How to Integrate Cell-Free DNA Screening With Sonographic Markers for Aneuploidy: An Update

Area of Science:

• Maternal-Fetal Medicine
• Prenatal Diagnostics
• Medical Ultrasound

Background:

• Sonologists identify soft markers in ~10% of second-trimester anatomy scans.
• Management of these findings, such as choroid plexus cysts (CPCs) and echogenic intracardiac focus (EIF), can be uncertain.
• This review focuses on six common sonographic markers: CPCs, ventriculomegaly (VM), EIF, urinary tract dilation (UTD), fetal echogenic bowel (FEB), and limb shortening.

Purpose of the Study:

• To outline appropriate management strategies for patients with specific sonographic soft markers.
• To review the role and integration of cell-free DNA (cfDNA) screening in the context of these ultrasound findings.
• To clarify the genetic and non-genetic implications of isolated versus associated soft markers.

Main Methods:

• Review of current literature and clinical guidelines regarding sonographic soft markers.
• Analysis of the diagnostic utility of cell-free DNA screening in conjunction with ultrasound findings.
• Discussion of the management pathways for specific fetal anomalies detected via ultrasound.

Main Results:

• Cell-free DNA screening is increasingly replacing traditional ultrasound markers for aneuploidy screening.
• Normal cfDNA results diminish the genetic significance of many isolated soft markers like CPCs and EIF.
• Certain findings, including VM, true FEB, significant limb shortening, and pyelectasis, still warrant further investigation for non-genetic causes.

Conclusions:

• Ultrasound markers are transitioning from primary aneuploidy screens to indicators for offering cfDNA testing.
• Isolated soft markers with normal cfDNA results are generally considered low-risk for aneuploidy.
• Further workup is recommended for specific markers to assess non-genetic associations, and positive cfDNA screens require diagnostic confirmation.