Relationship Between the Timing of Fetal Nasal Bone Abnormalities and Fetal Chromosomal Anomalies: A Retrospective Study in a Chinese Cohort
Authors: Wei Yiyun , Wei Changqiang , Pan， Weicheng , Cheng Jinlian , Tan Xuemei , Pang Lihong 
Published: January 2024

Abstract
Objective:
The primary objective of this study is to explore the potential correlation between the timing of fetal nasal bone abnormalities and the occurrence of fetal chromosomal anomalies. Nevertheless, there is a paucity of research addressing the possible relationship between the precise timing of nasal bone abnormalities and their correlation with the specific type and severity of chromosomal anomalies. Furthermore, the study aims to explore the synergistic utilization of copy number variation sequencing (CNV-seq) and chromosome karyotype analysis as a combined approach for prenatal diagnosis.
Methods:
This study enrolled a total of 128 women who were diagnosed with fetal nasal bone absence or hypoplasia and underwent prenatal diagnosis. Samples obtained through amniocentesis or cordocentesis were analyzed using CNV-seq and chromosome karyotype analysis. Follow-up was conducted for all cases. The timing of nasal bone abnormalities, gestational age at detection, and the types of chromosomal anomalies identified were analyzed and compared.
Result：
A total of 129 samples were collected. Chromosomal anomalies were detected in 20 cases (15.75%) out of 127, comprising 17 cases of aneuploid abnormality, 1 case of structural abnormality, and 2 cases of large fragment duplication. CNV-seq identified 4 additional cases of pathogenic copy number variations and 9 cases of uncertain significance copy number variations (VUS), increasing the detection rate of chromosome abnormalities to 24.03% (31/129).
Ultrasound identified nasal bone anomalies in 77 fetuses during both the first and second trimesters (Group 1) and in 52 fetuses during the second trimester (Group 2). Group 1 exhibited a significantly higher prevalence of genomic abnormalities compared to Group 2 [31.27% (24/77) vs 13.46% (7/52), χ2=5.331, P＜0.05]. Furthermore, a significant difference was observed in the incidence of chromosomal abnormalities between cases of solitary nasal bone anomaly and those with combined nasal bone anomalies [14.46% (12/83) vs 41.30% (19/46), χ2=11.685, P＜0.01]. However, no significant difference was found in the incidence of chromosomal abnormalities between fetuses with nasal bone absence and those with nasal bone hypoplasia [27.96% (26/93) vs 13.89% (5/36), χ2=2.814, P＞0.05].
Ultrasonography conducted during both the early and second trimesters revealed that fetuses exhibiting abnormal nasal bone development were at a higher risk of chromosomal abnormalities compared to those where abnormal nasal bone development was first detected in the second trimester. Fetal nasal bone anomaly should be regarded as a significant marker for prenatal diagnosis and utilized as the foundation for additional testing, especially when combined with other soft markers or structural abnormalities that significantly elevate the probability of chromosomal abnormalities. The combination of chromosome karyotype analysis and CNV-seq should be employed to improve diagnostic accuracy and furnish supplementary information for evaluating fetal prognosis.
Conclusion:
This study sheds light on the potential relationship between the timing of fetal nasal bone abnormalities and fetal chromosomal anomalies. The findings have implications for antenatal screening and diagnostic strategies, emphasizing the importance of considering both the presence of the nasal bone and its timing when evaluating the risk of chromosomal anomalies. Further research is warranted to confirm and extend these preliminary findings, potentially enhancing the accuracy and effectiveness of prenatal screening programs.