Taking advantage of the disruptive impact of cell-free fetal DNA screening for aneuploidy

Abstract

U ltrasound is an important diagnostic tool that is universally applied in obstetric care. One of the advantages of the technology is that it can be applied to a number of potential obstetric complications. The precise role for ultrasound in pregnancy continues to evolve as obstetric practice changes. At present, most Australasian women are offered routine obstetric ultrasound scans at 11-13 and 18-20 weeks' gestation. The timing of these investigations has been dictated largely by the ability to identify congenital abnormalities. Maternal serum AFP was first used to identify neural tube defects in universal screening programmes and performs best at 16-18 weeks' gestation. 1 The efficacy of the test relies on accurate pregnancy datingand the added value of ultrasound as a diagnostic tool for neural tube defects, rather than merely being a dating tool, was soon recognised. 2 Ultrasound performed better at a slightly later gestational time pointand the morphology scan has been embedded as a 18-to 20-week test ever since.The development of the 12-week 'nuchal translucency' scan has also been closely associated with maternal serum screening. Soon after the introduction of routine neural tube defect screening using AFP, researchers recognised that serum markers were also altered in pregnancies affected by chromosomal abnormality, leading to the development of multiple marker algorithms that screen for trisomy 21 and other common forms of aneuploidy. 3,4 Ultrasound markers for trisomy 21 were also identified and could be assessed using similar statistical techniques to provide women with a personalised risk of carrying an affected fetus. [5][6][7] For the last 20 years, we have been in 'steady state', reporting a 11-to 13-week 'nuchal translucency' scan as a component of combined first trimester screening (cFTS) for chromosomal abnormality and an 18-to 20-week scan to detect structural abnormality. 8,9 At 11-13 weeks, we have been able to detect 90% of pregnancies affected by trisomy 21 and other common chromosomal abnormalities (albeit with a 5% false-positive rate) and at 18-20 weeks, we have had variable successdetecting up to 95% of fetuses affected by neural tube defects but only 50% of fetuses that have major cardiac defects. [10][11][12] While we might be comfortable, even a little complacent with our performance, all this will now change.The development of genomic technologies that detect and accurately quantify small amounts of cell-free fetal DNA (cffDNA) in maternal plasma has proven to be a game changer. Norton et al. recently demonstrated that this technology is highly effective in screening for trisomy 21quoting sensitivity, specificity and positive predictive values of 100% (95% CI: 90.7-100), 99.94% (95% CI: 98.99-99.97) and 80.9% (95% CI: 66.7-90.9) respectively. 13 The test can be applied at an earlier gestation (from 9 or 10 weeks' gestation) and samples can be flown across the world to specialist labsso there is no need for extensive local operator training. In the world of aneuploidy screening, the...

Population-based impact of noninvasive prenatal screening on screening and diagnostic testing for fetal aneuploidy

“…Opinion leaders have argued that first-trimester ultrasound continues to have an important role in the NIPS era for the detection of fetal structural anomalies and prediction of obstetric complications. 18,19 Several retrospective studies examining the additional information provided by the early ultrasound in the NIPS era have emphasized its important role for accurate pregnancy dating, and diagnosis of fetal demise, multiple gestation, fetal structural anomalies, and placental and maternal pathology. 20,21 From a public health perspective, early diagnosis of fetal abnormalities may not change final pregnancy outcomes as most would be detected at the midtrimester morphology scan.…”