First‐trimester screening strategies: A balance between costs, efficiency and diagnostic yield

Abstract

What's already known about this topic?� An early scan at 11-13 + 6 weeks offers the ideal opportunity for a first detailed anatomical assessment of the fetus.� Non-invasive prenatal testing (NIPT) is superior to the combined test to screen for common trisomies, especially trisomy 21, in both singleton and twin pregnancies. What does this study add?� In first-trimester screening strategies based on NIPT and ultrasound, many factors must be considered when choosing how to combine the two methods. We propose four screening strategies with different pro-and contra arguments.� The article may help choose the strategy that best fits local needs and health economic considerations. | INTRODUCTIONThe introduction of non-invasive prenatal testing (NIPT) by cell-free DNA (cfDNA) has reshaped the way first-trimester screening (FTS) is performed. In several countries NIPT is offered as second line screening, after the combined test (CT) including nuchal translucency (NT) measurement and maternal serum biochemistry (free beta-HCG and PAPP-A). 1 However, there is an increasing tendency to completely replace the CT with NIPT. 2,3 It is undisputed that, in a direct comparison with the CT, NIPT is a superior screening method for common trisomies, especially trisomy 21, in both singleton and twin pregnancies. [4][5][6] The performance diminishes when microdeletions are also tested or a genome-wide approach is offered. 7 In fact, the screen-positive rate increases, the positive predictive value decreases and counseling couples to ensure informed consent becomes more challenging. [8][9][10] The additional value of these expanded menus needs to be balanced against this background. Replacing the CT with NIPT may result in a loss of the opportunity for a first detailed anatomical assessment of the fetus, which is highly valued by women. 11,12 It is known that about 30%-50% of fetal abnormalities can always be detected in the first trimester and that while some are strongly associated with chromosomal aberrations, others are isolated. 13,14 Notably, their prevalence exceeds that of genetic anomalies, especially in younger women who constitute the majority of the reproductive population. 15 Although there is still an ongoing debate, it seems reasonable that screening for structural anomalies should have its own place, next to NIPT, in the current FTS paradigm. 14,[16][17][18][19][20] The primary aim of this commentary is to present four different screening strategies combining NIPT and ultrasound in the first trimester (NIPT after CT, NIPT after a 12-13 weeks anatomical assessment, NIPT without a 12-13 weeks anatomical assessment and NIPT followed by a 12-13-week anatomical assessment) with their pro and contra arguments. We are aware that the ultimate decision on which strategy to offer will be nationally determined by costeffectiveness arguments, availability of local resources, and health policy priorities. We recognize that some pro-and contra-argumentsThis is an open access article under the terms of the Creative Commons Attribution-...

Eliminating first trimester combined testing: Consequences for early detection of significant fetal anomalies

“…Future research should focus on the right moment of FTAS, before or after cfDNA testing and evaluate its additional healthcare costs. 32 However, a recent study showed that FTAS before cfDNA testing is a more cost-effective strategy for noninvasive prenatal aneuploidy screening compared to cfDNA alone. 33…”

The first trimester: The new focal point for prenatal screening and diagnosis

“…The ongoing debate about how best to integrate NIPT with ultrasound and the combined first trimester screen is addressed in a commentary by Bardi and colleagues 7 . It is notable that the rapid diffusion of NIPT, stimulated by important financial interests, has not been emulated by first trimester ultrasound screening.…”

“…Research continues to bring new insights on the diagnostic ability of the early ultrasound scan: the fetal heart, 11 the central nervous system 12,13 skeletal dysplasias 14 and increased nuchal translucency 15 . Also, among the first trimester screening strategies for congenital anomalies discussed by Bardi et al., early anatomical assessment occupies a central role, from the most advanced to more traditional screening menus 7 …”

“…6 The ongoing debate about how best to integrate NIPT with ultrasound and the combined first trimester screen is addressed in a commentary by Bardi and colleagues. 7 It is notable that the rapid diffusion of NIPT, stimulated by important financial interests, has not been emulated by first trimester ultrasound screening. A decade after the publication of the seminal article by Syngelaki on the early diagnosis of structural anomalies, 8 many challenges persist in this area, as illustrated by the multinational overview by Bronsgeest et al 9 A systematic protocol for first structural anomaly ultrasound has not achieved widespread implementation, and robust datasets on early detection of fetal defects are still emerging.…”

“…15 Also, among the first trimester screening strategies for congenital anomalies discussed by Bardi et al, early anatomical assessment occupies a central role, from the most advanced to more traditional screening menus. 7 One of the concerns with early fetal anatomy ultrasound, which can facilitate earlier terminations for fetal anomalies, is the potential loss of information from a detailed autopsy. The review by Simcock et al 16 illustrates the recent advances in this field emphasizing the superior post-mortem image quality in fetuses provided by micro-CT and High Frequency-MRI compared to more established non-invasive autopsy techniques.…”