Uptake, outcomes, and costs of implementing non-invasive prenatal testing for Down’s syndrome into NHS maternity care: prospective cohort study in eight diverse maternity units

Abstract

Objective To investigate the benefits and costs of implementing non-invasive prenatal testing (NIPT) for Down’s syndrome into the NHS maternity care pathway.Design Prospective cohort study.Setting Eight maternity units across the United Kingdom between 1 November 2013 and 28 February 2015.Participants All pregnant women with a current Down’s syndrome risk on screening of at least 1/1000.Main outcome measures Outcomes were uptake of NIPT, number of cases of Down’s syndrome detected, invasive tests performed, and miscarriages avoided. Pregnancy outcomes and costs associated with implementation of NIPT, compared with current screening, were determined using study data on NIPT uptake and invasive testing in combination with national datasets.Results NIPT was prospectively offered to 3175 pregnant women. In 934 women with a Down’s syndrome risk greater than 1/150, 695 (74.4%) chose NIPT, 166 (17.8%) chose invasive testing, and 73 (7.8%) declined further testing. Of 2241 women with risks between 1/151 and 1/1000, 1799 (80.3%) chose NIPT. Of 71 pregnancies with a confirmed diagnosis of Down’s syndrome, 13/42 (31%) with the diagnosis after NIPT and 2/29 (7%) after direct invasive testing continued, resulting in 12 live births. In an annual screening population of 698 500, offering NIPT as a contingent test to women with a Down’s syndrome screening risk of at least 1/150 would increase detection by 195 (95% uncertainty interval −34 to 480) cases with 3368 (2279 to 4027) fewer invasive tests and 17 (7 to 30) fewer procedure related miscarriages, for a non-significant difference in total costs (£−46 000, £−1 802 000 to £2 661 000). The marginal cost of NIPT testing strategies versus current screening is very sensitive to NIPT costs; at a screening threshold of 1/150, NIPT would be cheaper than current screening if it cost less than £256. Lowering the risk threshold increases the number of Down’s syndrome cases detected and overall costs, while maintaining the reduction in invasive tests and procedure related miscarriages.Conclusions Implementation of NIPT as a contingent test within a public sector Down’s syndrome screening programme can improve quality of care, choices for women, and overall performance within the current budget. As some women use NIPT for information only, the Down’s syndrome live birth rate may not change significantly. Future research should consider NIPT uptake and informed decision making outside of a research setting.

Trial by Dutch laboratories for evaluation of non‐invasive prenatal testing. Part II—women's perspectives

“…Results from two questionnaire studies also showed that NIPT will probably be used more readily in women who just want to prepare themselves 24, 25. In a UK study, where women were offered NIPT as a second screening test through the National Health Service (NHS), 31% (13/42) of women with a confirmed diagnosis of Down syndrome after NIPT continued the pregnancy, compared to 7% (2/29) after direct invasive testing 26. It needs to be established if this remains true once NIPT is fully incorporated in prenatal care.…”

Response to Wald et al

“…NIPS has previously been shown to be a superior test compared with combined screening methods involving serum markers and ultrasound scanning. 2 Wald et al confirm the superiority of NIPS over the combined test when implemented in routine hospitalbased service in the United Kingdom. Furthermore, in the discussion section, the authors extrapolate findings to discuss the advantages of the reflex pathway over the contingent pathway.…”

“…2 Therefore, in England and Wales, National Health Service commissioners have opted for an evaluative rollout of NIPS as a second-stage test in a population of pregnancies already found to have a higher chance of being affected by a trisomy by conventional methods (a "combined test" first stage).…”

“…When comparing any NIPS pathway to conventional screening, there is an expectation of a reduction in the number of invasive diagnostic tests because of its greater specificity. 2 In the context of a contingent versus a reflex model, the authors cite a report that 18% of women recalled after the first stage in a contingent model proceeded straight to diagnostic testing at the risk of increasing the number of diagnostic tests and the falsepositive rate when compared with reflex testing. 1 A different framing is that after the first stage in the contingent model, parents were free to decline to consent to NIPS and opt for the certainty of a diagnostic procedure.…”

Prenatal reflex DNA screening for trisomies 21, 18, and 13

“…This approach ("contingent screening") has been the subject of various studies. [3][4][5][6] A weakness with this approach is the need to recall women for counseling and to obtain an extra blood sample for the DNA screening test. This recall is likely to make the women acutely anxious; some may choose to proceed directly to an amniocentesis or chorionic villus sampling with the associated risks to the pregnancy.…”