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Backgroud: A systematic analysis was conducted to investigate the molecular etiology of fetal cleft lip and/or palate (CL/P) and the association between various types of CL/P and copy number variations (CNVs), as well as their impact on birth outcomes. Methods: In this retrospective study conducted between January 2016 and July 2022, a cohort of pregnancies diagnosed with fetal CL/P was enrolled and comprehensive clinical data for all cases were extracted from our medical record database, including demographic data about the pregnancies, ultrasound findings, results of Chromosomal microarray (CMA), as well as relevant pregnant and perinatal outcomes. Results: Among the 358 cases, 32 clinically significant variants in 29 (8.1%) fetuses with CL/P were detected by CMA. In 338 singleton pregnancies, the diagnostic yield of CMA in the context of CL/P fetuses was determined to be 7.7% (26/338). CP cases exhibited a relatively higher prevalence of pathogenic/likely pathogenic CNVs at a rate of 25% (3/12), followed by CLP cases at 8.0% (23/288). Notably, the CL group did not demonstrate any pathogenic/likely pathogenic CNV findings among the examined cases (0/38). The diagnostic rate of clinically significant variants was notably higher in the non-isolated CL/P group than in the isolated CL/P group (11/33, 33.3% vs. 15/305, 4.9%, p < 0.001). Within the remaining 20 twin pregnancies, three clinically significant variants (15%) were observed. Conclusions: This study provides powerful evidence supporting the efficacy of CMA as a valuable tool for facilitating the prenatal genetic diagnosis of fetal CL/P. The presence of CP and CLP in fetal cases demonstrated a relatively higher incidence of pathogenic/likely pathogenic CNVs. Moreover, when these cases were accompanied by additional ultrasound abnormalities, the likelihood of identifying diagnostic CNVs significantly increased. Conversely, cases of CL alone might not be associated with positive CNVs. The present data may significantly enhance prenatal diagnosis accuracy and facilitate informed genetic counseling for cases of fetal CL/P. [ABSTRACT FROM AUTHOR]

Background: Ultrasound serves as a valuable tool for the early detection of fetal bowel dilatation, yet the correlation between fetal bowel dilatation and gastrointestinal malformations remains to be further investigated. This study aims to explore the relationship by conducting a follow-up and analysis of fetuses with bowel dilation. Methods: A retrospective analysis was conducted on 113 fetuses with bowel dilatation at our center from July 2014 to December 2019. The location and degree of bowel dilatation were analyzed. ROC curves were constructed based on the diameter of the bowel and its ratio to fetal gestational age. Results: In total, 40 of 41 cases (97.6%) with upper gastrointestinal dilatation (double-bubble sign) and 46 of 72 cases (63.9%) with lower gastrointestinal dilatation were diagnosed with gastrointestinal malformations postnatally. The AUC of the dilatation diameter was 0.854 with a cutoff value of 18.05 mm in patients with lower gastrointestinal dilatation. The ratio of the diameter to gestational age (D/GA) showed a higher AUC of 0.906 with a cutoff value of 0.4931. Conclusions: The presence of the double-bubble sign in fetuses indicates a close association with duodenal obstruction. The risk of gastrointestinal malformations increases when the bowel diameter exceeds 18.05 mm, particularly when the D/GA surpasses 0.4931. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the clinical utility of two dimensional (2D) ultrasound combined with spatiotemporal image correlation (STIC) in diagnosing interrupted aortic arch (IAA) in fetal life. Methods: A total of 53 cases of fetal IAA were diagnosed using 2D ultrasound combined with STIC, and 53 normal fetuses of the same gestational week were selected. These cases were retrospectively analyzed to assess the utility of employing 2D ultrasound combined with STIC in the diagnosis of IAA. Results: 2D ultrasound combined with STIC detected 22 cases of type A IAA, 24 cases of type B IAA, and seven cases of type C IAA. Furthermore, combining 2D ultrasound with STIC enabled dynamic visualization of the IAA, aiding in prenatal diagnosis. The diagnostic coincidence rate of IAA was found to be higher in the HD‐flow combined with STIC than that in the 2D combined with HD‐flow. Conclusion: HD‐flow combined with STIC can assist in diagnosing fetal IAA, and this technique has important clinical value. [ABSTRACT FROM AUTHOR]

Aim: To investigate the types, associated anomalies and postnatal outcomes of fetal hepatic venous system (HVS) variants by ultrasound in China.Material and Methods: A large-scale and prospective investigation of HVS variants for low-risk singleton pregnant women was performed in three academic tertiary referral care centers in China. Ultrasound imaging wasused for the identification and follow-up of anatomical variants. Follow-up was conducted once every four weeks prenatally and every two months postnatally, mainly concerned on the adverse events that may appear.Results: There were 20848 cases with anatomical variants of fetal HVS identified from 46179 candidates during the study period. Following the anatomical position of variants occurring, four main divisions were present: main portal vein variants (17.9%), intrahepatic portal vein variants (21.30%), intrahepatic persistent right umbilical vein (0.27%) and hepatic vein variants (5.67%). In the fetal period, the pregnancy of all cases was normally continued, except that the pregnancy of two cases, which were associated with multiple anomalies and were terminated by their parents. After birth, approximately 99.47% of the cases with isolated variants orbeing associated no clinic significant anomalies were normally alive. Approximately 0.50% cases were associated with simple ventricular septum defect or tetralogy of Fallot and further treatment was needed.Conclusion: The anatomical variants of fetal HVS may appear as numerical, morphological or positional variants of MPV, intrahepatic PV branches, intrahepatic PRUV and HVs. The majority of cases are isolated or their associated anomalies are not clinically significant and have normal lifeafter birth. [ABSTRACT FROM AUTHOR]

Background: Methylmalonic aciduria (MMA), a rare inherited disorder, is the most common organic aciduria in China, and prenatal diagnosis has contributed to its prevention. However, the prenatal diagnosis of MMA using cultured amniocytes or chorionic villi to detect gene mutations is exclusively applicable to families with a definite genetic diagnosis. To evaluate the reliability of mass spectrometry assays for the prenatal diagnosis of MMA, we conducted a retrospective study of our 10 years' experience. Materials and methods: This retrospective compare study reviewed the medical records for maternal and fetuses data for 287 mothers with a family history of MMA from June 2010 to December 2020. Methylmalonate and propionylcarnitine in cell-free amniotic fluid were measured using a stable isotope dilution method (GC/MS) and MS/MS-based method (LC/MS/MS). Total homocysteine (tHcy) was measured by fluorescence polarization immunoassay. Depending on the presence of disease-causing gene mutations in probands, gene studies on amniocytes from 222 pregnant women were performed. Results: For 222 fetuses of the families with definite genetic diagnosis, gene analyses were performed using cultured amniocytes. 52 fetuses were affected by MMA, whereas 170 were "unaffected". For GC/MS and LC/MS/MS, the specificity was 96.5% and 95.9%, sensitivity was 71.2% and 84.6%, respectively. The positive and negative predictive values were 86.0% and 91.6% and 86.3% and 95.3%, respectively. Propionylcarnitine/butyrylcarnitine ratio showed the highest accuracy and could thus serve as a sensitive indicator to identify those at a risk for MMA. When GC/MS and LC/MS/MS were performed in parallel, the specificity was 92.5% and sensitivity was 95.6%. When evaluating tHcy, the positive and negative predictive values were 95.0% and 96.1%, respectively. In 65 fetuses without family genetic diagnosis, 11 were finally confirmed to have MMA and 54 were "unaffected" by amniotic fluid biochemical assays. The 54 children showed normal urine organic acids and healthy development after birth. Conclusions: Amniotic fluid biochemical assays using GC/MS and LC/MS/MS in parallel increased the accuracy of prenatal diagnosis of MMA. Propionylcarnitine is a more reliable marker than methylmalonic acid in amniotic fluid. Further, tHcy is recommended for the prenatal diagnosis of combined MMA and homocysteinemia. [ABSTRACT FROM AUTHOR]

Background: Oculofaciocardiodental (OFCD) syndrome is an X-linked dominant syndrome caused by BCOR variants , which manifests only in females and presumed leading to male lethality. Herein, we aim to present a prenatal diagnosis for OFCD syndrome associated with a novel hemizygous variant in BCOR gene. Case presentation: A 29-year-old pregnant woman from Quanzhou Fujian Province, China, with fetal ultrasound anomalies, was enrolled in this study. A normal 46, XY karyotype with no abnormalities was observed in the fetus detected on microarray. Furthermore, a whole-exome sequencing (WES) detection result demonstrated that a novel hemizygous variant of c.251dupT (p.N87Kfs*6) in the BCOR gene was identified in the fetus, which was a frameshift mutation and classified as a likely pathogenic variant, and may lead to OFCD syndrome according to the clinical feature of the fetus. In this case, male lethality had not occurred by the end of the second trimester, then termination of the pregnancy was conducted at a gestational age of 26 weeks. Sanger sequencing of parental samples revealed that the variant was maternally transmitted, which was consistent with the OFCD syndrome phenotypic features observed in her. Conclusions: In the study, we first present the affected male with a novel variant in BCOR that leads to the OFCD syndrome. Additionally, our study broadened the spectrum of BCOR results in the OFCD syndrome and provided the valuable references for prenatal genetic consultation. [ABSTRACT FROM AUTHOR]

BACKGROUND: Severe environmental pollution and contaminants left in the environment due to the abuse of chemicals, such as methylmercury, are associated with an increasing number of embryonic disorders. Ultrasound imaging has been widely used to investigate embryonic development malformation and dysorganoplasia in both research and clinics. However, this technique is limited by its low contrast and lacking functional parameters such as the ability to measure blood oxygen saturation (SaO2) and hemoglobin content (HbT) in tissues, measures that could be early vital indicators for embryonic development abnormality. Herein, we proposed combining two highly complementary techniques into a photoacoustic-ultrasound (PA-US) dual-modality imaging approach to noninvasively detect early mouse embryo abnormalities caused by methylmercury chloride (MMC) in real time. OBJECTIVES: This study aimed to assess the use of PA-US dual-modality imaging for noninvasive detection of embryonic toxicity at different stages of growth following prenatal MMC exposure. Additionally, we compared the PA-US imagining results to traditional histological methods to determine whether this noninvasive method could detect early developmental defects in utero. METHODS: Different dosages of MMC were administrated to pregnant mice by gavage to establish models of different levels of embryonic malformation. Ultrasound, photoacoustic signal intensity (PSI), blood oxygen saturation (SaO2), and hemoglobin content (HbT) were quantified in all experimental groups. Furthermore, the embryos were sectioned and examined for pathological changes. RESULTS: Using PA-US imaging, we detected differences in PSI, SaO2, HbT, and heart volume at embryonic day (E)14.5 and E11.5 for low and high dosages of MMC, respectively. More important, our results showed that differences between control and treated embryos identified by in utero PAUS imaging were consistent with those identified in ex vivo embryos using histological methods. CONCLUSION: Our results suggest that noninvasive dual-modality PA-US is a promising strategy for detecting developmental toxicology in the uterus. Overall, this study presents a new approach for detecting embryonic toxicities, which could be crucial in clinics when diagnosing aberrant embryonic development. [ABSTRACT FROM AUTHOR]

Background: The prenatal BACs-on-Beads™ (PNBoBs™) assay has been applied worldwide for prenatal diagnosis. However, there are neither guidelines nor consensus on choosing patients, sample types, or clinical pathways for using this technique. Moreover, different perspectives have emerged regarding its clinical value. This study aimed to evaluate its clinical utility in the context of clinical practice located in a prenatal diagnostic center in Xiamen, a city in southeast China. Methods: We tested 2,368 prenatal samples with multiple referral indications using both conventional karyotyping and PNBoBs™. Positive results from PNBoBs™ were verified using current gold-standard approaches. Results: The overall rates for the detection of pathogenic copy number variation (pCNV) by karyotyping and PNBoBs™ were 1.9% (46/2,368) and 2.0% (48/2,368), respectively. The overall detection rate of karyotyping combined with PNBoBs™ for pCNV was 2.3% (54/2,368). A total of 13 cases of copy number variation (CNV)with a normal karyotype were detected by PNBoBs™. Another case with a normal karyotype that was detected as a CNV of sex chromosomes by PNBoBs™ was validated to be maternal cell contamination by short tandem repeat analysis. Conclusion: Karyotyping combined with PNBoBs™ can improve both the yield and efficiency of prenatal diagnosis and is appropriate in the second trimester in all patients without fetal ultrasound anomalies who undergo invasive prenatal diagnosis. [ABSTRACT FROM AUTHOR]

Objective: In this study, we report the indications for prenatal cytogenetic diagnosis of triploid cases, in an attempt to identify clues to early diagnosis.Study Design: This was a retrospective analysis of prenatal cases of triploidy during a 9-year period at mainland China. Clinical data were reviewed for these cases, including maternal demographics, indications for invasive testing, fetal ultrasound findings, and pregnancy outcomes.Results: A total of 22 singleton pregnancies affected with triploid fetuses were detected. The fetal karyotype included 69,XXX (72.7%) and 69,XXY (27.3%). Eighteen cases were identified by the first trimester screening program. One case was missed by maternal cell-free DNA testing, but detected by second trimester anatomy scan. Three cases escaped the first trimester screening and were detected by second trimester anatomy scan.Conclusions: The present study demonstrates that most triploid cases can be diagnosed prenatally during the first trimester. The early asymmetrical fetal growth restriction, structural anomalies, and extremely high risk serum screening result for trisomy 21 or 18 should alert the physicians to the investigation of triploidy.Key Message: Ultrasound-based first-trimester screening plays a major role in early diagnosis of fetal triploidy. Future replacement of routine first-trimester screening by cell-DNA testing might miss the chance of early diagnosis and management of triploid pregnancies. [ABSTRACT FROM AUTHOR]

Objectives: To describe a new sonographic feature of the C‐sign for prenatal diagnosis of jejunal atresia and evaluate its role in prenatal jejunal atresia, particularly preceding bowel dilatation and polyhydramnios. Methods: This was a retrospective study from a tertiary maternal hospital. Patients with prenatal sonographic examination and confirmed small bowel atresia postdelivery were included. All sonographic images were reviewed by two senior sonographers. Comparison of sonographic images between prenatal jejunal and ileal atresia using the C‐sign resembles the shape of the entire duodenum and other traditional sonographic features. The control group without bowel atresia was assessed for the presence of the C‐sign. Results: The C‐sign and combined bowel dilatation with polyhydramnios were more frequent in jejunal atresia than ileal atresia, but the C‐sign can be used to detect jejunal atresia earlier. The C‐sign can be more likely to diagnose jejunal atresia in persisting bowel dilatation and polyhydramnios. The C‐sign was not reported in any of the control fetuses. Conclusion: The C‐sign is a new sonographic feature that can be used to improve the prenatal accuracy and early detection of jejunal atresia. However, further prospective validation is needed. [ABSTRACT FROM AUTHOR]

The aim of this study was to analyse the factors associated with fetal pleural effusion over the past five years in a single institute in the South of China. Between January 2011 and May 2016, 129 foetuses with pleural effusion were referred to the Fetal Medicine Unit in Guangzhou's Women and Children's Medical Center. Seventy-nine women accepted an invasive procedure to rule out chromosomal abnormalities, fetal anaemia, intrauterine infections or some of the submicroscopic chromosomal abnormalities. Our results showed that chromosomal anomalies occurred in 15.2% (12/79) of cases including 8 Turner syndrome (45, X) (10.1%), 3 trisomy 21 (3.8%) and 1 trisomy 13 (1.3%). Pathological microdeletion or microduplication syndrome occurred in 3 out of 36 (8.3%) prenatal samples with normal karyotype and structural defects. Eight foetuses (10.1%) affected with haemoglobin Bart's disease showed pleural effusion at second or third trimester. Two cases (2.5%) were found to have an intrauterine infection. In conclusion, fetal pleural effusion has a close correlation with chromosomal abnormality. CMA may increase the detection rate of chromosomal aberrations, especially for micro-deletion or micro-duplication syndromes. In the South of China, Thalassemia must be considered when a fetal pleural effusion is detected.Impact statementWhat is already known on this subject? The aetiology of fetal pleural effusion includes a chromosomal abnormality, a congenital heart disease, congenital infections and a number of genetic syndromes.What do the results of this study add? This is the first retrospective study to analyse the aetiology of fetal pleural effusion in one institute in the South of China.What are the implications of these findings for clinical practice and/or further research? Besides the chromosomal abnormality, micro-deletion and micro-duplication syndromes were also detected in our study. We feel that thalassemia must be considered when fetal pleural effusion is detected in South China. [ABSTRACT FROM AUTHOR]

Background: Congenital pulmonary airway malformation (CPAM) is an increasingly recognized disease with potential mortality. Owing to limited published studies, the true incidence is yet to be determined. We carried out this prospective study with the aim to estimate its true incidence on a population basis.Methods: An antenatal ultrasonography program was implemented since 2009. Fetuses with suspected intra-thoracic lesions were monitored by regular follow-ups. Antenatal course, postnatal outcomes, and other demographics were compared to those of patients with CPAM in the previous decades (1989-2008). The incidence of CPAM was calculated in different periods.Results: 66 CPAM patients were identified between 2009 and 2014 with 62 patients being detected by antenatal scan. In contrast, 45 patients were identified between 1989 and 2008 with 27 patients being detected antenatally. The incidence rate during the past and recent period was estimated as ~1 in 27,400 and ~1 in 7200 live births, respectively (p = 0.024).Conclusion: With increasing awareness of clinicians and the universal use of latest ultrasound technology, it is likely that more CPAM cases will be detected in the future. Here, we presented our best estimated incidence rate of CPAM, yet only a larger scale study can reveal its true incidence. [ABSTRACT FROM AUTHOR]

Objective: To assess the feasibility and performance of the first-trimester combined screening test for trisomy 21 in a resource-limited setting in mainland China.Design: Prospective observational cohort study.Setting: First Affiliated Hospital of Kunming Medical University, China.Population: Ten thousand four hundred and forty-two pregnant women requesting first-trimester screening.Methods: The combined screening test was performed from May 2012 to December 2014. Women with a high-risk result (≥1:600) were offered further confirmatory tests after counselling. The threshold for high risk was determined by Monte Carlo simulation to achieve a 5% false-positive rate according to the local age distribution. Pregnancy outcome and screening results were recorded for all women and monthly audits were conducted.Main Outcome Measures: Sensitivity, screen positive rate, cost per case of Down syndrome detected.Results: Six hundred and ten women (5.8% of the total screened) had a high-risk screening test, of whom 274 (44.9%) underwent a diagnostic test and 169 (27.7%) opted for a noninvasive prenatal screening test (NIPT); 160 (26.2%) declined further testing after counselling. The pregnancy outcome was available for 10 174 (97.4%) of the women. The observed incidence of Down syndrome was 0.13% (1/750). All 14 women with a trisomy 21 pregnancy had a high-risk screening test result. The cost per Down syndrome detected was RMB596 686 compared with RMB1.79 million if all had been screened by NIPT.Conclusions: The combined screening test appears to be a more cost-effective strategy in mainland China. Screening performance in China would be improved by adopting Chinese-specific models, external quality control and assurance, and establishing risk thresholds appropriate for the age distribution of the population.Tweetable Abstract: Combined first-trimester Downs screening in China was improved by adopting Chinese-specific models and external QC. [ABSTRACT FROM AUTHOR]

Background Fetal interrupted aortic arch (IAA) is a rare cardiac anomaly and its prenatal diagnosis is challenging. The purpose of our report is to evaluate the use of two-dimensional echocardiography (2 DE) and 4D echocardiography with B-flow imaging and spatiotemporal image correlation (4D BF- STIC) in detecting IAA type A ( IAA-A). Materials & Methods Twenty-three cases of confirmed IAA-A identified by fetal echocardiography were involved in the study. The fetal echocardiography image data were reviewed to analyze the ratio of right ventricle to left ventricle ( RV/ LV) diameter, the ratio of main pulmonary artery to ascending aorta ( MPA/ AAO) diameter, and the correlation of RV/ LV diameter ratio and size of ventricular septal defect ( VSD). 4D BF- STIC was performed in 21 fetuses using the sagittal view (4D BF- STIC-sagittal) and the four-chamber view (4D BF- STIC-4 CV) as initial planes of view. An additional 183 normal fetuses were also included in our study. RV/ LV and MPA/ AAO ratios were calculated and compared with that of IAA-A fetuses. Fetal 2 DE, 4D BF- STIC-sagittal, and 4D BF- STIC-4 CV were used to visualize the aortic arch and its associated neck vessels. Six subgroups were evaluated according to gestational age. Results Fetal 2 DE, 4D BF- STIC-sagittal, and 4D BF- STIC-4 CV made the correct prenatal diagnosis of IAA-A in 19/23 (82.6%), 14/21 (66.7%), and 19/21 (90.5%) of patients, respectively. A significantly enlarged MPA combined with symmetric ventricles was found in the IAA-A fetuses, while the size of the VSD was negatively correlated with RV/ LV ratio. 4D BF- STIC-sagittal and 4D BF- STIC-4 CV were better than traditional 2D ultrasound in detecting the aortic arch and neck vessels between 17 and 28 gestational weeks and 29 to 40 gestational weeks in normal fetuses. Conclusion It is demonstrated that IAA-A could be diagnosed by traditional fetal echocardiography, while 4D technique could better display the anatomic structure and the spatial relationships of the great arteries. Use of volume reconstruction may promote its clinical usage and help prenatal diagnosis. [ABSTRACT FROM AUTHOR]