2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-Fetal Placental Discordance as an Explanation for False Negative SNP-based NIPT

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The study investigates the frequency of fetal placental discordance (FPD) as a reason for false negative (FN) results in non-invasive prenatal testing (NIPT). FN results occur in less than 1/10,000 singleton cases and can be caused by various factors such as FPD, placental mosaicism, specimen identification discrepancy, or NIPT screen failure. The study aims to highlight the importance of testing products of conception (POC) to identify other genetic causes for pregnancy loss.<br /><br />The researchers analyzed 40 cases with FN SNP-based NIPT results that also had SNP-based chromosomal microarray analysis (CMA) performed on POC tissue. The FN result was reported based on prenatal diagnostic testing, POC tissue analysis, or a liveborn sample. Cases with inconclusive results or testing on fetal tissue only were excluded from the analysis. The remaining 33 cases were divided into those with testing on placental villi only or both fetal and villi tissue.<br /><br />Of the 33 cases with POC tissue results, 57.6% showed either FPD or mosaicism within the villi. This suggests that FPD can be a cause of FN NIPT results. However, the rate of FPD may be underestimated as not all POC samples include placental tissue or multiple placental dissections.<br /><br />The study concludes that SNP-based POC testing, along with fetal tissue testing, can identify FPD and mosaicism in the placenta as a cause of FN NIPT results. The findings highlight the value of POC testing in providing valuable information about the cause of pregnancy loss, even in cases with normal NIPT results.<br /><br />Disclosure: All authors are employees of Natera, Inc. and hold stock or options in the company. The authors acknowledge Dr. J. Bryce Ortiz from Natera, Inc. for poster development and editorial support.

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Co-Author - Jennifer Lemoine, MS, CGC; Co-Author - Cindy Trotter, MS; Presenting Author - Katrina Merrion, MS; Co-Author - Melissa K. Maisenbacher, MS, CGC; Co-Author - Russell Jelsema, MD, FACOG; Co-Author - Karine Hovanes, PhD, FACMG; Co-Author - Wenbo Xu, MD, PhD, FACMG; Submitter Only - J. Bryce Ortiz, PhD;

Meta Tag

Cell free DNA/cfDNA

Fetal Pathology

NextGen Sequencing

Noninvasive prenatal screening (NIPS)

Prenatal Diagnosis

Co-Author Jennifer Lemoine, MS, CGC

Co-Author Cindy Trotter, MS

Co-Author Melissa K. Maisenbacher, MS, CGC

Co-Author Russell Jelsema, MD, FACOG

Co-Author Karine Hovanes, PhD, FACMG

Co-Author Wenbo Xu, MD, PhD, FACMG

Presenting Author Katrina Merrion, MS

Submitter Only J. Bryce Ortiz, PhD

Keywords

fetal placental discordance

false negative results

non-invasive prenatal testing

placental mosaicism

specimen identification discrepancy

NIPT screen failure

testing products of conception

genetic causes for pregnancy loss

SNP-based NIPT results

SNP-based chromosomal microarray analysis