title: Universal Prenatal Chromosomal Microarray Analysis: Additive Value and Clinical Dilemmas in Fetuses with a Normal Karyotype.
abstract: ObjectiveTo assess the additive value of prenatal chromosomal microarray analysis (CMA) for all indications and the likelihood of detecting pathologic copy number variations (CNVs) based on specific indications.MethodsA retrospective analysis was performed on amniocentesis and chorionic villi sampling results obtained between 2010 and 2014 in a single institution. A total of 3,314 consecutive patients undergoing invasive genetic testing for different indications were offered CMA in addition to standard karyotype. The prevalence of pathologic CNVs was compared between patients with low-risk indications and those with high-risk indications. Likewise, the prevalence of pathologic CNVs among patients with different sonographic abnormalities was calculated and compared with the low-risk group. Chi-square and Fisher exact tests were used for statistical analysis.ResultsThe prevalence of pathologic CNVs was significantly higher in patients with high-risk indications and specifically those with sonographic abnormalities, compared with the low-risk group (2.8 and 5.9% vs. 0.4%, respectively; allp< 0.05).ConclusionPrenatal CMA detected clinically relevant CNVs in fetuses with a normal karyotype. Major structural malformations and nuchal translucency (NT) ≥ 3.0 mm are associated with the highest risk for a CMA abnormality. Nevertheless, the prevalence of pathologic CNVs in the low-risk population was high enough (1:250) to consider genetic counseling in this group.
authors.affiliation: Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Lenox-Hill Hospital, New York, New York.
authors.forename: Eran
authors.initials: E
authors.lastname: Bornstein
authors.affiliation: Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Lenox-Hill Hospital, New York, New York.
authors.forename: Sharon
authors.initials: S
authors.lastname: Berger
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas.
authors.forename: Sau W
authors.initials: SW
authors.lastname: Cheung
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas.
authors.forename: Kristen T
authors.initials: KT
authors.lastname: Maliszewski
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas.
authors.forename: Ankita
authors.initials: A
authors.lastname: Patel
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas.
authors.forename: Amber N
authors.initials: AN
authors.lastname: Pursley
authors.affiliation: Statistics and Data Management, New York University College of Nursing and College of Dentistry, New York, New York.
authors.forename: Erez
authors.initials: E
authors.lastname: Lenchner
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas.
authors.forename: Carlos
authors.initials: C
authors.lastname: Bacino
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas.
authors.forename: Arthur L
authors.initials: AL
authors.lastname: Beaudet
authors.affiliation: Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Lenox-Hill Hospital, New York, New York.
authors.forename: Michael Y
authors.initials: MY
authors.lastname: Divon
mesh_terms: D000649:Amniocentesis; D015193:Chorionic Villi Sampling; D002869:Chromosome Aberrations; D000013:Congenital Abnormalities / Q000000981:diagnostic imaging* / Q000235:genetics*; D056915:DNA Copy Number Variations; D005260:Female; D005817:Genetic Counseling; D005820:Genetic Testing / Q000379:methods*; D006801:Humans; D059785:Karyotype; D008297:Male; D046228:Microarray Analysis; D011247:Pregnancy; D012189:Retrospective Studies; D012307:Risk Factors; D016216:Ultrasonography, Prenatal