Non-invasive prenatal testing for fetal aneuploidy by genome-wide massively parallel sequencing, a clinical outcome study

Abstract

OBJECTIVE
To provide clinical follow-up on non-invasive prenatal testing (NIPT) for detecting fetal aneuploidy by genome-wide massively parallel sequencing.

METHODS
A retrospective study was carried out on 4,435 cases of NIPT, performed between 1 November 2014 and 31 December 2016, in the Centre of Medical Genetics of UZ Brussel, in very close collaboration with the ULB Erasme Centre of Human Genetics. Test results were confirmed by postnatal clinical outcome and/or invasive diagnostic testing. In case of test failure, we assessed the impact of a variety of factors on the success rate of repeat sampling. We searched for unknown factors attributing to test failure by reviewing the patient's medical history.

RESULTS
A negative screening result was obtained in 4,279 cases (96.48%). No false negative results for trisomy 21, 18 and 13 were reported in a subgroup of 606 patients with follow-up pregnancy outcome. In 95 cases (2.14%), NIPT resulted in a positive screening result, including 47 high risk results for common fetal aneuploidy (41 trisomy 21, four trisomy 18 and two trisomy 13 cases) and 48 high risk results for other chromosomal abnormalities. Contributing factors to false positive results, confined placental mosaicism, vanishing twin or maternal CNV, were identified. The overall sensitivity of NIPT was 100% for trisomies 21, 18 and 13 and specificity was 99.34%, 99.84% and 99.84%, for trisomy 21, 18 and 13, respectively.
Ultimately, 61 cases (1.38%) were classified as test failure, for which low fetal fraction was the main reason. We describe an influence on test failure of specific maternal conditions, including obesity, low molecular weight heparin treatment and hypothyroidism.

CONCLUSION
NIPT is a highly accurate screening test for fetal aneuploidy. Confirmatory invasive testing is still necessary before pregnancy termination, since false positive results are possible, especially when other chromosomal abnormalities are detected. Determining fetal fraction remains important in order to prevent false negative results.

Date of Award	19 Jun 2017
Original language	English
Awarding Institution	Vrije Universiteit Brussel