Obesity increases the risk of failure of noninvasive prenatal screening regardless of gestational age

Yared, Edom; Dinsmoor, Mara J.; Endres, Loraine; Berg, Melissa J. Vanden; Hoell, Christin; Lapin, Brittany; Plunkett, Beth A.

doi:10.1016/j.ajog.2016.03.018

Cited by 27 publications

(30 citation statements)

References 25 publications

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“…Among patients initially receiving a “no‐call” by the SNP method, approximately 42% will submit a redraw and receive a result (Figure a) . Subsequently, the rate of invasive procedures among remaining patients will determine the proportion of aneuploidies that are detected (we assume that redraws and invasive testing are 100% sensitive to establish an upper limit on the detection rate).…”

Section: Resultsmentioning

confidence: 99%

“…Our model demonstrates that while setting a minimum fetal fraction threshold may help to maintain high per‐patient analytical sensitivity, it may ultimately prove to be counter‐productive. Based upon published clinical data, the probability of detecting a trisomy 21 case after an initial “no‐call” using the SNP method is only ~74% (Figure b).…”

Section: Discussionmentioning

confidence: 99%

“…This is potentially due to T21 samples showing slightly elevated fetal fractions relative to disomic pregnancies, while those of T18—and in some cases T13—have reportedly lower fetal fractions . In addition, fetal fraction is negatively correlated with maternal weight, further illustrating the importance of maximizing detection performance in low fetal fraction samples . Other factors that reduce clinical sensitivity, such as sample contamination and confined placental mosaicism, should impact all NIPS methods as currently practiced …”

Section: Discussionmentioning

confidence: 99%

“…A key concern has been how these methods perform on the minority of patients with low abundance of circulating fetal DNA (i.e., low fetal fraction samples), where separating signal from noise becomes challenging . Low fetal fraction is associated with high maternal body‐mass index and certain fetal aneuploidies . In order to maintain high per‐patient sensitivity, some tests avoid reporting results to patients with fetal fractions below a preset threshold, referred to as a “no‐call” result.…”

Section: Introductionmentioning

confidence: 99%

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Noninvasive prenatal screening at low fetal fraction: comparing whole-genome sequencing and single-nucleotide polymorphism methods

Artieri¹,

Haverty²,

Evans³

et al. 2017

Prenat Diagn

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Objective Performance of noninvasive prenatal screening (NIPS) methodologies when applied to low fetal fraction samples is not well established. The single-nucleotide polymorphism (SNP) method fails samples below a predetermined fetal fraction threshold, whereas some laboratories employing the whole-genome sequencing (WGS) method report aneuploidy calls for all samples. Here, the performance of the two methods was compared to determine which approach actually detects more fetal aneuploidies.Methods Computational models were parameterized with up-to-date published data and used to compare the performance of the two methods at calling common fetal trisomies (T21, T18, T13) at low fetal fractions. Furthermore, clinical experience data were reviewed to determine aneuploidy detection rates based on compliance with recent invasive screening recommendations. ResultsThe SNP method's performance is dependent on the origin of the trisomy, and is lowest for the most common trisomies (maternal M1 nondisjunction). Consequently, the SNP method cannot maintain acceptable performance at fetal fractions below~3%. In contrast, the WGS method maintains high specificity independent of fetal fraction and has >80% sensitivity for trisomies in low fetal fraction samples. ConclusionThe WGS method will detect more aneuploidies below the fetal fraction threshold at which many labs issue a no-call result, avoiding unnecessary invasive procedures.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Noninvasive prenatal screening at low fetal fraction: comparing whole-genome sequencing and single-nucleotide polymorphism methods

Artieri¹,

Haverty²,

Evans³

et al. 2017

Prenat Diagn

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“…Thus, increasing BMI and obesity are correlated with an increased risk of a failed cffNIPT result. Yared et al [7] suggested a failure rate of 24.3% among obese women (BMI ≥30) compared with 3.7% in nonobese women. Consequently, there are limitations in the use of NIPT technology in the population of obese pregnant women.…”

Section: Introductionmentioning

confidence: 99%

Does Maternal Body Mass Index Affect the Quantity of Circulating Fetal Cells Available to Use for Cell-Based Noninvasive Prenatal Test in High-Risk Pregnancies?

Kruckow¹,

Schelde²,

Hatt³

et al. 2018

Fetal Diagn Ther

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We present the first study that investigates the effect of maternal body mass index (BMI) on the quantity of circulating fetal cells available to use in cell-based noninvasive prenatal test (cbNIPT). cbNIPT has been proposed as a superior alternative to noninvasive prenatal test from cell-free fetal DNA. Kølvraa et al. [Prenat Diagn. 2016 Dec; 36(12): 1127–34] established that cbNIPT can be performed on as few as one fetal cell, and Vestergaard et al. [Prenat Diagn. 2017 Nov; 37(11): 1120–4] demonstrated that these fetal trophoblast cells could be used successfully in cbNIPT to detect chromosomal and sub-chromosomal abnormalities. This study on 91 pregnant women with high-risk pregnancies suggests that cbNIPT should not be hampered by an increased BMI because every pregnancy, irrespective of the BMI, has rendered fetal cells for downstream genetic analysis. The mean number of fetal cells per sample was 12.6, with a range of 1–43 cells in one sample. ANOVA showed that increasing maternal BMI tends to decrease the number of fetal cells, but not significantly.

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Enrichment of fetal and maternal long cell‐free DNA fragments from maternal plasma following DNA repair

et al. 2019

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Objective Cell‐free DNA (cfDNA) fragments in maternal plasma contain DNA damage and may negatively impact the sensitivity of noninvasive prenatal testing (NIPT). However, some of these DNA damages are potentially reparable. We aimed to recover these damaged cfDNA molecules using PreCR DNA repair mix. Methods cfDNA was extracted from 20 maternal plasma samples and was repaired and sequenced by the Illumina platform. Size profiles and fetal DNA fraction changes of repaired samples were characterized. Targeted sequencing of chromosome Y sequences was used to enrich fetal cfDNA molecules following repair. Single‐molecule real‐time (SMRT) sequencing platform was employed to characterize long (>250 bp) cfDNA molecules. NIPT of five trisomy 21 samples was performed. Results Size profiles of repaired libraries were altered, with significantly increased long (>250 bp) cfDNA molecules. Single nucleotide polymorphism (SNP)‐based analyses showed that both fetal‐ and maternal‐derived cfDNA molecules were enriched by the repair. Fetal DNA fractions in maternal plasma showed a small but consistent (4.8%) increase, which were contributed by a higher increment of long fetal cfDNA molecules. z ‐score values were improved in NIPT of all trisomy 21 samples. Conclusion Plasma DNA repair recovers and enriches long cfDNA molecules of both fetal and maternal origins in maternal plasma.

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Obesity increases the risk of failure of noninvasive prenatal screening regardless of gestational age

Cited by 27 publications

References 25 publications

Noninvasive prenatal screening at low fetal fraction: comparing whole-genome sequencing and single-nucleotide polymorphism methods

Noninvasive prenatal screening at low fetal fraction: comparing whole-genome sequencing and single-nucleotide polymorphism methods

Does Maternal Body Mass Index Affect the Quantity of Circulating Fetal Cells Available to Use for Cell-Based Noninvasive Prenatal Test in High-Risk Pregnancies?

Enrichment of fetal and maternal long cell‐free DNA fragments from maternal plasma following DNA repair

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