Recipient organisationGreat Ormond Street Hospital for Children NHS Foundation Trust
Funding£2.4M
PeriodJan 2009 — Sept 2015
In plain English
AI plain-English summary
Pregnant women currently face a 1% miscarriage risk from invasive prenatal testing, but a simple blood test could replace it. This project evaluates whether analysing fetal DNA and RNA floating in maternal blood can reliably diagnose Down’s syndrome, single-gene disorders like cystic fibrosis, and fetal sex for medical reasons—without the need for needles into the womb. The problem is that non-invasive prenatal diagnosis (NIPD) is already creeping into NHS use without proper standards. No one has systematically checked its accuracy, cost-effectiveness, or how it affects couples’ choices. This research fills that gap by testing the technology on clinical cohorts, running economic analyses, and interviewing families about their preferences. If successful, NIPD could eliminate the miscarriage risk from prenatal testing entirely, allow earlier diagnosis, and save the NHS money by reducing invasive procedures and hospital visits. The team will produce a ready-to-use implementation plan for NHS commissioners, covering laboratory standards, staff training, and ethical safeguards. This is applied health services research with a direct route to changing clinical practice within the next few years.
View original technical description
AIMTo improve the quality of NHS prenatal diagnostic services by evaluating early non-invasive prenatal diagnosis (NIPD) based on cell free fetal (cff) DNA and RNA extracted from maternal plasma. We will:1.Confirm laboratory standards for NIPD for:a.Fetal sex determinationb.Single gene disordersc.Down’s syndrome (DS)2.Evaluate NIPD for those indications using the ACCE framework (Analytic and Clinical validity, Clinical utility, and Ethical, legal and social aspects) including:a.Evaluating cost effectivenessb.Determining couples’ choices, preferences and needs c.Considering wider ethical, legal and social issuesd.Developing competences for health professionals3.Develop an implementation plan for use by commissioners to establish NIPD as an NHS service. BACKGROUNDCurrent prenatal genetic diagnosis requires invasive testing from 11 weeks and carries a 1% miscarriage risk. cffDNA and cffRNA in maternal blood offer a source of fetal genetic material which will be safer to obtain, requiring only a maternal blood sample, allowing earlier diagnosis and potential health service savings due to fewer invasive tests and patient episodes. Some NHS laboratories already offer limited NIPD and there is an urgent need to evaluate it thoroughly including the sensitivity, specificity and clinical utility with development of laboratory and clinical standards before it ‘seeps’ further into practice.RESEARCH PLANSOur work will focus on developing an implementation plan. It forms three integrated workstreams:1.Technology development2.Evaluation 3.ImplementationWe will address three uses for NIPD:a. Medically indicated sex determinationb. Single gene disorder diagnosisc. DS diagnosisClinical cohorts will form the study base including women:i. undergoing fetal sex determination using NIPD for medical reasons ii. having standard prenatal diagnosis for cystic fibrosis, thalassaemia & HbSC, FGFR2 & FGFR3 mutations (Achondroplasia, Aperts etc)iii. undergoing NIPD for conditions in (ii) iv. with a high DS screening risk in 3 district hospitals v. recruited at booking before DS screening1. Technology developmentFor fetal sexing and single gene disorders NIPD will be based on detection or exclusion of paternally inherited alleles or those arising denovo.Thus for X-linked and recessive conditions detection of Y sequences or the paternal allele indicates need for invasive testing but absence suggest an unaffected fetus. For DS, the utility of cffRNA single nucleotide polymorphisms (SNPs) allelic ratios in UK populations will be evaluated using published SNPs and others we have developed.For all uses, the sensitivity and specificity of NIPD using cffDNA and RNA extracted from maternal blood will be evaluated, and standard operating procedures and reference materials developedNIPD for sex determination is already in limited use and standards for this will be developed early in the project. We anticipate offering NIPD for the other conditions later in the programme.2. Evaluationa. Economic analysis will evaluate cost, cost-effectiveness and budget impact of NIPD for all 3 uses using standard methods and data collected from the clinical cohorts.b. Couples views and information needs will be determined using one-to-one interviews, questionnaires and focus groups with those at risk of disorders being tested. Conjoint analysis will be used to determine their preferences for testing.c. Wider ethical issues will be explored using conceptual ethical analysis and a vignette study of health professionals to determine whether NIPD will impair counselling and informed choice. d. Education requirements will be determined by needs analysis mapped against the national competences3. ImplementationWorkshops with stakeholders will identify implementation issues. These will be used with data from workstreams 1 and 2 to produce a comprehensive plan to aid commissioners with the introduction of NIPDRESEARCHERS AND ENVIRONMENT The team includes most UK groups interested in NI
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