Quality Assurance of Non-Invasive Prenatal Screening (NIPS) for Fetal Aneuploidy Using Positive Predictive Values as Outcome Measures.

Wendy Dinonno,Dianne Keen-Kim,Kimberly Martin,Paul Billings,Peter Benn,Melissa Egbert,Susan Zneimer,Zachary Demko

doi:10.3390/jcm8091311

Abstract

Non-invasive prenatal screening (NIPS) based on the analysis of cell-free DNA in maternal plasma has been shown to have high sensitivity and specificity. We gathered follow-up information for pregnancies in women with test-positive NIPS results from 2014–2017 with quarterly assessments of positive predictive values (PPVs). A non-inferiority analysis with a minimum requirement of 70%/80% of expected performance for trisomy 21 and 18 was used to ensure testing met expectations. PPVs were evaluated in the context of changes in the population receiving testing. For all quarters, PPVs for trisomies 21 and 18 exceeded the requirement of > 70% of the reference PPV. Overall observed PPVs for trisomy 21, 18, 13 and monosomy X were similar for women aged <35 (90.9%, 95% Confidence Interval (CI) 88.6–92.7%) compared to women with advanced maternal age (94.5%, 95% CI 93.1–95.6%). Despite significant declines in test-positive rates from 1.18% to 0.62% for trisomy 21, and from 0.75% to 0.48% for trisomies 18, 13 and monosomy X combined, PPVs remained stable through the four-year interval. We conclude that quarterly evaluation of PPV provides an overview of past testing and helps demonstrate long-term consistency in test performance, even in the setting of increasing use by women with lower a priori risks.

Highlights

Non-invasive prenatal screening (NIPS) for fetal chromosomal abnormalities is clinically available from many laboratories around the world [1]
NIPS is high-complexity, multi-component testing where the distinction between affected and unaffected cases relies on recognizing relatively minor differences in DNA patterns. It is incumbent on the provider laboratories to clearly demonstrate adequate test performance both prior to launch and after the test is clinically available through ongoing quality assurance processes
We present summary statistical measures of test performance based on positive predictive values (PPVs) and show how this can be used in quality assessment

Summary

Introduction

Non-invasive prenatal screening (NIPS) for fetal chromosomal abnormalities is clinically available from many laboratories around the world [1]. Initial proof-of-principle studies, clinical trials, and some clinical experience reports have documented high sensitivity and specificity of the testing, relative to traditional fetal aneuploidy screening [2,3]. NIPS is high-complexity, multi-component testing where the distinction between affected and unaffected cases relies on recognizing relatively minor differences in DNA patterns. It is incumbent on the provider laboratories to clearly demonstrate adequate test performance both prior to launch and after the test is clinically available through ongoing quality assurance processes.

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