Prenatal Screening for Down Syndrome and Chromosomal Anomalies

(PEGASUS-2 Trial)

Not currently recruiting at 6 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method to screen for Down syndrome and other chromosomal conditions in unborn babies. Researchers compare a first-tier non-invasive prenatal screening (NIPS), which requires only a blood sample, to traditional methods that combine blood tests and ultrasounds. The goal is to determine if the simpler NIPS can effectively replace older methods. Pregnant women between 10 and 14 weeks along who seek prenatal screening but do not plan to pay for their own NIPT might be suitable candidates. As an unphased trial, this study offers participants the chance to contribute to potentially groundbreaking advancements in prenatal screening.

Will I have to stop taking my current medications?

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

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Previous studies have shown that first-tier Non-invasive prenatal screening (NIPS) is very safe and accurate. It avoided the need for more invasive tests in 98% of cases and rarely missed any conditions it checked for, with a false-negative rate of just 0.06%. For Down syndrome, it detected 98.8% of cases, with a false-positive rate of only 0.04%. This demonstrates that NIPS is both effective and safe, with very few incorrect results.

Research indicates that invasive prenatal testing can safely diagnose genetic conditions early in pregnancy. It provides detailed information about the baby's chromosomes, which are structures in cells that carry genes. Although invasive tests involve taking a sample from around the baby and carry some risk, experienced healthcare providers consider them safe.

Overall, both screening methods in this study are well-tolerated. NIPS is non-invasive and poses minimal risk, while invasive testing is safe when needed for further diagnosis. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it could redefine prenatal screening for Down syndrome and other chromosomal anomalies. The trial explores using First-tier Non-invasive Prenatal Screening (NIPS) as an initial step, which is less invasive than traditional methods like amniocentesis. This means it can provide early and reliable results with just a simple blood test. Additionally, it aims to reduce the number of unnecessary invasive procedures, which carry risks for both the mother and the baby. By comparing it with the standard method of second-tier NIPS following biochemical screening, researchers hope to demonstrate that starting with NIPS could be a more effective and safer option for expectant mothers.

What evidence suggests that this trial's treatments could be effective for prenatal screening?

Research shows that Non-invasive prenatal screening (NIPS), available to participants in the First-tier NIPS arm of this trial, effectively detects chromosomal issues like Down syndrome. Studies indicate that NIPS correctly identifies these conditions 92% to 99% of the time and confirms their absence with over 99% accuracy. This means it excels at detecting these conditions and rarely gives false alarms. Additionally, 98% of cases using NIPS did not require further invasive tests. Participants in the Standard of care arm may undergo Second-tier NIPS, which also performs well, with many choosing it and very few false negatives. Overall, NIPS is a reliable and less invasive option for prenatal screening. ^{1 2 4 6 7}

Who Is on the Research Team?

Sylvie Langlois, MD FRCPC

Principal Investigator

University of British Columbia

Francois Rousseau, MD MSc FRCPC

Principal Investigator

CHU de Québec - Université Laval

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

Citations

1. sciencedirect.com sciencedirect.com/science/article/pii/S109836002105214X

Outcome of publicly funded nationwide first-tier ... With test sensitivities ranging between 92% and 99% for the viable trisomies 21, 18, and 13 and a specificity of >99%, NIPS outperforms traditional combined ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/33564150/

Outcome of publicly funded nationwide first-tier ... Results: Trisomies 21, 18, and 13 were detected in respectively 0.32%, 0.07%, and 0.06% of cases, with overall positive predictive values (PPVs) ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10417786/

Non-Invasive Prenatal Testing (NIPT): Reliability, Challenges ... The study showed that 98% of cases avoided invasive diagnostic procedures while having a very low false-negative rate of 0.06%. 2.1.3. India.

4. nature.com nature.com/articles/s41598-024-73183-4

Clinical strategy study on prenatal screening and ... Clinical performance of non-invasive prenatal served as a first-tier screening test for trisomy 21, 18, 13 and sex chromosome aneuploidy in a ...

5. frontiersin.org frontiersin.org/journals/public-health/articles/10.3389/fpubh.2025.1535381/full

Cost-effectiveness of different screening strategies for ... The universal NIPT screening strategy demonstrated the best effectiveness, detecting 163 DS cases with the highest net benefit and a cost- ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S1098360022010048

ACMG Practice Guideline Noninvasive prenatal screening ... Specifically, the detection rate for fetal trisomy 21 (T21) was 98.8% (95% CI = 97.8%-99.3%) with a corresponding false-positive rate (FPR) of 0.04% (95% CI = ...

7. bmj.com bmj.com/content/354/bmj.i3426

prospective cohort study in eight diverse maternity units Of 71 pregnancies with a confirmed diagnosis of Down's syndrome, 13/42 (31%) with the diagnosis after NIPT and 2/29 (7%) after direct invasive ...