36, Cri-du-chat).

SMART Trial (Dar et al., 2022; n=18,289) and multi-center evaluations

Effect: Sensitivity 75.0% and PPV 23.7% for 22q11.2 deletion syndrome; PPVs as low as 6.45% for general CNV panels

Clinical reading: Unlike common aneuploidies, microdeletions do not correlate with maternal age. Screening suffers from high false-alarm rates, maternal CNV confounding, and disproportionate diagnostic invasive follow-ups.

Targeted

Secondary Findings

Lever & MechanismBest Landmark EvidenceMeasured Effect & Clinical ReadingVerdict
Occult Maternal Malignancy Workup for Atypical Genomic cfDNA Profiles

Diagnostic maternal oncologic evaluation when cfDNA exhibits multiple chromosomal copy-number aberrations or repeated assay failures.

Cohort studies (Ji et al., 2019; Turriff et al., 2024; n=107 evaluated patients)

Effect: PPV for maternal malignancy reaches 48.6% overall and 95.9% in cases displaying copy-number shifts on 3 or more chromosomes

Clinical reading: Circulating tumor DNA sheds into maternal plasma alongside placental DNA. Unexplained genome-wide aneuploidies demand targeted maternal clinical evaluation (MRI, hematologic review) rather than repeated pregnancy-only screening.

Case by case

Questions for specialist consultations

High-yield clinical and laboratory inquiries directly derived from the evidence record.

  1. When cfDNA returns high-risk for monosomy X or a rare autosomal trisomy with normal fetal anatomy, what is the protocol for timing amniocentesis over chorionic villus sampling to bypass confined placental mosaicism?
  2. If a test failure or non-reportable result occurs due to low fetal fraction, does maternal BMI or gestational age indicate redrawing, or is direct diagnostic amniocentesis warranted given the baseline aneuploidy risk?
  3. What specific multigene diagnostic microarray or cytogenomic resolution will be applied to the invasive sample to capture abnormalities not covered by standard cfDNA?
  4. How does the clinic handle incidental multiple chromosomal copy-number abnormalities that point toward maternal genomic alterations or occult malignancy?

Queued for next research sweep

Frontier clinical trials, emerging biology, and targeted subgroup outcomes tracked by the autonomous research worker.

  • SMART 2 registry: Long-term pediatric neurodevelopmental confirmation of expanded microdeletion cfDNA screening
  • Clinical implementation trials evaluating cfDNA fragment-size selection and single-molecule sequencing without minimum fetal fraction thresholds
  • Prospective trials on Whole-Body Diffusion-Weighted MRI algorithms for occult maternal neoplasia detected via prenatal cfDNA screening
  • International prospective validations of Mosaic Ratio (MR) bioinformatic thresholds in differentiating placental mosaicism from true fetal mosaicism
Historical timeline (7 milestones, 1997–2026)
  1. 1997

    Discovery of Cell-Free Fetal DNA in Maternal Plasma

    Identification of circulating cell-free fetal DNA in maternal peripheral blood established the biological foundation for non-invasive prenatal screening.

  2. 2011

    Clinical introduction of non-invasive prenatal testing

    Non-invasive prenatal testing (NIPT) using maternal plasma cell-free DNA is introduced into clinical practice for fetal aneuploidy screening.

  3. 2017

    Discovery of NIPT as a Maternal Cancer Screen

    Large-scale study characterizes the incidental detection of maternal malignant neoplasms through abnormal cfDNA profiles originally intended for fetal screening.

  4. 2019

    First Korean Clinical Practice Guidelines for Prenatal Aneuploidy Screening

    The Korean Society of Maternal-Fetal Medicine established the first national practice guidelines for maternal serum and cell-free DNA prenatal screening.

  5. 2023

    Establishment of NIPT as a Screen for Maternal Malignancy

    A large-scale retrospective study of over 2 million samples quantified the risk of maternal malignancy following atypical SNP-based cfDNA results.

  6. 2025

    Introduction of Mosaic Ratio for PPV Refinement

    Establishment of a framework using Mosaic Ratios (MR) to differentiate fetal from placental mosaicism, dramatically increasing the specificity of high-risk results.

  7. 2026

    Validation of 1 Mb CNV Detection in GW-NIPT

    Retrospective cohort validation of genome-wide noninvasive prenatal testing with fetal fraction enrichment demonstrated reliable detection of subchromosomal copy number variants down to 1 megabase.

Evidence by study design (34 findings across T1–T6)

Strongest support first. The bar beside each finding shows its grade.

Synthesis of trials

  1. #1 The 2019 Korean Society of Maternal-Fetal Medicine clinical practice guidelines recommend offering cell-free DNA screening for autosomal trisomies 21, 18, 13 and sex chromosome aneuploidies to all pregnant women at 10 weeks or beyond, but advise against screening for microdeletions or in multiple gestations.

    DebatedClinical Practice Guidelines for Prenatal Aneuploidy Screening and D… (2021)

    Reflects regional practice recommendations regarding the scope and limitations of prenatal cell-free DNA screening.

  2. #2 Non-invasive prenatal testing provides high sensitivity and low false-positive rates for autosomal aneuploidies but remains a screening modality that requires genetic counseling and confirmatory invasive diagnostic cytogenetics for high-probability findings.

    Copy Number Variant Detection by NIPT: Biological Constraints and th… (2026); Noninvasive prenatal testing: an overview (2025); Clinical performance of non-invasive prenatal served as a first-tier… (2020); Cytogenetic confirmation of a positive NIPT result: evidence-based c… (2016); and 1 more

    Distinguishes cfDNA screening from definitive diagnostic testing due to potential biological discrepancies like confined placental mosaicism or maternal copy number alterations.

  3. #3 The weighted procedure-related risk of pregnancy loss before 24 weeks is 0.30% (95% CI 0.11-0.49%) following amniocentesis and 0.20% (95% CI -0.13 to 0.52%) following chorionic villus sampling (CVS) in meta-analysis of controlled studies.

    Risk of miscarriage following amniocentesis or chorionic villus samp… (2019)

    Quantifying the procedure-related miscarriage risk of invasive diagnostic testing is essential when counseling pregnant individuals on prenatal cytogenetic options.

  4. #4 Maternal age and body mass index (BMI) are negatively correlated with fetal fraction in cell-free DNA (cfDNA) screening, potentially impacting test reliability.

    Maternal and Fetal Factors Affecting Cell-Free Fetal DNA (cffDNA) Fr… (2023)

    Sufficient fetal fraction is required for accurate screening, and older age or higher BMI can dilute fetal DNA concentration.

  5. #5 Performing a detailed ultrasound following a high-risk cfDNA result markedly improves the absolute positive predictive value for trisomy 18 and trisomy 13 (by up to 40% and 71%, respectively), with a smaller additive improvement of up to 12% for trisomy 21.

    Impact of a detailed ultrasound in pregnancies with high-risk cell-f… (2026)

    Ultrasonographic markers are highly specific adjuncts that improve pre-test probability before invasive diagnostic testing, particularly for trisomies with lower baseline cfDNA PPVs.

  6. #6 Next-generation sequencing-based cfDNA screening (SNP method) demonstrates higher detection rates and lower false-positive rates for trisomies 21, 18, and 13 compared to massively parallel shotgun sequencing (MPSS).

    ContestedA Critical Evaluation of Validation and Clinical Experience Studies … (2022)

    Meta-analysis data indicates performance differences across NIPT methodologies, with SNP-based analysis showing statistically superior results.

Observational, large

  1. #7 Whole-genome sequencing-based non-invasive prenatal screening without a 4% fetal-fraction cutoff achieved sensitivities of 99.7% for trisomy 21, 96.8% for trisomy 18, and 94.3% for trisomy 13 while maintaining a low test-failure rate of 0.1% in a cohort of 58,105 singleton pregnancies.

    Clinical experience across the fetal‐fraction spectrum of a non‐inva… (2019)

    Demonstrates that fetal fraction cutoffs may be unnecessarily restrictive for whole-genome sequencing prenatal screens.

  2. #8 The positive predictive value (PPV) of cell-free DNA screening for common autosomal trisomies increases substantially with advancing maternal age, reaching a combined PPV of 98.8% in women aged 45 years and older.

    Counseling prior to cfDNA screening: are we giving the right numbers? (2025); Clinical performance of non-invasive prenatal served as a first-tier… (2020)

    Prior risk of fetal aneuploidy increases sharply with maternal age, directly elevating the positive predictive value of cfDNA screening.

  3. #9 Confined placental mosaicism, vanishing twin syndrome, and maternal mosaicism are the primary biological causes of false-positive NIPT results.

    Assessment of Placental Chromosomal Mosaicism during Prenatal Cell-F… (2025); Placental, maternal, fetal, and technical origins of false-positive … (2023); Integration of noninvasive DNA testing for aneuploidy into prenatal … (2014)

    NIPT measures DNA from the placenta, not directly from the fetus, meaning discrepancies between placental and fetal genotypes are expected.

  4. #10 Early amniocentesis (11-14 weeks) and transabdominal chorionic villus sampling (CVS) achieve successful genetic results in over 99.8% of cases with low spontaneous abortion risks (0.18-0.25%).

    Early Amniocentesis Versus Transabdominal Chorionic Villus Sampling … (2026)

    A 15-year prospective cohort confirms that both early invasive routes are highly effective and safe for definitive first-trimester diagnosis.

  5. #11 Confined placental mosaicism is present in 33.3% of pregnancies with false-positive cell-free DNA results, occurring most frequently in cases testing positive for monosomy X (75.5%) and rare autosomal trisomies (57.9%).

    Placental cytogenetic testing for confined placental mosaicism and o… (2026)

    Because circulating fetal cell-free DNA originates predominantly from apoptotic trophoblast cells rather than the fetus itself, confined placental mosaicism is a primary source of discordant false-positive screening results.

  6. #12 The implementation of routine cfDNA screening has reduced the overall volume of invasive diagnostic procedures and shifted the primary indication for invasive testing from advanced maternal age to abnormal ultrasonographic findings.

    Trends in Invasive Prenatal Testing, Diagnosis, and Abortion for Fet… (2025); Changes in the utilization of prenatal diagnosis. (2004)

    First-tier cfDNA testing provides high-accuracy non-invasive reassurance, reserving amniocentesis and chorionic villus sampling for higher-risk indications.

  7. #13 NIPT can incidentally detect maternal malignancies and benign uterine fibroids, which present as non-reportable or abnormal genomic profiles in approximately 10 per 100,000 cases.

    Placental, maternal, fetal, and technical origins of false-positive … (2023); Incidental Detection of Maternal Neoplasia in Noninvasive Prenatal T… (2017); Integration of noninvasive DNA testing for aneuploidy into prenatal … (2014)

    Circulating tumor DNA or maternal copy-number alterations can mimic fetal aneuploidy signals, providing a potential early biomarker for maternal health.

  8. #14 Atypical SNP-based cfDNA results can identify maternal malignancies (such as lymphoma or breast cancer) in approximately 66.7% of suspicious cases, despite an overall low incidence (1 in 52,748).

    Maternal Malignancy After Atypical Findings on Single-Nucleotide Pol… (2023)

    Maternal DNA contributes to the total cell-free DNA pool; abnormal patterns can reflect underlying maternal genomic instability from cancer.

  9. #15 Cell-free DNA screening across more than 30,000 multifetal gestations demonstrated positivity rates of 1.50% for trisomy 21, 0.47% for trisomy 18, and 0.21% for trisomy 13, with an average fetal fraction of 12.2% and a non-reportable rate of 5.95%.

    A new era in aneuploidy screening: cfDNA testing in >30,000 multifet… (2019)

    Provides large-scale clinical experience data for non-invasive prenatal testing performance in twin and higher-order multiple pregnancies.

  10. #16 The positive predictive value of cell-free DNA screening for sex chromosome aneuploidies increases in advanced maternal age pregnancies, reaching 23.81% for 45,X, 53.33% for 47,XXX, 78.95% for 47,XXY, and 66.67% for 47,XYY among verified cases.

    Noninvasive prenatal testing for assessing foetal sex chromosome ane… (2021)

    Because the background incidence of maternal meiotic nondisjunction events such as 47,XXX and 47,XXY increases with maternal age, the test's positive predictive value improves in older cohorts.

  11. #17 Cell-free DNA screening performance for microdeletions, copy number variants, and rare autosomal aneuploidies exhibits substantially lower positive predictive values than for common trisomies, with reported PPVs as low as 6.45% for copy number variants in clinical cohorts.

    Copy Number Variant Detection by NIPT: Biological Constraints and th… (2026); Cell-free fetal DNA testing and its correlation with prenatal indica… (2021)

    Analytical limitations and biological confounding from composite maternal-placental genomic signals impair screening accuracy for subchromosomal aberrations.

  12. #18 Non-invasive prenatal testing (NIPT) demonstrates high accuracy for Trisomy 21 (PPV 80-93.3%) but lower and variable predictive values for Trisomy 18 (60-81%) and Trisomy 13 (14.28-55.3%) in clinical populations.

    Assessment of Placental Chromosomal Mosaicism during Prenatal Cell-F… (2025); Noninvasive prenatal testing for chromosome aneuploidies and subchro… (2019)

    Large cohort studies consistently show that NIPT is most reliable for Trisomy 21, while detection rates for other aneuploidies are more sensitive to biological confounders.

  13. #19 Genome-wide non-invasive prenatal screening identified maternal Xp22.31 copy-number deletions in 19 out of 13,156 pregnant women, facilitating the prenatal diagnosis of X-linked ichthyosis in male fetuses.

    Maternal Xp22.31 copy-number variations detected in non-invasive pre… (2022)

    Shows an secondary clinical benefit of maternal genomic screening during prenatal cfDNA evaluation.

  14. #20 Failure to obtain a result from first-trimester targeted cell-free DNA screening occurs in 3.4% of singletons and increases independently with advanced maternal age (OR 1.02 per year, 95% CI 1.01-1.04), higher maternal weight, and lower gestational age.

    First‐trimester screening for trisomies by cfDNA testing of maternal… (2019)

    Understanding technical test failure predictors is directly relevant to screening performance in advanced maternal age populations.

  15. #21 Application of the Mosaic Ratio (MR) to cfDNA sequencing data can significantly refine Positive Predictive Values, distinguishing between non-mosaic trisomies (PPV >93%) and mosaic trisomies (PPV 0-50%).

    DebatedAssessment of Placental Chromosomal Mosaicism during Prenatal Cell-F… (2025)

    While data shows improved PPV, there is currently limited official guidance on standardized clinical application of Mosaic Ratio metrics.

  16. #22 Fetal fraction enrichment techniques in genome-wide NIPT enable the reliable detection of microdeletions and microduplications down to 1 megabase (Mb).

    Frontier / fringeBreaking the 7 Mb barrier: Clinical cohort validation of genome-wide… (2026)

    This represents a significant advancement in screening resolution beyond common trisomies, though clinical validation in larger unselected cohorts is ongoing.

  17. #23 Unusual or nonreportable prenatal cfDNA screening results can indicate occult maternal cancer, with malignancy confirmed in 48.6% (52/107) of evaluated asymptomatic pregnant or postpartum patients, particularly those displaying copy-number gains and losses across three or more chromosomes (95.9% positive predictive value).

    DebatedPrenatal cfDNA Sequencing and Incidental Detection of Maternal Cancer (2024)

    Prenatal cfDNA captures maternal as well as fetoplacental circulating DNA, making maternal malignancies an important biological cause of discordant or abnormal results.

  18. #24 Target-enrichment sequencing incorporating allelic deconvolution, fragment length, and meiotic recombination mapping identifies fetal aneuploidies, microdeletions, and monogenic variants with 100% sensitivity and 99.3% specificity in clinical plasma samples.

    DebatedGenetic deconvolution of fetal and maternal cell-free DNA in materna… (2022)

    Advanced bioinformatic deconvolution methods can overcome maternal background cfDNA interference, though wide-scale clinical adoption is still emerging.

  19. #25 Single-nucleotide polymorphism-based cell-free DNA screening detects 22q11.2 deletion syndrome with 75.0% sensitivity (95% CI 42.8-94.5%) and a positive predictive value of 23.7% (95% CI 11.44-40.24%) at an observed population prevalence of 1 in 1524.

    DebatedPrenatal Screening and Diagnostic Considerations for 22q11.2 Microde… (2023); Cell-free DNA screening for prenatal detection of 22q11.2 deletion s… (2022); Noninvasive prenatal testing for chromosome aneuploidies and subchro… (2019); Clinical experience with a single‐nucleotide polymorphism‐based non‐… (2017)

    Expands cfDNA screening beyond common whole-chromosome trisomies to subchromosomal microdeletions, demonstrating moderate positive predictive value.

  20. #26 In a nationwide Danish registry study of 64,207 procedures, overall fetal loss rates before 24 weeks were 1.4% after amniocentesis and 1.9% after CVS, did not correlate with maternal age, and were significantly higher in departments performing fewer procedures.

    Fetal loss rate after chorionic villus sampling and amniocentesis: a… (2009)

    Shows that overall postprocedural loss is linked to operator or departmental procedural volume rather than maternal age.

  21. #27 Size-selection enrichment of cell-free fetal DNA fragments (below 160 bp) doubles the fetal fraction and reduces test failure rates from 0.7% to 0.1%.

    An enrichment method to increase cell-free fetal DNA fraction and si… (2019)

    Improving the fetal fraction is critical for reducing false negatives and failures, especially in high-BMI or early gestational age pregnancies.

Observational, small or case-based

  1. #28 Confined placental mosaicism can cause discordant false-positive cell-free DNA screening results, leading recommendations to prefer amniocentesis over chorionic villus sampling for prenatal confirmation when fetal ultrasonography is normal.

    DebatedConfined placental mosaicism: Distribution of chromosomally abnormal… (2024); Prenatal diagnosis after high chance non-invasive prenatal testing f… (2023); Confined placental mosaicism for 22q11.2 deletion as the etiology fo… (2017)

    Clarifies the mechanism behind discordant screening results and informs the selection of invasive diagnostic modalities.

  2. #29 Repeat cell-free DNA testing in the third trimester has poor sensitivity for confirming confined placental mosaicism, failing to detect mosaicism in 41.7% of confirmed cases.

    DebatedRepeat cell-free DNA screening after initial false-positive results … (2025)

    Third-trimester repeat cfDNA screening frequently reverts to low risk despite persistent placental mosaicism, limiting its utility for resolving discordant results.

  3. #30 False-positive cell-free DNA screening results not attributable to confined placental mosaicism are significantly associated with elevated maternal body mass index and reduced fetal fraction.

    Repeat cell-free DNA screening after initial false-positive results … (2025)

    Maternal adiposity increases maternal cfDNA dilution, lowering fetal fraction and increasing technical and biological screening discordances.

  4. #31 Standard cfDNA screening may miss approximately 24% of chromosomal abnormalities that are detectable by high-resolution invasive karyotyping.

    DebatedDiscordant circulating fetal DNA and subsequent cytogenetics reveal … (2015)

    Screening is limited to specific chromosomes, whereas karyotyping provides a whole-genome view, highlighting the importance of invasive testing for high-risk patients.

  5. #32 Cell-free DNA from a demised 'vanishing twin' can persist in maternal plasma and cause discordant sex or aneuploidy results for at least 15 weeks post-demise.

    Prolonged duration of persistent cell‐free fetal DNA from vanishing … (2018)

    Biological factors like vanishing twins are a recognized cause of false-positive NIPT results, though the duration of persistence can be highly variable.

Preclinical or mechanistic

  1. #33 A targeted capture enrichment assay for non-invasive prenatal testing detected sub-chromosomal deletions and duplications down to 0.5 Mb without false positives in a proof-of-concept study of 71 samples.

    Targeted capture enrichment assay for non-invasive prenatal testing … (2017)

    Validates technical feasibility for expanding non-invasive screening to microdeletions and microduplications.

Opinion, news or unverified

  1. #34 In singleton pregnancies, cell-free DNA screening achieves pooled detection rates of 99.2% for trisomy 21, 96.3% for trisomy 18, 91.0% for trisomy 13, 90.3% for monosomy X, and 93.0% for other sex chromosome aneuploidies, with false-positive rates ranging from 0.09% to 0.23%.

    Implications of fetoplacental mosaicism on cell‐free DNA testing: a … (2016)

    Meta-analytic evidence confirms cfDNA has high sensitivity and specificity for major fetal aneuploidies, although performance varies by specific chromosomal condition.

Where the record disagrees (3 controversies)

  • Controlled meta-analyses (Salomon et al. 2019) isolate a true procedure-attributable fetal loss rate of 0.2-0.3%, whereas older unselected national cohort registries (e.g., Danish registry 2009) reported background crude pregnancy loss rates of 1.4-1.9% post-procedure without controlling for underlying structural/chromosomal indications.

    Findings #3, #26

  • Commercial and academic platforms contest whether SNP-based cfDNA inherently outperforms massively parallel shotgun sequencing (MPSS) across detection rate and false-positive rates, as comparative claims are largely vendor-sponsored and sensitive to fetal fraction thresholds.

    Findings #6

  • Claims asserting 100% sensitivity or reliable down-to-1 Mb CNV detection rely on single-center proof-of-concept cohorts or bioinformatic modeling that have not demonstrated analytical consistency in large prospective multi-center trials.

    Findings #22, #24

Node lineage & crossover disciplines

Parent lineage, active node, direct child sub-branches, and associated crossover disciplines across the Tree of Knowledge.

Hierarchy:
Natural & Life SciencesMedicine, Health & LongevityReproductive Medicine & Human FertilityAdvanced Maternal Age & Pregnancy After 40Prenatal Cytogenetics and Cell-Free DNA ScreeningFetal Fraction Determinants and Test Failure DynamicsNon-Invasive Prenatal Testing and Cell-Free Fetal DNA DynamicsPrenatal Cytogenetic Techniques and Invasive Diagnostic ProtocolsSubchromosomal Structural Variations and Microdeletion Screening
+ Associated nodes:
Clinical Efficacy & Obstetric Outcomes (intersects) Clinical Nutrition and Assisted Reproductive Technology Outcomes (intersects) Hyaluronan Biochemistry & Endometrial Adhesion Mechanisms (intersects) Impact on Endometrial Receptivity and Fecundity (intersects) Micronutrient Supplementation in Ovarian Aging (intersects) Reproductive Nutrition, Dietary Patterns & Ovulatory Function (intersects) Ovarian Refractoriness and Endocrine Environment (intersects) Ovarian Reserve and Primordial Follicle Activation (intersects) Patient Stratification & Indications (intersects) Perinatal Safety & Neonatal Outcomes (intersects) Perinatal Safety and Maternal Epigenetic Outcomes (intersects) Micronutrient, Antioxidant & Mitochondrial Fertility Supplementation (intersects)

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Primary indexed sources (95)

Primary scientific literature, systematic reviews, and clinical trial registrations indexed for this branch.

  1. Placental cytogenetic testing for confined placental mosaicism and obstetrical outcomes after discordant cell-free DNA screening results. — Raymond Y, Fernando S, Menezes M et al. American journal of obstetrics & gynecology MFM, 2026, cohort, 2 citations · DOI: 10.1016/j.ajogmf.2025.101887
  2. Copy Number Variant Detection by NIPT: Biological Constraints and the Limits of Prenatal Genomic Inference — Dorina Merhala, Béla Veszprémi, Reka Anna Vass Genes, 2026, expert opinion · DOI: 10.3390/genes17060636
  3. Noninvasive Implantation Potential vs Morphology-Based Selection in IVF Single Blastocyst Transfer Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, 2026, rct
  4. Impact of a detailed ultrasound in pregnancies with high-risk cell-free DNA for common autosomal aneuploidies: a systematic review and meta-analysis — Elena D’Alberti, Sara Sorrenti, Karl Oliver Kagan et al. European Journal of Obstetrics & Gynecology and Reproductive Biology, 2026, systematic review · DOI: 10.1016/j.ejogrb.2026.115258
  5. Breaking the 7 Mb barrier: Clinical cohort validation of genome-wide NIPT with fetal fraction enrichment and BinDel for detection of 1 Mb microdeletions and - duplications — Karmen Vaiküll, Priit Paluoja, Signe Mölder et al. medRxiv, 2026, cohort · DOI: 10.64898/2026.02.10.26345955
  6. Prenatal Blood Typing With Next Generation Sequencing (NGS) - an Implementation Study in HDFN (PREFAB) Karolinska University Hospital, 2026, rct
  7. Early Amniocentesis Versus Transabdominal Chorionic Villus Sampling for Early Invasive Prenatal Diagnosis: A 15-Year Prospective Cohort Study — Petra Podobnik, Tomislav Meštrović, Mario Podobnik et al. Genes, 2026, cohort · DOI: 10.3390/genes17101194
  8. Noninvasive prenatal testing: an overview — Alice Poulton, Lisa Hui Australian Prescriber, 2025, guideline, 16 citations · DOI: 10.18773/austprescr.2025.019
  9. NIPT of Maternal Plasma-Originated cfDNA: Applications and Guide for the Implementation — Francisco Javier Fernández‐Martínez, M Mar Gil Mira, Cristina González González et al. The Application of Clinical Genetics, 2025, guideline, 8 citations · DOI: 10.2147/tacg.s451444
  10. Assessment of Placental Chromosomal Mosaicism during Prenatal Cell-Free DNA Screening Refines Positive Predictive Values for Fetal Trisomy — Nicola Jane Flowers, Clare J Love, Katrina L. Scarff et al. Clinical Chemistry, 2025, cohort, 7 citations · DOI: 10.1093/clinchem/hvaf076
  11. Prenatal Management of Spinal Muscular Atrophy in the Era of Genetic Screening and Emerging Opportunities in In Utero Therapy — Silvestar Mežnarić, Andrej Belančić, Valentino Rački et al. Biomedicines, 2025, expert opinion, 5 citations · DOI: 10.3390/biomedicines13081796
  12. Prenatal Screening for Chromosomal Defects — V. Frisová Reproductive Medicine, 2025, expert opinion, 3 citations · DOI: 10.3390/reprodmed6020015
  13. Repeat cell-free DNA screening after initial false-positive results and term placental analysis for confined mosaicism: a prospective cohort study — Yvette C. Raymond, Shavi Fernando, Melody A. Menezes et al. Archives of Gynecology and Obstetrics, 2025, cohort, 3 citations · DOI: 10.1007/s00404-025-08162-9
  14. Counseling prior to cfDNA screening: are we giving the right numbers? — Tania Elger, Jiri Sonek, Natalia Prodan et al. Archives of Gynecology and Obstetrics, 2025, computational, 1 citations · DOI: 10.1007/s00404-025-08108-1
  15. Trends in Invasive Prenatal Testing, Diagnosis, and Abortion for Fetal Aneuploidy. — Arruda E, Lee J, Shine K et al. American journal of perinatology, 2025, cohort, 1 citations · DOI: 10.1055/a-2566-9262
  16. Critical Factors in the Analytical Work Flow of Circulating Tumor DNA-Based Molecular Profiling — Paul van der Leest, Ed M. D. Schuuring Clinical Chemistry, 2024, expert opinion, 51 citations · DOI: 10.1093/clinchem/hvad194
  17. Prenatal cfDNA Sequencing and Incidental Detection of Maternal Cancer — Amy E. Turriff, Christina M. Annunziata, Ashkan A. Malayeri et al. New England Journal of Medicine, 2024, cohort, 48 citations · DOI: 10.1056/nejmoa2401029
  18. Confined placental mosaicism: Distribution of chromosomally abnormal cells over the term placenta — Geerke M. Eggenhuizen, S. van Veen, Nicole van Koetsveld et al. Placenta, 2024, cohort, 9 citations · DOI: 10.1016/j.placenta.2024.06.008
  19. Haemolysis overestimates plasma oxidative stress biomarkers in free-ranging roe deer — Amandine Herrada, Pauline Vuarin, François Débias et al. Comparative Biochemistry and Physiology Part A Molecular & Integrative Physiology, 2024, 4 citations · DOI: 10.1016/j.cbpa.2024.111750
  20. The efficacy of expanded non-invasive prenatal testing (NIPT) in a high-risk twin pregnancies cohort. — Meng M, Chen J, Yang Y et al. Acta obstetricia et gynecologica Scandinavica, 2024, 1 citations · DOI: 10.1111/aogs.14958
  21. Placental, maternal, fetal, and technical origins of false-positive cell-free DNA screening results — Yvette C. Raymond, Shavi Fernando, Melody A. Menezes et al. American Journal of Obstetrics and Gynecology, 2023, expert opinion, 36 citations · DOI: 10.1016/j.ajog.2023.11.1240
  22. Prenatal Screening and Diagnostic Considerations for 22q11.2 Microdeletions — Natalie Blagowidow, Beata Nowakowska, Erica M. Schindewolf et al. Genes, 2023, expert opinion, 33 citations · DOI: 10.3390/genes14010160
  23. Maternal Malignancy After Atypical Findings on Single-Nucleotide Polymorphism–Based Prenatal Cell-Free DNA Screening — Georgina Goldring, Cindy Trotter, Jeffrey T. Meltzer et al. Obstetrics and Gynecology, 2023, cohort, 19 citations · DOI: 10.1097/aog.0000000000005107
  24. Maternal and Fetal Factors Affecting Cell-Free Fetal DNA (cffDNA) Fraction: A Systematic Review — Majid Zaki‐Dizaji, Arman Shafiee, Omid Kohandel Gargari et al. Journal of Reproduction & Infertility, 2023, systematic review, 18 citations · DOI: 10.18502/jri.v24i4.14149
  25. Prenatal diagnosis after high chance non-invasive prenatal testing for trisomies 21, 18 and 13, chorionic villus sampling or amniocentesis? – Experience at a district general hospital in the United Kingdom — Collins Ejakhianghe Maximilian Okoror, Suruchi Arora European Journal of Obstetrics & Gynecology and Reproductive Biology X, 2023, expert opinion, 11 citations · DOI: 10.1016/j.eurox.2023.100211
  26. Paternal Age and Fetal Aneuploidy Clinique Ovo, 2023, cohort
  27. Cell-free DNA screening for prenatal detection of 22q11.2 deletion syndrome. — Dar P, Jacobsson B, Clifton R et al. American journal of obstetrics and gynecology, 2022, cohort, 72 citations · DOI: 10.1016/j.ajog.2022.01.002
  28. Genetic deconvolution of fetal and maternal cell-free DNA in maternal plasma enables next-generation non-invasive prenatal screening — Chenming Xu, Chenming Xu, Jianli Li et al. Cell Discovery, 2022, cohort, 39 citations · DOI: 10.1038/s41421-022-00457-4
  29. A Critical Evaluation of Validation and Clinical Experience Studies in Non-Invasive Prenatal Testing for Trisomies 21, 18, and 13 and Monosomy X — Zachary Demko, Brittany Prigmore, PETER A. BENN Journal of Clinical Medicine, 2022, meta analysis, 21 citations · DOI: 10.3390/jcm11164760
  30. Maternal Xp22.31 copy-number variations detected in non-invasive prenatal screening effectively guide the prenatal diagnosis of X-linked ichthyosis — Xinxin Tang, Zhiwei Wang, Shuting Yang et al. Frontiers in Genetics, 2022, cohort, 15 citations · DOI: 10.3389/fgene.2022.934952
  31. Maternal Copy Number Imbalances in Non-Invasive Prenatal Testing: Do They Matter? — Michaela Hýblová, Andrej Gnip, Marcel Kucharík et al. Diagnostics, 2022, 9 citations · DOI: 10.3390/diagnostics12123056
  32. Cell-Free Fetal Deoxyribonucleic Acid (cffDNA) Analysis as a Remarkable Method of Non-Invasive Prenatal Screening. — Raj H, Yelne P Cureus, 2022, 2 citations · DOI: 10.7759/cureus.29965
  33. Case Report: Prenatal Identification of a De Novo Mosaic Neocentric Marker Resulting in 13q31.1→qter Tetrasomy in a Mildly Affected Girl. — Dharmadhikari AV, Pereira EM, Andrews CC et al. Frontiers in genetics, 2022, case report, 1 citations · DOI: 10.3389/fgene.2022.906077
  34. The Emergence and Global Spread of Noninvasive Prenatal Testing — Vardit Ravitsky, Marie‐Christine Roy, Hazar Haidar et al. Annual Review of Genomics and Human Genetics, 2021, systematic review, 150 citations · DOI: 10.1146/annurev-genom-083118-015053
  35. Noninvasive prenatal testing for assessing foetal sex chromosome aneuploidy: a retrospective study of 45,773 cases — Xinran Lu, Chao-hong Wang, Yuxiu Sun et al. Molecular Cytogenetics, 2021, cohort, 37 citations · DOI: 10.1186/s13039-020-00521-2
  36. Cell-free fetal DNA testing and its correlation with prenatal indications — Jingwei Wang, Yongnan Lyu, Bin Qiao et al. BMC Pregnancy and Childbirth, 2021, cohort, 34 citations · DOI: 10.1186/s12884-021-04044-5
  37. Clinical Practice Guidelines for Prenatal Aneuploidy Screening and Diagnostic Testing from Korean Society of Maternal-Fetal Medicine: (1) Prenatal Aneuploidy Screening — Seung‐Ah Choe, Hyun‐Joo Seol, Ji Young Kwon et al. Journal of Korean Medical Science, 2021, guideline, 14 citations · DOI: 10.3346/jkms.2021.36.e27
  38. Cell-free fetal DNA screening for detection of microdeletion syndromes: a cost-effectiveness analysis. — Avram CM, Shaffer BL, Sparks TN et al. The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians, 2021, 12 citations · DOI: 10.1080/14767058.2019.1647161
  39. Stage 2 Registered Report: Variation in neurodevelopmental outcomes in children with sex chromosome trisomies: testing the double hit hypothesis — Dianne F. Newbury, Nuala H. Simpson, Paul Andrew Thompson et al. Wellcome Open Research, 2021, 1 citations · DOI: 10.12688/wellcomeopenres.14677.4
  40. Non-invasive prenatal testing (NIPT) by low coverage genomic sequencing: Detection limits of screened chromosomal microdeletions — Marcel Kucharík, Andrej Gnip, Michaela Hýblová et al. PLoS ONE, 2020, in vitro, 41 citations · DOI: 10.1371/journal.pone.0238245
  41. Clinical performance of non-invasive prenatal served as a first-tier screening test for trisomy 21, 18, 13 and sex chromosome aneuploidy in a pilot city in China. — Liu Y, Liu H, He Y et al. Human genomics, 2020, cohort, 37 citations · DOI: 10.1186/s40246-020-00268-2
  42. Use of noninvasive prenatal screening with cell-free DNA in late pregnancy with sonographic soft markers. — Wan JH, Zhen L, Han J et al. European journal of obstetrics, gynecology, and reproductive biology, 2020, 3 citations · DOI: 10.1016/j.ejogrb.2020.07.036
  43. Stage 2 Registered Report: Variation in neurodevelopmental outcomes in children with sex chromosome trisomies: testing the double hit hypothesis — Dianne F. Newbury, Nuala H. Simpson, Paul Andrew Thompson et al. Wellcome Open Research, 2020, 1 citations · DOI: 10.12688/wellcomeopenres.14677.3
  44. Isolation of Cell Free Fetal DNA From Spent Culture Medium and Its Potential Role for Preimplantation Genetic Diagnosis (PGD). Damascus University, 2020, cohort
  45. Performances of a Snp-Based Noninvasive Prenatal Test — Malena Götte, Marta Bianchi, Aline Wolter et al. Zenodo (CERN European Organization for Nuclear Research), 2020 · DOI: 10.5281/zenodo.3953714
  46. VP30.05: The utility of maternal plasma cell‐free fetal DNA screening in prenatal diagnosis of 22q11.2 microdeletion syndrome — K. Law, Yuen Ha Ting Ultrasound in Obstetrics and Gynecology, 2020 · DOI: 10.1002/uog.22796
  47. Risk of miscarriage following amniocentesis or chorionic villus sampling: systematic review of literature and updated meta‐analysis — Laurent Julien Salomon, Alexandros Sotiriadis, Camilla Bernt Wulff et al. Ultrasound in Obstetrics and Gynecology, 2019, systematic review, 366 citations · DOI: 10.1002/uog.20353
  48. First‐trimester screening for trisomies by cfDNA testing of maternal blood in singleton and twin pregnancies: factors affecting test failure — Slavyana Galeva, Maria M. Gil, L. Konstantinidou et al. Ultrasound in Obstetrics and Gynecology, 2019, cohort, 91 citations · DOI: 10.1002/uog.20290
  49. Noninvasive prenatal testing for chromosome aneuploidies and subchromosomal microdeletions/microduplications in a cohort of 8141 single pregnancies. — Hu H, Wang L, Wu J et al. Human genomics, 2019, cohort, 83 citations · DOI: 10.1186/s40246-019-0198-2
  50. An enrichment method to increase cell-free fetal DNA fraction and significantly reduce false negatives and test failures for non-invasive prenatal screening: a feasibility study — Ping Hu, Dong Liang, Yangyi Chen et al. Journal of Translational Medicine, 2019, cohort, 72 citations · DOI: 10.1186/s12967-019-1871-x
  51. A new era in aneuploidy screening: cfDNA testing in >30,000 multifetal gestations: Experience at one clinical laboratory — Brittany Dyr, Theresa Boomer, Eyad A. Almasri et al. PLoS ONE, 2019, cohort, 26 citations · DOI: 10.1371/journal.pone.0220979
  52. Clinical experience across the fetal‐fraction spectrum of a non‐invasive prenatal screening approach with low test‐failure rate — Susan E. Hancock, Rotem Ben‐Shachar, Christa Adusei et al. Ultrasound in Obstetrics and Gynecology, 2019, cohort, 24 citations · DOI: 10.1002/uog.21904
  53. Usefulness and reliability of cell free fetal DNA screening for main trisomies in case of atypical profile on first trimester maternal serum screening — Julie Carrara, Alexandre Joseph Vivanti, Jacques C. Jani et al. Journal of Translational Medicine, 2019, 10 citations · DOI: 10.1186/s12967-019-02152-7
  54. Diagnostic Test Accuracy Systematic Reviews: Evaluation of Completeness of Reporting and Elaboration on Optimal Practices — Jean‐Paul Salameh uO Research (University of Ottawa), 2019, systematic review
  55. The interplay between KIAA0753 and TBCCD1 in the control of ciliogenesis and the cell cytoskeleton architecture — David C. Ferreira, Bruno Carmona, Sofia Nolasco et al. Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT), 2019
  56. Next-generation sequencing and the impact on prenatal diagnosis — Rhiannon Mellis, Natalie Jane Chandler, Lyn S. Chitty Expert Review of Molecular Diagnostics, 2018, expert opinion, 64 citations · DOI: 10.1080/14737159.2018.1493924
  57. Prolonged duration of persistent cell‐free fetal DNA from vanishing twin — Kirsten M. Niles, Ally Murji, David A. Chitayat Ultrasound in Obstetrics and Gynecology, 2018, case report, 37 citations · DOI: 10.1002/uog.19004
  58. A novel array CGH-based non-invasive prenatal test for common trisomies — Karampetsou E University College London (University of London), 2018
  59. Amniocentesis and chorionic villus sampling for prenatal diagnosis — Žarko Alfirević, Kate Navaratnam, Faris Mujezinović Cochrane Database of Systematic Reviews, 2017, systematic review, 412 citations · DOI: 10.1002/14651858.cd003252.pub2
  60. Clinical experience with a single‐nucleotide polymorphism‐based non‐invasive prenatal test for five clinically significant microdeletions — Kimberly A. Martin, S. Iyengar, A. Kalyan et al. Clinical Genetics, 2017, case series, 110 citations · DOI: 10.1111/cge.13098
  61. Incidental Detection of Maternal Neoplasia in Noninvasive Prenatal Testing — Nilesh G. Dharajiya, Daniel S. Grosu, Daniel H. Farkas et al. Clinical Chemistry, 2017, registry, 108 citations · DOI: 10.1373/clinchem.2017.277517
  62. Rapid, ultra low coverage copy number profiling of cell-free DNA as a precision oncology screening strategy — Daniel H. Hovelson, Chia‐Jen Liu, Yugang Wang et al. Oncotarget, 2017, unknown, 52 citations · DOI: 10.18632/oncotarget.21163
  63. Cell‐free fetal DNA analysis in maternal plasma as screening test for trisomies 21, 18 and 13 in twin pregnancy — G. Le Conte, Alexandra Letourneau, Jacques C. Jani et al. Ultrasound in Obstetrics and Gynecology, 2017, cohort, 46 citations · DOI: 10.1002/uog.18838
  64. Assessment of circulating copy number variant detection for cancer screening — Bhuvan Molparia, Eshaan Nichani, Ali Torkamani PLoS ONE, 2017, computational, 42 citations · DOI: 10.1371/journal.pone.0180647
  65. Targeted capture enrichment assay for non-invasive prenatal testing of large and small size sub-chromosomal deletions and duplications. — Neofytou MC, Tsangaras K, Kypri E et al. PloS one, 2017, in vitro, 30 citations · DOI: 10.1371/journal.pone.0171319
  66. Confined placental mosaicism for 22q11.2 deletion as the etiology for discordant positive NIPT results — Megan E. Bunnell, C. Zhang, Charles Lee et al. Prenatal Diagnosis, 2017, case report, 29 citations · DOI: 10.1002/pd.5022
  67. Improving the Positive Predictive Value of Non-Invasive Prenatal Screening (NIPS) — Charles M. Strom, Ben Anderson, David Tsao et al. PLoS ONE, 2017, 19 citations · DOI: 10.1371/journal.pone.0167130
  68. New genes and pathways implicated in Rett syndrome: considerations and future applications — Mario Lucariello Tesis Doctorals en Xarxa (Consorci de Serveis Universitaris de Catalunya), 2017
  69. Implications of fetoplacental mosaicism on cell‐free DNA testing: a review of a common biological phenomenon — Francesca Romana Grati Ultrasound in Obstetrics and Gynecology, 2016, expert opinion, 85 citations · DOI: 10.1002/uog.15975
  70. Noninvasive Prenatal DNA Testing: The Vanguard of Genomic Medicine — Lisa Hui, Diana W. Bianchi Annual Review of Medicine, 2016, systematic review, 69 citations · DOI: 10.1146/annurev-med-072115-033220
  71. Cytogenetic confirmation of a positive NIPT result: evidence-based choice between chorionic villus sampling and amniocentesis depending on chromosome aberration — Diane Van Opstal, Malgorzata Ilona Srebniak Expert Review of Molecular Diagnostics, 2016, expert opinion, 67 citations · DOI: 10.1586/14737159.2016.1152890
  72. Methods for genome-wide DNA methylation analysis in human cancer — Shicai Fan, Wenming Chi Briefings in Functional Genomics, 2016, expert opinion, 40 citations · DOI: 10.1093/bfgp/elw010
  73. Noninvasive disease diagnostics using engineered synthetic urinary biomarkers — Andrew Warren DSpace@MIT (Massachusetts Institute of Technology), 2016
  74. Detection of fetal subchromosomal abnormalities by sequencing circulating cell-free DNA from maternal plasma. — Zhao C, Tynan J, Ehrich M et al. Clinical chemistry, 2015, computational, 119 citations · DOI: 10.1373/clinchem.2014.233312
  75. Noninvasive Prenatal Screening for Genetic Diseases Using Massively Parallel Sequencing of Maternal Plasma DNA — Lyn S. Chitty, Yuk Ming Dennis Lo Cold Spring Harbor Perspectives in Medicine, 2015, expert opinion, 81 citations · DOI: 10.1101/cshperspect.a023085
  76. Discordant circulating fetal DNA and subsequent cytogenetics reveal false negative, placental mosaic, and fetal mosaic cfDNA genotypes — Roger V. Lebo, Robert W. Novak, Katherine B. Wolfe et al. Journal of Translational Medicine, 2015, case series, 49 citations · DOI: 10.1186/s12967-015-0569-y
  77. Cell‐free DNA testing in a trisomy 21 pregnancy with confined placental mosaicism for a cell line with trisomy for both chromosomes 18 and 21 — Kristy Crooks, Ginger Elizabeth Edwardsen, Siobhan O'Connor et al. Clinical Case Reports, 2015, 5 citations · DOI: 10.1002/ccr3.421
  78. Evaluating the results of the Momguard noninvasive prenatal test — Hae‐Jin Hu, Young-Jun Kwon, Mijin Oh et al. Journal of genetic medicine, 2015, 2 citations · DOI: 10.5734/jgm.2015.12.2.96
  79. Invasive Prenatal Diagnosis: Chorionic Villus Sampling — Panos J. Antsaklis, Aris J Antsaklis, Michael Sindos et al. Donald School Journal of Ultrasound in Obstetrics & Gynecology, 2015, 1 citations · DOI: 10.5005/jp-journals-10009-1416
  80. Integration of noninvasive DNA testing for aneuploidy into prenatal care: what has happened since the rubber met the road? — Bianchi DW, Wilkins-Haug L Clinical chemistry, 2014, expert opinion, 114 citations · DOI: 10.1373/clinchem.2013.202663
  81. Advances in genetic prenatal diagnosis and screening. — Hardisty EE, Vora NL Current opinion in pediatrics, 2014, 16 citations · DOI: 10.1097/mop.0000000000000145
  82. Noninvasive Cell-Free DNA-Based Prenatal Detection of Microdeletions Using Single Nucleotide Polymorphism–Targeted Sequencing — Matthew Rabinowitz, Melissa S. Savage, Barbara J. Pettersen et al. Obstetrics and Gynecology, 2014, 16 citations · DOI: 10.1097/01.aog.0000447172.98639.e5
  83. Noninvasive Prenatal Testing Using Cell-free DNA in Maternal Circulation — PETER A. BENN Journal of Fetal Medicine, 2014, 5 citations · DOI: 10.1007/s40556-014-0021-z
  84. The non-invasive prenatal test (NIPT) for trisomy 21 — Frank Hulstaert, Mattias Neyt, Wilfried Gyselaers 2014, 4 citations · DOI: 10.57598/r222c
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  86. Initial clinical laboratory experience in noninvasive prenatal testing for fetal aneuploidy from maternal plasma DNA samples — Tracy A. Futch, John C. Spinosa, Sucheta Bhatt et al. Prenatal Diagnosis, 2013, case series, 181 citations · DOI: 10.1002/pd.4123
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