Reexamining the optimal nuchal translucency cutoff for diagnostic testing in the cell-free DNA and microarray era: results from the Victorian Perinatal Record Linkage study.

Autor: Hui L; Reproductive Epidemiology Group, Murdoch Children's Research Institute, Parkville, Victoria, Australia; Department of Obstetrics, Mercy Hospital for Women, Heidelberg, Victoria, Australia; Department of Obstetrics and Gynaecology, University of Melbourne, Parkville, Victoria, Australia; Northern Hospital Epping, Epping, Victoria, Australia. Electronic address: lisa.hui@unimelb.edu.au., Pynaker C; Reproductive Epidemiology Group, Murdoch Children's Research Institute, Parkville, Victoria, Australia., Bonacquisto L; Victorian Clinical Genetics Services, Murdoch Children's Research Institute, Parkville, Victoria, Australia., Lindquist A; Reproductive Epidemiology Group, Murdoch Children's Research Institute, Parkville, Victoria, Australia; Department of Obstetrics, Mercy Hospital for Women, Heidelberg, Victoria, Australia., Poulton A; Reproductive Epidemiology Group, Murdoch Children's Research Institute, Parkville, Victoria, Australia., Kluckow E; Reproductive Epidemiology Group, Murdoch Children's Research Institute, Parkville, Victoria, Australia; Department of Obstetrics and Gynaecology, University of Melbourne, Parkville, Victoria, Australia., Hutchinson B; Department of Obstetrics, Mercy Hospital for Women, Heidelberg, Victoria, Australia., Norris F; Victorian Clinical Genetics Services, Murdoch Children's Research Institute, Parkville, Victoria, Australia., Pertile MD; Victorian Clinical Genetics Services, Murdoch Children's Research Institute, Parkville, Victoria, Australia; Department of Paediatrics, University of Melbourne, Parkville, Victoria, Australia., Gugasyan L; Cytogenetics, Monash Pathology, Monash Medical Centre, Clayton, Victoria, Australia., Kulkarni A; Cytogenetics, Monash Pathology, Monash Medical Centre, Clayton, Victoria, Australia., Harraway J; Sullivan Nicolaides Pathology, Brisbane, Australia., Howden A; Cytogenetics, Melbourne Pathology, Collingwood, Victoria, Australia., McCoy R; Department of Molecular Genetics, Australian Clinical Labs, Clayton, Victoria, Australia., da Silva Costa F; Department of Gynecology and Obstetrics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil; Department of Obstetrics and Gynaecology, Monash University, Clayton, Victoria, Australia., Menezes M; Department of Paediatrics, University of Melbourne, Parkville, Victoria, Australia; Monash Ultrasound for Women, Richmond, Victoria, Australia., Palma-Dias R; Department of Obstetrics and Gynaecology, University of Melbourne, Parkville, Victoria, Australia; Women's Ultrasound Melbourne, East Melbourne, Victoria, Australia; Ultrasound Services, Royal Women's Hospital, Parkville, Victoria, Australia., Nisbet D; Department of Medicine and Radiology, University of Melbourne, Parkville, Victoria, Australia; Women's Ultrasound Melbourne, East Melbourne, Victoria, Australia; Ultrasound Services, Royal Women's Hospital, Parkville, Victoria, Australia., Martin N; Virtus Diagnostics and Pathology Services, Spring Hill, Queensland, Australia., Bethune M; Department of Medicine and Radiology, University of Melbourne, Parkville, Victoria, Australia; Specialist Women's Ultrasound, Box Hill, Victoria, Australia., Poulakis Z; Prevention Innovation Group, Population Health, Murdoch Children's Research Institute, Parkville, Victoria, Australia; Department of Paediatrics, University of Melbourne, Parkville, Victoria, Australia; Victorian Infant Hearing Screening Program, Centre for Community Child Health, Royal Children's Hospital, Parkville, Victoria, Australia., Halliday J; Reproductive Epidemiology Group, Murdoch Children's Research Institute, Parkville, Victoria, Australia; Department of Paediatrics, University of Melbourne, Parkville, Victoria, Australia.
Jazyk: angličtina
Zdroj: American journal of obstetrics and gynecology [Am J Obstet Gynecol] 2021 Nov; Vol. 225 (5), pp. 527.e1-527.e12. Date of Electronic Publication: 2021 May 03.
DOI: 10.1016/j.ajog.2021.03.050
Abstrakt: Background: The American College of Obstetricians and Gynecologists and the Society for Maternal-Fetal Medicine recently recommended offering genetic counseling and diagnostic testing for enlarged nuchal translucency at ≥3.0 mm, regardless of previous negative screening with noninvasive prenatal testing.
Objective: This study aimed to perform a population-based, individual record linkage study to determine the optimal definition of an enlarged nuchal translucency for the detection of atypical chromosome abnormalities.
Study Design: This was a retrospective study of women resident in Victoria, Australia, undergoing combined first-trimester screening during the 24-month period from January 2015 to December 2016. Linkages between statewide results for combined first-trimester screening, prenatal diagnostic procedures, and postnatal cytogenetic results from products of conception and infants up to 12 months of age were used to ascertain the frequency and type of chromosome abnormality by gestation and nuchal translucency measurement. An atypical chromosome abnormality was defined as any major chromosome abnormality other than whole chromosome aneuploidy involving chromosomes 21, 18, 13, X, and Y.
Results: Of the 81,244 singleton pregnancies undergoing combined first-trimester screening, 491 (0.60%) had a nuchal translucency of ≥3.5 mm, 534 (0.66%) had a nuchal translucency of 3.0 to 3.4 mm, and 80,219 (98.74%) had a nuchal translucency of < 3.0 mm. When grouped by nuchal translucency multiples of the median (MoM), 192 (0.24%) had a nuchal translucency of ≥3.0 MoM, 513 (0.63%) had a nuchal translucency of 1.9 to 2.9 MoM, and 80,539 (99.13%) had a nuchal translucency of <1.9 MoM. A total of 1779 pregnancies underwent prenatal or postnatal diagnostic testing, of which 89.60% were performed by whole-genome single-nucleotide polymorphism chromosomal microarray. The frequency of total major chromosome abnormalities was significantly higher in the group with a nuchal translucency of ≥3.5 mm (147 of 491, 29.94%) than the group with a nuchal translucency of 3.0 to 3.4 mm (21 of 534, 3.93%) or a nuchal translucency of <3.0 mm (71 of 80,219, 0.09%) (P<.001). There were 93 atypical chromosome abnormalities in the total screened cohort. The frequency of an atypical chromosome abnormality was 4.07% (95% confidence interval, 2.51-6.22), 0.37% (95% confidence interval, 0.05-1.35), and 0.09% (95% confidence interval, 0.07-0.11) in the groups with a nuchal translucency of ≥3.5 mm, 3.0 to 3.4 mm, and <3.0 mm, respectively. The frequency of atypical chromosome abnormalities was 4.69% (95% confidence interval, 2.17-8.71), 2.53% (95% confidence interval, 1.36-4.29), and 0.09% (95% confidence interval, 0.07-0.11) in the groups with a nuchal translucency of ≥3.0 MoM, 1.9 to 2.9 MoM, and <1.9 MoM, respectively. When defining thresholds for offering diagnosis with chromosomal microarray at 11 to 13 weeks, both a nuchal translucency threshold of 1.9 MoM and a fixed threshold of 3.0 mm captured 22 of 93 fetuses (23.7%) with an atypical chromosome abnormality. Of these, 50.0% had a coexisting fetal abnormality on ultrasound. However, the gestation-specific threshold of 1.9 MoM had a better specificity than 3.0 mm. The positive predictive value of an enlarged nuchal translucency for any atypical chromosome abnormality was 1 in 47 for nuchal translucency of >3.0 mm and 1 in 32 for nuchal translucency of >1.9 MoM. Our nuchal translucency threshold of 1.9 MoM captured 0.87% of fetuses, thus approximating the 99th centile.
Conclusion: A gestational age-adjusted nuchal translucency threshold of 1.9 MoM or 99th centile is superior to the fixed cutoff of 3.0 mm for the identification of atypical chromosome abnormalities. The risk of an atypical chromosome abnormality in a fetus with an enlarged nuchal translucency is more than tripled in the presence of an additional ultrasound abnormality.
(Copyright © 2021 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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