87: noninvasive prenatal testing: 100,000 patients–clinical impact
TRANSCRIPT
Poster Session I www.AJOG.org
Thursday, February 6, 2014 d 10:00 am e 12:00 pm d Hilton Exhibition Center
ULTRASOUND, FETUS, GENETICS
Abstracts 87 e 236
87
Noninvasive prenatal testing: 100,000 patientseclinicalimpactRon McCullough1, Eyad Almasri1, Xiaojun Guan1, Paul Oeth1,Allan Bombard1, Juan-Sebastian Saldivar11Sequenom Center For Molecular Medicine, San Diego, CAOBJECTIVE: As the first laboratory to offer massively parallelsequencing-based NIPT for aneuploidies we have been able to collectthe largest clinical population experience data to date, including>100,000 clinical samples from all 50 states, including 13 interna-tional countries. The objective of this study is to give a robust clinicalpicture of the current laboratory performance of the MaterniT21PLUS LDT.STUDY DESIGN: Data contained within this study were generated inour CLIA-licensed, CAP-accredited laboratory between August 2012to June 2013 in patients with high-risk pregnancies. Samples wereassessed for trisomies 13, 18, 21 and for the presence of chromosomeY-specific DNA. Samples received between February and June 2013were also tested for allosome aneuploidies 46,X; 47,XXY; 47, XYY;and 47,XXX.RESULTS: NIPT patients most commonly undergo testing at anaverage of 15 weeks and 3 days gestation; are 35.1 years of age at thetime of testing. The positivity rate for 47,+21 was 1.51%. This wasfollowed by 0.45% and 0.21% rate for 47,+18 and 47,+13, respec-tively. NIPT positivity rates are similar to previous large clinicalstudies of aneuploidy rates in women of maternal age � 35 under-going amniocentesis. 11,300 samples were identified as high-risk byserum biochemical screening. Of these, the positivity rate by NIPTwas only 2.3%, giving a 96.0% false positive rate for serumscreening. Additionally, 3519 patients had multifetal gestations(3.5%); of these, only 92 had positive NIPT results, potentiallyreducing (in twins) the number of invasive procedures by 97.4%(7038 to 184).CONCLUSION: Although NIPT has only been commercially offered for2+ years, the clinical impact for both patient and clinician has beendramatic. The risks associated with invasive testing have beenreduced by providing another important assessment of aneuploidystatus in the high risk population. The accuracy and positivity rateare as predicted by clinical validations and the test demonstratesimprovement over the current standards of care.
Positive results for patients maternal age� 35 years
S58 American Journal of Obstetrics & Gynecology Supplement to JANUARY 2
88
A Bayesian model demonstrating the positive andnegative predictive values and screening limitations of cellfree fetal DNA (CFF)Thomas Westover1, Corey Westover1, Richard Fischer11Cooper Medical School Rowan University, Dept Obgyn Division MaternalFetal Medicine, Camden, NJOBJECTIVE: Recent literature suggests that aneuploidy screening usingCFF has a higher sensitivity (sens) and specificity (spec) thantraditional age-based and ultrasound/serum-based methods. Thepurpose of this study was to use Bayesian analysis to demonstrate thepositive predictive value (PPV) and negative predictive value (NPV)of CFF testing under varying hypothetical test characteristics andacross varied pretest prevalence rates.STUDY DESIGN: We used Bayesian analysis to calculate the PPV andNPV of fetal trisomy at various pretest prevalence (prev) rates whileartificially varying the sensitivity and specificity. PPV was calculatedusing the formula PPV ¼ [(sens)(prev)] divided by [(sens)(prev) +(1-spec)(1-prev)]. NPV ¼ [(spec)(1-prev)] divided by [(spec)(1-prev) + (1-sens)(prev)]. We first fixed the sens at 99% and varied thespec from 95% to 99.9% in order to calculate the PPV’s and NPV’s atpretest prevalence rates ranging from 1 in 10,000 to 1 in 50. We thenfixed the spec at 99% and varied the sens from 95% to 99.9% tocalculate the PPV’s and NPV’s at the same pretest prevalence rates.RESULTS: The initial columns in the attached results table show thePPV’s and NPV’s of a positive or negative CFF test at a fixedsensitivity of 99% and variable specificities. The subsequent columnsshow the PPV’s and NPV’s of a positive or negative CFF test at afixed spec of 99% and variable sensitivities. Depending on the aprioriprevalence and the test characteristics, the PPV’s ranged from 1 in1.05 to 1 in 506. The NPV’s demonstrated a much wider range from1 in 971 to 1 in 9,989,011.CONCLUSION: We used Bayesian modeling to calculate the PPV’s andNPV’s of CFF testing under varying pretest prevalence rates andvarying test characteristics. The results demonstrate that CFF testingretains the characteristics of a screening test and not a diagnostictest. The limitations of CFF testing should be recognized by clini-cians and patients during genetic counseling.
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