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

Hartwig, Tanja Schlaikjær; Ambye, Louise; Sørensen, Steen; Jørgensen, Finn Stener

doi:10.1002/pd.5049

Cited by 197 publications

(194 citation statements)

References 61 publications

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“…Using cell‐free placental DNA in maternal blood, which is suspected to originate from placental trophoblast cells, to estimate the risk of aneuploidy in the fetus itself has introduced new challenges in the interpretation of this prenatal screening test. Results of analysis of cell‐free placental DNA may be comparable with those from chromosome analysis after short term culture, which could explain some of the false positive results . Also, when offering noninvasive techniques without prior cFTS, it is possible that even a very low frequency of trisomic cells will be disclosed in some placentas, thereby identifying chromosomal mosaicism that would not have been identified using the previous techniques.…”

Section: Discussionmentioning

confidence: 99%

Prognosis for pregnancies with trisomy 16 confined to the placenta: A Danish cohort study

et al. 2018

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Objective To evaluate the risk of adverse pregnancy outcome when trisomy 16 confined to the placenta is diagnosed and to identify possible prognostic markers for adverse outcomes in these pregnancies. Method Registered cases (n = 49) of trisomy 16 diagnosed prenatally in Denmark from 1990 to 2013 were included. Results Twenty‐five of the pregnancies intended to be continued had confined placental trisomy 16 mosaicism (CPM16). Adverse pregnancy outcome was seen in 17 CPM16 pregnancies (68%), ranging from mild small for gestational age (SGA) to fetal malformations and intrauterine demise. For cases ascertained by combined first trimester screening, the median concentration of pregnancy associated plasma protein A (PAPP‐A) was 0.17 MoM (IQR: 0.11 MoM). Adverse pregnancy outcome showed a trend toward an association with a high frequency of trisomic cells. Eight children (32%) were born at term with a normal birth weight and no malformations. Conclusion The risk of adverse pregnancy outcome in case of CPM16 is correlated to ascertainment by combined first trimester screening and tends to be associated with a high frequency of trisomic cells in the placenta. We recommend that variables including ascertainment, the frequency of trisomic cells, and the maternal serum concentration of PAPP‐A are taken into consideration when evaluating the prognosis in CPM16 while acknowledging that these factors are strongly correlated.

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Section: Discussionmentioning

confidence: 99%

Prognosis for pregnancies with trisomy 16 confined to the placenta: A Danish cohort study

et al. 2018

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“…The current NIPT methodology thus relies on identifying a chromosomal abnormality in an amalgamation of maternal and fetal DNA fragments, which can lead to false positive results, and its performance can be affected by a below average fetal fraction (<4%). cfDNA‐based NIPT is also potentially influenced by maternal chromosomal mosaicism or maternal malignancies . It thus remains a screening test requiring diagnostic testing for confirmation of positive results.…”

Section: Introductionmentioning

confidence: 99%

Reliable detection of subchromosomal deletions and duplications using cell‐based noninvasive prenatal testing

et al. 2018

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Objective To gather additional data on the ability to detect subchromosomal abnormalities of various sizes in single fetal cells isolated from maternal blood, using low‐coverage shotgun next‐generation sequencing for cell‐based noninvasive prenatal testing (NIPT). Method Fetal trophoblasts were recovered from approximately 30 mL of maternal blood using maternal white blood cell depletion, density‐based cell separation, immunofluorescence staining, and high‐resolution scanning. These trophoblastic cells were picked as single cells and underwent whole genome amplification for subsequent genome‐wide copy number analysis and genotyping to confirm the fetal origin of the cells. Results Applying our fetal cell isolation method to a series of 125 maternal blood samples, we detected on average 4.17 putative fetal cells/sample. The series included 15 cases with clinically diagnosed fetal aneuploidies and five cases with subchromosomal abnormalities. This method was capable of detecting findings that were 1 to 2 Mb in size, and all were concordant with the microarray or karyotype data obtained on a fetal sample. A minority of fetal cells showed evidence of genome degradation likely related to apoptosis. Conclusion We demonstrate that this cell‐based NIPT method has the capacity to reliably diagnose fetal chromosomal abnormalities down to 1 to 2 Mb in size.

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“…Cumulatively, NIPT has an approximately 1% false‐positive rate, one‐third of which has a biological explanation such as maternal copy number variant, maternal mosaicism, maternal malignancy, confined placental mosaicism, fetal mosaicism or a vanishing twin. The rate of vanishing twin pregnancy detected by NIPT ranges from 0.42 to 0.6%.…”

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confidence: 99%