BACKGROUND AND PURPOSE:

• Multiple strategies for aneuploidy screening are currently being evaluated
• cfDNA has superior performance characteristics compared to standard first trimester screening (NT + markers) but may miss fetal anatomic/chromosomal anomalies that can be initially detected on ultrasound
• Kagan et al. (Ultrasound Obstet Gynecol, 2017) compared the performance of first trimester standard combined screening with an approach that uses the combination of a detailed ultrasound exam and cfDNA analysis

METHODS:

• Prospective randomized control trial of normal first-trimester ultrasound exam at 11 to 13 weeks’ gestation (2015-2016)
• Subjects were randomized into two groups of assessing aneuploidy risk
  • Standard screening
  • Ultrasound and cfDNA screening if ultrasound is normal
• Blood was retained for standard serum markers in case the cfDNA result was inconclusive
• Primary outcome
  • Number of false positives in screening for trisomy 21
  • False positive defined as normal karyotype if risk for trisomy 21 was >1:100, irrespective of the method of risk calculation

RESULTS:

• 688 women with normal first-trimester ultrasounds were randomized into each group (1) Standard screening cohort and (2) ultrasound + cfDNA cohort
• All 7 cases of DS were detected on ultrasound based on enlarged NT or fetal anomalies, as were trisomy 13 and 18 cases
• When comparing risk assessment using standard screening vs ultrasound + cfDNA cohorts, there were no major demographic differences
• The ultrasound + cfDNA cohort median risk for trisomy 21 was 1 in 10,000
  • None of the cases had a risk above 1:100 [95% CI 0.0 – 0.5%]
• The standard screening cohort median risk for trisomy 21 was 1 in 3,786
  • > 1:100 risk was identified in 17 (2.5%) pregnancies (95% CI 1.5 – 3.9%)

CONCLUSION:

• A first-trimester screening for trisomy 21 using ultrasound, NT measurement, and cfDNA in women without ultrasound anomalies is associated with a significant reduction in the false positive rate compared to standard screening
• This study suggests first trimester serum markers (β-hCG and PAPPA) should not be used
• By including a detailed ultrasound, disadvantages of cfDNA only testing only are overcome
  • Anatomic assessment provided by ultrasound
  • Saving blood for markers if necessary can address the problem of inconclusive cfDNA results

Learn More – Primary Sources:

First trimester screening based on ultrasound and cfDNA vs. first-trimester combined screening – a randomized controlled study.

Related ObG Topics:

Invasive Testing: Are All Centers Seeing a Similar Steep Decline in Procedures?

cfDNA vs. Routine Screening – How Do They Compare?

How Accurate is NIPT as a Screening Test for Chromosomal Aneuploidies?

SMFM Guidance – The Role of Prenatal Ultrasound and NIPT 

Down Syndrome / Trisomy 21: Clinical Findings and Prenatal Considerations