The implementation and impact of non-invasive prenatal testing (NIPT) for Down's syndrome into antenatal screening programmes: A systematic review and meta-analysis

Abstract

Background: Non-invasive prenatal testing (NIPT) is a widely adopted maternal blood test that analyses foetal originating DNA to screen for foetal chromosomal conditions, including Down's syndrome (DS). The introduction of this test, which may have implications for important decisions made during pregnancy, requires continual monitoring and evaluation. This systematic review aims to assess the extent of NIPT introduction into national screening programmes for DS worldwide, its uptake, and impact on pregnancy outcomes.

Methods and findings: The study protocol was published in PROSPERO (CRD42022306167). We systematically searched MEDLINE, CINAHL, Scopus, and Embase for population-based studies, government guidelines, and Public Health documents from 2010 onwards. Results summarised the national policies for NIPT implementation into screening programmes geographically, along with population uptake. Meta-analyses estimated the pooled proportions of women choosing invasive prenatal diagnosis (IPD) following a high chance biochemical screening result, before and after NIPT was introduced. Additionally, we meta-analysed outcomes (termination of pregnancy and live births) amongst high chance pregnancies identified by NIPT. Results demonstrated NIPT implementation in at least 27 countries. Uptake of second line NIPT varied, from 20.4% to 93.2% (n = 6). Following NIPT implementation, the proportion of women choosing IPD after high chance biochemical screening decreased from 75% (95% CI 53%, 88%, n = 5) to 43% (95%CI 31%, 56%, n = 5), an absolute risk reduction of 38%. A pooled estimate of 69% (95% CI 52%, 82%, n = 7) of high chance pregnancies after NIPT resulted in termination, whilst 8% (95% CI 3%, 21%, n = 7) had live births of babies with DS.

Conclusions: NIPT has rapidly gained global acceptance, but population uptake is influenced by healthcare structures, historical screening practices, and cultural factors. Our findings indicate a reduction in IPD tests following NIPT implementation, but limited pre-NIPT data hinder comprehensive impact assessment. Transparent, comparable data reporting is vital for monitoring NIPT's potential consequences.

Fig 1. PRISMA diagram.

Diagram to show the flow of screening stages and number of papers at each stage of the systematic review. It includes details from both the initial search up to 10th May 2022, and the updated search on 29th March 2023.

Fig 2. Autonomous regions that have implemented NIPT into antenatal screening guidelines for Down’s syndrome.

Presenting data from included studies in part A. This includes data from Gadsboll et al., [16] describing national NIPT implementation following survey responses by clinical experts (labelled in figure). Map created using Mapchart.net under a CC BY 4.0 license, with permission from Minas Giannekas, original copyright [2023]. NIPT = non-invasive prenatal testing.

Fig 3. Flow diagram for each pathway of NIPT implementation described in our included studies.

NIPT has been implemented as both a first or second line screen, in some cases the option of both is offered to those undergoing screening for Down’s syndrome. NIPT = non-invasive prenatal testing, CVS = chorionic villus sampling, NT = nuchal translucency.

Fig 4. Forest plots for meta-analyses of proportions of IPDs chosen by higher chance pregnancies after biochemical screening for DS.

A) pre-NIPT implementation B) post-NIPT implementation. C) Odds ratio meta-analysis, comparing the pre and post NIPT implementation time periods for the odds of having an IPD procedure in higher chance women.

Fig 5. Forest plot of the pooled estimate for proportion of higher chance pregnancies (resulting from biochemical screening) that went on to have an invasive prenatal diagnosis (IPD) after NIPT was implemented as a second line screen.

Fig 6

A) Forest plot of pooled proportion of women with a high chance NIPT result that opt for an IPD procedure (NIPT available as a first line screening test); B) Forest plot of pooled proportion women with high chance NIPT result that opt for an IPD (NIPT available as a second line screening test).

Fig 7. Forest plot of the proportion of terminations of pregnancy following a high chance NIPT result for DS, in the post-NIPT period.

Fig 8. Forest plot of meta-analysis of proportion for live births of babies with Down’s syndrome born after a high chance NIPT result.