Objective:To investigate the genetic causes of fetuses with abnormal nasal bone development in early pregnancy.Methods:A retrospective study was conducted which involved 422 cases of singleton pregnancies with nasal bone development abnormalities indicated by ultrasound screening at 11 to 13 weeks and 6 days of gestation, who underwent chorionic villus sampling for prenatal diagnosis at the Prenatal Diagnosis and Genetic Center, Maternity & Child Health Hospital of Guangxi Zhuang Autonomous Region from January 2015 to May 2023. All cases underwent chromosomal karyotype analysis and single nucleotide polymorphism array (SNP-array) analysis. Based on whether other abnormal ultrasound indicators were present, the cases were divided into isolated (175 cases) and non-isolated groups (247 cases). The results of invasive prenatal diagnosis, distribution of chromosomal abnormalities, detection of copy number variation (CNV) in fetuses with nasal bone development abnormalities, the relationship between maternal age, number of abnormal ultrasound indicators and chromosomal abnormalities, and pregnancy outcomes were analyzed. Statistical analysis was performed using the Chi-square test (continuity correction Chi-square test or Fisher's exact test). Results:(1) Among the 422 cases, 262 cases (62.1%) showed no abnormalities with both detection techniques; 160 cases had abnormalities, including 145 cases (34.4%) had consistent abnormal results and types of abnormalies with the two techniques; two cases (0.5%) had chromosomal translocations detected by karyotype analysis but not by SNP-array analysis; 13 cases (3.1%) had no abnormalities detected by karyotype analysis but had abnormal SNP-array results. This study's overall detection rate of chromosomal abnormalities was 37.9% (160/422), with an additional detection rate of 4.7% (13/275) using SNP-array technology. (2) Among the 160 cases of chromosomal abnormalities, there were 140 cases of aneuploidy, 18 cases of CNV, and two cases of chromosomal translocation. The overall detection rate of chromosomal abnormalities and the detection of aneuploidy, and pathogenic CNV in the non-isolated group was higher than that in the isolated group [74.3% (130/175) vs. 12.1% (30/247), χ2=168.02; 68.0% (119/175) vs. 8.5% (21/247), χ2=163.56; 5.7% (10/175) vs. 0.8% (2/247), χ2=4.74; all P<0.05]. Eighteen cases of CNV were detected using SNP-array technology, including eight cases in the isolated group and ten cases in the non-isolated group. (3) The age of the 422 pregnant women was (33.1±5.4) years. In both isolated and non-isolated groups, the detection rate of chromosomal abnormalities was higher in women of advanced age (expected delivery age ≥35 years) than those not [isolated group: 20.0% (17/85) vs. 8.6% (14/162), χ2=6.55; non-isolated group: 82.1% (69/84) vs. 65.9% (60/91), χ2=5.92; both P=0.010]; regardless of maternal age, the detection rate of chromosomal abnormalities in the non-isolated group was significantly higher than that in the isolated group ( χ2 were 65.28 and 92.42, respectively, both P<0.001). (4) In the non-isolated group, the detection rates of chromosomal abnormalities were 69.0% (78/113) and 83.9% (52/62) when nasal bone abnormalities were combined with one or more other abnormal ultrasound indicators, respectively. When combined with increased nuchal translucency, the detection rate of fetal chromosomal abnormalities was 73.2% (71/97), higher than the detection rate when combined with other single indicators (7/16) ( χ2=5.57, P=0.020). (5) Among the 262 cases with negative karyotype analysis and SNP-array results, 241 cases (92.0%) resulted in live births, with a gestational age at delivery of 39 weeks (32-41 weeks); 12 cases (4.6%) resulted in induced labor, five cases (1.9%) resulted in miscarriage, and four cases (1.5%) were lost to follow-up. The live birth rate in the isolated group was higher than that in the non-isolated group [86.9% (213/245) vs. 20.2% (35/173), χ2=187.00, P<0.001]. Conclusions:Fetuses with nasal bone developmental abnormalities in early pregnancy have a higher detection rate of chromosomal abnormalities and CNV. Invasive prenatal diagnosis is recommended for cases of nasal bone developmental abnormalities in early pregnancy, whether isolated or non-isolated. When combined with other abnormal indicators, the genetic etiology of the fetus is more complex, and detailed genetic counseling should be provided to the patient.

Objective:To investigate the genetic causes of fetuses with abnormal nasal bone development in early pregnancy.Methods:A retrospective study was conducted which involved 422 cases of singleton pregnancies with nasal bone development abnormalities indicated by ultrasound screening at 11 to 13 weeks and 6 days of gestation, who underwent chorionic villus sampling for prenatal diagnosis at the Prenatal Diagnosis and Genetic Center, Maternity & Child Health Hospital of Guangxi Zhuang Autonomous Region from January 2015 to May 2023. All cases underwent chromosomal karyotype analysis and single nucleotide polymorphism array (SNP-array) analysis. Based on whether other abnormal ultrasound indicators were present, the cases were divided into isolated (175 cases) and non-isolated groups (247 cases). The results of invasive prenatal diagnosis, distribution of chromosomal abnormalities, detection of copy number variation (CNV) in fetuses with nasal bone development abnormalities, the relationship between maternal age, number of abnormal ultrasound indicators and chromosomal abnormalities, and pregnancy outcomes were analyzed. Statistical analysis was performed using the Chi-square test (continuity correction Chi-square test or Fisher's exact test). Results:(1) Among the 422 cases, 262 cases (62.1%) showed no abnormalities with both detection techniques; 160 cases had abnormalities, including 145 cases (34.4%) had consistent abnormal results and types of abnormalies with the two techniques; two cases (0.5%) had chromosomal translocations detected by karyotype analysis but not by SNP-array analysis; 13 cases (3.1%) had no abnormalities detected by karyotype analysis but had abnormal SNP-array results. This study's overall detection rate of chromosomal abnormalities was 37.9% (160/422), with an additional detection rate of 4.7% (13/275) using SNP-array technology. (2) Among the 160 cases of chromosomal abnormalities, there were 140 cases of aneuploidy, 18 cases of CNV, and two cases of chromosomal translocation. The overall detection rate of chromosomal abnormalities and the detection of aneuploidy, and pathogenic CNV in the non-isolated group was higher than that in the isolated group [74.3% (130/175) vs. 12.1% (30/247), χ2=168.02; 68.0% (119/175) vs. 8.5% (21/247), χ2=163.56; 5.7% (10/175) vs. 0.8% (2/247), χ2=4.74; all P<0.05]. Eighteen cases of CNV were detected using SNP-array technology, including eight cases in the isolated group and ten cases in the non-isolated group. (3) The age of the 422 pregnant women was (33.1±5.4) years. In both isolated and non-isolated groups, the detection rate of chromosomal abnormalities was higher in women of advanced age (expected delivery age ≥35 years) than those not [isolated group: 20.0% (17/85) vs. 8.6% (14/162), χ2=6.55; non-isolated group: 82.1% (69/84) vs. 65.9% (60/91), χ2=5.92; both P=0.010]; regardless of maternal age, the detection rate of chromosomal abnormalities in the non-isolated group was significantly higher than that in the isolated group ( χ2 were 65.28 and 92.42, respectively, both P<0.001). (4) In the non-isolated group, the detection rates of chromosomal abnormalities were 69.0% (78/113) and 83.9% (52/62) when nasal bone abnormalities were combined with one or more other abnormal ultrasound indicators, respectively. When combined with increased nuchal translucency, the detection rate of fetal chromosomal abnormalities was 73.2% (71/97), higher than the detection rate when combined with other single indicators (7/16) ( χ2=5.57, P=0.020). (5) Among the 262 cases with negative karyotype analysis and SNP-array results, 241 cases (92.0%) resulted in live births, with a gestational age at delivery of 39 weeks (32-41 weeks); 12 cases (4.6%) resulted in induced labor, five cases (1.9%) resulted in miscarriage, and four cases (1.5%) were lost to follow-up. The live birth rate in the isolated group was higher than that in the non-isolated group [86.9% (213/245) vs. 20.2% (35/173), χ2=187.00, P<0.001]. Conclusions:Fetuses with nasal bone developmental abnormalities in early pregnancy have a higher detection rate of chromosomal abnormalities and CNV. Invasive prenatal diagnosis is recommended for cases of nasal bone developmental abnormalities in early pregnancy, whether isolated or non-isolated. When combined with other abnormal indicators, the genetic etiology of the fetus is more complex, and detailed genetic counseling should be provided to the patient.