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NCT Number: NCT04077060

First Trimester Risk Assessment Based on Ultrasound and Cell-free DNA vs Combined Screening

There is an ongoing debate regarding how cell-free DNA (cfDNA) screening can best be incorporated into current prenatal screening algorithms for chromosomal abnormalities.

Test performance of cfDNA has been shown to be better that first-trimester combined screening (FTCS). However, the cost of the cfDNA testing is considered too high to adopt as first line screening. Moreover, FTCS includes a detailed ultrasound examination of the fetus with nuchal translucency (NT) measurement that allows for early detection of fetal abnormalities.

An approach in which every woman are offered an early anatomy scan along with cfDNA may also be a reasonable option. Recently a randomized controlled trial, including 1,518 women with singleton pregnancy undergoing first-trimester screening, compared the screening performance of FTCS with an approach that uses the combination of a detailed ultrasound examination and cfDNA analysis. The trial showed that first-trimester risk assessment for trisomy 21 that includes a detailed ultrasound examination along cfDNA was associated with a significant reduction in the false-positive rate compared with FTCS. This approach obviates the need for maternal serum free beta-human chorionic gonadotropin and pregnancy-associated plasma protein-A in screening for fetal aneuploidy.

Despite robust evidence on the very high detection rate of cfDNA in detecting trisomy 21, literature is lacking on data regarding women's experience and emotional well-being and satisfaction after test-results of women offered cfDNA compared to those offered FTCS.

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Key information

Conditions

Aneuploidy Chromosome Aberrations Pathologic Processes Pathological Conditions, Signs and Symptoms

Age range

18 year–45 year

Sex eligibility

Female

Study type

Interventional

Phase

Not applicable

Primary location

Gabriele Saccone

Naples, 80129, Italy

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Pregnant women with singleton gestations
  • ≤12 6/7 weeks of gestation
  • Normal ultrasound examination at the time of randomization
  • >18 <45 years
  • Crown-rump length (CRL) <84 mm at the time of randomization

Exclusion criteria

  • Multiple gestations, including vanishing twins
  • >12 6/7 weeks of gestation
  • Ectopic pregnancy
  • Abnormal ultrasound examination at the time of first prenatal visit
  • Women who are unconscious, severly ill, mentally handicapped, or under the age of 18 years.
  • Women who have already planned for invasive prenatal testing, e.g. for a history of prior child or pregnancy with chromosomal or genetic abnormalities
  • CRL >84mm at the time of randomization

Treatment and study plan

NIPT

Diagnostic Test

Women randomized in the intervention group will be offered cfDNA screening, along with an early detailed anatomy scan, including nuchal measurement, at 11-13 weeks of gestation. cfDNA analysis will include a simultaneous microarray-based assay of non-polymorphic (chromosomes 13, 18, 21, X and Y) and polymorphic loci to estimate chromosome proportion and fetal fraction. NIPT will be performed at the time of randomization or after if gestational age at randomization < 9 6/7 weeks of gestation.

Women in both groups will be given oral counseling by obstetricians and will be counseled about test procedures, reporting time, test sensitivity and specificity, and the necessity to confirm abnormal screening results with invasive testing.

combined screening

Diagnostic Test

Control group includes the standard of care. In our department, first-trimester risk assessment is performed routinely at 11-13 weeks of gestation by FTCS as per standard of care. FTCS includes crown-rump length, NT measurements, and a detailed ultrasound examination based on ISUOG guidelines. All operators who perform this examination are certified by the UK Fetal Medicine Foundation (FMF). A specific risk for aneuploidy is not calculated if NT measurement is >3.5 mm or if fetal anomaly is identified. These cases are deemed to be at a very high risk for chromosomal abnormalities and are offered invasive testing.

Primary outcomes

  1. reassurance

    Time frame: at the time of screening test

    women will be asked about three questions, with up to 35 point for each question. 1) are you reassured about the test? 2) are you sure the test is correct? 3) test give me certain reassurance about the syndrome of my child

  2. Anxiety

    Time frame: at the time of screening test

    anxiety test assessed by State-Trait Anxiety Inventory (STAI)

  3. Satisfaction of the pregnant women

    Time frame: 11-13 weeks of gestation

    women will be asked if retrospectively they are happy with the assigned screening test as post-test satisfaction questionnaire:

    • Not all applicable (5 points)
    • Hardly applicable (10 points)
    • Somewhat applicable (20 points)
    • Very much applicable (35 points)

  4. False positive rate

    Time frame: 1 week after test

    False positive rate for any trosomy and for trisomy 21

  5. Anxiety

    Time frame: at the time of screening test

    anxiety test assessed by The Pregnancy-Related Anxiety Questionnaire (PRAQ-R)

Sponsors and collaborators

Lead sponsor

Federico II University

Other

Registry information

Official study title

First Trimester Risk Assessment Based on Ultrasound and Cell-free DNA vs Combined Screening: Women's Experience

Important dates

Study start
2019
Primary completion
2020
Study completion
2020
First posted
Sep 4, 2019
Registry last updated
Feb 24, 2020

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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