Clinical experience and follow-up with large scale single-nucleotide polymorphism-based noninvasive prenatal aneuploidy testing

Pe'er Dar, Kirsten J. Curnow, Susan J. Gross, Megan P. Hall, Melissa Stosic, Zachary Demko, Bernhard Zimmermann, Matthew Hill, Styrmir Sigurjonsson, Allison Ryan, Milena Banjevic, Paula L. Kolacki, Susan W. Koch, Charles M. Strom, Matthew Rabinowitz, Peter Benn

Research output: Contribution to journalArticle

136 Citations (Scopus)

Abstract

Objective We sought to report on laboratory and clinical experience following 6 months of clinical implementation of a single-nucleotide polymorphism-based noninvasive prenatal aneuploidy test in high- and low-risk women. Study Design All samples received from March through September 2013 and drawn ≥9 weeks' gestation were included. Samples that passed quality control were analyzed for trisomy 21, trisomy 18, trisomy 13, and monosomy X. Results were reported as high or low risk for fetal aneuploidy for each interrogated chromosome. Relationships between fetal fraction and gestational age and maternal weight were analyzed. Follow-up on outcome was sought for a subset of high-risk cases. False-negative results were reported voluntarily by providers. Positive predictive value (PPV) was calculated from cases with an available prenatal or postnatal karyotype or clinical evaluation at birth. Results Samples were received from 31,030 patients, 30,705 met study criteria, and 28,739 passed quality-control metrics and received a report detailing aneuploidy risk. Fetal fraction correlated positively with gestational age, and negatively with maternal weight. In all, 507 patients received a high-risk result for any of the 4 tested conditions (324 trisomy 21, 82 trisomy 18, 41 trisomy 13, 61 monosomy X; including 1 double aneuploidy case). Within the 17,885 cases included in follow-up analysis, 356 were high risk, and outcome information revealed 184 (51.7%) true positives, 38 (10.7%) false positives, 19 (5.3%) with ultrasound findings suggestive of aneuploidy, 36 (10.1%) spontaneous abortions without karyotype confirmation, 22 (6.2%) terminations without karyotype confirmation, and 57 (16.0%) lost to follow-up. This yielded an 82.9% PPV for all aneuploidies, and a 90.9% PPV for trisomy 21. The overall PPV for women aged ≥35 years was similar to the PPV for women aged <35 years. Two patients were reported as false negatives. Conclusion The data from this large-scale report on clinical application of a commercially available noninvasive prenatal test suggest that the clinical performance of this single-nucleotide polymorphism-based noninvasive prenatal test in a mixed high- and low-risk population is consistent with performance in validation studies.

Original languageEnglish (US)
Pages (from-to)527.e1-527.e17
JournalAmerican Journal of Obstetrics and Gynecology
Volume211
Issue number5
DOIs
StatePublished - Nov 1 2014

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Aneuploidy
Single Nucleotide Polymorphism
Down Syndrome
Karyotype
Gestational Age
Turner Syndrome
Quality Control
Surrogate Mothers
Weights and Measures
Validation Studies
Lost to Follow-Up
Spontaneous Abortion
Chromosomes
Mothers
Parturition
Pregnancy

Keywords

  • low-risk
  • noninvasive prenatal testing
  • single-nucleotide polymorphism
  • trisomy 21

ASJC Scopus subject areas

  • Obstetrics and Gynecology
  • Medicine(all)

Cite this

Clinical experience and follow-up with large scale single-nucleotide polymorphism-based noninvasive prenatal aneuploidy testing. / Dar, Pe'er; Curnow, Kirsten J.; Gross, Susan J.; Hall, Megan P.; Stosic, Melissa; Demko, Zachary; Zimmermann, Bernhard; Hill, Matthew; Sigurjonsson, Styrmir; Ryan, Allison; Banjevic, Milena; Kolacki, Paula L.; Koch, Susan W.; Strom, Charles M.; Rabinowitz, Matthew; Benn, Peter.

In: American Journal of Obstetrics and Gynecology, Vol. 211, No. 5, 01.11.2014, p. 527.e1-527.e17.

Research output: Contribution to journalArticle

Dar, P, Curnow, KJ, Gross, SJ, Hall, MP, Stosic, M, Demko, Z, Zimmermann, B, Hill, M, Sigurjonsson, S, Ryan, A, Banjevic, M, Kolacki, PL, Koch, SW, Strom, CM, Rabinowitz, M & Benn, P 2014, 'Clinical experience and follow-up with large scale single-nucleotide polymorphism-based noninvasive prenatal aneuploidy testing', American Journal of Obstetrics and Gynecology, vol. 211, no. 5, pp. 527.e1-527.e17. https://doi.org/10.1016/j.ajog.2014.08.006
Dar, Pe'er ; Curnow, Kirsten J. ; Gross, Susan J. ; Hall, Megan P. ; Stosic, Melissa ; Demko, Zachary ; Zimmermann, Bernhard ; Hill, Matthew ; Sigurjonsson, Styrmir ; Ryan, Allison ; Banjevic, Milena ; Kolacki, Paula L. ; Koch, Susan W. ; Strom, Charles M. ; Rabinowitz, Matthew ; Benn, Peter. / Clinical experience and follow-up with large scale single-nucleotide polymorphism-based noninvasive prenatal aneuploidy testing. In: American Journal of Obstetrics and Gynecology. 2014 ; Vol. 211, No. 5. pp. 527.e1-527.e17.
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abstract = "Objective We sought to report on laboratory and clinical experience following 6 months of clinical implementation of a single-nucleotide polymorphism-based noninvasive prenatal aneuploidy test in high- and low-risk women. Study Design All samples received from March through September 2013 and drawn ≥9 weeks' gestation were included. Samples that passed quality control were analyzed for trisomy 21, trisomy 18, trisomy 13, and monosomy X. Results were reported as high or low risk for fetal aneuploidy for each interrogated chromosome. Relationships between fetal fraction and gestational age and maternal weight were analyzed. Follow-up on outcome was sought for a subset of high-risk cases. False-negative results were reported voluntarily by providers. Positive predictive value (PPV) was calculated from cases with an available prenatal or postnatal karyotype or clinical evaluation at birth. Results Samples were received from 31,030 patients, 30,705 met study criteria, and 28,739 passed quality-control metrics and received a report detailing aneuploidy risk. Fetal fraction correlated positively with gestational age, and negatively with maternal weight. In all, 507 patients received a high-risk result for any of the 4 tested conditions (324 trisomy 21, 82 trisomy 18, 41 trisomy 13, 61 monosomy X; including 1 double aneuploidy case). Within the 17,885 cases included in follow-up analysis, 356 were high risk, and outcome information revealed 184 (51.7{\%}) true positives, 38 (10.7{\%}) false positives, 19 (5.3{\%}) with ultrasound findings suggestive of aneuploidy, 36 (10.1{\%}) spontaneous abortions without karyotype confirmation, 22 (6.2{\%}) terminations without karyotype confirmation, and 57 (16.0{\%}) lost to follow-up. This yielded an 82.9{\%} PPV for all aneuploidies, and a 90.9{\%} PPV for trisomy 21. The overall PPV for women aged ≥35 years was similar to the PPV for women aged <35 years. Two patients were reported as false negatives. Conclusion The data from this large-scale report on clinical application of a commercially available noninvasive prenatal test suggest that the clinical performance of this single-nucleotide polymorphism-based noninvasive prenatal test in a mixed high- and low-risk population is consistent with performance in validation studies.",
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T1 - Clinical experience and follow-up with large scale single-nucleotide polymorphism-based noninvasive prenatal aneuploidy testing

AU - Dar, Pe'er

AU - Curnow, Kirsten J.

AU - Gross, Susan J.

AU - Hall, Megan P.

AU - Stosic, Melissa

AU - Demko, Zachary

AU - Zimmermann, Bernhard

AU - Hill, Matthew

AU - Sigurjonsson, Styrmir

AU - Ryan, Allison

AU - Banjevic, Milena

AU - Kolacki, Paula L.

AU - Koch, Susan W.

AU - Strom, Charles M.

AU - Rabinowitz, Matthew

AU - Benn, Peter

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N2 - Objective We sought to report on laboratory and clinical experience following 6 months of clinical implementation of a single-nucleotide polymorphism-based noninvasive prenatal aneuploidy test in high- and low-risk women. Study Design All samples received from March through September 2013 and drawn ≥9 weeks' gestation were included. Samples that passed quality control were analyzed for trisomy 21, trisomy 18, trisomy 13, and monosomy X. Results were reported as high or low risk for fetal aneuploidy for each interrogated chromosome. Relationships between fetal fraction and gestational age and maternal weight were analyzed. Follow-up on outcome was sought for a subset of high-risk cases. False-negative results were reported voluntarily by providers. Positive predictive value (PPV) was calculated from cases with an available prenatal or postnatal karyotype or clinical evaluation at birth. Results Samples were received from 31,030 patients, 30,705 met study criteria, and 28,739 passed quality-control metrics and received a report detailing aneuploidy risk. Fetal fraction correlated positively with gestational age, and negatively with maternal weight. In all, 507 patients received a high-risk result for any of the 4 tested conditions (324 trisomy 21, 82 trisomy 18, 41 trisomy 13, 61 monosomy X; including 1 double aneuploidy case). Within the 17,885 cases included in follow-up analysis, 356 were high risk, and outcome information revealed 184 (51.7%) true positives, 38 (10.7%) false positives, 19 (5.3%) with ultrasound findings suggestive of aneuploidy, 36 (10.1%) spontaneous abortions without karyotype confirmation, 22 (6.2%) terminations without karyotype confirmation, and 57 (16.0%) lost to follow-up. This yielded an 82.9% PPV for all aneuploidies, and a 90.9% PPV for trisomy 21. The overall PPV for women aged ≥35 years was similar to the PPV for women aged <35 years. Two patients were reported as false negatives. Conclusion The data from this large-scale report on clinical application of a commercially available noninvasive prenatal test suggest that the clinical performance of this single-nucleotide polymorphism-based noninvasive prenatal test in a mixed high- and low-risk population is consistent with performance in validation studies.

AB - Objective We sought to report on laboratory and clinical experience following 6 months of clinical implementation of a single-nucleotide polymorphism-based noninvasive prenatal aneuploidy test in high- and low-risk women. Study Design All samples received from March through September 2013 and drawn ≥9 weeks' gestation were included. Samples that passed quality control were analyzed for trisomy 21, trisomy 18, trisomy 13, and monosomy X. Results were reported as high or low risk for fetal aneuploidy for each interrogated chromosome. Relationships between fetal fraction and gestational age and maternal weight were analyzed. Follow-up on outcome was sought for a subset of high-risk cases. False-negative results were reported voluntarily by providers. Positive predictive value (PPV) was calculated from cases with an available prenatal or postnatal karyotype or clinical evaluation at birth. Results Samples were received from 31,030 patients, 30,705 met study criteria, and 28,739 passed quality-control metrics and received a report detailing aneuploidy risk. Fetal fraction correlated positively with gestational age, and negatively with maternal weight. In all, 507 patients received a high-risk result for any of the 4 tested conditions (324 trisomy 21, 82 trisomy 18, 41 trisomy 13, 61 monosomy X; including 1 double aneuploidy case). Within the 17,885 cases included in follow-up analysis, 356 were high risk, and outcome information revealed 184 (51.7%) true positives, 38 (10.7%) false positives, 19 (5.3%) with ultrasound findings suggestive of aneuploidy, 36 (10.1%) spontaneous abortions without karyotype confirmation, 22 (6.2%) terminations without karyotype confirmation, and 57 (16.0%) lost to follow-up. This yielded an 82.9% PPV for all aneuploidies, and a 90.9% PPV for trisomy 21. The overall PPV for women aged ≥35 years was similar to the PPV for women aged <35 years. Two patients were reported as false negatives. Conclusion The data from this large-scale report on clinical application of a commercially available noninvasive prenatal test suggest that the clinical performance of this single-nucleotide polymorphism-based noninvasive prenatal test in a mixed high- and low-risk population is consistent with performance in validation studies.

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KW - noninvasive prenatal testing

KW - single-nucleotide polymorphism

KW - trisomy 21

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