Non-Invasive Prenatal Testing (NIPT) in pregnancies with trisomy 21, 18 and 13 performed in a public setting – factors of importance for correct interpretation of results

Tanja S. Hartwig; Louise Ambye; Lene Werge; Martin Kenneth Weiergang; Pernille Nørgaard; Steen Sørensen; Finn Stener Jørgensen

doi:10.1016/j.ejogrb.2018.04.042

Non-Invasive Prenatal Testing (NIPT) in pregnancies with trisomy 21, 18 and 13 performed in a public setting – factors of importance for correct interpretation of results

Tanja S. Hartwig^*, Louise Ambye, Lene Werge, Martin Kenneth Weiergang, Pernille Nørgaard, Steen Sørensen, Finn Stener Jørgensen

^*Corresponding author for this work

Department of Clinical Medicine

13 Citations (Scopus)

Abstract

Objectives: We have established an open source platform for non-invasive prenatal testing (NIPT) based on massively parallel whole-genome sequencing in a public setting. The objective of this study was to investigate factors of importance for correct interpretation of NIPT results to ensure a high sensitivity and specificity. Study design: This investigation is a retrospective case-control study performed in a public NIPT center. The study included 108 aneuploid cases and 165 euploid controls. MPS was performed on circulating cell-free DNA in maternal blood. The pipeline included automated library preparation and sequencing on a HiSeq1500 (Illumina). The software programmes WISECONDOR and SeqFF were used for data analysis of aneuploidy status and fetal fraction of cell-free DNA, respectively. Lower limit of fetal fraction for aneuploidy testing was 0.02. Results: We identified four false negative aneuploidy cases of which two were explained by a vanishing twin. The number of no-call cases due to low fetal fraction was 8 out of 273 (2.9%). The sensitivity and specificity, when no-calls and vanished twins were excluded, were 100% and 99.5% for T21, 91% and 99.2% for T18, and 100% and 99.6% for T13. By multiple regression analysis we found a significant association between fetal fraction and gestational age, maternal BMI and ART treatment. Conclusion: With a non-commercial open source NIPT set-up having the same high test-performance as reported by large private laboratories, we show that fetal fraction, a vanishing twin, BMI, gestational age and ART treatment are important factors in the interpretation of NIPT results.

Original language	English
Journal	European Journal of Obstetrics Gynecology and Reproductive Biology
Volume	226
Pages (from-to)	35-39
Number of pages	5
ISSN	0301-2115
DOIs	https://doi.org/10.1016/j.ejogrb.2018.04.042
Publication status	Published - 2018

Keywords

Aneuploidy
Cell-free DNA
Non-Invasive prenatal testing
Prenatal diagnosis
Sensitivity and specificity

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10.1016/j.ejogrb.2018.04.042

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Hartwig, T. S., Ambye, L., Werge, L., Weiergang, M. K., Nørgaard, P., Sørensen, S., & Jørgensen, F. S. (2018). Non-Invasive Prenatal Testing (NIPT) in pregnancies with trisomy 21, 18 and 13 performed in a public setting – factors of importance for correct interpretation of results. European Journal of Obstetrics Gynecology and Reproductive Biology, 226, 35-39. https://doi.org/10.1016/j.ejogrb.2018.04.042

Non-Invasive Prenatal Testing (NIPT) in pregnancies with trisomy 21, 18 and 13 performed in a public setting – factors of importance for correct interpretation of results. / Hartwig, Tanja S.; Ambye, Louise; Werge, Lene et al.
In: European Journal of Obstetrics Gynecology and Reproductive Biology, Vol. 226, 2018, p. 35-39.

Research output: Contribution to journal › Journal article › Research › peer-review

Hartwig, TS, Ambye, L, Werge, L, Weiergang, MK, Nørgaard, P, Sørensen, S & Jørgensen, FS 2018, 'Non-Invasive Prenatal Testing (NIPT) in pregnancies with trisomy 21, 18 and 13 performed in a public setting – factors of importance for correct interpretation of results', European Journal of Obstetrics Gynecology and Reproductive Biology, vol. 226, pp. 35-39. https://doi.org/10.1016/j.ejogrb.2018.04.042

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abstract = "Objectives: We have established an open source platform for non-invasive prenatal testing (NIPT) based on massively parallel whole-genome sequencing in a public setting. The objective of this study was to investigate factors of importance for correct interpretation of NIPT results to ensure a high sensitivity and specificity. Study design: This investigation is a retrospective case-control study performed in a public NIPT center. The study included 108 aneuploid cases and 165 euploid controls. MPS was performed on circulating cell-free DNA in maternal blood. The pipeline included automated library preparation and sequencing on a HiSeq1500 (Illumina). The software programmes WISECONDOR and SeqFF were used for data analysis of aneuploidy status and fetal fraction of cell-free DNA, respectively. Lower limit of fetal fraction for aneuploidy testing was 0.02. Results: We identified four false negative aneuploidy cases of which two were explained by a vanishing twin. The number of no-call cases due to low fetal fraction was 8 out of 273 (2.9%). The sensitivity and specificity, when no-calls and vanished twins were excluded, were 100% and 99.5% for T21, 91% and 99.2% for T18, and 100% and 99.6% for T13. By multiple regression analysis we found a significant association between fetal fraction and gestational age, maternal BMI and ART treatment. Conclusion: With a non-commercial open source NIPT set-up having the same high test-performance as reported by large private laboratories, we show that fetal fraction, a vanishing twin, BMI, gestational age and ART treatment are important factors in the interpretation of NIPT results.",

keywords = "Aneuploidy, Cell-free DNA, Non-Invasive prenatal testing, Prenatal diagnosis, Sensitivity and specificity",

author = "Hartwig, {Tanja S.} and Louise Ambye and Lene Werge and Weiergang, {Martin Kenneth} and Pernille N{\o}rgaard and Steen S{\o}rensen and J{\o}rgensen, {Finn Stener}",

year = "2018",

doi = "10.1016/j.ejogrb.2018.04.042",

language = "English",

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AU - Hartwig, Tanja S.

AU - Ambye, Louise

AU - Werge, Lene

AU - Weiergang, Martin Kenneth

AU - Nørgaard, Pernille

AU - Sørensen, Steen

AU - Jørgensen, Finn Stener

PY - 2018

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N2 - Objectives: We have established an open source platform for non-invasive prenatal testing (NIPT) based on massively parallel whole-genome sequencing in a public setting. The objective of this study was to investigate factors of importance for correct interpretation of NIPT results to ensure a high sensitivity and specificity. Study design: This investigation is a retrospective case-control study performed in a public NIPT center. The study included 108 aneuploid cases and 165 euploid controls. MPS was performed on circulating cell-free DNA in maternal blood. The pipeline included automated library preparation and sequencing on a HiSeq1500 (Illumina). The software programmes WISECONDOR and SeqFF were used for data analysis of aneuploidy status and fetal fraction of cell-free DNA, respectively. Lower limit of fetal fraction for aneuploidy testing was 0.02. Results: We identified four false negative aneuploidy cases of which two were explained by a vanishing twin. The number of no-call cases due to low fetal fraction was 8 out of 273 (2.9%). The sensitivity and specificity, when no-calls and vanished twins were excluded, were 100% and 99.5% for T21, 91% and 99.2% for T18, and 100% and 99.6% for T13. By multiple regression analysis we found a significant association between fetal fraction and gestational age, maternal BMI and ART treatment. Conclusion: With a non-commercial open source NIPT set-up having the same high test-performance as reported by large private laboratories, we show that fetal fraction, a vanishing twin, BMI, gestational age and ART treatment are important factors in the interpretation of NIPT results.

AB - Objectives: We have established an open source platform for non-invasive prenatal testing (NIPT) based on massively parallel whole-genome sequencing in a public setting. The objective of this study was to investigate factors of importance for correct interpretation of NIPT results to ensure a high sensitivity and specificity. Study design: This investigation is a retrospective case-control study performed in a public NIPT center. The study included 108 aneuploid cases and 165 euploid controls. MPS was performed on circulating cell-free DNA in maternal blood. The pipeline included automated library preparation and sequencing on a HiSeq1500 (Illumina). The software programmes WISECONDOR and SeqFF were used for data analysis of aneuploidy status and fetal fraction of cell-free DNA, respectively. Lower limit of fetal fraction for aneuploidy testing was 0.02. Results: We identified four false negative aneuploidy cases of which two were explained by a vanishing twin. The number of no-call cases due to low fetal fraction was 8 out of 273 (2.9%). The sensitivity and specificity, when no-calls and vanished twins were excluded, were 100% and 99.5% for T21, 91% and 99.2% for T18, and 100% and 99.6% for T13. By multiple regression analysis we found a significant association between fetal fraction and gestational age, maternal BMI and ART treatment. Conclusion: With a non-commercial open source NIPT set-up having the same high test-performance as reported by large private laboratories, we show that fetal fraction, a vanishing twin, BMI, gestational age and ART treatment are important factors in the interpretation of NIPT results.

KW - Aneuploidy

KW - Cell-free DNA

KW - Non-Invasive prenatal testing

KW - Prenatal diagnosis

KW - Sensitivity and specificity

U2 - 10.1016/j.ejogrb.2018.04.042

DO - 10.1016/j.ejogrb.2018.04.042

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SN - 0301-2115

VL - 226

SP - 35

EP - 39

JO - European Journal of Obstetrics Gynecology and Reproductive Biology

JF - European Journal of Obstetrics Gynecology and Reproductive Biology

ER -

Non-Invasive Prenatal Testing (NIPT) in pregnancies with trisomy 21, 18 and 13 performed in a public setting – factors of importance for correct interpretation of results

Abstract

Keywords

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