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CMECNE

What Is the Best Follow-Up Diagnostic Test After a High-Risk NIPT Result?

Learning Objectives and CME/Disclosure Information

This activity is intended for healthcare providers delivering care to women and their families.

After completing this activity, the participant should be better able to:

1. Contrast the differences between placental and fetal tissues in relation to cytogenetic differences
2. Choose the preferable confirmatory test following a positive noninvasive prenatal screening test

Estimated time to complete activity: 0.25 hours

Faculty:

Susan J. Gross, MD, FRCSC, FACOG, FACMG
President and CEO, The ObG Project

Disclosure of Conflicts of Interest

Postgraduate Institute for Medicine (PIM) requires faculty, planners, and others in control of educational content to disclose all their financial relationships with ineligible companies. All identified conflicts of interest (COI) are thoroughly vetted and mitigated according to PIM policy. PIM is committed to providing its learners with high quality accredited continuing education activities and related materials that promote improvements or quality in healthcare and not a specific proprietary business interest of an ineligible company.

The PIM planners and others have nothing to disclose. The OBG Project planners and others have nothing to disclose.

Faculty: Susan J. Gross, MD, receives consulting fees from Cradle Genomics, and has financial interest in The ObG Project, Inc.

Planners and Managers: The PIM planners and managers, Trace Hutchison, PharmD, Samantha Mattiucci, PharmD, CHCP, Judi Smelker-Mitchek, MBA, MSN, RN, and Jan Schultz, MSN, RN, CHCP have nothing to disclose.

Method of Participation and Request for Credit

Fees for participating and receiving CME credit for this activity are as posted on The ObG Project website. During the period from Dec 31 2017 through Jan 25 2023, participants must read the learning objectives and faculty disclosures and study the educational activity.

If you wish to receive acknowledgment for completing this activity, please complete the test and evaluation. Upon registering and successfully completing the test with a score of 100% and the activity evaluation, your certificate will be made available immediately.

Joint Accreditation Statement

In support of improving patient care, this activity has been planned and implemented by the Postgraduate Institute for Medicine and The ObG Project. Postgraduate Institute for Medicine is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.

Physician Continuing Medical Education

Postgraduate Institute for Medicine designates this enduring material for a maximum of 0.25 AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Continuing Nursing Education

The maximum number of hours awarded for this Continuing Nursing Education activity is 0.2 contact hours.

Read Disclaimer & Fine Print

BACKGROUND AND PURPOSE:

DNA that circulates in the maternal compartment is mostly derived from placenta (cytotrophoblast layer) and not the fetus
Fetal and placental cells both originate from the fertilized oocyte, but diverge early in pregnancy into distinct tissues
- Placenta can tolerate different cell lines (mosaicism) and may not perfectly match the fetal chromosomal complement, resulting in false positive and negative NIPS results
There are other causes that may result in false positive and negative NIPS reports, such as vanishing twin or maternal chromosomal anomalies
Therefore, there is universal agreement that a positive cfDNA report requires confirmation based on invasive testing with either CVS or amniocentesis
Grati et al. (Prenatal Diagnosis, 2015) used an extensive database to determine how often placental DNA (CVS results) matched fetal DNA (amniocentesis results), broken out by chromosome and cellular layer, to determine whether amniocentesis and/or CVS is the more appropriate confirmatory test.

METHODS:

Data on 52,673 karyotypes were analyzed to determine frequency of mosaicism involving cytophoblasts, for trisomies 21 (T21), 18 (T18), 13 (T13) and monsomy X (MX)
Karyotypes were obtained from cytorophoblast (outer layer, DNA source for NIPS), mesenchyme and confirmatory amniocentesis

RESULTS:

Using cytotrophoblast karyotype as a proxy for NIPS, authors posited the following

After a high-risk NIPS result, mosaicism on confirmatory CVS requiring a follow up amniocentesis would be:
- 2% in T21
- 4% in T18
- 22% in T13
- 59% in MX
When mosaicism is detected by CVS, the likelihood of fetal confirmation by amniocentesis would be:
- 44% in T21
- 14% in T18
- 4% in T13
- 26% in MX

CONCLUSION:

For T21/18, confirmatory CVS may still be an option, especially if there is a clinical indication to obtain early results
- Small but still real risk for inconclusive results
For MX/T13, amniocentesis seems most appropriate for follow-up after high risk cfDNA result due to high likelihood of a mosaic result on confirmatory CVS
The authors state “If an ultrasound anomaly suggesting the suspected karyotype anomaly is found, CVS could be offered to the patient regardless of risk of need for a secondary procedure because an early diagnosis may be preferable.”

Learn More – Primary Sources:

The type of feto-placental aneuploidy detected by cfDNA testing may influence the choice of confirmatory diagnostic procedure

Diagnostic cytogenetic testing following positive noninvasive prenatal screening results: a clinical laboratory practice resource of the American College of Medical Genetics and Genomics (ACMG)

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What Is the Best Follow-Up Diagnostic Test After a High-Risk NIPT Result?