Prenatal ultrasound findings and clinical outcomes of uniparental disomy: a retrospective study.

BACKGROUND: Uniparental disomy is the inheritance of a homologous chromosome pair or part of homologous chromosomes from only one parent. However, the clinical significance of uniparental disomy and the difference among the prognosis of involvement of different chromosomes remain unclear. OBJECTIVE: To assess the associated prenatal ultrasound presentations and clinical outcomes of uniparental disomy on different chromosomes and to analyze the relationship between prenatal ultrasound markers and clinical outcomes. STUDY DESIGN: We retrospectively analyzed data from fetuses with uniparental disomy diagnosed using chromosome microarray analysis with the Affymetrix CytoScan HD array at our institution between January 2013 and September 2022. The relationship between prenatal ultrasound findings, the involved chromosome(s), and clinical outcomes was evaluated. RESULTS: During the study period, 36 fetuses with uniparental disomy were diagnosed, and two cases were excluded for non-available postnatal data. Finally, 34 fetuses were included in our study, of which 30 (88.2%) had uniparental disomy occurring on a single chromosome, while four (11.8%) were identified with uniparental disomy on different chromosomes. The most frequently involved chromosomes were chromosomes 16, X and 2, which presented in 8 (23.5%), 5 (14.7%) and 4 (11.8%), respectively. Prenatal ultrasound abnormalities were detected in 21 fetuses, with the most common category being multiple abnormalities (12 (57.1%)). Fetal growth restriction was identified in 14 (41.2%) fetuses, all of which coexisted with other abnormal findings. The rate of adverse perinatal outcomes in patients with uniparental disomy and fetal abnormalities was significantly higher than those without abnormalities (76.2% versus 15.4%, P = 0.002). The incidence of fetal or neonatal death was significantly higher in fetuses with fetal growth restriction than those without (85.7% versus 30.0%, P = 0.004). CONCLUSIONS: The prognosis of fetuses with uniparental disomy combined with fetal abnormalities, especially fetal growth restriction, was much poorer than those without.

Frontal lobe development in fetuses with growth restriction by using ultrasound: a case-control study.

BACKGROUND: Fetal growth restriction (FGR) occurs in up to 10% of pregnancies and is a leading cause of perinatal mortality and neonatal morbidity. Three-dimensional ultrasonography of intracranial structure volume revealed significant differences between fetuses with FGR and appropriate for gestational age (AGA) fetuses. We aimed to compare the frontal lobe development between fetuses with FGR and appropriately grown fetuses and evaluate the impact of fetal circulatory redistribution (FCR) on frontal lobe development in fetuses with FGR. METHODS: We performed a case-control study at our institution from August 2020 to April 2021. The frontal antero-posterior diameter (FAPD) and occipito-frontal diameter (OFD) were measured on the trans-ventricle view and we calculated the Z-scores for FAPD and OFD standardized for gestational age (GA) and transverse cerebellar diameter (TCD) by performing a standard regression analysis followed by weighted regression of absolute residual values in appropriately grown fetuses. We calculated the FAPD/OFD ratio as 100 × FAPD/OFD and FAPD/HC (head circumference) as 100 × FAPD/HC. To compare intracranial parameters, we randomly selected a control group of appropriately grown fetuses matched with the FGR group at the time of ultrasonography. We performed between-group comparisons of the FAPD Z-score, OFD Z-score, FAPD/OFD ratio and FAPD/HC. Similarly, we compared intracranial parameters between fetuses with FGR with and without FCR. RESULTS: FAPD/OFD ratio was curvilinear related to all the independent variables (GA, BPD, FL, and TCD). Compared with appropriately grown fetuses, fetuses with FGR showed a significantly lower FAPD/OFD ratio, FAPD Z-score, and FAPD/HC. There was no significant difference in the FAPD Z-score, FAPD/OFD ratio, and FAPD/HC between FGR fetuses with and without FCR. CONCLUSIONS: The FAPD/OFD ratio varied during pregnancy, with a mild reduction before and a mild increase after about 33 gestational weeks. Fetuses with FGR showed reduced frontal lobe growth; moreover, fetal frontal lobe development disorders were not significantly different in fetuses with FCR. TRIAL REGISTRATION: Date: 09-27-2017; Number: [2017]239.

Genetic anomalies in fetuses with tetralogy of Fallot by using high-definition chromosomal microarray analysis.

BACKGROUND: The etiology of TOF is complex and the genesis of TOF has been associated with environmental factors and genetic disorders, including chromosomal anomalies, aneuploidies, 22q11.2 deletion and single-gene disease. Previous literatures have shown that a chromosome alteration in about 30% patients with TOF and recently published articles reported that 22q11.2 deletion syndrome accounts for 16% cases with TOF diagnosed postnatally. CMA now is considered as gold standard for detecting genetic anomalies in fetuses with congenital malformations. CMA could detect a 6.6-25% incremental yield of CNVs in CHDs. The aim of this study was to assess the genetic anomalies in fetal tetralogy of Fallot (TOF) by using high-definition CMA. METHODS: This retrospective study reviewed all the fetuses diagnosed with TOF between 2013 and 2018. Prenatal ultrasongraphic findings, including cardiac angle, and the findings of CMA using Affymetrix CytoScan HD array were collected. RESULTS: Ninety-six fetuses with TOF and known genetic results were enrolled. Right aortic arch was the most common associated anomalies (22.9%). One fetus with trisomy 18, one with 46, XX, t (7;10)(q36;q22), one with 47, XYY and five with trisomy 21 were identified. Clinically significant CNVs occurred in 6.8% and uncertain significant CNVs in 3.4% fetal TOF with normal karyotype. A total of four cases with 22q11.2 microdeletion and two fetuses with Yq11.223q11.23 microduplication have been identified. Genetic anomalies, including chromosomal aberrations and pathogenic CNVs, were significantly higher in the TOF with extracardiac anomaly group than in the TOF without extracardiac anomaly group (P = 0.005). Abnormal cardiac angle was noticed in 24.0% fetal TOF. Genetic anomalies were more common in the TOF with abnormal cardiac angle than with normal cardiac angle (P = 0.001). On the other hand, abnormal cardiac angle was noticed in 64.3% fetal TOF with genetic anomalies while abnormal cardiac angle occurred in 17.1% fetal TOF with normal genetic results (P = 0.001). CONCLUSIONS: Genetic testing should be offered, specially using microarray analysis, for the fetal TOF with abnormal cardiac angle or extracardiac defects.

Systemic Venous Drainage Is Associated with an Unfavorable Prenatal Behavior in Fetal Bronchopulmonary Sequestration.

OBJECTIVE: This study aimed to determine the significance of the venous drainage pattern of bronchopulmonary sequestration (BPS) in the prenatal course. METHODS: The venous drainage pattern of fetuses with BPS was determined with high-definition flow and confirmed by postnatal three-dimensional computed tomography angiography scan or autopsy. The volume of BPS lesions during gestation was recorded by the three-dimensional ultrasonographic Virtual Organ Computer-Aided Analysis software. The relationship between venous drainage pattern and prenatal characteristics was determined. RESULTS: Seventy-one fetuses were enrolled: 35 with systemic venous drainage (SVD) and 36 with pulmonary venous drainage (PVD). The volumes of BPS lesions significantly increased from the middle second trimester to the later second trimester in the SVD group. A marked decrease from the later second trimester to the third trimester was observed in the PVD group. The incidences of associated anomalies, hydrops, and polyhydramnios in the SVD group were 14.2, 23.3, and 33.3%, respectively, significantly higher than those in the PVD group (0, 0, and 5.6%, respectively). CONCLUSIONS: Our data indicate that SVD is correlated with a higher risk of associated anomalies and an unfavorable prenatal course in fetal BPS. Identification of the venous drainage pattern is of clinical significance in predicting the prenatal behavior of fetal BPS.

Fetal right aortic arch: associated anomalies, genetic anomalies with chromosomal microarray analysis, and postnatal outcome.

OBJECTIVES: The aim of the study was to assess the associated prenatal findings, genetic anomalies with chromosomal microarray analysis (CMA) and postnatal outcome of fetal right aortic arch (RAA). METHODS: This retrospective study reviewed 92 fetuses diagnosed with RAA and the findings of CMA using Affymetrix CytoScan HD array in our institution between 2013 and 2016. RESULTS: Postnatal data were not available for six cases, and genetic data were not available for 26 cases. Tetralogy of the Fallot was the most frequently associated anomaly. Among the 60 fetuses with known karyotype, one was 46, X, Yqh+, der(13)t(8;13)(q22.3;q33.2), one was 47, XYY and the remaining were normal. Our study showed that CMA could detect uncertain significant copy number variants in 5.2% of fetal RAA and pathogenic copy number variants in 5.2%, all of which were microdeletion in chromosome 22q11.21. The genetic anomalies, gestational age at delivery and postnatal death were not significantly different between RAA-no intracardiac anomalies and RAA-intracardiac anomalies group. One infant with aberrant left subclavian artery needed to perform a surgery for respiratory symptom. CONCLUSIONS: A right aortic arch is associated with 22q11.2 deletion syndrome in approximately 5% of cases, and, therefore, prenatal testing, preferably using CMA, should be offered. © 2017 John Wiley & Sons, Ltd.

Chromosomal and subchromosomal anomalies associated to small for gestational age fetuses with no additional structural anomalies.

OBJECTIVES: To assess the chromosomal and subchromosomal anomalies in small for gestational age (SGA) fetuses with no additional structural anomalies and their clinical outcomes. METHODS: This study retrospectively reviewed the 128 SGA fetuses with no additional anomalies and underwent genetic testing with karyotyping and chromosomal microarray analysis (CMA). Stratified analysis was performed according to the existence of maternal risk factors for SGA (yes or no), gestational age at onset (before or after 32 weeks), presence of oligohydraminos (yes or no), and umbilical artery Doppler flow (normal or abnormal). RESULTS: Chromosomal anomalies were identified in 6 (4.7%) SGA fetuses and pathogenic subchromosomal anomalies in 4 (3.1%) by microarray analysis. Chromosomal and subchromosomal anomalies were more frequently observed in cases with oligohydraminos (P = .017) and with early-onset SGA (P = .042). No differences were observed in relation to the existence of maternal risk factors and abnormal umbilical artery Doppler flow. Overall survival rate was 75.0% with different rates in the early and the late onset group (P < .001). CONCLUSIONS: There is a 3.3% incremental yield of subchromosomal anomalies in CMA above karyotyping in SGA fetuses. Chromosomal microarray analysis is recommended in SGA fetuses with no additional structural anomalies, especially coexisting with oligohydraminos and being early onset.

MCDA twins with discordant malformations: submicroscopic chromosomal anomalies detected by chromosomal microarray analysis and clinical outcomes.

OBJECTIVE: To evaluate whether discrepant copy number variations (CNVs) contribute to the risk for discordant congenital anomalies in monochorionic diamniotic (MCDA) twins. METHODS: We conducted a parallel testing using both G-banding for standard karyotyping and chromosomal microarray analysis (CMA) with Affymetrix CytoScan HD array in MCDA twins with discordant malformations. RESULTS: During the study period, 193 MCDA twins with discordant malformations were detected and followed up. Multiple anomalies and cardiac defects were detected most frequently among the fetuses with malformations. Among all the 119 MCDA twins that were successfully performed fetal karyotyping, discordance of chromosomal aberrations were identified in nine cases, including one with discordant trisomy 18, seven with discordant monosomy X, one twin with 47, XXY and the co-twin with 45, X [7]/46, XY[43]. CMA revealed pathological CNVs in four out of the 110 fetuses with normal karyotype and the detection rate of uncertain clinical significance was 3.6% (4/110). Discordance of CNVs was detected in 5.5% (3/55) among the 55 MCDA twins with normal karyotype. Monozygosity was confirmed in all the 61 MCDA twins that were performed CMA. CONCLUSIONS: Large whole chromosome abnormalities are more common between discordant twins rather than smaller CNVs in this study. © 2016 John Wiley & Sons, Ltd.

Clinical Outcomes after Selective Fetal Reduction of Complicated Monochorionic Twins with Radiofrequency Ablation and Bipolar Cord Coagulation.

AIMS: To review pregnancy outcomes, complication rates and neonatal neural development of selective termination procedures for complicated monochorionic (MC) twins. METHODS: This was a retrospective review of the pregnancies that underwent selective reduction with radiofrequency ablation (RFA) and bipolar cord coagulation (BCC) in our institution. RESULTS: Forty-eight cases underwent selective reduction with BCC and the remaining 45 with RFA. Overall survival was not statistically different between the RFA and BCC groups (71.1 and 62.5%, p = 0.379). With regard to the indications, the survival rates were not significantly different for twin to twin transfusion syndrome, twin reversed arterial perfusion, discordant anomalies and selective intrauterine growth restriction. Preterm premature rupture of membrane was not statistically different between the BCC and RFA groups (47.9 and 33.3%, p = 0.153). Five foetuses presented with abnormal middle cerebral artery-peak systolic velocity in the BCC group and 4 in the RFA group (p = 0.829). In the BCC group, neurological injury was detected in 2 neonates, presenting with cerebral dysplasia on MR scanning. In the RFA group, intracranial haemorrhage Grade III was detected in one neonate with cranial ultrasound (p = 0.607). CONCLUSIONS: Overall survival and complication rates following selective reduction in complicated MC twin pregnancies is similar irrespective of whether the reduction was performed using RFA or BCC. Key Message: It seems that selective reduction in MC pregnancies with RFA does not carry a significant decrease in the overall survival and complication rates than the cases with BCC. According to our data, neurodevelopmental impairment of the co-twins is relatively seldom after selective reduction.

Fetal persistent left superior vena cava in cases with and without chromosomal anomalies.

OBJECTIVES: The objectives of this study are to determine and compare the prevalence of persistent left superior vena cava (PLSVC) in chromosomally normal and abnormal fetuses and to evaluate the potential of PLSVC as a screening marker for chromosomal abnormalities. METHODS: Women undergoing routine fetal sonographic examinations were evaluated once for the presence of PLSVC. PLSVC was diagnosed on the basis of the identification of an additional vessel in the left of the pulmonary artery in a three-vessel trachea view. Associated abnormalities, karyotypes, and outcomes were analyzed. RESULTS: A total of 164 (0.7%, 164/25 171) cases of PLSVC were detected and successfully followed-up. The detection rates were 0.5% (81/17 535) and 1.1% (83/7636) in the low-risk and high-risk cases, respectively. The incidence of PLSVC was lower among the chromosomally or clinically normal (0.4%, 110/24 914) compared with chromosomally abnormal fetuses (7.8%, 20/257, p < 0.001). Additional defects were identified in 90% (18/20) of the PLSVC fetuses with chromosomal anomalies, a rate that was higher than those fetuses with chromosomal normal (61.8%, 68/110). CONCLUSIONS: Persistent left superior vena cava is more common among chromosomally abnormal than normal fetuses, and PLSVC fetuses with other defects are more highly associated with chromosomal disorders than isolated PLSVC fetuses. Isolated PLSVC is a benign vascular anomaly and may not affect outcomes.

Prenatal diagnosis of prevalence of the right heart: associated anomalies and outcome predictors.

OBJECTIVES: To analyze the characteristics, associations, and outcomes of prevalence of the right heart and to evaluate the use of sonography to predict the risk of a poor prognosis in fetuses with this condition. METHODS: We conducted a retrospective cohort study of 182 fetuses with prevalence of the right heart. At the initial evaluation, the left ventricle (LV) and right ventricle (RV) sizes, left atrium and right atrium sizes, great artery diameters, appearance of the aortic arch and ductus arteriosus arch, and flow direction across the foramen ovale and aortic arch were documented. Malformations were documented in fetuses with intracardiac anomalies, who were divided into groups with and without coexisting extracardiac defects. The RV-LV diameter ratio and main pulmonary artery-to-aortic root diameter ratio were calculated and compared. The following variables were analyzed: coexisting intracardiac anomalies, associated extracardiac anomalies, diagnosis before 24 gestational weeks, fetal growth restriction, reversed flow across the foramen ovale, reversed flow in the aortic arch, and RV-LV ratio greater than 2.0. Relationships between these sonographic findings and the prognosis were evaluated by multivariable logistic regression. RESULTS: Of the 182 fetuses, 1 (0.5%) had intrauterine death, and 25 (13.7%) had neonatal death; 1 (0.5%) had selective reduction, and 106 (58.2%) underwent termination of pregnancy; 49 (26.9%) survived at this writing. The mean RV-LV ratio was 1.67. Multivariable logistic regression revealed that only 2 sonographic parameters, coexisting intracardiac anomalies (odds ratio, 17.75; 95% confidence interval, 4.18-75.26) and diagnosis before 24 weeks (odds ratio, 17.26; 95% confidence interval, 1.80-165.39) were significantly associated with a poor prognosis. CONCLUSIONS: The sonographic parameters of coexisting intracardiac anomalies and diagnosis before 24 gestational weeks are significant independent predictors of a poor prognosis in fetuses with prevalence of the right heart. Combinations of these risk factors may be useful in prenatal consultation.

Evaluation of the trachea in fetuses with double aortic arch using prenatal ultrasound: a retrospective cohort study.

BACKGROUND: Double aortic arch is the most common form of complete vascular ring. The trachea and/or esophagus could be compressed by the complete vascular ring, which may lead to early respiratory and/or esophageal symptoms in children with double aortic arch. Accurate prenatal assessment of tracheal compression could provide relevant information for perinatal clinical management of double aortic arch and emergency treatment of infants with double aortic arch. The fetal trachea is filled with amniotic fluid and can be clearly visualized with prenatal ultrasound. Previous studies reported the use of prenatal ultrasound to measure the tracheal internal diameters in normal fetuses and showed a linear correlation between the fetal tracheal internal diameters and gestational age. However, to the best of our knowledge, few studies have quantitatively evaluated tracheal compression in fetuses with double aortic arch using ultrasound. OBJECTIVE: This study aimed to evaluate the tracheal compression caused by the vascular ring in fetuses with double aortic arch using prenatal ultrasound and to analyze the relationship between tracheal compression and postnatal clinical symptoms. STUDY DESIGN: The data of fetuses with double aortic arch diagnosed with prenatal ultrasound at 2 institutions from January 2011 to April 2021 were retrospectively analyzed. Singleton pregnancies with normal fetuses as the control group were prospectively recruited. The tracheal compression-evaluated by comparing the tracheal internal diameter z scores against the gestational age-was assessed in fetuses with double aortic arch and in normal fetuses. The live-born infants with double aortic arch were divided into symptomatic and asymptomatic groups for the comparison of z scores. The receiver operating characteristic curve for the tracheal internal diameter z score cutoffs and prediction of symptomatic infants with double aortic arch was plotted. Intraobserver and interobserver agreements were investigated. RESULTS: A total of 26 fetuses with double aortic arch were diagnosed, and 14 fetuses (53.8%) with double aortic arch were delivered alive. Among the 14 live-born infants, 7 (50.0%) were symptomatic, whereas 7 (50.0%) were asymptomatic. The tracheal internal diameter z scores were significantly lower in the double aortic arch group than in the normal groups (-0.62±1.36 vs 0.00±0.78; P<.001). The tracheal internal diameter z scores were significantly lower in the symptomatic group than in the asymptomatic group (-1.42±0.92 vs -0.49±0.96; P=.018). The area under the curve was 0.878 (95% confidence interval, 0.689-1.000). Using a tracheal internal diameter z scores cutoff of -1.21, the sensitivity was 71%, and the specificity was close to 100%. The intraclass correlation coefficients of interobserver and intraobserver agreements were 0.987 (95% confidence interval, 0.980-0.992) and 0.975 (95% confidence interval, 0.955-0.987), respectively. CONCLUSION: The clinical symptoms in infants with double aortic arch were associated with prenatal tracheal compression, which can be prenatally evaluated using ultrasound. If fetuses are diagnosed with double aortic arch, prenatal surveillance of the tracheal internal diameters and comparison with z score reference ranges could provide pertinent information that would aid perinatal clinical management.

Development and validation of a predictive model for fetal cerebral maturation using ultrasound for fetuses with normal growth and fetal growth restriction.

Background: Investigation of fetal cerebral maturation (FCM) is necessary and important to provide crucial prognostic information for normal and high-risk fetuses. The study aimed to develop a valid and quantitative predictive model for assessing FCM using ultrasound and validate the model for fetuses with normal and restricted growth. Methods: This was a multicenter prospective observational study. Fetuses with normal growth recruited from a university teaching hospital (Center 1) and a municipal maternal unit (Center 2) were included in the training set and external validation set 1, respectively. The 124 growth-restricted fetuses enrolled in Center 1 were included in validation set 2. FCM was used to describe the gestational age (GA) in this study. The model was developed based on the sum of fetal cranial parameters (total fetal cranial parameters), including head circumference (HC) and depths of the insula (INS) and sylvian fissure (SF), parieto-occipital fissure (POF), and calcarine fissure (CF). A regression model, constructed based on total fetal cranial parameters and predicted GA, was established using the training set and validated using external validation set 1 and validation set 2. Results: The intra- and interobserver intraclass correlation coefficients for HC, and depths of the INS and SF, POF, and CF were >0.90. An exponential regression equation was used to predict FCM: predicted GA of FCM (weeks) =11.16 × exp (0.003 × total fetal cranial parameters) (P<0.001; adjusted R2=0.973), standard error of estimate, 0.67 weeks. The standard error of the predicted GA of FCM from the model was ±4.7 days. In the validation set 1, the mean standard error of the developed prediction model for FCM was 0.97 weeks. The predictive model showed that FCM was significantly delayed in validation set 2 (2.10±1.31 weeks, P<0.001), considering the GA per the last menstrual period. Conclusions: The predictive performance of the FCM model developed in this study was excellent, and the novel model may be a valuable investigative tool during clinical implementation.

Accuracy, agreement, and reliability of fetal cardiac measurements using 4-dimensional spatiotemporal image correlation.

OBJECTIVES: The purpose of this study was to evaluate the accuracy, agreement, and reliability of 4-dimensional sonography using spatiotemporal image correlation (STIC) in fetal cardiac measurements during the second and third trimesters. METHODS: Four-dimensional cardiac STIC volumes were acquired from 150 low-risk singleton pregnancies at gestational ages of 18 to 38 weeks. A total of 11 dimensions of the fetal heart and great vessels were analyzed by two different observers. Accuracy was assessed by comparing the measurements acquired by 4-dimensional STIC with those determined by 2-dimensional echocardiography by calculating the mean error and mean percent error and depicted by Bland-Altman plots. Absolute agreement and reliability of STIC-based measurements were evaluated on the basis of an intraclass correlation coefficient (ICC). RESULTS: For STIC-based measurements of cardiac dimensions, good accuracy was achieved by the two experienced observers (mean percent error, -3.10% to 0.87% for observer A; -2.49% to -0.33% for observer B), and absolute agreement was almost perfect (ICC, 95% confidence interval, 0.916-0.993 for observer A; 0.957-0.990 for observer B). Interobserver ICCs among the two observers were between 0.909 and 0.990 (95% confidence interval), whereas intraobserver ICCs for observer A were between 0.894 and 0.989, and those for observer B were between 0.893 and 0.985, showing no significant differences in the reliability of SITC with regard to observers. CONCLUSIONS: Four-dimensional sonography with STIC is a feasible and accurate method for fetal cardiac dimension measurements in the second and third trimesters. It is in good agreement with 2-dimensional echocardiography and can be performed by different observers.

Four-dimensional sonography with spatiotemporal image correlation and tomographic ultrasound imaging in the prenatal diagnosis of anomalous pulmonary venous connections.

OBJECTIVES: To determine whether the use of 4-dimensional (4D) sonography with spatiotemporal image correlation (STIC) and tomographic ultrasound imaging (TUI) can provide additional information with respect to 2-dimensional (2D) echocardiography in the prenatal diagnosis of anomalous pulmonary venous connections. METHODS: The study population consisted of 10 cases that were initially suspected to have total or partial anomalous pulmonary venous connections by prenatal 2D echocardiography between January 2008 and April 2011. All 10 cases were further examined and analyzed by 4D sonography with STIC-TUI. Detailed postnatal surgery or autopsy was performed on all 10 fetuses. RESULTS: Total anomalous pulmonary venous connections were found in 5 cases, and a partial connection was diagnosed in 1 fetus postnatally. The remaining 4 cases were confirmed to have normal pulmonary venous connections. Four of the 5 fetuses with anomalous pulmonary venous connections had an additional major cardiac defect; 1 fetus had an isolated connection. Anomalous drainage was supracardiac to the superior vena cava in 2 cases, cardiac to the coronary sinus in 3, and partially infracardiac to the portal vein in remaining case. The pulmonary venous connections were completely and correctly visualized with 2D echocardiography in 2 of the 10 cases, partially identified in 4, and not distinguished completely in 4. Four-dimensional sonography imaging with STIC-TUI clearly visualized the connections in 9 of the 10 cases, and the remaining case was partially identified. CONCLUSIONS: Four-dimensional sonography with STIC-TUI facilitates visualization of pulmonary venous connections, thus supplying additional information with respect to 2D echocardiography in the prenatal diagnosis of anomalous pulmonary venous connections.

Comparisons of foramen ovale flap in the fetuses with true and false positive diagnosis of coarctation of the aorta.

Background: Accurate diagnosis of coaractation of aorta (CoA) remains challenging because of its relatively low sensitivity and specificity. It is difficult to distinguish true CoA from a normal physiological right-sided dominance or ventricular discrepancy caused by intracardiac minor anomalies. Redundant foramen ovale flap (RFOF) may cause ventricular disproportion. Methods: All fetuses suspected with CoA on routine screening ultrasound were retrospectively reviewed and allotted into two groups: postnatally confirmed CoA (true positive group) and prenatally suspected CoA but without CoA postnatally (false positive group). Sixty-nine normal fetuses were included as a normal group (normal group). The diameters of FOF and left atrium (LA) were measured in the four-chamber view and FOF/LA ratio ≥0.65 was considered as RFOF. Cardiac parameters between groups were compared. Results: Fifty-seven fetuses undergoing echocardiography for suspicion of CoA were enrolled; 11 (19.2%) had CoA postnatally. A significant linear relationship was identified between ventricular discrepancy degree and FOF prominence (P<0.001, R=0.48). A significant linear relationship was also identified between the RFOF and disproportion of the great arteries (P<0.001, R=0.42). FOF prominence significantly differed between groups true positive and false positive (P<0.001). RFOF occurred significantly differently in the true positive and false positive groups (56.5% vs. 0.91%, P=0.002). Cardiac parameters, including the aortic valve (AO) z-score (P=0.785), aortic isthmus (AOi) z-score (P=0.944), pulmonary artery (PA) z-score (P=0.693), PA/AO ratios (P=0.055), left ventricle (LV) z-score (P=0.192) and right ventricle (RV)/LV ratios (P=0.225), were comparable between fetuses with and without CoA after birth except RV z-score (P=0.035). Conclusions: There is no statistical difference of cardiac parameters between fetuses with and without CoA after birth except RV diameter. The proportion of fetuses with RFOF is significantly greater in patients without CoA. Fetal echocardiography including bulging of the FOF in the LA should be investigated for suspected CoA to decrease false positive diagnosis of CoA.

[Prenatal diagnosis of trisomy 18 syndrome with sonogram index scoring system].

OBJECTIVE: To explore the value of sonogram index scoring system in the prenatal diagnosis of trisomy 18 syndrome. METHODS: Neonates who had prenatal sonographic screening in our tertiary center were followed up from January 2004 to December 2009. The fetuses who were suspected with abnormalities received karyotype analysis. All fetuses were divided into case group (trisomy 18 group) and the control group (non-trisomy 18 group). The latter group was constituted of fetuses with trisomy 21, trisomy 13, other chromosomal abnormalitis and fetuses with normal karyotype. Logistic regression analysis was done to decide the individual sonographic features of trisomy 18. A score was assigned for ultrasound markers according to their likelihood ratios for trisomy 18 syndrome. A score of 3 was assigned for the sonographic features with likelihood ratio over 200, 2 for those with likelihood ratio between 100 and 200, and 1 for those with likelihood ratio less than 100. The diagnostic efficacy of the ultrasound index scoring system was evaluated by diagnostic test. The optimal cutoff value was determined by receiver operating characteristic (ROC) curve. RESULTS: The study group included 59 fetuses with trisomy 18. And 26 486 fetuses did not have trisomy 18 syndrome, including 93 fetuses with trismoy 21, 19 fetuses with trisomy 13, 134 fetuses with other chromosomal abnormalities, 3739 fetuses with normal karyotype and 22 501 fetuses with normal appearance after birth. Two or more structural defects were observed in each trisomy 18 fetus. The highest incidence of sonogram abnormalities was extremities abnormalities (85%, 50/59), followed by cardiac defects (83%, 49/59) and central nervous system (CNS) malformations (75%, 44/59). Overlapping fingers, ventricular septal defect and strawberry-shaped skull were the most common abnormalities in extremities abnormalities, cardiac defects and CNS malformations, respectively. Logistic regression identified 16 markers, including choroid plexus cyst, strawberry-shaped skull, enlarged cisterna magna, holoprosencephaly, low-set ears, ventricular septal defect, hypoplastic left heart syndrome, etc. Different scores were assigned according to the likelihood ratios of these markers. In trisomy 18 group, fetuses with the sonographic score of 1, 4, 9, 10 to 16 were 2% (1/59), 9% (5/59), 10% (6/59) and 32% (19/59) respectively, whereas in non-trisomy 18 group they were 2.549% (675/26 486), 0.215% (57/26 486), 0.004% (1/26 486) and zero, respectively. When a score of 4 was used as the cutoff value for diagnosing fetal trisomy 18, the sensitivity and specificity were 0.966 and 0.997, respectively. The area under ROC curve was 0.999. CONCLUSIONS: The ultrasound index scoring system may help to quantify the ultrasound features and has a good diagnostic value for fetal trisomy 18 syndrome. The cutoff value of 4 has the best diagnostic efficacy.

Prenatal diagnosis of chromosomal aberrations in fetuses with conotruncal heart defects by genome-wide high-resolution SNP array.

Objectives: To explore chromosomal variations, including copy number variations (CNVs), in fetuses with conotruncal heart defect (CTD).Methods: During a 5-year period, a total of 129 fetuses with ascertained CTDs were investigated for chromosomal abnormalities using quantitative fluorescence PCR (QF-PCR) and chromosomal microarray analysis (CMA). Fetuses were divided into two subgroups: benign group (with normal QF-PCR results and benign CNVs) and nonbenign group [with aneuploidies, nonbenign CNVs [pathogenic CNVs and CNVs of unknown significance (VOUS)]. Data on fetal structural malformations, chromosomal variations, and pregnancy outcomes were collected and compared.Results: Of the 129 cases, 17 were found to have common aneuploidies. In the remaining 112 cases with normal a QF-PCR result, pathogenic CNVs, CNVs of VOUS, and benign CNVs were identified in 5.3, 5.3, and 4.5%, respectively. Compared with benign group, fetuses in nonbenign group had a significantly higher rate of neurologic defects (13.8 versus 3.0%, p < .05), overall extracardiac anomalies (86.2 versus 45.0%, p < .05), and perinatal death (57.1 versus 18.4%, p < .05), whereas, no significant difference in that of associated cardiovascular anomalies was noted (48.2 versus 46.0%, p = .29). Among the extracardiac anomalies, thymus abnormalities were strongly associated with nonbenign CNVs (33.3 versus 1% of fetuses in benign group, p < .05).Conclusions: Pathogenic CNVs, in addition to chromosomal aneuploidies, contributed to the pathogenesis of CTD. The presence of associated extracardiac anomalies including thymus abnormalities correlated with a higher probability of nonbenign chromosomal variations, which was associated with an unfavorable outcome.

Prenatal surveillance of bronchopulmonary sequestration using 3-dimensional ultrasonography.

OBJECTIVE: The purpose of this study was to assess the growth of fetal lung lesions using 3-dimensional ultrasonography (3DUS) and to note the clinical outcomes of infants with congenital bronchopulmonary sequestration (BPS) diagnosed prenatally. METHODS: Twenty-two cases of intrathoracic BPS diagnosed prenatally occurred between May 2005 and September 2008. The volume of the BPS lesion (V(mass)) and the volume of the fetal chest (V(chest)) were measured with the 3DUS software Virtual Organ Computer-Aided Analysis (VOCAL; GE Healthcare, Kretztechnik, Zipf, Austria). The clinical outcomes of all cases were recorded. RESULTS: Among 22 cases with fetal BPS, 8 were terminated, and 2 were lost to follow-up. The growth pattern of the BPS lesions was assessed in 12 live-born cases with 2 or 3 3DUS measurements per case. There was no statistically significant difference between the V(mass) (P = .859) and V(mass)/V(chest) (P = .078) at 19 to 24 weeks' gestational age (WGA) and greater than 24 to 30 WGA, but there was a statistically significant difference between the V(mass) (P = .010) and V(mass)/V(chest) (P = .008) at greater than 24 to 30 WGA and greater than 30 to 39 WGA. The lung lesion resolved spontaneously before birth in 4 fetuses and postnatally in 2 infants. All 12 fetuses survived to term without any prenatal intervention, were born without any evidence of neonatal respiratory impairment, and did not undergo surgical resection of the mass. CONCLUSIONS: Our data showed that fetuses with BPS had a favorable clinical outcome, and the pulmonary mass decreased during late pregnancy and resolved spontaneously. Three-dimensional ultrasonography with VOCAL provides a useful method for assessing the growth of pulmonary lesions.