Using rapid genome sequencing for prenatal diagnosis of congenital malformations

Evaluation of Rapid First-line Genome Sequencing for Prenatal Diagnosis of Congenital Malformations in Comparison With Chromosomal Microarray and Exome Sequencing

This study is testing if quick genetic testing during pregnancy can better diagnose birth defects seen on ultrasounds compared to traditional methods.

Quick facts

• Study type: Observational
• Enrollment: 180 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Centre Hospitalier Universitaire Dijon (Academic / other)
• Locations: 1 site (Dijon)
• Trial ID: NCT06252415 on ClinicalTrials.gov

What this trial studies

This study evaluates the effectiveness of rapid genome sequencing as a first-line diagnostic tool for congenital malformations during pregnancy, comparing it to traditional methods like chromosomal microarray and exome sequencing. It focuses on pregnancies between 17 to 34 weeks of gestation that present with ultrasound anomalies. The study involves collecting amniotic fluid and blood samples from both parents, along with conducting semi-structured online interviews to gather qualitative data. The goal is to improve diagnostic rates and inform couples about their pregnancy management options.

Who should consider this trial

Good fit: Ideal candidates include pregnant women between 17 to 34 weeks of gestation with ultrasound anomalies and couples who may benefit from an etiological diagnosis.

Not a fit: Patients who are not pregnant or those with no ultrasound anomalies may not receive any benefit from this study.

Why it matters

Potential benefit: If successful, this approach could significantly enhance the diagnostic accuracy for congenital malformations, leading to better-informed decisions for expectant parents.

How similar studies have performed: Other studies have shown promising results with genome sequencing in postnatal diagnostics, but this specific application in prenatal settings is relatively novel.

Eligibility criteria

Inclusion Criteria:

* Pregnancies (17 - 34 weeks of gestation (WG)) with US anomalies namely either i) two major anomalies, ii) one major and one minor anomalies, or iii) one anomaly (major or minor) with a strong suspicion of genetic cause (such as corpus callosum anomaly);
* Couples for whom an etiological diagnosis could modify the pregnancy outcome and/or the pre and/or postnatal management;
* Pregnant women who receive invasive prenatal sampling for ES+CMA;
* Sufficient quantity of amniotic fluid to collect an additional sample for GS;
* Possibility of blood samples from the pregnant woman and the biological father;
* Written consent for genetic analysis from pregnant woman and biological father of foetus;
* Provision of signed and dated of both parents' consent form for the study.

For the exploratory qualitative objective/endpoint:

- A least one member of the couple willing to accept 2 telephone or video consultations, and able to speak and understand French.

Exclusion Criteria:

* Refusal of the pregnant woman or biological father to participate in the study; or refusal to collect blood samples from one or both parents;
* Pregnancy before 17 WG or after 34 WG (to limit the risk of reporting results after birth);
* Isolated increase nuchal translucency on ultrasound;
* Couples for whom an etiological diagnosis would not modify the pregnancy outcome;
* Pregnant woman and biological father not affiliated to a social security system or not beneficiaries of such a system;
* Pregnant woman and/or biological father who are protected and unable to understand the protocol and express their consent;
* Pregnant women and/or biological fathers under legal protection (guardianship, tutorship) or to a court order

For the exploratory qualitative objective/endpoint:

- The two members of the couple unable to carry out two one-hour telephone interviews in French.

Where this trial is running

Dijon

• Chu Dijon Bourgogne — Dijon, France (Recruiting)

Study contacts

• Study coordinator: Laurence OLIVIER-FAIVRE

Conditions Congenital Malformation