Replacement of Cytogenetics by aCGH in Prenatal Diagnosis

Completed

• Conditions: Prenatal Diagnosis
• Interventions: Diagnostic Test: aCGH

• Registration Number: NCT03955588
• Lead Sponsor: The University of Hong Kong

Brief Summary

Conventional cytogenetics has been the gold standard for chromosomal analysis in prenatal diagnosis. It allows a microscopic examination for any structural abnormalities of chromosome with a turn-around time of 2 to 3 weeks and it is also labour intensive. Array comparative genome hybridisation (aCGH) provides a platform for a higher resolution analysis of chromosomal aberrations in a shorter period of time. The effectiveness of its application in prenatal diagnosis has been examined. The main clinical limitation lies on the difficult interpretation of certain copy number variants (CNV). Our previous study has demonstrated an increase diagnostic yield of 3.2% using aCGH over conventional cytogenetics in the first-tier test study and by 6% as a further test in a cohort of fetuses with ultrasound abnormality and normal karyotype findings. This finding were consistent with the overall reported of 5.2% to 10% increased detection rate by other studies. Various authorities have also approved the use of aCGH as an adjunct diagnostic tool in prenatal cases with fetal ultrasound abnormalities.

The presence study aims to demonstrate the clinical acceptability on the use of aCGH to replace cytogenetics in prenatal diagnosis. For patients requiring invasive prenatal diagnosis by chorionic villus sampling or amniocentesis, they will be offered the options of having either conventional cytogenetics or aCGH. A standard unbiased counselling procedure will be performed by well trained midwives. For patients opting for conventional cytogenetics, the current procedure of karyotyping will be performed. For those opting for aCGH, a quantitative fluorescent Polymerase Chain Reaction (PCR) will be performed first to exclude common aneuploidies and triploidies. aCGH will be arranged for those with normal PCR results and conventional cytogenetics will be reserved for visualization of clinically significant CNVs.

All patients will be asked to complete the same questionnaire that has been adopted for the study on "Questionnaire survey on Knowledge and Acceptance on Application of whole genome array Comparative Genomic Hybridisation (aCGH) in Prenatal Diagnosis".

Detailed Description

Conventional cytogenetics has been the gold standard for chromosomal analysis in prenatal diagnosis. It allows a microscopic examination for any structural abnormalities of chromosome with a turn-around time of 2 to 3 weeks and it is also labour intensive. Array comparative genome hybridisation (aCGH) provides a platform for a higher resolution analysis of chromosomal aberrations in a shorter period of time. The effectiveness of its application in prenatal diagnosis has been examined (Callaway, Shaffer, Chitty, Rosenfeld, \& Crolla, 2013). The main clinical limitation lies on the difficult interpretation of certain copy number variants (CNV). Our previous study has demonstrated an increase diagnostic yield of 3.2% using aCGH over conventional cytogenetics in the first-tier test study and by 6% as a further test in a cohort of fetuses with ultrasound abnormality and normal karyotype findings (Kan et al., 2014). This finding were consistent with the overall reported of 5.2% to 10% increased detection rate by other studies (de Wit et al., 2014; Hillman et al., 2013; Hillman et al., 2011). Various authorities have also approved the use of aCGH as an adjunct diagnostic tool in prenatal cases with fetal ultrasound abnormalities (American College of Obstetricians \& Gynecologists, 2013; Novelli et al., 2012).

Study Timeline

• Study Start: 2014-11-21
• Primary Completion: 2016-02-28
• Study Completion: 2016-02-28
• Status Verified: 2019-05
• Study First Submitted: 2019-05-07
• Study First Submitted QC: 2019-05-15
• Last Update Submitted: 2019-05-15
• Study First Posted: 2019-05-20
• Last Update Posted: 2019-05-20

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 51

Inclusion Criteria

All pregnant women requiring chorionic villus sampling or amniocentesis at Tsan Yuk Hospital

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Exclusion Criteria

Patients who cannot read or understand Chinese or English

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Women undergoing invasive prenatal diagnostic procedures	aCGH	For women requiring invasive prenatal diagnosis by chorionic villus sampling or amniocentesis, they will be offered the options of having either conventional cytogenetics or aCGH.

Primary Outcome Measures

Name	Time	Method
The preference of aCGH to conventional cytogenetics	At the time of recruitment	Proportion of subjects choosing aCGH

Secondary Outcome Measures

Name	Time	Method
Cost-effectiveness analysis of chromosomal microarray as primary test for prenatal diagnosis in Hong Kong	After completion of the aCGH for the last recruited subject in 2016	Laboratory workflow and cost of replacing conventional karyotype by aCGH are compared. The cost-effectiveness analysis is based on the diagnostic rate (number of diagnoses made/ sample size) as a measure of outcome effectiveness.