Abstract
ABSTRACT
Objective
Cell‐free DNA whole‐genome screening (cfDNA‐WG) is offered at our institution to patients with abnormal fetal ultrasound findings who decline diagnostic testing. We describe the cfDNA‐WG performance in this clinical population.
Methods
We conducted a retrospective cohort study of singleton pregnancies with abnormal fetal ultrasound findings between April 2018 and July 2024. Descriptive data were abstracted via chart review. When diagnostic testing was performed, this was compared to the cfDNA‐WG results.
Results
376 subjects met the inclusion criteria. Ultrasound findings included multiple congenital anomalies (
n
= 123), isolated structural anomaly (
n
= 132), isolated soft marker (
n
= 63), thickened nuchal translucency (
n
= 50), and fetal growth restriction (
n
= 8). cfDNA‐WG was abnormal in 24 cases (6.4%). Most abnormal results (87.5%) were common whole‐chromosome aneuploidies: Trisomy 21 (
n
= 10), Trisomy 18 (
n
= 6), Trisomy 13 (
n
= 2), and Monosomy
X
(
n
= 3). Other abnormal results included one rare autosomal trisomy (Trisomy 22) and two copy number variants. Diagnostic testing was performed in 42 subjects (11.2%), with seven discordant results, including trisomy 8, four single‐gene disorders, and two chromosomal mosaicisms.
Conclusions
In this cohort with abnormal ultrasound findings, abnormal cfDNA‐WG results primarily reflected common aneuploidies detectable by standard cfDNA. There were five cases with normal cfDNA‐WG in fetuses with significant genetic disorders, limiting the value of normal results.