NIPT for Down’s syndrome – what new evidence means for the UK

Mark Kroese

16 April 2015

Non-invasive cell–free DNA prenatal testing (NIPT) is an exciting new development in antenatal care, since it offers the potential to reduce the need for invasive antenatal testing and the associated risk of miscarriage. Efforts to evaluate this test in the form of clinical research trials have been underway for some years. Whilst the technique has demonstrated good performance as a screening test for the detection of Down’s syndrome (trisomy 21) and other trisomies among high-risk populations, robust evidence of performance in routine antenatal populations has been lacking – until now.

The recently published results  of the NEXT study of NIPT by Norton et al. raises questions on what these mean for antenatal care in the UK. 

Key findings

This blinded prospective study involving nearly 16,000 women in the analysis has provided considerable and high quality evidence to support the significant improvement in test performance by cell–free DNA (cfDNA) NIPT in the detection of trisomy 21 (Down’s syndrome) against standard combined screening testing. This is illustrated in the false positive rate for NIPT of 0.06% (95% CI- 0.03 -0.11) compared to 5.4% (95% CI – 5.1- 5.8) in the standard screening group. The positive predictive value for NIPT testing was 80.9% (95% CI 66.7- 90.9) compared to 3.4% (95% CI 2.3 – 4.8) for standard screening testing.

Limitations of the study

The study did however show that 3% of women did not get a NIPT result for technical reasons (n=488), and the prevalence of aneuploidy in this group was higher than in the overall group. The performance of NIPT could have been affected had these women been included in the results. There also appeared to be a significant total number of women excluded from the analysis (n=3114); the largest number among these were women lost to follow up (n=1489).

The authors, in their thorough discussion of the study, did advocate care and further consideration of a number of issues before the implementation of NIPT for general prenatal aneuploidy screening, including:

  • Current screening approaches can identify risk for a number of fetal abnormalities not detectable by NIPT
  • Further understanding is needed of the expectations and choice behaviours of women to whom the test is offered
  • How  the care needs of women with NIPT ’no results’ should be addressed
  • The need for cost utility studies
Crucially, the study did not investigate models of care and the test performance within these models for the use of NIPT in an antenatal care setting.

Implications for UK antenatal policy and care

Considerable further research is required to address questions like these before implementation of cfDNA NIPT can be considered in the UK National Health Service (NHS) as a replacement for current trisomy screening approaches. This is in fact an important opportunity for the UK to contribute to this specific research endeavour, as it already has a significant track record in NIPT research and well established NHS antenatal care pathways to enable investigation of new test performance and cost effectiveness. UK based research funding bodies should not miss this chance to build on the expertise available and inform the future use of cfDNA NIPT in antenatal care, ensuring that women derive the greatest possible benefit from this innovation.