Clinical trial NCT05290701: Evaluating Prenatal Exome Sequencing Study
Official title: Evaluating Prenatal Exome Sequencing Study
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Congenital Anomalies
Mendelian Disorders
Genetic Diseases, Inborn
Keywords: Prenatal diagnosis
Next Generation Sequencing
Whole Exome Sequencing
Patient perspectives
Clinical Utility
Lead sponsor: Leiden University Medical Center
Sponsor class: OTHER
First posted: 2022-03-22
Enrollment: 235
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Pregnant women with one or more ultrasound findings during the current pregnancy who consent to pES, and their partner.

Brief summary: This study evaluates the impact of the various outcomes of pES (definitive diagnosis, probable diagnosis and IF) on clinical decision making and on parental psychological wellbeing, compared between different analysis strategies to investigate the clinical utility, defined as the balance between potential harms and benefits.

Detailed description: Foetal anomalies as detected on prenatal ultrasound are present in 2-3% of pregnancies. The diagnosis of a genetic syndrome as the underlying cause often has significant consequences for the prognosis and therefore also a significant impact on parental reproductive decision making. In addition to chromosomal testing, prenatal exome sequencing (pES) is increasingly being offered. Although prenatal diagnostic rates are promising, no studies report on the actual implementation of pES in routine care and thus several important knowledge gaps remain regarding clinical utility (the balance between potential harms and benefits) and the preferred analysis strategy (broad versus targeted analysis). A broad analysis has a possible higher diagnostic yield, but it is unknown whether the increased chance of finding an uncertain diagnosis and Incidental Findings outweighs this benefit when it comes to clinical decision making and parental psychological wellbeing. The central aim of this study is to address the knowledge gaps raised above, and increase clinical utility by using the obtained data to improve analysis strategies and to potentially identify new genes.

Eligibility criteria: Inclusion Criteria:

* At least one fetal anomaly detected in the current pregnancy, irrespective of gestational age;
* Pregnancy ongoing;
* Mother at least 18 years old and providing consent for pES;
* If father is available: father at least 18 years old and providing consent for pES.

Exclusion Criteria:

There are no exclusion criteria.

Primary outcomes:
measure: Percentage of definitive diagnoses, probable diagnoses and incidental findings (IF)
timeFrame: 2 years
Secondary outcomes:
measure: Patients perspectives on probable diagnoses and incidental findings including psychological wellbeing as measured by questionnaires.
timeFrame: 2 years
measure: Clinical impact of prenatal exome sequencing (pES)
timeFrame: 2 years
measure: Impact of different analysis strategies on the distribution of the various outcomes of pES (definitive diagnosis, probable diagnosis and incidental findings)
timeFrame: 2 years
Other outcomes:
measure: Number of identified new disease genes
timeFrame: 2 years
Locations:
city: Leiden
country: Netherlands
facility: Leiden University Medical Centre
state: Zuid-Holland
Study officials:
References: