Clinical Trial: Trisomy of Chromosome 21 Diagnosis by High Output Sequencing

Study Status: Completed
Recruit Status: Completed
Study Type: Observational

Official Title: Trisomy of Chromosome 21 Diagnosis by High Output Sequencing of Foetal Circulating DNA in Mother Blood at First Trimester of Pregnancy.

Brief Summary: Demonstrate that the High output shotgun sequencing of the foetal DNA in the maternal blood could allow a complete discrimination between the mothers of a trisomic fetus 21 or a DISOMIQUE foetus 21 from the first quarter of the pregnancy, and so to obtain a reliable alternative in invasive procedure.

Detailed Summary:

Justification of the research :

The trisomy 21 is the most frequent cause of handicap of genetic origin with an incidence of 1.3/1 000 births which increases with the maternal age. Several strategies of antenatal screening were developed. The High Authority of Health recently recommended to propose to the pregnant women a 1st trimester combined screening, realized between 11+0 and 13+6 weeks of amenorrhoea, associating measure of the NUCALE translucency and dosage in maternal serum : PAPP-A (Pregnancy Associated Plasma Protein A) and βhCG (free β human Chorionic 1st trimester Gonadotrophin). However, the sensibility of these screening tests is about 80 % for 5 % of positive false. The diagnosis of aneuploidy is then established on a population classified at high risk, by a foetal karyotype (requiring an invasive procedure : biopsy of trophoblast or amniocentesis). A positive screening increase maternal and medical anxiety. Furthermore, the inappropriate combination of the tests is at the origin of numerous useless invasive procedures (national rate of amniocentesis of 11 %), at risk of foetal losses (0,5 in 1 %). This inflation of invasive procedures leads to so many losses of not affected children as trisomic children and to a badly known maternal morbidity.

Several studies showed that 10 % of the free DNA found from the first quarter of the pregnancy in the maternal plasma is of foetal origin and that this DNA is specific of the foetal nuclear DNA of the current pregnancy. This opened the way of a possible not invasive antenatal diagnosis of the foetal aneuploidy which collided during the last 10 years with the performances limited by the isolation and by the sequencing of the foetal DNA in the maternal plasma. A new technique of analysis by broadband sequencing of the DNA circulating in the maternal blood for
Sponsor: Assistance Publique - Hôpitaux de Paris

Current Primary Outcome: The diagnostic performances of the quantification of the DNA resulting from the chromosome 21 by High output shotgun sequencing [ Time Frame: 24 MONTHS ]

The diagnostic performances(sensibility and specificity)of the quantification of the DNA resulting from the chromosome 21 by High-througput shotgun sequencing will be estimated in comparison with the results of the traditional cytogenetics obtained by culture of amniocytes or trophoblaste (gold standards).


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • The time necessary for the treatments of samples: [ Time Frame: 24 MONTHS ]
    this one will be estimated at the time means necessities to treat ten first ones and the last ten takings of the study
  • The cost by taking. [ Time Frame: 24 MONTHS ]
    The cost in euro of the high output shotgun sequencing for one blood sample
  • The repeatability of the quantification: [ Time Frame: 24 MONTHS ]
    this will be made by the realization of a double quantification, blind at ten drawn lots patients (these patients will be taken by two tubes instead of the only one and the laboratory will treat both tubes blind, as if they corresponded to two different patients.).


Original Secondary Outcome: Same as current

Information By: Assistance Publique - Hôpitaux de Paris

Dates:
Date Received: April 28, 2010
Date Started: March 2010
Date Completion:
Last Updated: January 2, 2014
Last Verified: February 2011