PErsonalized Genomics for Prenatal Abnormalities Screening USing Maternal Blood

Not Applicable

Active, not recruiting

• Conditions: Prenatal Disorder; Aneuploidy
• Interventions: Diagnostic Test: Traditional integrated prenatal screening; Diagnostic Test: First-tier Non-invasive prenatal screening (NIPS); Diagnostic Test: Second-tier Non-invasive prenatal screening (NIPS); Diagnostic Test: Invasive prenatal testing for fetal aneuploidy

• Registration Number: NCT03831256
• Lead Sponsor: CHU de Quebec-Universite Laval

Brief Summary

This project aims to provide high- quality evidence to inform decisions by health care organisations about using first-tier non-invasive prenatal screening (NIPS) to replace traditional screening tests for trisomy 21, and potentially to screen for other fetal chromosome anomalies. We will compare the current screening approach of second-tier NIPS with the use of first-tier NIPS in a large cohort of pregnant women.

Detailed Description

There is some data on the performance of NIPS as a first tier screening test but our systematic review has shown that no trial comparing the effectiveness (utility) of 2nd-tier NIPS with that of first-tier NIPS has been published . Further it is important for health care decision makers to have evidence produced in Canada since the geographical context of healthcare can affect uptake as well as patient decision and thus their healthcare trajectories. There is a need for a trial that is between an explanatory trial and a pragmatic trial to provide the types of answer that we aim to document in the present state of knowledge on NIPS-based screening strategies in Canada. Our Objective is to perform a pan-Canadian large-scale comparative utility (clinical outcomes) study of first-tier NIPS (expanded or not) as compared to the new standard of care (NIPS as a 2nd tier test performed much later during pregnancy and only in high risk pregnancies).

Study Timeline

• Study First Submitted: 2019-01-21
• Study First Submitted QC: 2019-02-04
• Study First Posted: 2019-02-05
• Study Start: 2020-01-13
• Primary Completion: 2023-12-31
• Status Verified: 2025-02
• Last Update Submitted: 2025-02-10
• Last Update Posted: 2025-02-12
• Study Completion: 2025-06-30

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: Female
• Target Recruitment: 7849

Inclusion Criteria

• Pregnant women 19 years or older wanting prenatal screening
• 10-13+6 wks determined by dating ultrasound or last menstrual period.
• Not intending to pursue self pay NIPT

Exclusion Criteria

• Known fetal anomaly at the time of recruitment
• Multiple gestation
• Known twin demise
• Planned CVS or amnio for known genetic condition.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Standard of care (2nd tier NIPS)	Traditional integrated prenatal screening	For the standard-of-care arm (2nd tier NIPS) women will undergo Traditional integrated prenatal screening i.e. traditional biochemical (+/- NT) and those with a positive screen for T21 or T18 will be offered Second-tier Non-invasive prenatal screening (NIPS) (for T21, T18, T13) or Invasive prenatal testing for fetal aneuploidy. Ultrasound examination in first and second trimester will be done based on clinical care practice ordered by health care provider. Pregnant women with a positive NIPS test will be offered Invasive prenatal testing for fetal aneuploidy (fetal chromosome analysis).
Standard of care (2nd tier NIPS)	Second-tier Non-invasive prenatal screening (NIPS)	For the standard-of-care arm (2nd tier NIPS) women will undergo Traditional integrated prenatal screening i.e. traditional biochemical (+/- NT) and those with a positive screen for T21 or T18 will be offered Second-tier Non-invasive prenatal screening (NIPS) (for T21, T18, T13) or Invasive prenatal testing for fetal aneuploidy. Ultrasound examination in first and second trimester will be done based on clinical care practice ordered by health care provider. Pregnant women with a positive NIPS test will be offered Invasive prenatal testing for fetal aneuploidy (fetal chromosome analysis).
Standard of care (2nd tier NIPS)	Invasive prenatal testing for fetal aneuploidy	For the standard-of-care arm (2nd tier NIPS) women will undergo Traditional integrated prenatal screening i.e. traditional biochemical (+/- NT) and those with a positive screen for T21 or T18 will be offered Second-tier Non-invasive prenatal screening (NIPS) (for T21, T18, T13) or Invasive prenatal testing for fetal aneuploidy. Ultrasound examination in first and second trimester will be done based on clinical care practice ordered by health care provider. Pregnant women with a positive NIPS test will be offered Invasive prenatal testing for fetal aneuploidy (fetal chromosome analysis).
First-tier NIPS	First-tier Non-invasive prenatal screening (NIPS)	For the intervention arm (1st tier NIPS) women will receive First-tier Non-invasive prenatal screening (NIPS) i.e. provide a blood sample between 10-13+5 weeks gestation with NIPS results within 7 - 10 days of sample collection. Ultrasound examination in first and second trimester will be done based on clinical care practice ordered by health care provider. In case of a failed NIPS test (expected to be between 2% and 4% of samples), a new blood sample will be drawn for NIPS retest as well as for a traditional SIPS(serum integrated prenatal screening) or QUAD(quadruple marker prenatal screening) screen (depending on gestational age). Pregnant women with a positive NIPS test will be offered Invasive prenatal testing for fetal aneuploidy (fetal chromosome analysis).
First-tier NIPS	Invasive prenatal testing for fetal aneuploidy	For the intervention arm (1st tier NIPS) women will receive First-tier Non-invasive prenatal screening (NIPS) i.e. provide a blood sample between 10-13+5 weeks gestation with NIPS results within 7 - 10 days of sample collection. Ultrasound examination in first and second trimester will be done based on clinical care practice ordered by health care provider. In case of a failed NIPS test (expected to be between 2% and 4% of samples), a new blood sample will be drawn for NIPS retest as well as for a traditional SIPS(serum integrated prenatal screening) or QUAD(quadruple marker prenatal screening) screen (depending on gestational age). Pregnant women with a positive NIPS test will be offered Invasive prenatal testing for fetal aneuploidy (fetal chromosome analysis).

Primary Outcome Measures

Name	Time	Method
Gestational age at diagnosis	Up to 24 weeks of gestational age	gestational age at final result in the sub-set of participants that have received a positive NIPS result and that have been offered diagnostic testing

Secondary Outcome Measures

Name	Time	Method
Gestational age at positive screening result	Up to 24 weeks of gestational age	gestational age at final result in the sub-set of participants that have received a positive screening result
proportion of women with no results	Up to 24 weeks of gestational age	proportion of women with no NIPS result at first and second attempt
Gestational age at negative screening result	Up to 24 weeks of gestational age	gestational age at final result in the sub-set of participants that have received a negative screening result
numbers of days for women with false positive result of screen to wait for result of definite test	Up to 24 weeks of gestational age	Difference between gestational age (in days) at first positive prenatal screening result and final negative screening result
Change in PROMIS-29 Score	At weeks of gestation 10-13, week 16 and week 22	The PROMIS-29 assesses seven health domains: physical function, anxiety, depression, fatigue, sleep disturbance, pain interference, and ability to participate in social roles and activities. Each of the seven domains has four questions which are scored on a five-point Likert scale. The PROMIS-29 scales will be scored using a T-score metric method available at the Assessment Center website (http://assessmentcenter.net). A score of 50 points represents the population average for each scale, and 10 points represent one standard deviation. Higher scores mean more of the specific scale's construct, which may indicate a desirable or an undesirable outcome. The assessment will be done at recruitment (10-13 weeks of gestation) and at week 16 and week 22 of gestation.
gestational age at termination of pregnancy	Up to 24 weeks of gestational age	Gestational age at termination of pregnancy for participants having volountary termination
Change in PROMIS Emotional Distress - Anxiety - Short Form 8a Score	At weeks of gestation 10-13, 16 and 22	The PROMIS-Anxiety short form assesses anxiety with 8 questions. The form includes 8 items and uses a scale of 1-5 (1=Never, 2=Almost never, 3= Sometimes, 4=Often, 5=Almost always). The raw score is the sum of the points for each response. A higher than average raw score indicates higher than average anxiety. A higher score represents higher levels of anxiety. The assessment will be done at recruitment (10-13 weeks of gestation) and at week 16 and week 22 of gestation.
Patient-Reported Experience Measure (PREM) - Score	At 22 weeks of gestation	A 17-questions validated PREM questionnaire on pregnancy experience that measures three dimensions - type of prenatal care received and test results (seven questions), pregnancy visits (four questions (scales 1-5) and prenatal screening experience (six questions).; A profile score by looking at frequencies of responses for each item will be used.
percentage of women undergoing invasive diagnostic testing	Up to 24 weeks of gestational age	see outcome title

Trial Locations

Locations (6)

CHU Ste-Justine; 🇨🇦 Montreal, Quebec, Canada

Prince Rupert Regional Hospital; 🇨🇦 Prince Rupert, British Columbia, Canada

CHU de Québec - Université Laval; 🇨🇦 Québec City, Quebec, Canada

Kelowna Regional Fertility Center; 🇨🇦 Kelowna, British Columbia, Canada

CIUSSS Côte-Nord; 🇨🇦 Sept-Îles, Quebec, Canada

Children's & Women's Health Centre; 🇨🇦 Vancouver, British Columbia, Canada