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NIPT Clinical Review · LabCorp Educational Program · May 6, 2025
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DISCLOSURE: This educational program is sponsored by LabCorp Genetics & Women's Health.
Dr. Onyeije has received honoraria for this presentation. All clinical opinions are his own independent professional judgment.
Sponsored Educational Dinner Program · Medcura · HSU's Gourmet

When NIPT Goes Silent:
What No-Call Results Cost Your Patients

Low fetal fraction · Atypical results · Mosaic flags · sgNIPT false negatives — the real clinical and human cost of results that don't report.

CO
Chukwuma Onyeije, MD, FACOG Maternal-Fetal Medicine · Atlanta Perinatal Associates · Medical Director
DATE Wednesday, May 6 · 6:30 PM
02
What We Cover Tonight
LEARNING OBJECTIVES
01
The no-call problem
Why an indeterminate result is never neutral for the patient, the ordering clinician, or the decision window.
02
Why results fail
Low fetal fraction, mosaic flags, atypical findings, and the architecture choices that turn signal into either an answer or silence.
03
Platform performance
Published head-to-head differences in non-reportable rates, PPV, twin performance, and rescue pathways.
04
sgNIPT for CF
The Wynn 2025 and Zemanick 2025 papers, what the data supports, and what still requires caution in counseling.
Tonight's frame: every slide asks the same clinical question. Does this platform get my patient an answer I can act on, in time?
ONYEIJE · ATLANTA PERINATAL ASSOCIATESLABCORP EDUCATIONAL PROGRAM · 2025
03
The No-Call Is Not a Neutral Event
CLINICAL STAKES
From my practice
A 38-year-old G2P1 at 11 weeks receives her NIPT: "Specimen may be mosaic. Result indeterminate." She calls the office in tears. Her OB calls me. We counsel her, repeat the draw on a different platform, and wait again.

Fourteen days later: the repeat result is normal. The first report created two weeks of anxiety, a second venipuncture, and a decision window with less certainty than the patient deserved.
Patient impact Fear rises immediately because "indeterminate" rarely feels neutral to a pregnant patient.
Clinical impact The ordering team now has to choose between redraw, platform switch, invasive testing, or no answer at all.
System impact The architecture of the assay, not the effort of the clinician, determines whether that first blood draw becomes useful information.
1.3%
sgNIPT no-call rate in Hoskovec et al. unselected cohort of 9,151 patients
Hoskovec et al., Genetics in Medicine 2023
0.8%
No-call rate among CF carriers in the Wynn et al. 2025 cohort of 100,106 patients
Wynn et al., J Cystic Fibrosis 2025
10–14
Typical days to resolution when a repeat draw is required
APA clinical experience; published literature
90%
Of Panorama non-reportable samples that yielded a result when retested with MaterniT
Rafalko et al., ISPD 2023 (LabCorp internal data)
Of those rescued MaterniT results, 39% were positive findings. Mosaic aneuploidy, maternal events, non-mosaic aneuploidy, and CNVs were being hidden behind the no-call label.Rafalko et al., ISPD poster 2023. Breakdown: 61% mosaic aneuploidy, 16% suspected maternal events, 14% non-mosaic aneuploidy, 5% subchromosomal CNVs, 4% multiple aneuploidies.
ONYEIJE · ATLANTA PERINATAL ASSOCIATESLABCORP EDUCATIONAL PROGRAM · 2025
04
Why NIPT Results Fail to Report
MECHANISMS
Causes of No-Call / Non-Reportable
Low Fetal Fraction (<4%)
Insufficient fetal cf-DNA. More common with early GA, high maternal BMI, and certain aneuploidies
"Atypical Result"
Data pattern falls outside expected biological categories — Panorama fails to issue a discrete result; no next steps offered
"Specimen May Be Mosaic"
Conflicting signals across fetal fractions — clinically ambiguous without a mosaicism ratio
Pre-analytical / Technical Failure
Hemolysis, insufficient volume, transport delay, sample compromise
What Happens Next in Practice
Repeat blood draw
Patient returns 7–14 days later; added wait, added anxiety
Platform switch
Clinician may not know to order from an alternate lab — often results in further delay
Invasive diagnostic testing
Anxiety-driven amniocentesis or CVS that may have been avoidable
No answer at all
Patient ages out of optimal decision window; some never get a result
💡
Key insight: Platform architecture — specifically whether the lab has fetal enrichment technology and a genome-flex rescue pathway — determines whether a low-fraction sample becomes a no-call or a reportable result.
ONYEIJE · ATLANTA PERINATAL ASSOCIATESLABCORP EDUCATIONAL PROGRAM · 2025
Section 02
MaterniT® vs. Panorama™:
What the Data Actually Show
Published performance metrics, non-reportable rates, and PPV across key clinical scenarios
06
Key Performance Comparison: MaterniT® vs. Panorama™
PUBLISHED DATA
Bottom line: the largest differences are not cosmetic. They show up in redraw burden, access in twins and triplets, 22q performance, and whether a low-fetal-fraction sample can be rescued.
Access and turnaround
Non-reportable rate, singletons
1%First draw
1.4%Does not include atypical results
Non-reportable rate, twins
<3.8%Screening twins since 2012
>10%Since 2019
Triplet pregnancies
17.3%Reportable pathway exists
ExcludedNot offered
Turnaround time
3-5 daysRoutine workflow
5-7 daysLonger wait to answer
Performance and rescue tools
22q (DiGeorge) PPV
90%-99%Soster 2023
53%Dar 2022
Trisomy 22 and trisomy 16 PPV
43.3% / 35.8%Published PPV
ExcludedNo assay coverage
Genome-Flex rescue and fetal enrichment
AvailableLow-fraction rescue pathway exists
ExcludedNo comparable rescue pathway
Mosaicism Ratio
AvailableMaterniT 21 PLUS only
Not availableNo quantitative ratio for counseling
Sources: LabCorp internal data; Natera website accessed June 2025; Dar et al. AJOG 2022; Rafalko et al. ISPD 2023; Soster et al. Front Genet 2023; Dugoff et al. AJOG 2023; MaterniT 21 PLUS comparison brochure L1553350, 2025.
ONYEIJE · ATLANTA PERINATAL ASSOCIATESLABCORP EDUCATIONAL PROGRAM · 2025
07
Fraternal Twin PPV — Where the Gap Is Widest
PUBLISHED PPV DATA
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Twin pregnancies are a common MFM referral. Platform selection matters more in twins — Panorama excludes triplets entirely and carries a >10% non-reportable rate even in dizygotic twins. MaterniT has been screening twins since 2012.
T21 PPV · DZ TWINS
100%
MaterniT®
88%
Panorama™
Dugoff et al. AJOG 2023; Kantor et al. Prenat Diagn 2022
T18 PPV · DZ TWINS
100%
MaterniT®
70%
Panorama™
Dugoff et al. AJOG 2023
T13 PPV · DZ TWINS
100%
MaterniT®
67%
Panorama™
Dugoff et al. AJOG 2023
22q PPV · SINGLETONS
90–99%
MaterniT®
53%
Panorama™
Soster et al. Front Genet 2023; Dar et al. AJOG 2022
Panorama also excludes: twin pregnancies with a donor egg, any surrogate twin pregnancy, triploidy screening, and microdeletions other than 22q in dizygotic twins. MaterniT excludes none of these.Source: Natera website accessed June 2025; Panorama sample report and requisition form
ONYEIJE · ATLANTA PERINATAL ASSOCIATESLABCORP EDUCATIONAL PROGRAM · 2025
08
Cases from My Practice at APA
DE-IDENTIFIED CLINICAL CASES · PERSONAL EXPERIENCE
CASE AAtypical / low fetal fraction, rescued by MaterniT fetal enrichment
Patient34-year-old G1P0 at 10w3d, BMI 36, no prior genetic history
Initial NIPTNo result returned because fetal fraction fell below the reportable threshold on an SNP-based platform
ResolutionRepeat sample processed with MaterniT fetal enrichment technology. Normal result reported within 4 days.
ImpactTotal delay: 11 days, additional counseling call, avoidable anxiety in the first trimester
CASE B"Specimen may be mosaic," then actionable counseling with Mosaicism Ratio
Patient39-year-old G2P1 at 11w1d, prior T21 pregnancy, already anxious
Initial NIPTAtypical result with possible mosaicism. No actionable data and no next-step framework from the original report.
ResolutionMaterniT 21 PLUS Mosaicism Ratio provided quantitative data. Patient then chose amniocentesis with informed consent grounded in real numbers.
ImpactThe diagnostic decision was made from usable data, not a vague flag. That difference changes counseling.
Cases are composite, de-identified representations of APA clinical experience. Individual outcomes vary. These cases do not constitute a clinical study or proof of superiority of any platform.
ONYEIJE · ATLANTA PERINATAL ASSOCIATESLABCORP EDUCATIONAL PROGRAM · 2025
Section 03
sgNIPT for Cystic Fibrosis:
Promise, Performance, and a Warning
What the 2025 peer-reviewed literature says — and what three families in Colorado wish clinicians had known
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The BTO sgNIPT Study — Wynn et al. 2025
J CYSTIC FIBROSIS · ARTICLE IN PRESS
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Study design: Retrospective review of 100,106 consecutive general-risk pregnant patients who underwent CF carrier screening at BTO's CLIA-certified laboratory. 3,621 CF carriers identified. All eligible CF carriers received reflex cell-free DNA fetal risk assessment. Outcomes solicited from 50% of low-risk and 100% of high-risk cases.
100%
Sensitivity in study cohort (13/13 affected fetuses identified as high-risk)
Wynn et al., J Cystic Fibrosis 2025 (95% CI: 75–100%)
65%
PPV among high-risk cases with known outcomes (13/20 confirmed affected)
Wynn et al., 2025 (95% CI: 47%–79%)
100%
PPV at the 9-in-10 risk tier — all 8 such cases were CF-affected
Wynn et al., 2025
98.7%
End-to-end sensitivity (including carrier screening step)
Wynn et al., 2025 (95% CI: 93.0–99.9%)
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Critical study limitation acknowledged by authors: Outcome data were available for only 13.2% of low-risk cases and 50% of high-risk cases. The 100% sensitivity claim is based on a subset with known outcomes — not the full cohort of 2,587 CF carriers. Zero false negatives in a selected sample ≠ zero false negatives in clinical practice. Wynn et al., J Cystic Fibrosis 2025 — Article in Press
ONYEIJE · ATLANTA PERINATAL ASSOCIATESLABCORP EDUCATIONAL PROGRAM · 2025
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Three Families. Three False Negatives. One Letter That Changed the Conversation.
ZEMANICK ET AL. · J CYSTIC FIBROSIS · NOV 2025
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University of Colorado MFM and Pediatric CF Clinic (Zemanick et al., 2025): Three infants received low-risk results on BTO's Unity sgNIPT and were later diagnosed with CF by newborn screen. One co-author, Dr. Zaretsky, is also a Medical Advisor to BTO and a co-author on the Wynn paper that advanced the original 100% sensitivity claim.
Case 1
Low 1:200
Family context
Sibling with CF: Yes · Meconium ileus: No
Parental variants
Maternal F508del · Paternal A559T
Fetal fraction
6.7%
Outcome
Newborn screen and diagnostic workup confirmed F508del / A559T, CF affected.
Case 2
Low <1:5000
Family context
Sibling with CF: Yes · Meconium ileus: No
Parental variants
Maternal F508del · Paternal F508del
Fetal fraction
4.4%
Outcome
Newborn screen and diagnostic workup confirmed F508del / F508del, CF affected.
Case 3
Low 1:1500
Family context
Sibling with CF: No · Meconium ileus: Yes
Parental variants
Maternal F508del · Paternal G330X
Fetal fraction
11%
Outcome
Newborn screen and diagnostic workup confirmed F508del / G330X, CF affected.
📊
Statistical analysis by Zemanick et al.: The probability of observing at least 3 false negatives by chance alone ranges from 2 in 100 to 8 in 1,000,000,000, depending on assumptions. This cluster should not be dismissed as random variation. Zemanick et al., J Cystic Fibrosis, Letter to the Editor, Nov 2025
ONYEIJE · ATLANTA PERINATAL ASSOCIATESLABCORP EDUCATIONAL PROGRAM · 2025
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The Foundation Study: Hoskovec et al., Genetics in Medicine 2023
PEER-REVIEWED PERFORMANCE DATA
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Study: 9,151 unselected pregnant patients from 240+ providers across 31 US states. 1,669 (18.2%) identified as heterozygous for ≥1 pathogenic variant and reflexed to sgNIPT. Outcomes collected for 201 pregnancies covering CF, beta-hemoglobinopathy, alpha-thalassemia, and SMA.
98.7%
Received informative result (no-call rate = 1.3%)
Complete cohort of 9,151 · Hoskovec 2023
93.3%
Sensitivity of sgNIPS (14/15 affected fetuses identified as high-risk)
Outcomes cohort · 95% CI: 68.1–99.8%
48.3%
Average PPV — higher than the 25% PPV ceiling of traditional dual-carrier screening
95% CI: 36.1–60.1% · Hoskovec 2023
99.4%
Negative predictive value (NPV)
95% CI: 96.0–99.9% · Hoskovec 2023
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Traditional carrier screening real-world sensitivity: only 35%
When 10% misattributed paternity AND 58% non-completion of paternal carrier screening are factored in — sgNIPS end-to-end sensitivity of 90% is dramatically superior.Hoskovec et al., Figure 3 — Calculated clinical performance of prenatal carrier screening
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One CF false negative in this cohort too
A neonate homozygous for the G542X rare variant was misclassified as low-risk (1:2000). The assay is designed to miss homozygous rare non-F508del variants — which account for 1.5–3.1% of US CF cases.Hoskovec 2023; Zvereff et al., Genetics in Medicine 2014
ONYEIJE · ATLANTA PERINATAL ASSOCIATESLABCORP EDUCATIONAL PROGRAM · 2025
13
What Every Ordering Physician Must Counsel Before sgNIPT
EVIDENCE-BASED COUNSELING POINTS
Use this as a counseling slide, not a data dump. Patients do not need every paper. They need a clear explanation of what the test can do, what it can miss, and what happens next.
No-call results happen
Hoskovec reported a 1.3% no-call rate; Wynn reported 0.8% in the CF-carrier sub-cohort. Roughly 1 in 100 patients may not get an answer on the first pass.
COUNSEL Tell the patient up front that a repeat draw or an alternative platform may be needed.
Positive does not mean diagnostic
PPV was 48.3% on average in Hoskovec and 65% in the Wynn CF cohort. A high-risk result is still a risk estimate.
COUNSEL Positive results should trigger confirmatory CVS or amniocentesis, not irreversible decisions.
Low-risk does not rule out all CF
The assay cannot detect homozygous rare CF variants other than F508del. Missed cases remain possible, especially in diverse populations.
HIGH RISK A low-risk result does not fully exclude CF in consanguineous or ethnically homogeneous populations.
ACOG still calls sgNIPT investigational
This is not yet standard-of-care replacement testing for traditional maternal and paternal carrier screening.
COUNSEL Present sgNIPT as a screening tool, while sequential maternal and paternal carrier screening remains the ACOG standard.
Partner testing still matters
sgNIPT gives pregnancy-specific risk. It does not replace knowing the true parental genotype combination for future pregnancies.
COUNSEL Recommend paternal carrier testing for future pregnancies. Saliva collection can reduce logistical barriers.
Therapy pathways still require diagnosis
A high-risk sgNIPT result alone does not qualify a patient for in utero treatment or definitive therapeutic planning.
INFORM High-risk results should lead to confirmatory testing before any treatment discussion.
Sources: Hoskovec et al. 2023; Wynn et al. 2025; Zemanick et al. 2025; APA BTO internal analysis 2025; ACOG Committee Opinion 691; ACMG guidelines Gregg et al. 2021.
ONYEIJE · ATLANTA PERINATAL ASSOCIATESLABCORP EDUCATIONAL PROGRAM · 2025
My Clinical Summary
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No-call is a clinical incident, not a neutral event. Fetal enrichment and the Genome-Flex pathway are not cosmetic features — they determine whether my patient gets an answer today or waits two more weeks.
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Mosaicism ratio data is actionable. "Specimen may be mosaic" is not. I need a number to counsel my patient. An ambiguous flag without quantitative data serves no one.
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sgNIPT for CF is promising but not ready to replace standard counseling pathways. Wynn et al. 2025 reported 100% sensitivity — in a selected cohort with incomplete outcome data. Zemanick et al. 2025 documented three false negatives that statistical analysis says are not random. ACOG still calls this investigational. I honor all of that simultaneously.
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Marketing claims are not clinical performance. "100% sensitivity" in a press release — later corrected to 93–97% — is not the same as peer-reviewed, independently confirmed, real-world sensitivity. Order based on published peer-reviewed data. Require it from every vendor.
My job is to get every patient an answer before the anxiety window closes and before a decision has to be made without adequate information. Platform selection is part of that clinical responsibility.
DISCLOSURES & KEY REFERENCES
Sponsored by LabCorp Genetics & Women's Health. Speaker received honoraria. Opinions are speaker's independent professional judgment.
Hoskovec et al., Genetics in Medicine 2023 · Wynn et al., J Cystic Fibrosis 2025 (in press) · Zemanick et al., J Cystic Fibrosis 2025 (letter to editor) · Rafalko et al., ISPD 2023 poster · Dar et al., AJOG 2022 · Dugoff et al., AJOG 2023 · Soster et al., Front Genet 2023 · LabCorp MaterniT comparison brochure L1553350 ©2025 · ACOG Practice Bulletin 226 · ACMG Gregg et al. 2021
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