Strengths and Limitations
A major strength of our study is the large sample size including 43,721
fetuses with low-pass GS and ultrasonography. Most previous studies
explored the yield of pCNV in fetuses with ultrasonographic phenotype by
using CMA frequently in small cohorts. Secondly, all anatomical system
anomalies were included rather than several common systems only, which
makes our study more representative and generalizable. In addition, the
contribution of aneuploidy/pCNV to fetuses with ultrasonographic
abnormalities was evaluated by comparing with the group without
identifiable anomalies, providing a powerful and objective guidance for
prenatal genetic diagnosis.
This study had some limitations. There was no further ultrasonographic
imaging
follow-up, which might have overestimated the contribution of
chromosomal aberrations in fetuses with normal ultrasonographic
findings. Also, postnatal outcome
data were unavailable to verify prenatal ultrasonographic anomalies.
Furthermore, this study only considered chromosomal-level variations,
and lacked gene-level variations. We expected future study could combine
whole exome sequencing and cytogenetic methods to improve the
identification of genetic disorder in fetuses with ultrasonographic
anomalies.34-36 Meanwhile, due to lack of fetuses with
normal ultrasonography and maternal age <35 years, no
comparison was performed for the yield of aneuploidy between fetuses
with abnormal ultrasonographic findings and control group. Finally, some
overlap may occur between soft markers and anomaly groups, as reports of
increased nuchal translucency, thickened nuchal fold and cystic hygroma
from different centers and at different gestational weeks, may present
within the same group. Despite our best efforts to classify the
ultrasonographic anomalies, an international uniform classification
system is still lacking. Therefore, we advocate implementation of such a
system to facilitate the comparability of cohorts.