ISUOG updated consensus statement on the impact of cfDNA aneuploidy testing on screening policies and prenatal ultrasound practice

The widespread use of fetal cell-free DNA (cfDNA)-based techniques to screen for trisomy 21 and other aneuploidies has expanded greatly the range of prenatal tests available over the last few years. cfDNA tests are being incorporated rapidly into prenatal care, thus changing the traditional approach to prenatal screening and diagnosis. However, although cfDNA techniques are highly efficient, their role and performance must be considered alongside and combined with other screening modalities. The role of prenatal ultrasound, in particular, needs to be reaffirmed as cfDNA testing becomes more widely available. It is important to emphasize that the main goal of prenatal screening is to provide accurate information that will facilitate the delivery of optimized antenatal care, with the best possible outcome for both mother and fetus. Women should be informed about the prevalence and the clinical manifestation of the disease of interest and about prenatal screening performance (detection rate, false-positive rate, positive predictive value in the general population, failure rate) by appropriately trained health professionals, allowing them to make an informed decision. It is the parent's choice to undergo such procedures, and their wishes should be determined and respected. Following such screening, women can be offered a choice, according to their calculated individual risk, of having no further testing, cfDNA testing or invasive testing. Cut-offs, defining two (low/high risk) or three (low/intermediate/high risk) groups, should be defined on a local/national basis and will be affected by public health priorities and available resources. Offering cfDNA testing should always be balanced with the potential and risk of conventional karyotyping, with or without microarray analysis, following invasive sampling. More importantly, the role of cfDNA testing as an alternative to standard invasive testing in women considered to be at very high risk after combined screening (> 1:10) but with no ultrasound anomaly should be evaluated in prospective studies. Expert opinion currently suggests that cfDNA testing should not replace routinely invasive testing in this group, based on the fact that, in this population, only 70% of the chromosomal abnormalities are trisomy 21, 18 or 13, and that chromosomal microarray analysis, if offered, is able to detect a large number of additional anomalies. Most current guidelines endorse cfDNA testing only for high- or intermediate-risk populations, for which comprehensive data exist. Experience in low-risk populations is increasing, apparently confirming the high detection rates published for high-risk populations. However, testing in low-risk women may impact on the quality of both pretest counseling and subsequent ultrasound screening. In particular, cfDNA testing should not replace first-trimester ultrasound and should not be offered when an ultrasound anomaly or markedly increased NT is detected. Using cfDNA in low-risk patients might be endorsed as a widely available option only when more data emerge and cfDNA costs decrease. An invasive test might be discussed in light of the recently reported reduction in the risk of invasive procedures3, 4, as well as the increase in cytogenetic resolution provided by microarray techniques. However, the cost of this option is not usually covered by most national insurance policies and it should not be recommended beyond the context of clinical trials and until sufficient peer-reviewed data and validation studies have been published. L. J. Salomon1, Z. Alfirevic2, F. Audibert3, K. O. Kagan4, D. Paladini5, G. Yeo6 and N. Raine-Fenning7, on behalf of the ISUOG Clinical Standards Committee. 1Department of Obstetrics and Fetal Medicine, Hôpital Necker-Enfants Malades, Assistance Publique-Hôpitaux de Paris, Paris Descartes University, Paris, France, SFAPE (Société Française d'Amélioration des Pratiques Echographique) and CFEF (College Français d'Echographie Foetale); 2Department for Women's and Children's Health, University of Liverpool, Liverpool, UK; 3Department of Obstetrics and Gynaecology, CHU Sainte Justine, University of Montreal, Montreal, QC, Canada; 4Department of Obstetrics and Gynecology, University of Tuebingen, Tuebingen, Germany; 5Fetal Medicine and Surgery Unit, Giannina Gaslini Institute, Genoa, Italy; 6Department of Maternal Fetal Medicine, Obstetric Ultrasound and Prenatal Diagnostic Unit, KK Women's and Children's Hospital, Singapore; 7Division of Obstetrics & Gynaecology, School of Clinical Sciences, University of Nottingham, Nottingham, UK