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.

Objective:To determine the diagnostic accuracy and prognosis of fetal congenital heart disease (CHD) detected by ultrasound at 11-13 weeks gestation.Methods:Fetuses at 11 to 13 + 6 weeks gestation in the Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region between January 2015 and December 2022 were prospectively collected. Standrardized ultrasound was used to examine the fetuses. For the suspected fetal CHD, the section of cardiac ultrasound was improved as far as possible, and ultrasonic results, prenatal diagnosis, pathological anatomy and pregnancy outcome were followed up. Results:A total of 539 cases of CHD were detected in 72 242 fetuses with mixed risk in the first trimester, the incidence was 0.75% (539/72 242). The incidence of CHD in the fetuses with positive soft markers was 9.20% (287/3 118), and the incidence of multiple fetal malformations was 16.22% (235/1 449). The diagnostic accordance rate of complex CHD was 97.42%. For complex CHD, the sensitivity, specificity, false positive rate and false negative rate of first-trimester ultrasound were 90.41%, 99.98%, 0.02%, 9.59%. Combined with the results of this study, the abnormal section model of complex CHD was recommended. A total of 252 cases underwent staining chromosomal microarray or gene sequencing, of which 42.46% (107/252) were positive.Conclusions:Standardized ultrasound examination has a very high detection rate for fetal CHD in the first trimester. Transverse scanning of the heart can significantly improve the display of gray scale cardiac section, and reference to the cardiac section pattern map is beneficial to the early diagnosis of fetal CHD.

Objective:To investigate the value of ultrasonography in diagnosis of transposition of great arteries of the fetus at 11-13 + 6 weeks gestation. Methods:A prospective study was conducted on fetuses screened by ultrasound in the first trimester in Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region between January 2015 and March 2022. Fetal heart structure was screened by three-section screening method. Fetuses with suspected transposition of the great arteries at 11-13 + 6 weeks gestation underwent followed-up ultrasound examination, chromosome and gene test results. The ultrasound characteristics and prognosis pregnancy outcomes were summarized. Results:Twenty-one cases of transposition of the great arteries were detected by ultrasonography, including complete transposition of great arteries (20 cases) and congenitaly corrected transposition of the great arteries (1 case). Two cases were miss diagnosed. Twenty-one cases showed parallel signs of two major arteries on grayscale outflow section at 11-13 + 6 weeks gestation. There were 6 cases with aneuploid ultrasonographic soft markers abnormality, 2 cases with extracardiac malformation. Chromosome and microarray analysis were performed in 13 cases. 4 cases with chromosomal abnormality. Four cases of chromosomal abnormalities were associated with ultrasonographic soft markers abnormality, and 1 case with extracardiac malformation.In the 23 cases, 20 cases were induced, 1 miscarried, and 2 delivered to term. Among the fetuses delivered at term, 1 case died before neonatal operation and 1 case survived. Conclusions:Standardized ultrasound scan at 11-13 + 6 weeks has high accuracy in diagnosis of transposition of the great arteries. And the incidence of chromosomal abnormality is high with ultrasonographic soft markers abnormality or extracardiac malformation.

Objective:To investigate the value of atrioventricular valve regurgitation in predicting atrioventricular septal defect (AVSD) in the first trimester.Methods:Fetuses were examined prospectively by ultrasound at 11-13 + 6 weeks in Maternity & Child Healthcare Hospital of Guangxi Zhuang Autonomous Region between February 2016 and February 2021. Congenital heart disease was screened and atrioventricular valve regurgitation was observed in fetuses of gestational age 11 to 13 + 6 weeks using color Doppler in four-chamber view and three vessels and trachea view. Results:Totally 43 549 fetuses of gestational age 11 to 13 + 6 weeks were screened by echocardiography, of whom 37 cases were screened out with AVSD, including complete atrioventricular septal defect (31 cases), partial atrioventricular septal defect(3 cases) and intermediate atrioventricular septal defect(1 cases), 2 cases were misdiagnosed, and ultrasonic scanning in the second trimester found 2 missed cases of intermediate atrioventricular septal defect. Atrioventricular valve regurgitation was observed in 91.89% of atrioventricular septal defects (34/37) in the first trimester, 59.46% (22/37) nuchal translucency greater than 95th percentile, 29.73% (11/37) absence of nasal bone, 32.43% (12/37) ductus venosus A wave inversion, and 40.54% (15/37) had tricuspid regurgitation. The sensitivity of common atrioventricular valve regurgitation in predicting atrioventricular septal defect is better than other ultrasonic indexes. Conclusions:Atrioventricular regurgitation can be used as a clue to predict atrioventricular septal defect in the first trimester, which is beneficial to detect atrioventricular septal defect in the first trimester.

Objective::The aim of the study was to investigate the pregnancy outcomes and possible influencing factors concerning complicated monochorionic (MC) multiple pregnancies undergoing selective fetal reduction using radiofrequency ablation (RFA).Methods::This retrospective cohort study included 54 women with complicated MC multiple pregnancy who underwent selective fetal reduction using RFA at the Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region from January 2015 to March 2020. According to the indications for RFA, the 54 women were divided into three groups: complex complications ( n = 30), structural anomalies ( n = 18), and triplet pregnancy ( n = 6). According to the gestational age for RFA, all patients were divided into three groups: 16-19 +6 weeks ( n = 17), 20-23 +6 weeks ( n = 17), and 24-26 +6 weeks ( n = 20). We analyzed the pregnancy outcomes (including the overall survival rate (OSR), gestational age at delivery, birth weight of newborns) and postoperative complications such as miscarriage, and intrauterine fetal death (IUFD) according to the indications and gestational age of reduction by using suitable statistical testing. Results::The OSR was 83.3% (45/54). The mean ± standard deviation ( SD) of gestation at the time of reduction was 21.6 ± 3.2 weeks. The GA at delivery was 34.0(32.0,37.5) weeks. The mean ± SD of newborns’ birth weight was 2118 ± 685 g. The overall rates of miscarriage, PROM, and IUFD were 9.3% (5/54), 7.4% (4/54), and 7.4% (4/54), respectively. According to the indications for reduction, the OSR for complex complications, structural anomalies, and triplet pregnancy groups were 83.3% (25/30), 83.3% (15/18), and 83.3% (5/6), respectively. Statistically significant differences were only found in the mean birth weight among the three groups ( P < 0.05). No significant difference was found in the rate of miscarriage, and mean gestation at delivery among the three groups ( P > 0.05). In the group with complex complications, the OSR of twin-to-twin transfusion syndrome, selective intrauterine growth restriction, twin reversed arterial perfusion sequence, and twin anemia polycythemia sequence were 66.7% (6/9), 93.3% (14/15), 80.0% (4/5), and 100.0% (1/1), respectively, with no significant difference among these groups ( P > 0.05). According to the gestational age of reduction, the OSRs among the three groups were 82.4% (14/17), 76.5% (13/17), and 90.0% (18/20), respectively, and the rate of miscarriage, IUFD, and mean gestation age at delivery among these groups showed no significant difference ( P > 0.05). Conclusion::Selective fetal reduction by RFA is an important treatment method for complicated MC multiple pregnancy, although it may lead to complications like miscarriage, and IUFD. The indication of reduction seems to affect the pregnancy outcome. An optimal treatment plan should be selected according to the patient’s conditions in clinical practice.

Objective::The aim of the study was to investigate the pregnancy outcomes and possible influencing factors concerning complicated monochorionic (MC) multiple pregnancies undergoing selective fetal reduction using radiofrequency ablation (RFA).Methods::This retrospective cohort study included 54 women with complicated MC multiple pregnancy who underwent selective fetal reduction using RFA at the Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region from January 2015 to March 2020. According to the indications for RFA, the 54 women were divided into three groups: complex complications ( n = 30), structural anomalies ( n = 18), and triplet pregnancy ( n = 6). According to the gestational age for RFA, all patients were divided into three groups: 16-19 +6 weeks ( n = 17), 20-23 +6 weeks ( n = 17), and 24-26 +6 weeks ( n = 20). We analyzed the pregnancy outcomes (including the overall survival rate (OSR), gestational age at delivery, birth weight of newborns) and postoperative complications such as miscarriage, and intrauterine fetal death (IUFD) according to the indications and gestational age of reduction by using suitable statistical testing. Results::The OSR was 83.3% (45/54). The mean ± standard deviation ( SD) of gestation at the time of reduction was 21.6 ± 3.2 weeks. The GA at delivery was 34.0(32.0,37.5) weeks. The mean ± SD of newborns’ birth weight was 2118 ± 685 g. The overall rates of miscarriage, PROM, and IUFD were 9.3% (5/54), 7.4% (4/54), and 7.4% (4/54), respectively. According to the indications for reduction, the OSR for complex complications, structural anomalies, and triplet pregnancy groups were 83.3% (25/30), 83.3% (15/18), and 83.3% (5/6), respectively. Statistically significant differences were only found in the mean birth weight among the three groups ( P < 0.05). No significant difference was found in the rate of miscarriage, and mean gestation at delivery among the three groups ( P > 0.05). In the group with complex complications, the OSR of twin-to-twin transfusion syndrome, selective intrauterine growth restriction, twin reversed arterial perfusion sequence, and twin anemia polycythemia sequence were 66.7% (6/9), 93.3% (14/15), 80.0% (4/5), and 100.0% (1/1), respectively, with no significant difference among these groups ( P > 0.05). According to the gestational age of reduction, the OSRs among the three groups were 82.4% (14/17), 76.5% (13/17), and 90.0% (18/20), respectively, and the rate of miscarriage, IUFD, and mean gestation age at delivery among these groups showed no significant difference ( P > 0.05). Conclusion::Selective fetal reduction by RFA is an important treatment method for complicated MC multiple pregnancy, although it may lead to complications like miscarriage, and IUFD. The indication of reduction seems to affect the pregnancy outcome. An optimal treatment plan should be selected according to the patient’s conditions in clinical practice.

Objective:To assess the value of ultrasonography in the diagnosis of fetal isomerism syndrome in the first trimester.Methods:Sonographic features of 15 fetuses with isomerism syndrome diagnosed in the Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region from January 2015 to March 2020 were reviewed. Ultrasonic characteristics in the first trimester were analyzed, and the ultrasonic characteristics of early mid-trimester and pathological anatomical results were combined for comparison.Results:There were 6 cases of left isomerism syndrome (LIS) and 9 cases of right isomerism syndrome (RIS) in the 15 fetues.Increased nuchal translucency(NT) (≥3.0 mm, 6 cases), reversed A wave in ductus venosus (10 cases), and atrio-ventricular valve regurgitation (14 cases) were found during the first trimester. There were 14 cases with abnormal visceral laterality. Of the 15 fetues, 14 cases with cardiac malformations, including 6 cases of functional single ventricle, 8 cases of complete atrioventricular septal defect (CAVSD), and 12 cases with great artery abnormalities. All of the 6 LIS cases had bradycardia, 3 cases had interruption of inferior vena cava (IVC). Six cases of RIS had juxtaposition of descending aorta and IVC, and 1 case of RIS had total anomalous pulmonary vein drainage. The major structural malformations were consistent with the early mid-trimester ultrasound examination or autopsy. Karyotype and chromosomal microarray were available in 12 cases and all were normal.Conclusions:Isomerism syndrome has high positive rate of fetal aneuploidies ultrasonographic marker, especially with the atrio-ventricular valve regurgitation, but the risk of chromosome abnormality is low. Ultrasound screening for fetal cardiac structural abnormalities is beneficial to the early diagnosis of isomerism syndrom in the first trimester.

Objective:To explore the feasibility and prognosis of prenatal ultrasonic diagnosis of fetal isolated vascular ring at 11-13 + 6 weeks. Methods:A total of 36 996 fetuses were selected to compare the results of ultrasound screening at 11-13 + 6 weeks and 20-24 weeks of pregnancy in Guangxi Maternity & Child Healthcare Hospital from January 2016 to January 2020, the reasons for missed diagnosis and misdiagnosis of fetal isolated vascular ring by ultrasonography in the first trimester were summarized. Results:Thirty-five cases were diagnosed as isolated vascular ring in the first trimester, including 19 cases right aortic arch combined with aberrant left subclavian artery with "U-shaped" vascular ring, 7 cases double aortic arch with "O-shaped" vascular ring, and 9 cases aberrant right subclavian artery with "C-shaped" vascular ring. While 155 cases were diagnosed as isolated vascular ring at 20-24 weeks of pregnancy, consisting of 18 cases of combined with aberrant left subclavian artery, 9 cases of double aortic arch, 126 cases of aberrant right subclavian artery and 2 cases of pulmonary artery sling, the diagnosis coincidence rates were 94.74%, 77.78%, 7.14%, 0(Kappa value were 0.97, 0.88, 0.13, 0). For the diagnosis of right aortic arch combined with aberrant left subclavian artery, double aortic arch and aberrant right subclavian artery in the first trimester, the specificities were 99.99%, 100%, 100%, the sensitivities were 100%, 77.78%, 7.14%, the false-positive rates were 0.01%, 0, 0, the false-negative rates were 0, 22.22%, 92.86%, and the Youden′s indices were 0.99, 0.78, 0.07.Conclusions:Right aortic arch combined with aberrant left subclavian artery and double aortic arch have high coincidence rate by ultrasonography in the first trimester, while the diagnostic coincidence rate of isolated aberrant right subclavian artery was low. Ultrasound screening for isolated vascular ring in the first trimester still needs ultrasound examination in the second trimester to exclude the minor cardiac malformations that are difficult to diagnose in the first trimester.

Objective: To investigate the echocardiographic characteristics, pathological anatomy and genetic abnormality of congenital absent semilunar valves in first trimester. Methods: Eleven cases of congenital absent semilunar valve fetus diagnosed at 11-13^{+ 6} weeks of gestation in Guangxi Magernity & Child Healthcare Hospital from December 2014 to December 2018 were analyzed. The characteristics of echocardiography and the abnormal microanatomy of cardiac tissue after labor induction was compared. Results: The crown-lump length of the 11 fetus was 46-74(62.0±9.2)mm, and nuchal translucency thickness(NT) was 2.4-10.4 (6.4±2.6)mm. The NT of 10 cases were greater than 3.0 mm. Color Doppler flow imaging revealed that biphasic bidirectional flow in the aortic arch and/or pulmonary artery at the 3VT view( "to-and-fro" ) in those 11 cases, and pansystolic turbulence and pandiastolic reflux spectrum were showed on spectral Doppler. Among them, there were 10 cases of " stealing type" , including 2 cases of isolate absent aortic valves, 3 cases of absent pulmonary valves and 5 cases of absent both aortic and pulmonary valves; and all the 10 cases had secondary ultrasonic manifestations of fetal heart failure. Chromosome analysis and detection of genes showed that 4 cases with Trisomy 13 syndrome, 3 cases with Trisomy 18 syndrome, 1 case with 22q11.2 deletion, 1 case with 12q24.32q24.33 deletion and 1 case was normal. Pathological anatomy revealed enlarged heart in 8 cases, isolate absent aortic valves in 2 cases (1 case complicated with pulmonary atresia, absence of ductus arteriosus and thymus), absent pulmonary valves in 3 cases, absent both aortic and pulmonary valves in 3 cases, relics of semilunar valves in 3 cases. And 2 cases of absent pulmonary valves and 3 cases of absent both aortic and pulmonary valves with short and thick ductus arteriosus. Only 1 case was congenital absent semilunar valve in " non-stealing type" without secondary ultrasonic manifestations of fetal heart failure. Chromosome analysis and detection of genes showed 22q11.2 deletion, and there were relics of semilunar valves in the pathological anatomy. It also combined with tetralogy of Fallot and absence of ductus arteriosus. Conclusions In first trimester, congenital absent semilunar valves are more common as " stealing type" . The echocardiographic features of congenital absent semilunar valves are the " in-out sign" of aorta arch and/or pulmonary artery and biphasic spectrum in spectral Doppler. Trisomy 13 syndrome and trisomy 18 syndrome significantly increased the risk of congenital absent semilunar valves in " stealing type" in first trimester.