Secondary non-invasive prenatal screening for fetal trisomy: an effectiveness study in a public health setting

To evaluate the effectiveness of secondary screening using non-invasive prenatal testing (NIPT) in a routine NHS setting including test performance, turn-around times (TATs) and no-call (failure to obtain result) rates. To examine the influence of maternal and fetal characteristics on test performance.

Retrospective cohort.

London teaching hospital.

A total of 8651 pregnancies undergoing screening for fetal trisomy using NIPT provided by an NHS cell-free DNA screening laboratory - the SAFE laboratory.

Screening test evaluation and TATs. Univariate and multivariate logistic regression analysis to identify significant predictors of no-call results and reported by low fetal fraction (<2%), very high fetal fraction (>40%) and processing failure.

Test performance, TATs and no-call rates, factors affecting no-call results.

Average TAT was 4.0 days (95% CI 4.0-4.2 days). Test sensitivities for trisomies 21 and 13/18 were 98.9% (95% CI 95.9-99.9%) and 90.4% (95% CI 80.0-96.8%), respectively. The overall no-call rate was 32/8651 (0.37%, 95% CI 0.26-0.52%). The overall risk of a no-call result was influenced by gestational age, dichorionic twin pregnancy, history of malignancy and pregnancies affected by trisomy 13/18, but not by maternal weight or use of low-molecular-weight heparin.

High-throughput NIPT can be effectively embedded into a public health NHS setting. TATs of 4 days and no-calls of <0.5% were well within clinically desirable tolerances. Gestational age, maternal weight, assisted reproductive techniques, use of low-molecular-weight heparin and past history of malignancy did not have major impacts on test no-call rates and should not constitute reasons for withholding the option of NIPT from women.

Turn-around times of 4 days, no-call (test failure) rates of 0.37% and highly accurate NIPT can be successfully embedded in the NHS.