Evaluation of the Relevance of Comparative Genomic Hybridization in Prenatal Diagnosis

Evaluation of the Contribution of Comparative Genomic Hybridization Compared to Karyotype for the Detection of Genetic Abnormalities According to Ultrasound Call Signs in Prenatal Screening: the Cohort of the Nancy Multidisciplinary Center for Prenatal Diagnosis From 2012 to 2018

Pre-natal diagnosis is developing nowadays thanks to the improvement of ultrasound performances but also of genetic analysis techniques.

The karyotype was previously the reference technique for genetic analysis. The development of comparative genomic hybridization, consisting of comparative genomic hybridization on DNA sequences and allowing the diagnosis of unbalanced chromosomal rearrangements, has made it possible to increase the resolution threshold for the detection of genetic anomalies. This technique can be performed both pre and post natal. In pre-natal, the indications for this genetic study are based on ultrasound signs and are regularly updated in the international literature. Due to the complete analysis of the genome and the increase of the resolution threshold, genetic anomalies not related to the detected ultrasound pathology may be discovered and may pose ethical problems from a genetic counseling point of view.

To date, the diagnostic performance of comparative genomic hybridization as a complement to karyotype is being confirmed and needs to be clarified in order to limit the risk of incidental discovery of genetic anomalies whose significance remains unknown.

Through the study that the investigator would like to carry out, the investigator seek to evaluate the diagnostic contribution of this comparative genomic hybridization technique compared to the data provided by the karyotype according to the various ultrasound call signs on the Nancy cohort of files presented to the multidisciplinary pre-natal diagnosis committee, since the launch of the comparative genomic hybridization in Nancy in 2012 until 2018.

Study Overview

• Status: Enrolling by invitation
• Conditions: Comparative Genomic Hybridization

• Study Type: Observational
• Enrollment (Anticipated): 830

Contacts and Locations

Study Locations

• France
  • Nancy, France, 54000
    • Nancy University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

• Sampling Method: Non-Probability Sample

Study Population

All patients who underwent amniocentesis or chorionic villus puncture during their pregnancy due to ultrasound call sign with CGH-array performed at the Nancy University Hospital genetics laboratory

Description

Inclusion Criteria:

• CGH-array performed for ultrasound findings at the genetic laboratory of the Nancy University Hospital from 01/10/2012 to 31/12/2018
• Results of the CGH-array presented to the multidisciplinary pre-natal diagnosis committee of Nancy

Exclusion Criteria:

• patients who objected to the use of their data for research purposes when signing the informed consent form given during the genetic consultation

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Retrospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CGH-array abnormality	An anomaly will be detected at CGH-array if its size is greater than or equal to 500 Kb. Size of these anomalies will be considered in a binary manner: < 10 Mb (i.e. not visible on karyotype) and ≥ 10 Mb (i.e. visible on karyotype)	baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Type of ultrasound call sign	The ultrasound signs will be defined by the ultrasound technician thanks to the recommended classification	baseline
Genotype-phenotype concordance	The genotype-phenotype concordance is defined by the cytogeneticist who delivers the results, according to the current scientific knowledge described in the literature	baseline
Particular gravity	The particular gravity (Yes/No) of the ultrasound sign is defined after consultation between the various health professionals gathered at the multidisciplinary pre-natal diagnosis committee (gynaecologist, paediatrician, geneticist, radiologist, histopathologists, surgeons, etc.).	baseline

Collaborators and Investigators

• Sponsor: Central Hospital, Nancy, France
• Investigators: Principal Investigator: Estelle PERDRIOLLE-GALET, Doctor, Central Hospital, Nancy, France

Publications and helpful links

General Publications

• Rudolf G, Lovrecic L, Tul N, Teran N, Peterlin B. The frequency of CNVs in a cohort population of consecutive fetuses with congenital anomalies after the termination of pregnancy. Mol Genet Genomic Med. 2019 Jun;7(6):e658. doi: 10.1002/mgg3.658. Epub 2019 Apr 19.
• Stosic M, Levy B, Wapner R. The Use of Chromosomal Microarray Analysis in Prenatal Diagnosis. Obstet Gynecol Clin North Am. 2018 Mar;45(1):55-68. doi: 10.1016/j.ogc.2017.10.002. Epub 2017 Dec 9.
• Lo JO, Shaffer BL, Feist CD, Caughey AB. Chromosomal microarray analysis and prenatal diagnosis. Obstet Gynecol Surv. 2014 Oct;69(10):613-21. doi: 10.1097/OGX.0000000000000119.
• Lee CN, Lin SY, Lin CH, Shih JC, Lin TH, Su YN. Clinical utility of array comparative genomic hybridisation for prenatal diagnosis: a cohort study of 3171 pregnancies. BJOG. 2012 Apr;119(5):614-25. doi: 10.1111/j.1471-0528.2012.03279.x. Epub 2012 Feb 7.
• Wou K, Levy B, Wapner RJ. Chromosomal Microarrays for the Prenatal Detection of Microdeletions and Microduplications. Clin Lab Med. 2016 Jun;36(2):261-76. doi: 10.1016/j.cll.2016.01.017. Epub 2016 Mar 28.
• Levy B, Wapner R. Prenatal diagnosis by chromosomal microarray analysis. Fertil Steril. 2018 Feb;109(2):201-212. doi: 10.1016/j.fertnstert.2018.01.005.
• Wapner RJ, Martin CL, Levy B, Ballif BC, Eng CM, Zachary JM, Savage M, Platt LD, Saltzman D, Grobman WA, Klugman S, Scholl T, Simpson JL, McCall K, Aggarwal VS, Bunke B, Nahum O, Patel A, Lamb AN, Thom EA, Beaudet AL, Ledbetter DH, Shaffer LG, Jackson L. Chromosomal microarray versus karyotyping for prenatal diagnosis. N Engl J Med. 2012 Dec 6;367(23):2175-84. doi: 10.1056/NEJMoa1203382.

Study record dates

Study Major Dates

• Study Start (Actual): March 30, 2021
• Primary Completion (Anticipated): April 1, 2021
• Study Completion (Anticipated): April 1, 2021

Study Registration Dates

• First Submitted: March 22, 2021
• First Submitted That Met QC Criteria: March 22, 2021
• First Posted (Actual): March 24, 2021

Study Record Updates

• Last Update Posted (Actual): April 6, 2021
• Last Update Submitted That Met QC Criteria: April 5, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Keywords: Prenatal diagnosis; Ultrasound sign
• Additional Relevant MeSH Terms: Pathologic Processes; Disease
• Other Study ID Numbers: 2020PI288

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No