Non Invasive Prenatal Testing of Down Syndrome

Not Applicable

Completed

• Conditions: Down Syndrome
• Interventions: Procedure: Invasive Prenatal Testing; Procedure: Non Invasive Prenatal Testing

• Registration Number: NCT02127515
• Lead Sponsor: Assistance Publique - Hôpitaux de Paris

Brief Summary

This is a randomized controlled trial in women at risk following combined prenatal screening for Down Syndrome. Women will be asked about their preferences between NIPT and routine prenatal diagnosis based on a dedicated questionnaire. Women will then be randomized between NIPT and standard invasive prenatal diagnosis.

Detailed Description

This is a randomized controlled trial in women at risk following combined prenatal screening for Down Syndrome. Women will be asked about their preferences between NIPT and routine prenatal diagnosis based on a dedicated questionnaire. Women will then be randomized between NIPT and standard invasive prenatal diagnosis.

The general objectives are :

* Promote the rapid and large implementation of Non Invasive Prenatal Testing (NIPT) for Down syndrome.

* Improve the management of women at risk after combined first trimester screening and reduce the number of invasive procedures and induced miscarriages .

* Evaluate NIPT medically (in reducing the rate of invasive sampling and related complications, diagnostic performance and feasibility and acceptability in routine practice) and based on cost-analysis in comparison with standard invasive prenatal diagnosis currently proposed .

* Clarify the conditions of implementation and dissemination of NIPT in the overall organization of prenatal screening for trisomy 21 (and provide data to later adjust or not the combination of tests and thresholds).

Promote the organization as networks of professionals involved in prenatal screening for trisomy 21 in order to allow the emergence of a national system of collection of outcomes to improve the quality of practices

The main judgement criteria are:

* Main:

- Percentage of fetal loss in each group

* Secondary:

* Percentage of invasive tests in each group (amniocentesis or chorionic villus sampling )

* Diagnostic performance of NIPT , in particular false positive and negative

* Percentage of results within 3 weeks and average time interval for results of NIPT

* Percentage of inconclusive results of DPANI

* Percentage of other anomalies discovered at invasive sampling

* Percentage of invasive samples taken despite normal NIPT (either because of later ultrasound anomaly or for maternal reinsurance)

* Association between maternal characteristics ( weight, height, parity , previous history , serum markers ... ) and the results of NIPT

* Cost analysis of NIPT in routine clinical practice

The study will include 2450 high risk women in order to be powered enough to detect a 1% reduction of miscarriages in the group undergoing NIPT instead of routine invasive prenatal diagnosis.

Study Timeline

• Study First Submitted: 2014-04-02
• Study Start: 2014-04-08
• Study First Submitted QC: 2014-04-28
• Study First Posted: 2014-04-30
• Primary Completion: 2016-11-07
• Study Completion: 2016-11-07
• Status Verified: 2021-03
• Last Update Submitted: 2021-03-23
• Last Update Posted: 2021-03-26

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 2111

Inclusion Criteria

• pregnant women over 18
• at risk for Down syndrome> 1/250 based on combined screening using ultrasound together with maternal serum markers and prior to fetal karyotyping
• singleton pregnancy
• pregnancy between 11SA et 18SA
• willing a fetal karyotype

Exclusion Criteria

• risk for Down syndrome< 1/250 or >1/5
• NT> 3 mm, PAPP-A or beta HCG <0.3 MoM or >5 MoM
• multiple pregnancy , vanishing twin
• morphological abnormalities at US
• Kown chromosomal anomaly in parents
• Patients not willing a fetal karyotype

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Invasive Prenatal Testing	Invasive Prenatal Testing	CVS or amniocentesis
Non Invasive Prenatal Testing	Non Invasive Prenatal Testing	Blood sample

Primary Outcome Measures

Name	Time	Method
Number or miscarriages	at birth

Secondary Outcome Measures

Name	Time	Method
Cost of invasive tests and NIPT in euros	at birth	measure in euros
Number or invasive tests	at birth
false positive and negative rates of NIPT	At birth
Dedicated questionnaire for patients	day 5

Trial Locations

Locations (1)

Hôpital Necker- Enfants Malades; 🇫🇷 Paris, France