Comment on “The importance of determining the limit of detection of non‐invasive prenatal testing methods”

Lüthgens, Kai; Binder, Andreas; Biskup, Dirk

doi:10.1002/pd.4854

Cited by 2 publications

(1 citation statement)

References 11 publications

(11 reference statements)

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“…Others have shown that reducing the cut‐off for FF from 4% to 2%, using their specific NIPT approach rather than a theoretically determined fixed FF cut‐off, a sixfold increased incidence of aneuploidy was observed in samples with 2% < FF < 4% versus samples with FF > 4% . However, as replied by Lüthgens et al , the included cohort described previously consists of only 25 aneuploidy cases with an FF below 4%, which is not enough to generate a robust validation study for the limit of detection.…”

Section: Fetal Fractionmentioning

confidence: 99%

Discordant non-invasive prenatal testing (NIPT) - a systematic review

et al. 2017

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With a high sensitivity and specificity, non-invasive prenatal testing (NIPT) is an incomparable screening test for fetal aneuploidy. However, the method is rather newly introduced, and experiences with discordant results are few. We did a systematic review of literature reporting details of false positive and false negative NIPT results. Discordant sex chromosome results were not included. We identified 22 studies reporting case details. In total, 206 discordant cases were included, of which 88% were false positive and 12% false negative. Details on maternal age, gestational age, platform/company, Z-score, fetal fraction, results and explanation were specified. The main reasons for discordant results were confined placental mosaicism, maternal copy number variation, vanished twin, maternal cancer and true fetal mosaicism. A very high percentage of cases (67%) were reported with no obvious biological or technical explanation for the discordant result. The included cases represent only a minor part of the true number of false positive or false negative NIPT cases identified in fetal medicine clinics around the world. To ensure knowledge exchange and transparency of NIPT between laboratories, we suggest a systematic recording of discordant NIPT results, as well as a quality assurance by external quality control and accreditation. © 2017 John Wiley & Sons, Ltd.

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Section: Fetal Fractionmentioning

confidence: 99%

Discordant non-invasive prenatal testing (NIPT) - a systematic review

et al. 2017

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Chromosomal phase improves aneuploidy detection in non-invasive prenatal testing at low fetal DNA fractions

Mello

Loh

Handsaker

et al. 2022

Sci Rep

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Non-invasive prenatal testing (NIPT) to detect fetal aneuploidy by sequencing the cell-free DNA (cfDNA) in maternal plasma is being broadly adopted. To detect fetal aneuploidies from maternal plasma, where fetal DNA is mixed with far-larger amounts of maternal DNA, NIPT requires a minimum fraction of the circulating cfDNA to be of placental origin, a level which is usually attained beginning at 10 weeks gestational age. We present an approach that leverages the arrangement of alleles along homologous chromosomes—also known as chromosomal phase—to make NIPT analyses more conclusive. We validate our approach with in silico simulations, then re-analyze data from a pregnant mother who, due to a fetal DNA fraction of 3.4%, received an inconclusive aneuploidy determination through NIPT. We find that the presence of a trisomy 18 fetus can be conclusively inferred from the patient’s same molecular data when chromosomal phase is incorporated into the analysis. Key to the effectiveness of our approach is the ability of homologous chromosomes to act as natural controls for each other and the ability of chromosomal phase to integrate subtle quantitative signals across very many sequence variants. These results show that chromosomal phase increases the sensitivity of a common laboratory test, an idea that could also advance cfDNA analyses for cancer detection.

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Comment on “The importance of determining the limit of detection of non‐invasive prenatal testing methods”

Cited by 2 publications

References 11 publications

Discordant non-invasive prenatal testing (NIPT) - a systematic review

Discordant non-invasive prenatal testing (NIPT) - a systematic review

Chromosomal phase improves aneuploidy detection in non-invasive prenatal testing at low fetal DNA fractions

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