2018 ISPD Conference

Evaluating individual laboratory performance for cffDNA NIPT for aneuploidies: report of the first international external quality assessment
Zandra Deans1, Farrah Khawaja1, Ros Hastings2, Katrina Rack2, Simon Patton3, Weronika Gutowska-Ding33, Lucy Jenkins4, Stephanie Allen5, Lyn Chitty6, Erik Sistermans7

1UK NEQAS for Molecular Genetics, Edinburgh, United Kingdom
2CEQAS, Oxford, United Kingdom
3EMQN, Manchester, United Kingdom
4NE Thames Regional Genetics Laboratory, London, United Kingdom
5Birmingham Women's NHS Foundation Trust, Birmingham, United Kingdom
6Genetics and Genomic Medicine, UCL Great Ormond Street Institute of Child Health and North-East Thames Regional Genetics Service, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK, London, london, United Kingdom
7Free University Medical Center, Amsterdam, Netherlands
Objectives
To deliver and maintain high standards for laboratory testing independent external quality assessment (EQA) is required. This provides important information for clinicians, laboratories and patients, demonstrating that accurate testing is being performed and reported. Providing an EQA for cell free fetal DNA (cffDNA) testing is challenging as sample acquisition (availability and scalability) is a limiting factor. We have previously reported the EQA to assess standards of reporting non-invasive prenatal testing (NIPT) for fetal aneuploidy. Here we describe the delivery and results of a large international pilot EQA for laboratory NIPT for aneuploidy using maternal plasma samples.
Methods
Eighty-six maternal plasma samples (10ml – 16ml) from pregnancies with known outcomes (low risk/high risk for trisomy 13,18 or 21) were obtained from the RAPID sample bank. All were double spun within 8 hours of blood draw, aliquoted and stored at -80oC. Three EQA providers (CEQAS, EMQN, and UK NEQAS for Molecular Genetics) delivered the pilot assessing the standard of testing and reporting of NIPT of maternal plasma for fetal aneuploidy. Maternal plasma (4ml) with clinical scenarios were distributed to participating laboratories to perform NIPT and submit reports. These submissions assessed and feedback provided for genotyping, interpretation and clerical accuracy.
Results
Ninety-five laboratories from 30 different countries participated. The use of maternal plasma allowed any testing methods to be applied. Case 1 was a referral following routine antenatal screening with a low risk for trisomy 13, 18 and 21. Case 2 was a confirmatory test for a high risk trisomy 21 result. Two critical errors were reported, one false positive for case 1 and an incorrect high risk trisomy 18 for case 2. Reports lacked details of methods performed and associated limitations, and many embedded important information within the body of the text making it difficult to identify key clinical recommendations.
Conclusions
The growing international demand for participation demonstrates the clinical need for an independent evaluation of NIPT practice. This pilot EQA has demonstrated that the use of real maternal samples distributed at ambient temperature has enabled global participation with very low sample failure rate (2%). The genotyping accuracy was good but review of the large number of reports submitted highlighted the need for further standardisation and guidance on NIPT reporting.