Prenatal Screening for Down Syndrome and Chromosomal Anomalies

(PEGASUS-2 Trial)

Recruiting at 5 trial locations

Overseen By Sylvie Langlois, MD FRCPC

Age: 18+

Sex: Female

Trial Phase: Academic

Sponsor: CHU de Quebec-Universite Laval

Disqualifiers: Fetal anomaly, Multiple gestation, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

7849 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications.

What data supports the effectiveness of the treatment for prenatal screening for Down Syndrome and chromosomal anomalies?

Research shows that non-invasive prenatal screening (NIPS) is highly effective in detecting chromosomal abnormalities like Down syndrome, with sensitivity and specificity rates of 99% or higher in both single and twin pregnancies. This means NIPS is very accurate in identifying these conditions, making it a reliable option for prenatal screening. ^{1 2 3 4 5}

Is non-invasive prenatal screening (NIPS) safe for humans?

Non-invasive prenatal screening (NIPS) is generally considered safe because it involves analyzing a sample of the mother's blood, which poses no risk to the pregnancy compared to invasive tests that require taking samples from the womb. ^{1 2 6 7 8}

How does the treatment for prenatal screening for Down Syndrome and chromosomal anomalies differ from other treatments?

The treatment for prenatal screening for Down Syndrome and chromosomal anomalies is unique because it includes non-invasive prenatal screening (NIPS) as a first-tier option, which is a blood test that analyzes fetal DNA in the mother's blood, reducing the need for invasive procedures like amniocentesis. This approach is less risky compared to traditional methods that require sampling amniotic fluid or placental tissue. ^{9 10 11 12 13}

Research Team

Sylvie Langlois, MD FRCPC

Principal Investigator

University of British Columbia

Francois Rousseau, MD MSc FRCPC

Principal Investigator

CHU de Québec - Université Laval

Eligibility Criteria

This trial is for pregnant women who are 19 or older, between 10-13+6 weeks into their pregnancy as confirmed by ultrasound or last menstrual period. They should want prenatal screening but not be planning to pay for NIPT themselves. Women with known genetic conditions, fetal anomalies at recruitment time, twin demise, or multiple pregnancies cannot participate.

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

You are pregnant with more than one baby.

Planned CVS or amnio for known genetic condition.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

First-tier NIPS

Participants provide a blood sample between 10-13+5 weeks gestation for NIPS, with results within 7-10 days. Ultrasound examinations are conducted in the first and second trimester.

Up to 24 weeks of gestational age

Multiple visits based on clinical care practice

Standard of care (2nd tier NIPS)

Participants undergo traditional integrated prenatal screening, with second-tier NIPS or invasive testing offered for positive screens.

Up to 24 weeks of gestational age

Multiple visits based on clinical care practice

Follow-up

Participants are monitored for outcomes such as gestational age at diagnosis and changes in PROMIS-29 scores.

Up to 24 weeks of gestational age

Treatment Details

Interventions

• First-tier Non-invasive prenatal screening (NIPS)
• Invasive prenatal testing for fetal aneuploidy
• Second-tier Non-invasive prenatal screening (NIPS)
• Traditional integrated prenatal screening

Trial Overview The study is testing if first-tier Non-invasive Prenatal Screening (NIPS) can replace traditional tests for detecting trisomy 21 and other chromosome abnormalities in fetuses. It compares the effectiveness of first-tier NIPS against second-tier NIPS and integrated prenatal screening in a large group of pregnant women.

Participant Groups

Group I: First-tier NIPS Experimental Treatment 2 Interventions

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).

Group II: Standard of care (2nd tier NIPS) Active Control 3 Interventions

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).

Who Is Running the Clinical Trial?

CHU de Quebec-Universite Laval

Lead Sponsor

Trials

177

Recruited

110,000+

Ottawa Hospital Research Institute

Collaborator

Trials

585

Recruited

3,283,000+

University of British Columbia

Collaborator

Trials

1,506

Recruited

2,528,000+

Canadian Institutes of Health Research (CIHR)

Collaborator

Trials

1,417

Recruited

26,550,000+

Laval University

Collaborator

Trials

439

Recruited

178,000+

St. Justine's Hospital

Collaborator

Trials

205

Recruited

87,300+

Genome Quebec

Collaborator

Trials

8

Recruited

19,800+

Ontario Research Fund

Collaborator

Trials

5

Recruited

8,600+

Genome Alberta

Collaborator

Trials

4

Recruited

13,700+

University of Alberta

Collaborator

Trials

957

Recruited

437,000+

Findings from Research

Non-invasive prenatal screening (NIPS) demonstrated 100% sensitivity and 99.91% specificity in detecting fetal chromosomal abnormalities across 32,361 pregnancies, making it a highly effective method for identifying trisomies 21, 18, and 13.

The performance of NIPS was consistent in both high-risk and low-risk pregnancies, indicating its reliability as a routine screening tool for fetal aneuploidies regardless of the mother's risk status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical evaluation of non-invasive prenatal screening in 32,394 pregnancies from Changzhi maternal and child health care hospital of Shanxi China. Li, X., Wang, L., Yao, Z., et al.[2022]

In a study of 450 mothers with singleton pregnancies, it was found that a higher fetal fraction (FF) of cell-free DNA in maternal blood is associated with fewer risks for both the mother and fetus compared to lower FF levels.

The study suggests that monitoring FF levels can provide valuable insights into pregnancy prognosis, aiding in better management of maternal and fetal health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of The Relationship between Cell-Free DNA Fetal Fraction of The Circulatory System and Fetal and Maternal Pregnancy Prognosis: A Prospective Study. Rezaie Keikhaie, K., Moshfeghi, M., Rezaie Kahkhaie, L., et al.[2023]

Non-invasive prenatal screening (NIPS) demonstrated a remarkable sensitivity of 100% and specificity of 99.46% in detecting major fetal chromosomal abnormalities, based on a study of 6,258 tests conducted in the Andalusian Health System.

The implementation of NIPS significantly reduced the need for invasive diagnostic procedures by 70%, thereby minimizing the risk of miscarriages associated with such invasive tests.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessment of a change of protocol of prenatal screening by inclusion of non-invasive prenatal diagnosis. Cabra-Rodríguez, R., Rodríguez, GB., Rosa, CS., et al.[2023]

References

1. Serbia pubmed.ncbi.nlm.nih.gov

Clinical evaluation of non-invasive prenatal screening in 32,394 pregnancies from Changzhi maternal and child health care hospital of Shanxi China. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Performance of non-invasive prenatal screening for fetal aneuploidy in twin pregnancies: a meta-analysis. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Obstetric professionals' perceptions of non-invasive prenatal testing for Down syndrome: clinical usefulness compared with existing tests and ethical implications. [2018]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Clinical Efficiency of Non-invasive Prenatal Screening for Common Trisomies in Low-Risk and Twin Pregnancies. [2021]

5. Iran pubmed.ncbi.nlm.nih.gov

Evaluation of The Relationship between Cell-Free DNA Fetal Fraction of The Circulatory System and Fetal and Maternal Pregnancy Prognosis: A Prospective Study. [2023]

6. Germany pubmed.ncbi.nlm.nih.gov

Assessment of a change of protocol of prenatal screening by inclusion of non-invasive prenatal diagnosis. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

Analyzing false-negative results detected in low-risk non-invasive prenatal screening cases. [2021]

8. England pubmed.ncbi.nlm.nih.gov

Non-invasive prenatal testing in mitigating concerns from invasive prenatal diagnostic testing: retrospective assessment of utility in an academic healthcare system in the US. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

A randomized comparative effectiveness trial of novel endoscopic techniques and approaches for Barrett's esophagus screening in the community. [2023]

10. United States pubmed.ncbi.nlm.nih.gov

Barrett's esophagus: novel strategies for screening and surveillance. [2020]

11. United States pubmed.ncbi.nlm.nih.gov

Assessment of chromosomal gains as compared to DNA content changes is more useful to detect dysplasia in Barrett's esophagus brush cytology specimens. [2008]

12. Australia pubmed.ncbi.nlm.nih.gov

Risk for esophageal neoplasia in Barrett's esophagus patients with mucosal changes indefinite for dysplasia. [2022]

13. United States pubmed.ncbi.nlm.nih.gov

Fluorescence in situ hybridization identifies high risk Barrett's patients likely to develop esophageal adenocarcinoma. [2019]