First Trimester Risk Assessment Based on Ultrasound and Cell-free DNA vs Combined Screening
Condition: Aneuploidy
MeSH terms: Aneuploidy
Study type: Interventional

Summary: 
      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.
    


Intervention name(s): NIPT; combined screening
Intervention type(s): Diagnostic Test; Diagnostic Test
Intervention description(s): 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.; 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.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Other