Efficiency of Non-Invasive Prenatal Testing in Detecting Fetal Copy Number Variation: A Retrospective Cohort Study.

Purpose: Screening of pathological copy number variations (CNVs) is important for early-diagnosis of hereditary disease. This study was designed to investigate the efficiency of non-invasive prenatal testing (NIPT) in detecting fetal CNVs. Methods: This retrospective analysis included fetuses with CNVs between January 2018 and December 2020. Karyotype analysis and CNV sequencing (CNV-seq) were performed. We then analyzed the positive predictive values of the subchromosomal microdeletions and microduplications. Results: Fifty-eight subjects with aberrant CNVs were screened after NIPT, among which 44 finally underwent amniocentesis. CNV-seq confirmed the presence of CNVs in 24 cases. This indicated that false positivity rate of NIPT was 45.5%. Among 24 cases with CNVs after CNV-seq, only 4 showed consistent findings with karyotype analysis, which showed that karyotyping analysis yielded a missed diagnosis rate of 83.3% for the genome CNV. Positive predictive value (PPV) was 50.0% for CNVs with a length of <5 Mb after NIPT screening. PPV for CNVs with a length of 5 Mb-10 Mb was 33.3%, while that for CNVs with a length of ≥10Mb was 60%. For CNVs duplication after NIPT, the PPV was 65.2%, while that for deletion was 36.4%. Conclusion: For CNVs detected after NIPT, it should be combined with ultrasonographic findings, karyotype analysis, CNV-seq or CMA to determine the pregnancy outcome. Expanding NIPT may increase the risk of unnecessary invasive surgery and unintended selective termination of pregnancy.

Prenatal diagnosis of 17q12 copy number variants in fetuses via chromosomal microarray analysis - A retrospective cohort study and literature review.

Purpose: 17q12 copy number variants (CNVs) have variable presentations and incomplete penetrance, challenging prenatal counseling and management. This study aims to investigate the intrauterine phenotype. Methods: We included 48 fetuses diagnosed with 17q12 microdeletion or microduplication by chromosomal microarray analysis. Results: For 17q12 deletion, renal anomalies were found in 35 fetuses (35/37, 94.6 %), with hyperechogenic kidneys (HEK, 28/37, 75.7 %) and multicystic dysplastic kidneys (17/37, 45.9 %) being the most common findings. Duodenal obstruction (DO) was most frequently combined in 17q12 duplication fetuses. In addition, cardiac abnormalities were the first reported prenatal phenotype in 17q12 duplication fetuses. Conclusion: Our study shows that HEK and DO are the most predominant presentations of 17q12 deletion and duplication, respectively, and cardiac structural abnormalities may be associated with the latter. Although 17q12 CNVs have incomplete penetrance and variable expressivity and may be mainly involved in neurodevelopmental disorders, their short-term prognosis appears positive.

[Declining Rate of Neural Tube Defects and Outcomes of Defective Infants in Shaanxi Province from 2003 to 2022].

Objective To evaluate the changes in the incidence of neural tube defects (NTDs) in Shaanxi province from 2003 to 2022,investigate the diagnosis time and outcomes of defective infants,and predict the incidence of NTDs in Shaanxi province from 2023 to 2025,thereby providing a basis for improving the birth defects surveillance system. Methods Data were collected from all the perinatal infants from 28 weeks of gestation to 7 days after birth in all the hospitals with obstetrical department in Shaanxi province during 2003-2022.The changes in the incidence of NTDs from 2003 to 2022 were analyzed based on the birth defects surveillance system. Results A total of 1 106 483 perinatal infants in Shaanxi province from 2003 to 2022 were surveyed,among which NTDs occurred in 848 perinatal infants,with an incidence of 7.66/10 000.The incidence was the highest (48.02/10 000) in 2005 and the lowest (0.57/10 000) in 2022.The NTDs in Shaanxi province were mainly spina bifida (55.90%),which was followed by anencephaly (25.71%) and encephalocele (18.40%).The incidences of the three declined with fluctuations (P<0.001).The results of the Joinpoint analysis showed that the incidence of NTDs decreased slowly with the annual percentage change of -4.04 from 2003 to 2014 and declined rapidly with the annual percentage change of -28.05 from 2014 to 2022.From 2003 to 2022,the average proportion of prenatal diagnosis of NTDs in Shaanxi province was 72.88%.Dead fetus (61.91%) was the main birth outcome,followed by live birth (26.77%),stillbirth (8.73%),and death within seven days after birth (2.59%).The incidence of NTDs in Shaanxi province from 2023 to 2025 were predicted by the GM (1,1) model as 0.49/10 000,0.41/10 000,and 0.35/10 000,respectively. Conclusion The incidence of NTDs in Shaanxi province declined significantly during 2003-2022,especially in a rapid manner after 2014.Dead fetus was the primary outcome of perinatal infants with NTDs,followed by live birth.

A De novo Mutation in the COL1A1 Gene Leading to Severe Osteogenesis Imperfecta: Case Report and Review of the Literature.

Introduction Osteogenesis imperfecta (OI) is the most common monogenic inherited skeletal dysplasia disorder. Mutations in the COL1A1/COL1A2 gene cause ∼85 to 90% of OI. Studies of cases have demonstrated that missense mutations are the primary cause of OI, with poor prognosis. Case Description We report the case of a fetus with skeletal abnormalities and subcutaneous edema. Ultrasound imaging revealed suspected skeletal malformations, including hypoplastic long bones of all four limbs, poorly ossified calvarium, unrevealing nasal bones, and generalized subcutaneous edema. Whole-exome sequencing revealed a heterozygous mutation in COL1A1 (c.2174G > T/p.(G725V), NM_000088.3). According to the American College of Medical Genetics and Genomics guidelines, it was determined to be a pathogenic variant and identified as a de novo variant (PS2 + PP3_strong + PM2_supporting), which has not been reported in the HGMD, gnomAD, ClinVar, or other databases. This variation causes a glycine-to-valine substitution at position 725, located within the Gly-Xaa-Yaa repeat in the helical domain of the collagen molecule. Conclusion The COL1A1 mutation (c.2174G > T/p.(G725V), NM_000088.3) is a novel pathogenic variant of severe OI. Our study expanded the OI COL1A1 gene variation profiles in the Chinese population and provided a theoretical foundation for prenatal diagnosis, genetic counseling, and obstetric management.

Prenatal Ultrasound Diagnosis of Unilateral Pulmonary Agenesis.

Pulmonary agenesis (PA) is a rare developmental malformation, with a frequency of approximately 1 in 10-15,000 pregnancies. Unilateral PA is often associated with other congenital anomalies, whereas bilateral PA is fatal. Prenatal diagnosis is rare and is diagnosed more frequently in the postnatal period than in the prenatal period. Is a challenge that may be difficult as it shares similar features with other more common pathologies. Ultrasound plays a crucial role in early diagnosis and management. Ultrasonographic findings for a correct prenatal diagnosis include mediastinum displacement with the absence of parenchymal or cystic tissue, decreased thoracic volume, an elevated diaphragm, cardiac axis deviation, and a hemithoracic cavity largely occupied by the heart. Cases of right PA have a worse prognosis compared to left PA, probably due to higher frequency of cardiac and great vessel abnormalities. A rare case of early prenatal ultrasound diagnosis of unilateral fetal PA, at 18 weeks of gestation, is reported.

Magnetic resonance imaging of abnormal placental shapes with correlation with pathologic findings.

OBJECTIVE: This study aimed to investigate the magnetic resonance imaging (MRI) characteristics of abnormal placental shapes (APS) compared with prenatal ultrasound. METHODS: From an initial cohort of 613 women with a high prevalence of placenta accreta spectrum (PAS) disorders, the MRI findings of 27 pregnant women with APS who underwent antenatal ultrasound and MRI examinations before delivery were retrospectively analyzed. The clinicopathological findings were used as the gold standard, and the sensitivity, specificity, and accuracy of antenatal MRI and a multidisciplinary team experienced in diagnosing APS were assessed. RESULTS: The 27 patients diagnosed with APS included 14 cases of succenturiate placenta, eight cases of the bilobed placenta, two cases of the circumvallate placenta, and one case each of placenta chorioangioma, placenta membranacea, and placental mesenchymal dysplasia. The sensitivity and specificity of APS classification with antenatal MRI were 40.74% (11/27) and 97.65% (498/510), respectively. Nonetheless, the multidisciplinary team achieved a higher sensitivity and specificity of up to 96.29% (26/27) and 99.22% (506/510), respectively. CONCLUSION: We have demonstrated the complementary role of MRI and ultrasound in the detection of placental shapes in the setting of MRI images, highlighting the importance of radiologists communicating with sonographers in the diagnosis of APS.

Fetal large tubular oesophageal duplication cyst: A case report.

Introduction: Oesophageal duplication cyst (EDC) is a rare congenital anomaly representing, after neuronal tumours, the second most common cause of posterior mass in children, with a prevalence of approximately 1/22,500 live births. Cervical cysts are very rare, and their antenatal detection is fairly uncommon. Methods: We report the case of an isolated large mediastinal and cervical tubular EDC diagnosed prenatally in the third trimester. Results: After birth, the baby became symptomatic developing respiratory distress due to the enlargement of the cyst and she underwent excision of the mass. The post-operative evolution was very good. Conclusion: Our purpose was to raise awareness of the ultrasonographic features of this condition, thus improving the rate of prenatal diagnosis and offering the parents a proper counselling regarding the prognosis and the need for a further multidisciplinary approach after birth.

A case of isolated malrotation without midgut volvulus diagnosed prenatally and treated by laparoscopic surgery.

BACKGROUND: Malrotation is a congenital condition that predisposes individuals to midgut volvulus, which can result in significant bowel resection. While most cases of malrotation are diagnosed by the age of 1 year, typically presenting with symptoms related to volvulus or bowel obstruction, some cases remain asymptomatic. In children with visceral malposition, gastroschisis, omphalocele, or diaphragmatic hernia, malrotation may be suspected before symptoms manifest. However, isolated malrotation without midgut volvulus diagnosed prenatally is rare. We herein present a case of isolated malrotation without midgut volvulus that was prenatally diagnosed and successfully treated with laparoscopic surgery. CASE PRESENTATION: A 30-year-old woman (gravida 3, para 1) underwent routine obstetric ultrasound, which revealed increased blood flow in the lower uterine segment and abnormal placental attachment. To rule out placenta percreta, magnetic resonance imaging was performed at 34 weeks of gestation. Incidentally, abnormal fetal intestinal arrangement was noted, with the colon localized in the left hemi-abdomen and the small intestine distributed in the right hemi-abdomen, raising suspicion of malrotation. Postnatal contrast studies confirmed the diagnosis of malrotation without midgut volvulus. Given the risk of midgut volvulus, a laparoscopic Ladd's procedure was performed on day 6 of life. The postoperative course was uneventful, and the patient was still symptom-free 1 year postoperatively. CONCLUSIONS: This case illustrates that malrotation can be prenatally diagnosed using fetal magnetic resonance imaging. Considering the risk of midgut volvulus, prophylactic Ladd's procedure should be performed in neonatal period. In cases where malrotation is not complicated by midgut volvulus, a laparoscopic Ladd procedure can be safely performed in neonates.

Fetal therapies - (Stem cell transplantation; enzyme replacement therapy; in utero genetic therapies).

Advances in ultrasound and prenatal diagnosis are leading an expansion in the options for parents whose fetus is identified with a congenital disease. Obstetric diseases such as pre-eclampsia and fetal growth restriction may also be amenable to intervention to improve maternal and neonatal outcomes. Advanced Medicinal Therapeutic Products such as stem cell, gene, enzyme and protein therapies are most commonly being investigated as the trajectory of treatment for severe genetic diseases moves toward earlier intervention. Theoretical benefits include prevention of in utero damage, smaller treatment doses compared to postnatal intervention, use of fetal circulatory shunts and induction of immune tolerance. New systematic terminology can capture adverse maternal and fetal adverse events to improve safe trial conduct. First-in-human clinical trials are now beginning to generate results with a focus on safety first and efficacy second. If successful, these trials will transform the care of fetuses with severe early-onset congenital disease.

New insight on etiology: A chorionic bump with partial mole pregnancy case report from Syria.

This case report presents the association of a chorionic bump with a partial mole pregnancy in a 37-year-old G3P2 woman. The differential diagnosis of a partial mole was considered after transvaginal ultrasonography revealed a chorionic bump. Subsequent pathological analysis confirmed the diagnosis. While the etiology of the chorionic bump remains dubious, we hypothesize an alternative explanation for chorionic bump formation based on the presence of three unique pathological features: necrosis, edema, and hemorrhage.

Utility of routine mid-trimester fetal ultrasound scan in detecting filar cysts and follow-up outcomes.

PURPOSE: To assess the value of routine mid-trimester fetal ultrasound scans in detecting FCs, as well as the related ultrasound and clinical follow-up outcomes. METHODS: A retrospective analysis was conducted on 1064 fetuses who underwent standardized ultrasound screening during the mid-trimester. During the examination, high-frequency ultrasound was used to examine the fetal spine. Different frequency ultrasound probes were used to compare and analyze the detection rates of FCs. We conducted follow-up ultrasound observations on all FCs and conducted long-term follow-up observations in terms of the motor function of the children after birth. RESULTS: Among 1064 fetuses detected by ultrasound, a total of 910 fetuses were completely evaluated using high-frequency and low-frequency ultrasound, and 24 FCs were found. In all 24 cases of FCs, 7 cases were detected using low-frequency ultrasound, while high-frequency ultrasound detected all cases. There was a significant difference in the detection rates between the two groups (χ2 = 26.323, P = 0.000). Of all the 24 FCs, 21 cysts disappeared spontaneously (87.5%); one fetus was induced for abortion due to a concurrent cleft lip; after multiple ultrasound examinations, it was found that the cyst persisted in one fetus; one case was not followed up by ultrasound. There was no statistically significant difference in the start of sitting and crawling time between the control group and the FCs group. CONCLUSION: Routine mid-trimester fetal ultrasound scan detect FCs, particularly when high-frequency ultrasound probes were routinely applied. Most FCs detected by prenatal ultrasound spontaneously disappear and have no impact on the motor function of the fetus after birth (with the conus medullaris located at or above the L3 level). The shortest time interval from the detection to the disappearance of the cyst was 11 days.

Proteomic Profiles of Maternal Plasma Extracellular Vesicles for Prediction of Preeclampsia.

PROBLEM: Preeclampsia is a heterogeneous syndrome of diverse etiologies and molecular pathways leading to distinct clinical subtypes. Herein, we aimed to characterize the extracellular vesicle (EV)-associated and soluble fractions of the maternal plasma proteome in patients with preeclampsia and to assess their value for disease prediction. METHOD OF STUDY: This case-control study included 24 women with term preeclampsia, 23 women with preterm preeclampsia, and 94 healthy pregnant controls. Blood samples were collected from cases on average 7 weeks before the diagnosis of preeclampsia and were matched to control samples. Soluble and EV fractions were separated from maternal plasma; EVs were confirmed by cryo-EM, NanoSight, and flow cytometry; and 82 proteins were analyzed with bead-based, multiplexed immunoassays. Quantile regression analysis and random forest models were implemented to evaluate protein concentration differences and their predictive accuracy. Preeclampsia subgroups defined by molecular profiles were identified by hierarchical cluster analysis. Significance was set at p < 0.05 or false discovery rate-adjusted q < 0.1. RESULTS: In preterm preeclampsia, PlGF, PTX3, and VEGFR-1 displayed differential abundance in both soluble and EV fractions, whereas angiogenin, CD40L, endoglin, galectin-1, IL-27, CCL19, and TIMP1 were changed only in the soluble fraction (q < 0.1). The direction of changes in the EV fraction was consistent with that in the soluble fraction for nine proteins. In term preeclampsia, CCL3 had increased abundance in both fractions (q < 0.1). The combined EV and soluble fraction proteomic profiles predicted preterm and term preeclampsia with an AUC of 78% (95% CI, 66%-90%) and 68% (95% CI, 56%-80%), respectively. Three clusters of preeclampsia featuring distinct clinical characteristics and placental pathology were identified based on combined protein data. CONCLUSIONS: Our findings reveal distinct alterations of the maternal EV-associated and soluble plasma proteome in preterm and term preeclampsia and identify molecular subgroups of patients with distinct clinical and placental histopathologic features.

Chromatin conformation capture in the clinic: 4C-seq/HiC distinguishes pathogenic from neutral duplications at the GPR101 locus.

BACKGROUND: X-linked acrogigantism (X-LAG; MIM: 300942) is a severe form of pituitary gigantism caused by chromosome Xq26.3 duplications involving GPR101. X-LAG-associated duplications disrupt the integrity of the topologically associating domain (TAD) containing GPR101 and lead to the formation of a neo-TAD that drives pituitary GPR101 misexpression and gigantism. As X-LAG is fully penetrant and heritable, duplications involving GPR101 identified on prenatal screening studies, like amniocentesis, can pose an interpretation challenge for medical geneticists and raise important concerns for patients and families. Therefore, providing robust information on the functional genomic impact of such duplications has important research and clinical value with respect to gene regulation and triplosensitivity traits. METHODS: We employed 4C/HiC-seq as a clinical tool to determine the functional impact of incidentally discovered GPR101 duplications on TAD integrity in three families. After defining duplications and breakpoints around GPR101 by clinical-grade and high-density aCGH, we constructed 4C/HiC chromatin contact maps for our study population and compared them with normal and active (X-LAG) controls. RESULTS: We showed that duplications involving GPR101 that preserved the centromeric invariant TAD boundary did not generate a pathogenic neo-TAD and that ectopic enhancers were not adopted. This allowed us to discount presumptive/suspected X-LAG diagnoses and GPR101 misexpression, obviating the need for intensive clinical follow-up. CONCLUSIONS: This study highlights the importance of TAD boundaries and chromatin interactions in determining the functional impact of copy number variants and provides proof-of-concept for using 4C/HiC-seq as a clinical tool to acquire crucial information for genetic counseling and to support clinical decision-making in cases of suspected TADopathies.

Evaluation of tracheal diameter and angles in fetuses with double aortic arch using prenatal ultrasound: implications for postnatal management.

Objective: This study aims to analyze the value of prenatal ultrasound in the screening, diagnosis, and treatment of double aortic arch (DAA) malformations. Methods: A retrospective analysis was conducted on 31 fetal cases with double aortic arch anomalies over a 12-year period from June 1, 2011 to June 1, 2023. The assessment included combined measurements of fetal tracheal internal diameter Z-score and DAA pinch angle, along with ultrasonographic findings, associated anomalies, genetic abnormalities, postnatal CTA images, and long-term postnatal outcomes. Results: Of the 31 fetal double aortic arch cases, 15 were right aortic arch dominant, 2 were left aortic arch dominant, and 14 had a balanced double arch. Genetic testing was performed on 19 cases, revealing abnormalities in 2 cases, including one Turner syndrome, and one carrier of ichthyosis gene with heterozygous deletion. Out of the total cases, 29 were delivered, and 2 cases were terminated. Prenatal diagnosis accurately identified 29 cases (29/31, 93.5%), which was confirmed by postnatal pathological anatomy, echocardiography, surgery or CTA. Fetal tracheal internal diameter Z-scores were significantly smaller in the symptomatic group than in the asymptomatic group (-1.27 ± 0.49 vs -0.68 ± 0.60, P = 0.018). The area under the curve was 0.776 (95% confidence interval, 0.593-0.960) using a tracheal internal diameter z-score cutoff of -0.73 with a sensitivity of 90% and specificity of 64.7%. The double arch pinch angle was significantly smaller in the symptomatic group than in the asymptomatic group [52.50° (38.25° to 59.00°) vs 60.00° (53.50° to 70.50°), P = 0.035]. The area under the curve was 0.744 (95% confidence interval, 0.554-0.935), and the sensitivity for determining the presence or absence of symptoms was 90% when the cutoff value was 62.5°, with a specificity of 47.1%. Fifteen cases opted for surgery with favorable surgical outcome. Conclusion: Prenatal echocardiography demonstrates good diagnostic efficacy for fetal double aortic arch. It is also essential to detect the presence of other underlying intra- and extracardiac malformations and genetic abnormalities. There is a significant difference in prenatal tracheal internal diameter Z-scores and double arch pinch angle between asymptomatic and symptomatic DAA infants. Symptomatic infants require early surgery, while asymptomatic infants should be monitored.

Whole Exome Sequencing Revealing a Novel PBX1 Gene Variant in a Chinese Family Causing Recurrent Neonatal Death.

BACKGROUND: Causative mutations of PBX1 are associated with congenital abnormalities of the kidney and urinary tract (CAKUT), often accompanied by hearing loss, abnormal ear morphology, or developmental delay. The aim of the present investigation was to introduce a novel variant in the PBX1 gene identified in a Chinese family, leading to recurrent neonatal mortality. METHODS: A pregnant woman (gravida 5, para 0), who had experienced recurrent neonatal deaths, sought genetic etiology diagnosis. Whole exome sequencing (WES) was conducted to identify sequence variants and copy number variants in the fetus presenting with posterior nuchal cystic hygroma and fetal hydrops. RESULTS: A novel NM_002585.4:c.694G>C(p.D232H) in PBX1 was identified in the fetus through trio whole exome sequencing (WES), revealing a paternal mosaic PBX1 variant in blood at 11.54% (6/52 variants reads). Subsequent parental Sanger sequencing confirmed the variant detected by WES. Ultimately, the variant was classified as likely pathogenic, leading the family to elect pregnancy termination at 17 weeks gestation. CONCLUSION: The novel variant in the PBX1 gene appears to be a significant factor contributing to recurrent neonatal deaths in the Chinese family. Such findings expand the spectrum of PBX1 gene variants and provide valuable perinatal guidance for diagnosing fetuses with PBX1 mutations.

Prenatal diagnosis and management of Apert syndrome in a low-middle income country: Case report.

INTRODUCTION AND IMPORTANCE: Apert syndrome is a rare autosomal dominant disorder characterized by craniosynostosis, midface hypoplasia, and syndactyly. Prenatal diagnosis of this condition can be challenging. This case report highlights the importance of recognizing characteristic ultrasound findings for timely diagnosis and genetic counselling. CASE PRESENTATION: A 37-year-old, gravida 1, para 0 woman underwent a routine third-trimester ultrasound at 31 weeks gestation. The examination revealed significant hydramnios, bilateral hand syndactyly, foot abnormalities, and an unusual head shape with a prominent forehead, flat occiput, hypertelorism, and low-set ears. These findings raised suspicion for Apert syndrome. Subsequent molecular analysis confirmed a mutation in the FGFR2 gene, confirming the diagnosis. Three-dimensional (3D) ultrasound imaging was utilized to provide the parents with a clearer understanding of the foetal anomalies, aiding in their decision-making process. Given the high risk of impaired intellectual development and the complexity of its management, the pregnancy was terminated at 33 weeks' gestation. CLINICAL DISCUSSION: This case emphasizes the role of comprehensive prenatal ultrasound in identifying potential foetal anomalies, even in the absence of prior risk factors. Characteristic sonographic findings, such as craniosynostosis, syndactyly, and hydramnios, should raise suspicion for the diagnosis, even in the absence of family history. Molecular confirmation through FGFR2 gene testing is essential for definitive diagnosis and informed genetic counselling. CONCLUSION: While Apert syndrome is rare, recognizing its characteristic sonographic features can facilitate timely diagnosis. The use of 3D ultrasound imaging can be invaluable in enhancing parental understanding and facilitating informed decision-making.

Prenatal Diagnosis, Course and Outcome of Patients with Truncus Arteriosus Communis.

Background: The objective of our study was to assess the prenatal course, associated anomalies and postnatal outcome and the predictive value of various prenatal parameters for survival in prenatally diagnosed cases of truncus arteriosus communis (TAC). Methods: We evaluated cases from four centers between 2008 and 2021. Results: In 37/47 cases (78.7%), classification into a Van Praagh sbtype was possible, most had TAC type A1 (18/37 = 48.6%). In 33/47 (70.2%) with available valve details on common trunk valve, most presented with tricuspid valves (13/33 = 39.4%). In the overall sample, 14/47 (29.8%) had relevant insufficiency, and 8/47 (17%) had stenosis. In total, 37/47 (78.7%) underwent karyotyping, with 15/37 (40.5%) showing abnormal results, mainly 22q11.2 microdeletion (9/37 = 24.3%). Overall, 17/47 (36.2%) had additional extracardiac anomalies (17/47 = 36.2%). Additional intracardiac anomalies were present in 30/47 (63.8%), or 32/47 (68.1%) if coronary anomalies were included. Four (8.5%) had major defects. Two (4.3%) intrauterine deaths occurred, in 10 (21.3%) cases, the parents opted for termination, predominantly in non-isolated cases (8/10 = 80.0%). A total of 35/47 (74.5%) were born alive at 39 (35-41) weeks. Three (8.6%) pre-surgical deaths occurred in non-isolated cases. In 32/35 (91.4%), correction surgery was performed. The postoperative survival rate was 84.4% (27/32) over a median follow-up of 51.5 months. Initial intervention was performed 16 (1-71) days postpartum, and 22/32 (68.8%) required re-intervention. Regarding prenatal outcome-predicting parameters, no significant differences were identified between the survivor and non-survivor groups. Conclusions: There exist limited outcome data for TAC. To our knowledge, this is the largest multicenter, prenatal cohort with an intention-to-treat survival rate of almost 85%.

Chromosomal Microarray Analysis in Fetuses with Ultrasound Abnormalities.

Objective: To explore and evaluate the value of chromosomal microarray analysis (CMA) in prenatal diagnosis of fetuses with ultrasound abnormalities. Methods: A retrospective analysis was performed on 370 fetuses with ultrasound abnormalities received invasive prenatal diagnosis at Meizhou People's Hospital from October 2022 to December 2023. Fetal specimens were analyzed by CMA, and the detection rates of aneuploidy and pathogenic (P)/likely pathogenic (LP) copy number variations (CNVs) in ultrasound structural abnormalities (malformations of fetal anatomy) and non-structural abnormalities (abnormalities of fetal nonanatomical structure) were analyzed. Results: There were 114 (30.8%) cases with isolated ultrasound structural abnormalities, 226 (61.1%) cases with isolated non-structural abnormalities (182 isolated ultrasound soft markers abnormalities, 30 isolated fetal growth restriction (FGR), and 8 isolated abnormalities of amniotic fluid volume), and 30 (8.1%) cases with both structural and non-structural abnormalities. The overall detection rate of aneuploidy and P/LP CNVs in isolated ultrasonic structural abnormalities was 5.3%, among which cardiovascular system abnormalities were the highest. In addition, the largest number of fetuses with non-structural abnormalities was nuchal translucency (NT) thickening (n = 81), followed by ventriculomegaly (n = 29), and nasal bone dysplasia (n = 24). The detection rate of chromosomal abnormalities of fetuses with abnormal ultrasound soft markers was 9.9%, and the detection rate in single abnormal ultrasound soft marker, and multiple ultrasound soft markers abnormalities was 9.7% (16/165) and 11.8% (2/17), respectively. Moreover, the detection rate of chromosomal abnormalities of fetuses with FGR and structural abnormalities combined with non-structural abnormalities was 6.7% (2/30), and 13.3% (4/30), respectively. Conclusion: The incidence of chromosomal abnormalities (aneuploidy and P/LP CNVs) varies among different fetal ultrasound abnormalities.

Balancing key stakeholder priorities and ethical principles to design a trial comparing intervention or expectant management for early-onset selective fetal growth restriction in monochorionic twin pregnancy: FERN qualitative study.

OBJECTIVES: As part of the FERN feasibility study, this qualitative research aimed to explore parents' and clinicians' views on the acceptability, feasibility and design of a randomised controlled trial (RCT) of active intervention versus expectant management in monochorionic (MC) diamniotic twin pregnancies with early-onset (prior to 24 weeks) selective fetal growth restriction (sFGR). Interventions could include laser treatment or selective termination which could lead to the death or serious disability of one or both twins. DESIGN: Qualitative semi-structured interviews with parents and clinicians. Data were analysed using reflexive thematic analysis and considered against the Principles of Biomedical Ethics. PARTICIPANTS AND SETTING: We interviewed 19 UK parents experiencing (six mothers, two partners) or had recently experienced (eight mothers, three partners) early-onset sFGR in MC twin pregnancy and 14 specialist clinicians from the UK and Europe. RESULTS: Participants viewed the proposed RCT as 'ethically murky' because they believed that the management of sFGR in MC twin pregnancy should be individualised according to the type and severity of sFGR. Clinicians prioritised the gestational age, size, decrease in growth velocity, access to the placental vessels and acceptability of intervention for parents. Discussions and decision-making about selective termination appeared to cause long-term harm (maleficence). The most important outcome for parents and clinicians was 'live birth'. For clinicians, this was the live birth of at least one twin. For parents, this meant the live birth of both twins, even if this meant that their babies had neurodevelopmental impairment or disabilities. CONCLUSIONS: All three pregnancy management approaches for sFGR in MC twin pregnancy carry risks and benefits, and the ultimate goal for parents is to receive individualised care to achieve the best possible outcome for both twins. An RCT was not acceptable to parents or clinicians or seen as ethically appropriate. Alternative study designs should be considered to answer this important research question.