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.

Fig 1 Flowchart showing numbers of women recruited and outcomes. CVS=chorionic villus sampling; DSS=Down’s syndrome screening; NIPT=non-invasive prenatal testing; T13=trisomy 13; T18=trisomy 18; T21=trisomy 21. *Including 15 women with risk ≥1/150 for T13/T18 and risk 1/151-1/1000 for T21. †Some women underwent DSS and declined further testing but were known to have had NIPT in private sector (n=37). ‡One additional woman accepted NIPT but no blood sample was obtained. §One procedure was not possible. ¶Two women initially had inconclusive NIPT results but were positive on repeat testing; these are included in inconclusive/failed pathway and also predicted to be affected pathway. **Includes one case (T13) that had amniocentesis later in pregnancy after detection of fetal abnormalities

Fig 2 Decision tree depicting current screening pathway and new pathway using non-invasive prenatal testing (NIPT) as contingent screening. In current screening pathway, women are offered invasive testing when their risk based on combined or quadruple test is ≥1/150. Small risk of procedure related miscarriage exists, so some women at high risk decide not to undergo any further testing. If result of invasive test is positive, women can decide to terminate pregnancy. In NIPT pathway, women are offered NIPT test after high risk result (depending on threshold: ≥1/150, ≥1/500, or ≥1/1000) based on combined or quadruple test. Pathways for different thresholds are similar except for threshold risk at which NIPT is offered as contingent screening. If NIPT test result is positive, invasive test is offered to confirm diagnosis. Some women with risk ≥1/150 after combined or quadruple test might decide to have invasive test directly and not have NIPT first. DS=Down’s syndrome

Fig 3 Benefits and costs of Down’s syndrome screening pathway nationally for current pathway and using non-invasive prenatal testing as contingent test for women with risk of ≥1/150, 1/500, and 1/1000. Estimates are based on population of 698 000

Fig 4 Marginal costs for different base prices of implementing non-invasive prenatal testing (NIPT) as contingent test for Down’s syndrome for women with screening risk ≥1/150, 1/500, or 1/1000. Dashed lines indicate costs without option of direct invasive prenatal testing (IPD); solid lines indicate costs allowing option of direct IPD without previous NIPT. Figures are based on national data