title: 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.
  
  
  METHODS
  Prospective cohort study.
  
  
  METHODS
  Eight maternity units across the United Kingdom between 1 November 2013 and 28 February 2015.
  
  
  METHODS
  All pregnant women with a current Down's syndrome risk on screening of at least 1/1000.
  
  
  METHODS
  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.
authors.affiliation: Genetics and Genomic Medicine, UCL Institute of Child Health, London WC1N 3BH, UK Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.
authors.forename: Lyn S
authors.initials: LS
authors.lastname: Chitty
authors.affiliation: Department of Statistics, Plymouth University, Plymouth, UK.
authors.forename: David
authors.initials: D
authors.lastname: Wright
authors.affiliation: Genetics and Genomic Medicine, UCL Institute of Child Health, London WC1N 3BH, UK.
authors.forename: Melissa
authors.initials: M
authors.lastname: Hill
authors.affiliation: Department of Applied Health Research, University College London, London, UK.
authors.forename: Talitha I
authors.initials: TI
authors.lastname: Verhoef
authors.affiliation: Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Daley
authors.affiliation: Genetics and Genomic Medicine, UCL Institute of Child Health, London WC1N 3BH, UK Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.
authors.forename: Celine
authors.initials: C
authors.lastname: Lewis
authors.affiliation: North-East Thames Regional Genetics Laboratory, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.
authors.forename: Sarah
authors.initials: S
authors.lastname: Mason
authors.affiliation: North-East Thames Regional Genetics Laboratory, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.
authors.forename: Fiona
authors.initials: F
authors.lastname: McKay
authors.affiliation: North-East Thames Regional Genetics Laboratory, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.
authors.forename: Lucy
authors.initials: L
authors.lastname: Jenkins
authors.affiliation: Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.
authors.forename: Abigail
authors.initials: A
authors.lastname: Howarth
authors.affiliation: PHG Foundation, Cambridge, UK.
authors.forename: Louise
authors.initials: L
authors.lastname: Cameron
authors.affiliation: Department of Obstetrics and Gynaecology, Nottingham University Hospitals, Nottingham, UK.
authors.forename: Alec
authors.initials: A
authors.lastname: McEwan
authors.affiliation: Antenatal Results and Choices (ARC), London, UK.
authors.forename: Jane
authors.initials: J
authors.lastname: Fisher
authors.affiliation: PHG Foundation, Cambridge, UK.
authors.forename: Mark
authors.initials: M
authors.lastname: Kroese
authors.affiliation: Department of Applied Health Research, University College London, London, UK.
authors.forename: Stephen
authors.initials: S
authors.lastname: Morris
mesh_terms: D003362:Cost-Benefit Analysis; D004314:Down Syndrome / Q000175:diagnosis* / Q000235:genetics; D005260:Female; D005820:Genetic Testing / Q000191:economics / Q000379:methods / Q000706:statistics & numerical data; D006801:Humans; D008423:Maternal Age; D010342:Patient Acceptance of Health Care / Q000706:statistics & numerical data; D011247:Pregnancy; D011256:Pregnancy Outcome; D011262:Pregnancy Trimester, Second; D011296:Prenatal Diagnosis / Q000191:economics / Q000379:methods / Q000706:statistics & numerical data; D011446:Prospective Studies; D006113:United Kingdom / Q000453:epidemiology