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Purpose: This is a retrospective comparative study. We aimed to analyze the results of karyotype and chromosomal microarray analysis (CMA) of amniotic fluid across different gestational weeks and evaluate the clinical value in prenatal diagnosis, particularly in the late pregnancies. Methods: Samples from 580 pregnant women of 18–23 weeks of gestation (mid-gestation group) and 196 pregnant women of 24–32 weeks of gestation (late group) were performed both standard G-band karyotype analysis and CMA. Results: Among the 580 pregnant women in the routine group, the most common indications were positive Down's screening (213/580, 36.7%), followed by advanced maternal age (196/580, 33.8%); while fetal structural anomalies on ultrasonography were the top reason for amniocentesis in the late group (56/196, 28.6%). In the routine group, the total detection rate was 12.1% (70/580), of which 4.1% (24/580) were identified by karyotype analysis and 11.2% (65/580) by CMA. The total detection rate was 15.3% (30/196) in the late group, of which 5.1% (10/196) were detected by karyotype analysis, and 14.3% (28/196) by CMA. Conclusion: Karyotype analysis and CMA are complementary in detecting chromosomal abnormalities. Amniotic cavity puncture in the karyotype analysis in 18–23 weeks of gestation and 24–32 weeks of gestation is safe and effective, more obvious effect on the latter. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to examine whether there is a correlation between different types of ventricular septal defects (VSD) and chromosomal abnormalities in the low-risk setting of non-invasive prenatal testing (NIPT) and to evaluate the prognosis of fetuses with varying types of VSD. Methods: Cases of pregnant women who underwent amniocentesis due to fetal VSD were collected by Tianjin Central Hospital of Obstetrics and Gynecology from May 2017 to May 2022. Exclusions were made for those without NIPT, with high-risk NIPT results, genetic disorders, and those lost to follow-up. Data collected included ultrasound classification of VSD, prenatal NIPT results, copy-number variations (CNVs) results, and neonatal outcomes. Results: The prevalence of pathogenic CNVs was investigated in 74 cases of VSDs. Of these cases, 45 were isolated VSDs (9 muscular and 36 non-muscular) and 29 were non-isolated VSDs (10 with intracardiac and 19 with extra-cardiac structural anomalies). The results revealed that the incidence of pathogenic CNVs was lower in isolated VSDs compared to non-isolated VSDs in a low-risk NIPT condition (χ2 = 9.344, P = 0.002). There was no significant difference in the prevalence of pathogenic CNVs between VSDs with intracardiac and extra-cardiac structural anomalies (P = 0.541). Moreover, VSDs associated with intracardiac structural anomalies had the highest rate of surgical intervention. Conclusion: When NIPT is low-risk and VSD is isolated, the likelihood of fetal chromosomal defects is not increased. However, if there are intra- or extra-cardiac structural abnormalities present alongside VSD, the possibility of pathogenic CNV is considerably greater, necessitating invasive prenatal diagnosis. Isolated muscular VSDs usually do not require surgery, which can be used as a basis for prenatal counseling regarding fetal VSD. [ABSTRACT FROM AUTHOR]

Purpose: Ebstein anomaly (EA) and tricuspid valve dysplasia (TVD) represent uncommon congenital malformations of the tricuspid valve. The purpose of this study is to report on current perinatal outcomes of EA/TVD in our center and to investigate clinical and fetal echocardiographic predictors of perinatal mortality. Methods and Results: We performed a retrospective study among fetuses diagnosed from January 2014 to December 2023. Clinical and echocardiographic data were obtained from hospital records of Research and Education Hospital. The primary outcome was perinatal mortality. Of 21 fetuses diagnosed, there were 1 lost to follow-up, 1 termination, and 7 demises. In the live-born cohort of 12 live-born patients, 2 died before discharge, yielding an overall perinatal mortality of 50%. The median gestational age at diagnosis was 23 for non-survivors and 24 weeks for survivors. Birth weight was lower in non-survivors (2430 g vs 2990 g). Tricuspid insufficiency severity varied insignificantly. Non-survivors exhibited higher rates of hydrops, functional atresia, and absent antegrade flow (p < 0.05). Two infants with severe tricuspid insufficiency and congenital abnormalities died postnatally. The limited dataset enables further analysis for a predictive model. Notably, all non-survivors displayed hydrops, functional atresia, and absent antegrade flow, hindering definitive determination of the most impactful parameter on survival estimation. Conclusion: Perinatal mortality remains notably elevated in fetuses with EA/TVD. The individuals at the highest risk are those with antegrade flow loss and functional atresia of pulmonary valve, this high-risk subgroup could benefit from targeted interventions, such as novel prenatal therapies or a more comprehensive perinatal approach involving optimized timing of delivery and postnatal interventional strategies. [ABSTRACT FROM AUTHOR]

Objective: We sought to analyze the genetic outcomes of fetuses with nuchal translucency (NT) > 95th centile, and determine whether prenatal genetic counseling, chromosomal microarray analysis (CMA) or non-invasive prenatal testing (NIPT) are truly beneficial for the outcomes of fetuses with increased NT > 95th centile and below 99th centile. Materials and methods: A total of 535 pregnant women were included in this study, with a fetal NT > 95th centile at 11–13+6 weeks of gestation from January 2017 to December 2020. 324 pregnant women with fetal NT > 95th centile and below 99th centile combined with other risk factors and NT > 99th centile received prenatal diagnostic karyotype analysis and CMA, and 211 pregnant women with fetal isolated increased NT > 95th centile and below 99th centile were selected to carry out NIPT. Results: A total of 211 pregnant women who underwent NIPT were included in the study, NIPT results showed that 8 high-risk cases were confirmed by prenatal diagnosis. Overall, the detection rate of NIPT was 3.79%. A total of 324 pregnant women with fetal NT > 95th centile and below 99th centile, along with other risk factors, and those with fetal NT > 99th centile, received karyotype analysis and CMA for prenatal diagnosis. Among them, a total of 73 genetic abnormalities were detected, including 45 cases of chromosomal aneuploidy, 7 cases of structural abnormalities, and 21 cases of copy number variations (CNVs) with a size of less than 10 Mb. In addition, the 73 women with genetic abnormalities are divided into three groups based on the NT measurement (Group 1: Fetuses with NT > 95th centile and below 99th centile, Group 2: Fetuses with NT > 99th centile, and Group 3: Fetuses with NT > 99th centile). 13.11% (8/61) of pathogenic genetic abnormalities (6 chromosomal aneuploidy, 1 structural abnormality, and 1 likely pathogenic CNV) will be missed if genetic counseling and prenatal genetic testing were not conducted in fetuses with increased NT > 95th centile and below 99th centile combined with other risks. Pathogenic CNVs were the most common abnormalities in group 3, and one likely pathogenic CNV was detected in group 1 and group 3, respectively, and a total of 14 CNVs of unknown clinical significance (VOUS) were detected. Conclusions: Through this study, we demonstrated that the critical value of NT > 95th centile for invasive detection or NIPT. Invasive testing combined with CMA may be recommended for fetuses with NT > 95th centile and below 99th centile and with other risks. But when isolated NT > 95th centile and below 99th centile, NIPT would be appropriate. [ABSTRACT FROM AUTHOR]

Background: Left–right laterality disorders are a heterogeneous group of disorders caused by an altered position or orientation of the thoracic and intra-abdominal organs and vasculature across the left–right axis. They mainly include situs inversus and heterotaxy. Those disorders are complicated by cardiovascular abnormalities significantly more frequently than situs solitus. Methods: In this study, 16 patients with a fetal diagnosis of laterality disorder with congenital heart defects (CHD) were evaluated with a single nucleotide polymorphism array (SNP-arry) combined with whole-exome sequencing (WES). Results: Although the diagnostic rate of copy number variations was 0 and the diagnostic rate of WES was 6.3% (1/16), the likely pathogenic gene DNAH11 and the candidate gene OFD1 were ultimately identified. In addition, novel compound heterozygous mutations in the DNAH11 gene and novel hemizygous variants in the OFD1 gene were found. Among the combined CHD, a single atrium/single ventricle had the highest incidence (50%, 8/16), followed by atrioventricular septal defects (37.5%, 6/16). Notably, two rare cases of common pulmonary vein atresia (CPVA) were also found on autopsy. Conclusion: This study identified the types of CHD with a high incidence in patients with laterality disorders. It is clear that WES is an effective tool for diagnosing laterality disorders and can play an important role in future research. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to investigate the performance, cost-effectiveness and additional findings of combined detailed ultrasound and biochemical screening for risks of major fetal trisomies in the first-trimester. Methods: This is a retrospective analysis study, we estimated the risk of trisomies 21, 18 and 13 based on maternal age, fetal nuchal translucency thickness, nasal bone, ductus venosus pulsatility index velocity, tricuspid regurgitation, fetal heart rate, free beta-human chorionic gonadotropin, and pregnancy-associated plasma protein A in singleton pregnant women, and performed non-invasive prenatal testing for women with risks of trisomy 21 between 1:500 and 1:300. Invasive diagnostic testing was performed for women with positive or failed non-invasive prenatal testing result and in the high-risk group of this screening method. The direct costs were compared between this strategy and the non-invasive prenatal testing which alone used as first-line screening for all pregnant women. Results: Among 25,155 singleton pregnant women who underwent screening, 24,361 were available for analysis, of these, 194 cases underwent non-invasive prenatal testing. Among the 24,361 women, 39, 19, and 7 had trisomies 21, 18 and 13, respectively. The use of this strategy could potentially detect approximately 94.87% of trisomy 21 cases, 100% of trisomy 18 cases, and 100% of trisomy 13 cases, with false-positive rates of 2.49%, 0.41%, and 0.49%, respectively. The overall detection rate and overall false-positive rates were 96.92% and 2.52%, respectively. The detection rate was 100% in the advanced age group and 94.12% in the general age group. Additionally, structural abnormalities were detected in 137 fetuses, and 44 fetuses had other chromosomal abnormalities. The total cost of this strategy was $3,730,843.30, and the cost per person tested was $153.15. The total cost of using non-invasive prenatal testing as the first-line strategy would be $6,813,387.04 and the cost per person tested was $279.68. Conclusions: Our strategy is an efficient and cost-effective approach for detecting major trisomies and identifying more fetuses with a potential abnormality. Therefore, this strategy is a valuable screening method and highly feasible in the clinical setting. [ABSTRACT FROM AUTHOR]

Purpose: This study aims to analyze the experience of a tertiary health center about the management of adnexal masses that have been diagnosed during pregnancy or detected accidentally during cesarean delivery. Methods: This is a retrospective review of 160 women who underwent concurrent surgery for adnexal mass during cesarean section, 24 women who delivered vaginally and subsequently had surgery due to the prenatal diagnosis of adnexal mass and 10 women who underwent surgery for adnexal mass during pregnancy. Corresponding to the delivery and surgery times, 200 women who had no diagnosis of pregnancy-associated adnexal mass served as controls. Results: The women in the control group and study groups had statistically similar gestational age at delivery, birth weight and preterm delivery (p > 0.05 for all). Miscarriage was significantly more frequent in women undergoing surgery for adnexal mass during pregnancy (p = 0.001). The women who had surgery for adnexal mass during pregnancy, at the time of cesarean section and following delivery were statistically similar with respect to surgery type and histopathological diagnosis (p > 0.05 for both). Malignancy was detected in none of the patients who underwent surgery for adnexal mass during pregnancy. Acute abdomen was the indication for the emergency surgery in six patients (3.5%) who had surgery for adnexal mass during pregnancy. Four patients (2.4%) had surgery for adnexal mass during pregnancy due to the high index of suspicion for malignancy. Conclusion: The risk of malignancy was relatively lower in this cohort of adnexal masses detected during pregnancy and cesarean delivery. Surgical management of adnexal masses should be postponed to postpartum period as such management leads to an increased risk of miscarriage. Unless there is a need for emergent surgery or cancer staging, vaginal delivery should be encouraged in women diagnosed with adnexal mass during pregnancy. [ABSTRACT FROM AUTHOR]

Purpose: To compare perinatal outcomes between active and routine management in true knot of the umbilical cord (TKUC). Methods: A retrospective study of singletons born beyond 22 6/7 weeks with TKUC. Active management included weekly fetal heart rate monitoring(FHRM) ≥ 30 weeks and labor induction at 36–37 weeks. Outcomes in active and routine management were compared, including composite asphyxia-related adverse outcome, fetal death, labor induction, Cesarean section (CS) or Instrumental delivery due to non-reassuring fetal heart rate (NRFHR), Apgar5 score < 7, cord Ph < 7, neonatal intensive care unit (NICU) admission and more. Results: The Active (n = 59) and Routine (n = 1091) Management groups demonstrated similar rates of composite asphyxia-related adverse outcome (16.9% vs 16.8%, p = 0.97). Active Management resulted in higher rates of labor induction < 37 weeks (22% vs 1.7%, p < 0.001), CS (37.3% vs 19.2%, p = 0.003) and NICU admissions (13.6% vs 3%, p < 0.001). Fetal death occurred exclusively in the Routine Management group (1.8% vs 0%, p = 0.6). Conclusion: Compared with routine management, weekly FHRM and labor induction between 36 and 37 weeks in TKUC do not appear to reduce neonatal asphyxia. In its current form, active management is associated with higher rates of CS, induced prematurity and NICU admissions. Labor induction before 37 weeks should be avoided. [ABSTRACT FROM AUTHOR]

Purpose: The identification and prognosis of the agenesis of the corpus callosum (ACC) for prenatal consultation are complex and currently unclear. This study aims to explore the correlated genetic mutations of prenatal ACC. Methods: We retrospectively analyzed 114 prenatal cases of ACC. All cases (n = 114) were subjected to chromosomal microarray analysis (CMA), and 66 CMA-negative cases underwent prenatal exome sequencing (pES) for further analysis. Results: CMA was diagnosed positively in 15/114 (13.2%) cases and pES was diagnosed positively in 24/66 (36.4%) CMA-negative cases. The detection rate of genetic causes between complete and partial ACCs was not significantly different (P > 0.05). Between isolated and non-isolated (other anomalies present) ACCs, the diagnostic rate of pES in non-isolated cases was significantly higher (P < 0.001), while CMA results did not differ (P > 0.05). The diagnostic rate of CMA was significantly increased in cases combined with intracranial and extracranial malformations (P = 0.014), while no CMA positivity was detected in cases combined with only intracranial malformations. Conclusion: For fetuses with prenatal ACC, further pES analysis should be recommended after negative CMA results. Chromosome abnormalities are less likely to occur when ACC with only intracranial malformations combined. [ABSTRACT FROM AUTHOR]

Hysteroscopy has truly revolutionized the field of diagnostic and operative gynecology. It is presently regarded as the gold standard method for both the diagnosis and treatment of intrauterine diseases and it has fundamentally altered the way gynecologists treat patients with such conditions. These pathologies can now be diagnosed and treated in an outpatient setting, thanks to technological advancements and instrument downsizing. Two hundred years of development and notable innovation are now reflected in the present hysteroscopic practice. This review attempts to trace the boundaries-pushing history of hysteroscopy by highlighting the advancements in technology and the therapeutic and diagnostic benefits offered by this groundbreaking approach. [ABSTRACT FROM AUTHOR]

Purpose: To explore the application possibility of macrocephalic sperm from a patient with 100% macrocephalic sperm and AURKC gene variations. Methods: We diagnosed a case of macrozoospermia with 100% macrocephalic sperm and 39.5% multi-tailed spermatozoa by morphological analysis. Whole-exome sequencing (WES) was used for the patient and his wife. Sanger sequencing technique was used to verify the AURKC mutations in the patient's parents and his offspring. Sperm's ploidy was tested by flow cytometry. The couple asked for intra-couple ART therapy. Results: The patient presented novel compound heterozygous AURKC mutations (c.434C > T, c.497A > T) by WES. Sanger sequencing validation showed that variant of c.434C > T was observed in his father and c.497A > T was observed in his mother. Flow cytometry revealed that there existed a certain proportion of haploid sperm. Macrocephalic spermatozoa whose heads were smaller than the diameter of injection needle were selected for microinjection. A singleton pregnancy was achieved after embryo transfer. Prenatal diagnosis revealed that the fetus had normal chromosomal karyotype. Sanger sequencing technique showed that the fetus carried a c.434C > T mutation in one AURKC allele. A 3730 g healthy male fetus was delivered at term. Conclusion: Our study reported a successful live birth from a patient with definite AURKC gene variants and may provide insights for such patients to choose donor sperm or their own sperm. [ABSTRACT FROM AUTHOR]

Purpose: To assess the incidence of associated structural anomalies, chromosomal/genetic abnormalities, infections, and perinatal outcomes of fetuses with ventriculomegaly (VM), also to evaluate the role of fetal magnetic resonance imaging (MRI) in detecting associated intracranial anomalies. Methods: Retrospective cohort study of 149 prenatally diagnosed pregnancies with fetal VM. VM was classified as mild (Vp = 10–12 mm), moderate (Vp = 12.1–15 mm), and severe (Vp > 15 mm). Fetal MRI was performed to 97 pregnancies. Results: The incidences of an associated CNS, non-CNS, chromosomal anomaly, genetic abnormality and fetal infection were 42.3%, 11.4%, 6.1%, 2.1% and 1.3%, respectively. Fetal MRI identified additional CNS anomalies in 6.7% of cases, particularly in severe VM. The incidences of perinatal outcomes were 18.8% termination of pregnancy, 4% intrauterine and 8.1% neonatal or infant death. The rates of fetuses alive at > 12 months of age with neurological morbidity were 2.6%, 11.1% and 76.9% for mild, moderate and severe isolated VM, respectively. Conclusion: The prognosis of fetuses with VM mostly depends on the severity and the associated anomalies. Mild to moderate isolated VM generally have favorable outcomes. Fetal MRI is particularly valuable in fetuses with isolated severe VM. [ABSTRACT FROM AUTHOR]

Purpose: To establish a reliable nomogram model to predict the risk of major adverse pregnancy outcomes in pregnant women with adenomyosis, and to provide a reference tool for the hierarchical management and the prenatal examination of pregnant women. Methods: We collected the clinical data of pregnant women with adenomyosis who were treated in the First Affiliated Hospital of Chongqing Medical University, the Women and Children's Hospital of Chongqing Medical University, and Yubei District People's Hospital of Chongqing from January 2014 to June 2020. They were divided into the training cohort and the validation cohort, respectively. In the training cohort, we screened out risk factors associated with major adverse pregnancy outcomes and established a model, which was subsequently validated. Results: In the training cohort, we found that previous parity, natural conception or not, type of adenomyosis, with or without endometriosis, history of infertility or adverse pregnancy outcomes, and history of uterine body surgery were associated with major adverse pregnancy outcomes of pregnant women with adenomyosis, and based on these factors, a nomogram model was constructed. The calibration curves of the model were well fitted in both the training and validation cohorts. The receiver-operating characteristic curve (ROC curve) showed that the area under the curve (AUC) was 0.873 and 0.851 in the training and validation cohorts, respectively. The optimal risk threshold of the model was 0.22, and this threshold can be applied to risk stratification of pregnant women. Conclusion: The nomogram model established in this study can reliably predict the risk of major APO in pregnant women with AD. [ABSTRACT FROM AUTHOR]

Purpose: Facial clefts belong to the most common congenital malformations and their prenatal diagnosis is a constant challenge. The aim of this study was to determine the accuracy of prenatal ultrasound in correctly classifying facial clefts. Furthermore, we aimed to specify the distribution of the type of clefts and underlying genetic conditions. Methods: All fetuses seen with suspected facial cleft in the Department of Obstetrics, Charité – Universitätsmedizin Berlin during a period of 23 years (1999–2022) were included in this retrospective study. Clefts were classified according to the classification of Nyberg. All additional prenatal findings were assessed and correlated with the outcome. The accuracy of prenatal diagnosis was assessed. Results: 292 patients were included in the study. The most common type of clefts were unilateral cleft lip and palate (CL-P) (53.6%) and bilateral CL-P (30.6%), followed by CL (8.1%), CP (5.1%) and median CL-P (2.6%). The overall pre- and postnatal concordance rate corresponding to a correct prenatal diagnosis was high, 88.9%, ranging from 73.7% (CL) to 93.7% (unilateral CL-P). Most of the median clefts (95.2%) and CP (93.3%) were associated with other sonographic abnormalities, as well as 52.2% of bilateral CL-P. Chromosomal abnormalities, mostly trisomy 13 and trisomy 18, were observed in in the median CL-P (47.6%), bilateral CL-P (31.1%) and CP (26.7%) groups, in contrast to the CL (9.1%) and unilateral CL-P (12.9%) groups. It was exceptional to have a chromosomal abnormality without additional malformations (4.8%). The mortality rate including one late miscarriage, 5 IUFD's, 74 TOPs and 6 palliative cares at birth was 29.8%, particularly high for median clefts (90.5%). Conclusion: Prenatal ultrasound exhibited a high accuracy to assess the type of facial clefts with an average rate of 88.9% (73.7%–93.7%) and a concordance rate of up to 93.7%, depending on the type of cleft. The search for additional malformations as well as clarifying underlying genetic conditions is essential. This allows for a targeted counseling of the parents and to best prepare for postnatal care, including surgery by the maxillofacial team. [ABSTRACT FROM AUTHOR]

This article discusses a case of prenatal diagnosis of a fetal condition called harlequin ichthyosis (HI). The case involves a 24-year-old woman who was referred for an ultrasound at 30 weeks gestation due to abnormal fetal profile and reduced movements. The ultrasound revealed typical dysmorphic facial features of HI, including ectropion of the eyelids and outward turning of the lip. The joints were immobile and the fingers and toes were in abnormal positions. After counseling, the couple decided to terminate the pregnancy. HI is a severe and rare autosomal recessive ichthyosis caused by a mutation in the lipid transporter ABCA12. Therapy for HI includes intensive neonatal care and administration of retinoids, but the survival rate is still low. [Extracted from the article]

Introduction: To assess the intention of actual pregnancy and its influence on glycated hemoglobin (HbA1c) profile before and during the pregnancy of women with previous diabetes mellitus (DM). Methods: Prospective cohort study included pregnant women with previous DM assisted from October/2018 to October/2019. Data were collected with standardized questionnaire and from medical records. Comparisons of variables of interest (Student's t test, Mann–Whitney or chi-square test) were performed between the group of women who did or denied report having interest to become pregnant. And a logistic regression analysis were performed considering prematurity or fetal/neonatal complication as dependent variables. Results: Sixty patients were included, with HbA1c mean of pre-pregnancy, first and third trimesters of 9.3, 8.1 and 6.8%, respectively. 7.7% women had HbA1c ≤ 6.5% in pre-pregnancy and 16.7% in first trimester. 83.3% reported having received guidance on the importance of glucose control and contraception before their current pregnancy. Although 28.3% reported the intention to become pregnant, only 28.3% reported regular use of any contraceptive method before it, none of which had HbA1c in the recommended goal for pregnancy. Glycemic control did not differ between groups intending or not to become pregnant. Women with adequate glycemic control in first trimester had a lower frequency of prematurity (p = 0.015) and fetal complications (p = 0.001), and better control at the end of pregnancy. Discussion: Although most of these women reported having had information about the importance of a planned pregnancy, adequate glycemic control of women with diabetes before and during the pregnancy is still not a reality nowadays. It might be necessary to improve medical communication in pregnancy planning. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the value of fetal nasal bone hypoplasia and other prenatal risk factors in predicting chromosomal abnormalities. Methods: In this retrospective cohort study, we collected data on singleton pregnancies diagnosed with fetal nasal bone hypoplasia during second-trimester ultrasound. Fetal karyotyping and chromosomal microarray analysis (CMA) were performed, and pregnancy outcomes were assessed. The association between fetal nasal bone hypoplasia and chromosomal abnormalities was evaluated according to whether other prenatal risk factors were observed. Results: Our final analysis included 351 pregnancies, of which 62 (17.7%) fetuses had chromosomal abnormalities, including 36 cases of trisomy-21, six cases of trisomy-18, one case each of trisomy-13, and 47, XYY syndrome, and 18 cases of copy number variations (CNVs). Among the 243 cases of isolated nasal bone hypoplasia, 28 (11.5%) cases of chromosomal aberrations were identified. The incidence was significantly higher if other soft markers or structural abnormalities were simultaneously detected. Pregnancy was terminated in 43 aneuploid fetuses and nine fetuses detected with CNVs. The parents of the fetuses diagnosed with 47, XYY syndrome and the other nine CNVs chose to continue the pregnancy, and no abnormalities were detected in the newborns. Furthermore, we found that other prenatal risk factors should be considered in evaluating the likelihood of chromosomal abnormalities in fetuses with nasal bone hypoplasia. Conclusions: Nasal bone hypoplasia is a highly specific soft marker that is associated with multiple chromosomal abnormalities. The risk of chromosomal abnormalities increases when combined with structural abnormalities or increased nuchal translucency (NT). Chromosomal microarray analysis is a powerful prenatal test for chromosomal abnormalities, which may be warranted in fetuses with nasal bone hypoplasia. [ABSTRACT FROM AUTHOR]

Background: This paper evaluated the clinical utility of massively parallel sequencing-based non-invasive prenatal testing (NIPT) for detecting trisomy 21 (T21), T18, T13, sex chromosome aneuploidies (SCA), and rare chromosome aneuploidies (RCA) among the data collected by a clinical laboratory in southern China. Methods: In a 3-year period between January 2017 and December 2019, over 40,000 pregnant women underwent NIPT clinical screening test for fetal T21, T18, T13, SCA, and RCA in our laboratory. NIPT samples were processed using the NextSeq CN500 platform. The positive results were confirmed by karyotyping, and chromosomal microarray analysis (CMA) or copy number variants (CNV) sequencing. Details of the pregnancy outcomes were collected via telephone interview. Results: NIPT results were available for 41,819 cases; 691 positive cases were reported. The overall sensitivity for detection of T21, T18, T13, SCA, and RCA was 99.21, 100.00, 100.00, 98.55, and 100.00%, and the specificity was 99.95, 99.94, 99.98, 99.69, and 99.92%, respectively. The positive predictive values (PPVs) for detection of T21, T18, T13, SCA, and RCA were 85.62, 45.24, 40.00, 34.17, and 13.51%, respectively, and those for detection of 45,X, 47,XXY, 47,XXX, 47,XYY, and 46,XY(delX) 20.00, 59.18, 28.95, 61.54, and 25.00%, respectively. Regarding pregnancy outcomes, 92.38% of the pregnancies with confirmed aneuploidies were terminated, and 91.20% of those identified as having a false-positive result were carried to term. Among 252 unconfirmed cases, 24.60% of the pregnancies were terminated and 38.10% carried to term, while 37.30% declined interview. Conclusions: NIPT is widely used to screen fetal aneuploidies based on its high sensitivity and specificity. However, in this study, the PPVs of NIPT in terms of detecting T18, T13, XO, XXX and RCA were < 50%. In addition, more than one-third of NIPT-positive women did not accept invasive prenatal diagnosis. Confirmatory diagnosis is strongly recommended for women with positive NIPT outcomes before any further decision is made. [ABSTRACT FROM AUTHOR]

This article discusses a case of prenatal diagnosis of proboscis lateralis, a rare craniofacial anomaly characterized by a soft, finger-like appendage below the forehead. The case involves a 31-year-old woman who was referred for an abnormal appearance of the fetal nose on ultrasound. The prenatal genetic examinations were normal, and the fetus was delivered without complications. The article emphasizes the importance of detailed ultrasound examination and genetic testing in cases of proboscis lateralis, and highlights the need for an interdisciplinary approach to postnatal treatment. [Extracted from the article]

A systematic evaluation of the fetal anatomy as part of the second trimester ultrasound examination in pregnancy is useful in detecting pregnancy complications, fetal abnormalities, and genetic diseases. We aim to illustrate the basic and detailed second trimester scan, according to current international and national guidelines, as well as to our own every-day practice in the Department for Prenatal Diagnosis at the University of Tübingen, Germany. [ABSTRACT FROM AUTHOR]

Objectives: To analyse additional structural and genetic anomalies in fetuses with acrania/exencephaly/anencephaly sequence (AEAS). Methods: A retrospective analysis of 139 fetuses with AEAS diagnosed between 2006 and 2020 in a single tertiary referral ultrasound department. Results: The median gestational age at diagnosis decreased from 15 weeks in 2006 to 13 weeks in 2020 (− 0.21 per each year; p = 0.009). In 103 fetuses, the defects were limited to the neural tube (NTD) (74.1%), in 36 fetuses (25.9%), there were additional structural non-NTD anomalies. The most common were ventral body wall defects present in 17.8% (23/139), followed by anomalies of the limbs (7.2%; 10/139), face (6.5%; 9/139) and heart (6.5%; 9/139). Genetic anomalies were diagnosed in 7 of the 74 conclusive results (9.5%; 7/74; trisomy 18, n = 5; triploidy, n = 1; duplication of Xq, n = 1). In univariate logistic regression models, male sex, limb anomalies and ventral body wall defects significantly increased the risk of genetic anomalies (OR 12.3; p = 0.024; OR 16.5; p = 0.002 and OR 10.4; p = 0.009, respectively). Conclusions: A significant number of fetuses with AEAS have additional structural non-NTD anomalies, which are mostly consistent with limb body wall complex. Genetic abnormalities are diagnosed in almost 10% of affected fetuses and trisomy 18 is the most common aberration. Factors that significantly increased the odds of genetic anomalies in fetuses with AEAS comprise male sex, limb anomalies and ventral body wall defects. [ABSTRACT FROM AUTHOR]

A 29-year-old primigravida at 31 weeks of gestation was referred for intrathoracic kidney (ITK). Ultrasound revealed left kidney intrathoracic placement with an anteriorly positioned ectopic adrenal gland. Magnetic resonance imaging confirmed diaphragmatic interruption and colon herniation. A female neonate, delivered at 37 weeks, underwent successful thoracoscopic repair for a left Bochdalek hernia. Despite compression of the left lung, notably optimistic lung-to-head ratio (LHR) values were observed, correlating with favorable outcomes. This case underscores the rare occurrence of ITK, its association with Bochdalek hernia, and the importance of comprehensive prenatal evaluations. [ABSTRACT FROM AUTHOR]

This article discusses a case of prenatal diagnosis of congenital eyelid eversion in a fetus with trisomy 21. A 27-year-old pregnant woman underwent genetic screening for trisomy 21 and a subsequent ultrasound at 39 weeks and 6 days revealed a soft tissue mass below the right eye of the fetus. The male infant was delivered via cesarean section and was found to have congenital bilateral upper eyelid eversion. The article emphasizes the importance of prompt identification and treatment of congenital eyelid eversion, particularly in cases of trisomy 21, as delays can lead to complications including vision loss. The authors suggest that clinicians should consider the diagnosis of eyelid eversion in fetuses with eyelid masses on ultrasound. [Extracted from the article]

Introduction: Fetal genital malformations represent a rare and heterogeneous group of congenital malformations of the disorders of sexual development (DSD) spectrum.Methods: A thorough literature review on the main topics in the prenatal approach towards DSD was conducted.Results: First, a thorough overview on prenatal characteristics of the most common fetal genital malformations of ovaries, uterus and external genitalia, and second, a standardized approach for differential diagnosis in the presence of direct and indirect prenatal signs of DSDs.Conclusions: This review is mainly directed towards the aspects of female genital malformations with  aspects of male DSD explained as well to aid in the prenatal differential diagnosis. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to explore the outcome in fetuses with prenatal diagnosis of absent pulmonary valve syndrome (APVS) on ultrasound imaging. Methods: A manual web scraping technique was utilized, where MEDLINE and EMBASE were searched along the combination with other relevant medical subject headings such as "absent pulmonary valve syndrome", "prenatal APVS" and "APVS/outcome". The observed outcomes encompassed the rate of chromosomal abnormalities, associations and malformations linked to APVS and fetuses with APVS. A quality assessment of the included studies was also performed. We used meta-analyses of proportions to combine data and fixed or random-effects models according to the heterogeneity of the results. Results: Seven studies including 199 fetuses with APVS were included in the analysis. The median gestational age at referral to the tertiary center was 24.8 weeks. An association to tetralogy of Fallot (TOF) could be seen in 84.4% of all cases. In total 140 out of 199 cases underwent invasive testing, with a total number of 55 abnormal karyotypes [39.3% (95% CI 31.1–47.9%)]. 35.2% of the patients opted for termination of pregnancy (95% CI 28.5–42.3%). Conclusion: The analysis underlines the distribution of fetuses with APVS, with 84.4% of cases presenting with TOF/APVS and only 12.6% having APVS/intact ventricular septum (IVS). Larger and more prospective study analyses is now needed, especially focusing on long-term follow-up periods of fetuses and children with APVS. Particularly as the postnatal course shows great variety depending on prenatal diagnosis. [ABSTRACT FROM AUTHOR]

Introduction: The evaluation of the performance of new methods, expected to provide cheaper and faster results than existing (reference) methods in the health field, is based on comparing the results obtained with this new method to those obtained with the existing method. The primary aim of this study is to examine the correlational and absolute agreement between measurement methods in clinical studies using Bland–Altman analysis and methodological (Ordinary Least Squares, Weighted Ordinary Least Squares, Deming, Weighted Deming, Passing–Bablok, Theil-Sen, and Passing–Bablok for Large Data Sets.) methods, and the secondary aim is to compare the accuracy and precision of Hadlock (I–V) formulas used for fetal weight estimation.The study was conducted on singleton pregnancies examined in the Prenatal Diagnosis and Treatment Unit of the Department of Obstetrics and Gynecology at Inonu University Faculty of Medicine and who gave birth in the Obstetrics Unit between 01.01.2020 and 01.09.2023, whose gestational ages were confirmed by first-trimester ultrasonography. Estimated fetal weights were calculated using Hadlock (I–V) formulas, and the agreement of these weights with birth weight was evaluated with Bland–Altman method.The comparison of estimated fetal weights calculated using Hadlock formulas with birth weight was analyzed using Bland–Altman analysis, ICC, and CCC values along with regression analyses. According to the mean difference values obtained by Bland–Altman analysis, the estimated fetal birth weights obtained by the Hadlock IV formula were most consistent with the actual birth weights.The estimated fetal weights obtained using the Hadlock IV formula resulted in the closest measurements to the birth weight. This study showcases the efficacy of a new web-based software, Method Comparison Software (MCS), which can be utilized for evaluating the agreement between different methods in clinical measurements.Materials and methods: The evaluation of the performance of new methods, expected to provide cheaper and faster results than existing (reference) methods in the health field, is based on comparing the results obtained with this new method to those obtained with the existing method. The primary aim of this study is to examine the correlational and absolute agreement between measurement methods in clinical studies using Bland–Altman analysis and methodological (Ordinary Least Squares, Weighted Ordinary Least Squares, Deming, Weighted Deming, Passing–Bablok, Theil-Sen, and Passing–Bablok for Large Data Sets.) methods, and the secondary aim is to compare the accuracy and precision of Hadlock (I–V) formulas used for fetal weight estimation.The study was conducted on singleton pregnancies examined in the Prenatal Diagnosis and Treatment Unit of the Department of Obstetrics and Gynecology at Inonu University Faculty of Medicine and who gave birth in the Obstetrics Unit between 01.01.2020 and 01.09.2023, whose gestational ages were confirmed by first-trimester ultrasonography. Estimated fetal weights were calculated using Hadlock (I–V) formulas, and the agreement of these weights with birth weight was evaluated with Bland–Altman method.The comparison of estimated fetal weights calculated using Hadlock formulas with birth weight was analyzed using Bland–Altman analysis, ICC, and CCC values along with regression analyses. According to the mean difference values obtained by Bland–Altman analysis, the estimated fetal birth weights obtained by the Hadlock IV formula were most consistent with the actual birth weights.The estimated fetal weights obtained using the Hadlock IV formula resulted in the closest measurements to the birth weight. This study showcases the efficacy of a new web-based software, Method Comparison Software (MCS), which can be utilized for evaluating the agreement between different methods in clinical measurements.Results: The evaluation of the performance of new methods, expected to provide cheaper and faster results than existing (reference) methods in the health field, is based on comparing the results obtained with this new method to those obtained with the existing method. The primary aim of this study is to examine the correlational and absolute agreement between measurement methods in clinical studies using Bland–Altman analysis and methodological (Ordinary Least Squares, Weighted Ordinary Least Squares, Deming, Weighted Deming, Passing–Bablok, Theil-Sen, and Passing–Bablok for Large Data Sets.) methods, and the secondary aim is to compare the accuracy and precision of Hadlock (I–V) formulas used for fetal weight estimation.The study was conducted on singleton pregnancies examined in the Prenatal Diagnosis and Treatment Unit of the Department of Obstetrics and Gynecology at Inonu University Faculty of Medicine and who gave birth in the Obstetrics Unit between 01.01.2020 and 01.09.2023, whose gestational ages were confirmed by first-trimester ultrasonography. Estimated fetal weights were calculated using Hadlock (I–V) formulas, and the agreement of these weights with birth weight was evaluated with Bland–Altman method.The comparison of estimated fetal weights calculated using Hadlock formulas with birth weight was analyzed using Bland–Altman analysis, ICC, and CCC values along with regression analyses. According to the mean difference values obtained by Bland–Altman analysis, the estimated fetal birth weights obtained by the Hadlock IV formula were most consistent with the actual birth weights.The estimated fetal weights obtained using the Hadlock IV formula resulted in the closest measurements to the birth weight. This study showcases the efficacy of a new web-based software, Method Comparison Software (MCS), which can be utilized for evaluating the agreement between different methods in clinical measurements.Conclusions: The evaluation of the performance of new methods, expected to provide cheaper and faster results than existing (reference) methods in the health field, is based on comparing the results obtained with this new method to those obtained with the existing method. The primary aim of this study is to examine the correlational and absolute agreement between measurement methods in clinical studies using Bland–Altman analysis and methodological (Ordinary Least Squares, Weighted Ordinary Least Squares, Deming, Weighted Deming, Passing–Bablok, Theil-Sen, and Passing–Bablok for Large Data Sets.) methods, and the secondary aim is to compare the accuracy and precision of Hadlock (I–V) formulas used for fetal weight estimation.The study was conducted on singleton pregnancies examined in the Prenatal Diagnosis and Treatment Unit of the Department of Obstetrics and Gynecology at Inonu University Faculty of Medicine and who gave birth in the Obstetrics Unit between 01.01.2020 and 01.09.2023, whose gestational ages were confirmed by first-trimester ultrasonography. Estimated fetal weights were calculated using Hadlock (I–V) formulas, and the agreement of these weights with birth weight was evaluated with Bland–Altman method.The comparison of estimated fetal weights calculated using Hadlock formulas with birth weight was analyzed using Bland–Altman analysis, ICC, and CCC values along with regression analyses. According to the mean difference values obtained by Bland–Altman analysis, the estimated fetal birth weights obtained by the Hadlock IV formula were most consistent with the actual birth weights.The estimated fetal weights obtained using the Hadlock IV formula resulted in the closest measurements to the birth weight. This study showcases the efficacy of a new web-based software, Method Comparison Software (MCS), which can be utilized for evaluating the agreement between different methods in clinical measurements. [ABSTRACT FROM AUTHOR]

Objective: The aim of our study was to investigate the normal cortical sulcus development in fetuses without central nervous system abnormality with transabdominal ultrasonography. Methods: Our study was planned as a cross-sectional study in our clinic between November 2011 and October 2012. The study group was selected among pregnant women who applied to our hospital for routine antenatal follow-up. Singleton pregnancies, between 15th and 32nd gestational weeks, were included in the study. During the routine fetal ultrasonographic examination of these pregnant women, sylvian sulcus, parietooccipital sulcus, calcarine sulcus, and cingulate sulcus length measurements were taken and the correlation of these values with gestational week was evaluated. Results: Three hundred and thirty-two patients were included in the study. Sylvian sulcus length, parietooccipital sulcus length, calcarine sulcus length, and cingulate sulcus length could be first measured respectively, at 15th, 17th, 17th and 25th gestational week. We found a positive correlation between gestational age and sylvian sulcus, parietooccipital sulcus, calcarine sulcus, and cingulate sulcus length measurements (p < 0.001). Conclusion: Sulcal development and cortical maturation can be evaluated prenatally with transabdominal ultrasonography of the central nervous system. [ABSTRACT FROM AUTHOR]

Objectives: Noninvasive prenatal testing (NIPT) is actually the most accurate method of screening for fetal chromosomal aberration (FCA). We used pregnancy outcome record to evaluate a complete data set of single nucleotide polymorphism-based test results performed by a Swiss genetics center. Materials and methods: The Panorama® test assesses the risk of fetal trisomies (21, 18 and 13), gonosomal aneuploidy (GAN), triploidy or vanishing twins (VTT) and five different microdeletions (MD). We evaluated all 7549 test results meeting legal and quality requirements taken in women with nondonor singleton pregnancies between April 2013 and September 2016 classifying them as high or low risk. Follow-up ended after 9 months, data collection 7 months later. Results: The Panorama® test provided conclusive results in 96.1% of cases, detecting 153 FCA: T21 n = 76, T18 n = 19, T13 n = 15, GAN n = 19, VTT n = 13 and MD n = 11 (overall prevalence 2.0%). Pregnancy outcome record was available for 68.6% of conclusive laboratory results, including 2.0% high-risk cases. In this cohort the Panorama® test exhibited 99.90% sensitivity for each trisomy; specificity was 99.90% for T21, 99.98% for T18 and 99.94% for T13. False positive rate was 0.10% for T21, 0.02% for T18 and 0.06% for T13. Conclusion: SNP-based testing by a Swiss genetics center confirms the expected accuracy of NIPT in FCA detection. [ABSTRACT FROM AUTHOR]

Purpose: We aimed to present the fetal ultrasound, cytogenetic/molecular testing and postmortem or postnatal clinical findings of cases with 22q11.2DS diagnosed prenatally. Materials and methods: A retrospective medical record review of 48 prenatal cases diagnosed with 22q11.2DS were evaluated in our institution. Detailed ultrasound examination was performed on all fetuses. Postmortem and postnatal examinations were evaluated. The microdeletions were detected by karyotyping or microarray, then confirmed by FISH. Descriptive statistical analysis was performed. Results: Demographic data of 48 prenatal cases including 46 singletons and 1 dichorionic diamniotic twin pregnancy were evaluated. The most common extracardiac anomaly was skeletal system anomalies (25%), in which PEV was the most frequent one (20.8%). Polyhydramnios rate was detected as 31%, in 6.6% as an isolated finding. Microdeletion has been detected by karyotyping in 13 cases (13/47, 27.7%) (including 2 unbalanced translocations), by FISH in 28 cases (28/48, 58.3%), by microarray/a-CGH testing in 7 cases. Microarray analysis showed that in one case with unbalanced translocation had two consecutive deletions; one was proximal and other one distal to critical region and not encompassing TBX1 gene but CRKL and LZTR1 genes. Conclusion: The current study demonstrates the whole spectrum of atypical phenotypic and genotypic variations of 22q11.2DS in the largest prenatal case series reported to date. Therefore, differential diagnosis should be considered not solely in CHD, but also in the presence of isolated clubfeet and polyhydramnios. Establishing the diagnosis in the prenatal period may allow a postnatal multidisciplinary approach, as well as affect the actual prevalence of the disease. [ABSTRACT FROM AUTHOR]

Purpose: To assess the spectrum of associated anomalies, the intrauterine course, postnatal outcome and management of fetuses with truncus arteriosus communis (TAC) Methods: All cases of TAC diagnosed prenatally over a period of 8 years were retrospectively collected in two tertiary referral centers. All additional prenatal findings were assessed and correlated with the outcome. The accuracy of prenatal diagnosis was assessed. Results: Thirty nine cases of TAC were diagnosed prenatally. Mean gestational age at first diagnosis was 22 weeks (range 13–38). Two cases were lost follow-up. Correct prenatal diagnosis of TAC was made in 87.5% and of TAC subtype in 90.5%. Prenatal diagnosis was incorrect in three cases: one newborn had aortic atresia with ventricular septal defect (VSD) postnatally, one had hypo-plastic right ventricle with dextro transposition of the great arteries (d-TGA) with coarctation of the aorta and a third newborn had tetralogy of fallot (TOF) with abnormal origin of the left pulmonary artery arising from the ascending aorta postnatally. These 3 cases were excluded from further analysis. In 26.5% of cases, TAC was an isolated finding. 38.2% of fetuses had additional chromosomal anomalies. Among them, microdeletion 22q11.2 was most common with a prevalence of 17.6% in our cohort. Another 3 fetuses were highly suspicious for non-chromosomal genetic syndromes due to their additional extra-cardiac anomalies, but molecular diagnosis could not be provided. Major cardiac and extra-cardiac anomalies occurred in between 8.8% and 58.8%, respectively. Predominantly, extra-cardiac anomalies occurred in association with chromosomal anomalies. Additionally, severe IUGR occurred in 17.6%. There were 14 terminations of pregnancy (41.2%), 1 (2.9%) intrauterine fetal death, 5 postnatal deaths (14.7%) and 14 (41.2%) infants were alive at last follow-up. Intention-to-treat survival rate was 70%. Mean follow-up among survivors was 42 months (range 6–104). Postoperative health status among survivors was excellent in 78.6%, but 46.2% needed repeated re-interventions due to recurrent pulmonary artery or conduit stenosis. The other 21.4% of survivors were significantly impaired due to non-cardiac problems. Conclusion: Truncus arteriosus communis is a rare and complex cardiac anomaly that can be diagnosed prenatally with high precision. TAC is frequently associated with chromosomal and extra-cardiac anomalies, leading to a high intrauterine and postnatal loss rate due to terminations and perioperative mortality. Without severe extra-cardiac anomalies, postoperative health status is excellent, independent of the subtype of TAC, but the prevalence of repeated interventions due to recurrent stenosis is high. [ABSTRACT FROM AUTHOR]

Purpose: To analyze the risk for clinically significant microarray aberrations in pregnancies with polyhydramnios.Methods: Data from all chromosomal microarray analyses (CMA) performed due to polyhydramnios between January 2013 and December 2019 were retrospectively obtained from the Ministry of Health Database. The rate of clinically significant (pathogenic and likely pathogenic) CMA findings in isolated and non-isolated polyhydramnios cohorts was compared to a local control group of 5541 fetuses with normal ultrasound, in which 78 (1.4%) abnormal results were demonstrated. Subgroup analyses were performed by the degree of polyhydramnios, week of diagnosis, maternal age, and the presence of additional sonographic anomalies.Results: In the isolated polyhydramnios cohort, 19/623 (3.1%) clinically significant CMA aberrations were noted, a significantly higher rate compared to the control population. However, the risk for abnormal CMA results in the 158 cases with mild polyhydramnios (AFI 25-29.9, or maximal vertical pocket 8-11.9 cm) did not significantly differ from pregnancies with normal ultrasound. Of 119 cases of non-isolated polyhydramnios (most frequently associated with cardiovascular (26.1%) and brain (15.1%) anomalies), 8 (6.7%) abnormal CMA findings were noted, mainly karyotype-detectable.Conclusion: Mild polyhydramnios was not associated with an increased rate of clinically significant microarray results, compared to pregnancies with normal ultrasound. An extensive anatomical sonographic survey should be performed in pregnancies with polyhydramnios, with consideration of fetal echocardiography. [ABSTRACT FROM AUTHOR]

Purpose: Placenta accreta spectrum (PAS) disorders can cause major intrapartum haemorrhage. The optimal management approach is not yet defined. We analysed available cases from a tertiary perinatal centre to compare the outcome of different individual management strategies. Methods: A monocentric retrospective analysis was performed in patients with clinically confirmed diagnosis of PAS between 07/2012 and 12/2019. Electronic patient and ultrasound databases were examined for perinatal findings, peripartum morbidity including blood loss and management approaches such as (1) vaginal delivery and curettage, (2) caesarean section with placental removal versus left in situ and (3) planned, immediate or delayed hysterectomy. Results: 46 cases were identified with an incidence of 2.49 per 1000 births. Median diagnosis of placenta accreta (56%), increta (39%) or percreta (4%) was made in 35 weeks of gestation. Prenatal detection rate was 33% for all cases and 78% for placenta increta. 33% showed an association with placenta praevia, 41% with previous caesarean section and 52% with previous curettage. Caesarean section rate was 65% and hysterectomy rate 39%. In 9% of the cases, the placenta primarily remained in situ. 54% of patients required blood transfusion. Blood loss did not differ between cases with versus without prenatal diagnosis (p = 0.327). In known cases, an attempt to remove the placenta did not show impact on blood loss (p = 0.417). Conclusion: PAS should be managed in an optimal setting and with a well-coordinated team. Experience with different approaches should be proven in prospective multicentre studies to prepare recommendations for expected and unexpected need for management. [ABSTRACT FROM AUTHOR]

Purpose: To analyze anatomic features and associated malformations in 37 prenatally detected cases of congenitally corrected transposition of the great arteries (ccTGA) and to evaluate the prenatal course, neonatal outcome and mid-term follow-up.Methods: Retrospective analysis of prenatal ultrasound of 37 patients with ccTGA in two tertiary centers between 1999 and 2019. All fetuses received fetal echocardiography and a detailed anomaly scan. Postnatal outcome and follow-up data were retrieved from pediatric reports.Results: Isolated ccTGA without associated cardiac anomalies was found in 13.5% (5/37), in all other fetuses additional defects such as VSD (73.0%), pulmonary obstruction (35.1%), tricuspid valve anomalies (18.9%), aortic arch anomalies (13.5%), ventricular hypoplasia (5.4%) or atrioventricular block (5.4%) were present. The rate of extracardiac malformations or chromosomal aberrations was low. There were 91.9% (34/37) live births and postnatal survival rates reached 91.2% in a mean follow-up time of 4.98 years. The prenatal diagnosis of ccTGA was confirmed postnatally in all but one documented live birth and the prenatal counselling regarding the expected treatment after birth (uni- versus biventricular repair) was reassured in the majority of cases. The postnatal intervention rate was high, 64.7% (22/34) received surgery, the intervention-free survival was 36.7%, 35.0% and 25.0% at 1 month, 1 year and 10 years, respectively.Conclusions: ccTGA is a rare heart defect often associated with additional heterogeneous cardiac anomalies that can be diagnosed prenatally. The presented study demonstrates a favorable outcome in most cases but the majority of patients require surgical treatment early in life. [ABSTRACT FROM AUTHOR]

Purpose: Noninvasive prenatal testing (NIPT) is a highly sensitive and specific method for detection of fetal chromosomal aneuploidies from maternal plasma. The objective of this study was to determine the performance of a new paired-end sequencing-based NIPT assay in 13,607 pregnancies from a single center in Germany.Methods: Samples from 13,607 pregnant women who previously underwent NIPT were analyzed using VeriSeq NIPT Solution v2 assay for presence of common fetal trisomies and monosomy X. Follow-up to determine clinical truth was carried out.Results: Of the 13,607 cases, 13,509 received a NIPT call resulting in a low study failure rate of 0.72%. There were 188 (1.4%) high-risk calls: 117 trisomy 21, 34 trisomy 18, 23 trisomy 13, one trisomy 21 + 13, and 13 monosomy X. High sensitivities and specificities of ≥ 98.89% were reported for all four aneuploidy conditions. Of the high-risk cases, clinical follow-up data were available for 77.1% (145/188). Clinical follow-up of high-risk calls revealed an overall positive predictive value of 84.8% (potential range 65.4-88.3%). NIPT results were provided for samples across a range of fetal fractions, down to 2% fetal fraction.Conclusion: The VeriSeq NIPT Solution v2 assay detected fetal chromosomal aneuploidies across a range of fetal fractions with high sensitivities and specificities observed based on known clinical outcomes, a high overall PPV, and a low failure rate. [ABSTRACT FROM AUTHOR]

Background: Nowadays several Prenatal Tests for Chromosomal Abnormalities Detection (PTCAD) are available. In those cases in which there is not an Institutional protocol to advise women about the available PTCAD, the choice of which one to undergo is up to the woman and largely depends on her knowledge about them. Therefore, we decided to evaluate, as a primary outcome, knowledge about PTCAD among pregnant women attending our Term Clinic. As a secondary outcome we evaluated the relationship between the patient's knowledge and the subsequently chosen PTCAD. Methods: From August 2017 to August 2018 an anonymous questionnaire with multiple-choice answers was administered to all pregnant women attending our Term antenatal Clinic, a tertiary obstetric unit in Catanzaro (Italy). Results: Three hundred and twenty-five pregnant women were enrolled in the study. We observed that 28.8% of the pregnant women that chose one of the PTCAD, avoided the first trimester combined screening test; among these, 11.4% were in favour of the cell-free foetal DNA test. The latter was erroneously considered diagnostic by 34.3% of the women that had chosen it. Conclusions: This study demonstrated that women's knowledge about PTCAD is poor and that there is a potentially dangerous confusion between the words 'screening' and 'diagnostic'. Informative campaigns about PTCAD and the application of dedicated antenatal counselling appointments should be a health-care priority to avoid unnecessary risks and costs for pregnant women and possible legal issues. [ABSTRACT FROM AUTHOR]

Purpose: Fetal arthrogryposis multiplex congenita (AMC) describes a heterogeneous disease entity characterized by multiple contractures affecting at least two different body areas. The aim of our study was to identify additional sonographic abnormalities in fetuses with AMC Type I–III associated with an unfavorable prognosis and to describe when those signs were first detected. Methods: This retrospective study included 41 pregnancies of suspected AMC diagnosed 1999–2017 at our tertiary referral center. The affected pregnancies were divided into the 3 AMC subgroups; the time of detection and outcome were analyzed. Prenatal sonograms, pediatric charts, genetic tests, and autopsy reports were studied. Results: Pregnancy outcome data were verifiable in 34 out of 41 cases; in 27 cases, AMC was confirmed. Hydrops was present in 50% of postnatally deceased fetuses, 53% of cases resulting in termination of pregnancy vs. 0% of the surviving 8 children. Absent stomach filling was found in 67% of the children with neonatal death. After subcategorization, the limb-involvement-only-group, 8% showed hydrops vs. 100% in system anomaly group vs. 70% in neuromuscular dysfunction cohort (p = 0.001). Scoliosis, nuchal edema, and absent stomach filling were significantly indicating for a neurological etiology. Conclusion: In addition to disease-defining sonographic findings, those with prognostic significance were identified. Hydrops, nuchal edema, scoliosis and absent stomach filling were associated with unfavorable outcomes implicating a neuromuscular etiology. This knowledge can help to predict the further course of the disease and support patient counseling. [ABSTRACT FROM AUTHOR]

Introduction: Neural tube defects (NTDs) are a group of heterogeneous congenital anomalies of the central nervous system (CNS). Acrania is a non-NTD congenital disorder related to the CNS. It can transform into anencephaly through the acrania-exencephaly-anencephaly sequence (AEAS). In AEAS, the cerebral tissue is not protected and is gradually destroyed due to exposure to the harmful effect of amniotic fluid and mechanical injuries. These lead to exencephaly and then into anencephaly. In contrast to primary anencephaly (NTDs), this type of anencephaly authors suggests calling secondary anencephaly.Objective: Analysis of the known prenatal ultrasonography (US) signs associated with AEAS. Simultaneously, the authors propose a new sign in the differentiation of acrania from exencephaly and anencephaly, called the "beret" sign.Methods: It is a two-centre retrospective observational study. As part of the study, 4060 US scans were analyzed.Results: In 10 cases, the absence of calvarium was diagnosed, allowing recognition of either AEAS stages or primary anencephaly. In 5 cases, cerebral structures were enclosed by an inertial rippled thin membrane, with a smooth outer contour. Between the described membrane and the brain structures, a thin anechoic space corresponding to cerebrospinal fluid was observed. This sign was defined as the "beret" sign. In these cases, acrania was diagnosed. In three cases calvarium was missing. The brain structures had an irregular appearance, did not wave and remained motionless. The outer contour was unequal as if divided into lobes. Amniotic fluid was anechoic. Exencephaly was diagnosed in these cases. In two cases calvarium, brain structures, and meninges were missing. The "frog eyes" sign and slightly echogenic amniotic fluid were visible. In this case, anencephaly was diagnosed.Conclusions: The "beret" sign seems to be a promising tool in the diagnosis of acrania. Furthermore, echogenicity of amniotic fluid could be useful during differentiation between primary and secondary anencephaly. [ABSTRACT FROM AUTHOR]

Background: Gallbladder duplication is a rare anatomic anomaly characterized by the presence of an accessory gallbladder.Objective: To appraise the prevalence and significance of prenatal diagnosis of duplication of gallbladder in a multicenter study.Methods: This was a multicenter case series with literature review. Clinical records of all consecutive pregnant women with a prenatal diagnosis of duplication of gallbladder, who were referred to our Centers were included in this study. The diagnosis of duplication of gallbladder was based on the evidence of double gallbladder in the standard abdominal circumference plane using grey scale. Postnatal magnetic resonance cholangiopancreatography (MRCP) 3D and postnatal neonatal abdominal ultrasound scan were offered soon after birth to confirm the diagnosis of double gallbladder. The systematic review was conducted using electronic databases from inception of each database through December 2019.Results: Five studies, including a total of seven cases, were identified as relevant and included in the systematic review. Gestational age at diagnosis ranged from 20 to 32 weeks of gestation. Associated findings were reported in only one case, where the fetus presented with a left-sided gallbladder, and bilateral renal agenesis with Potter sequence. None of the included cases reported abnormal karyotype. Our cases series included nine cases (0.03%) of double gallbladder with postnatal confirmation, with an overall incidence of this anomaly of 0.03%.Associated findings were reported in only two cases, one with IUGR and omphalocele, that opted for I-TOP, and one with single umbilical artery. Except for the I-TOP, neonatal outcome was favorable in all cases.Conclusions: Duplication of the gallbladder is a very rare malformation with only seven cases reported in the literature diagnosed prenatally. This anomaly is not associated with abnormal karyotype, and the neonatal outcome is favorable if there are no other associated abnormalities. [ABSTRACT FROM AUTHOR]

Background: Despite the well-known second trimester ultrasound signs, current possibilities of in utero surgical repair of open spina bifida require a timely detection of the spine defect.Objective: To evaluate the diagnostic accuracy of the ratio between brain stem (BS) diameter and its distance to the occipital bone (BSOB) (BS/BSOB ratio) in the detection of fetuses with open spina bifida at first trimester ultrasound.Methods: A systematic review and meta-analysis of diagnostic accuracy was performed by searching seven electronic databases from their inception to February 2019 for all studies assessing the association between BS/BSOB ratio and diagnosis of spine bifida. Diagnostic accuracy of BS/BSOB ratio in prenatal diagnosis of spine bifida was assessed as sensitivity, specificity, positive and negative likelihood ratios (LR + and LR-), and area under the curve (AUC) on SROC curves.Results: Four studies, including 17,598 fetuses with 23 cases of open spina bifida, were included in the meta-analysis. BS/BSOB ratio showed pooled sensitivity of 0.70 (95% CI 0.47-0.87; I2 = 78.3%), specificity of 1.00 (95% CI 0.99-1.0; I2 = 99.2%), LR + and LR- of 51.44 (95% CI 9.53-277.64; I2 = 85.5%) and 0.23 (95% CI 0.04-1.17; I2 = 64.8%), respectively, and an AUC of 0.9649.Conclusion: First trimester BS/BSOB ratio has a high diagnostic accuracy in detecting fetuses with open spina bifida. [ABSTRACT FROM AUTHOR]

Purpose: Isolated classic bladder exstrophy (CBE) is the most common variant of the bladder-exstrophy-epispadias complex (BEEC). The BEEC represents a spectrum ranging from isolated epispadias over CBE to the most severe form, cloacal exstrophy. We report on a series of 12 cases with CBE diagnosed prenatally and illustrate the spectrum of prenatal ultrasound findings with comparison to prior published reports on this entity.Methods: This was a retrospective study involving 12 fetuses with CBE at two large tertiary referral centers in Germany over a 14-year period (2004-2018).Results: Median diagnosis was made with ultrasound in 24 + 5 (IQR25,75: 21 + 2, 29 + 0) weeks of gestation. All fetuses presented with the pathognomonic findings non-visualization of the fetal bladder and protruding abdominal mass below the umbilical cord insertion. All fetuses showed normal kidney anatomy and normal amniotic fluid throughout pregnancy. Epispadia was visible prenatally on ultrasound in 6/8 male fetuses. 1/12 Parents opted for termination of pregnancy, 11/12 fetuses were live born and received reconstructive surgery.Conclusions: Isolated CBE is an extremely rare prenatal sonographic finding. Prenatal diagnostics should exclude additional malformations within the spectrum of cloacal malformations. [ABSTRACT FROM AUTHOR]

Objective: To analyze the types of treatment of abnormally invasive placenta (AIP) and to investigate the self-reported physical and mental short- and long-term sequelae.Methods: This single-center observational study was performed between 2003 and 2017. Women with prenatal or intrapartum diagnosis of AIP were identified through the departmental database. Classification was performed according to the time of diagnosis establishment and the type of treatment. Medical complications overall and according to the type of treatment were analyzed. Data about women's perception of diagnosis, treatment, and short- and long-term sequelae were gathered by questionnaire.Results: Cases were classified into four groups: prenatal diagnosis, cesarean hysterectomy (A, n = 10); prenatal diagnosis, expectant management (B, n = 19); intrapartum diagnosis, cesarean hysterectomy (C, n = 6); intrapartum diagnosis, conservative therapy (D, n = 20). Depth of invasion, total units of transfused red blood cells, and the need for reoperation differed between the treatment groups. Expectant management was successful in 94.7% of cases. Irrespective of the treatment group, 73.3% of women perceived the condition as serious or life-threatening; 30.0% utilized psychological support; and 36.7% reported persistent pain or problems. 37.5% of women after uterine preservation had another live birth, AIP recurred in 44.4% of cases.Conclusion: Conservative management of AIP is feasible in selected cases. The condition is perceived as life-threatening and has a lasting impact on the physical, mental, and reproductive health of those affected. This finding merits further investigation. AIP continues to be a condition with high morbidity. [ABSTRACT FROM AUTHOR]

Purpose: Alterations in renal dimensions may be an early manifestation of deviation from normality, with possible repercussions beyond intrauterine life. The objective of this study was to establish reference curves for fetal kidney dimensions and volume from 14 to 40 weeks of gestation.Methods: This is a prospective longitudinal study of 115 Brazilian participants in the "WHO multicentre study for the development of growth standards from fetal life to childhood: the fetal component". Pregnant women with clinical and sociodemographic characteristics allowing the full potential fetal growth were followed up from the first trimester until delivery. These women underwent serial sonographic evaluation of fetal kidneys. The longitudinal, anteroposterior and transverse diameters of both fetal kidneys were measured, in addition to calculation of kidney volume. By quantile regression analysis, reference curves of renal measurements related to gestational age were built.Results: Standard normal sonographic values of renal biometry were defined during pregnancy. Reference values for the 10th, 50th and 90th centiles of different fetal kidney measurements (longitudinal, anteroposterior, transverse and volume) from the 14th to the 40th week of gestation were fitted.Conclusion: The reference curves presented should be of the utmost importance for screening and diagnosis of alterations in renal development during the intrauterine period. [ABSTRACT FROM AUTHOR]

Purpose: Uterine rupture during labor is a rare but life-threatening complication after previous cesarean section (CS). Prenatal risk is assessed using ultrasound thickness measurement of the lower uterine segment (LUS). Due to inhomogeneous study results, however, clinical obstetrics still lacks for standard protocols and reliable reference values. As 3 T magnetic resonance imaging (MRI) has not yet been sufficiently studied regarding LUS diagnostics after previous CS, we sought to evaluate its feasibility focusing on thickness measurements and typical characteristics of the CS-scar region in comparison to ultrasound and the intraoperative status.Methods: In this prospective study, 25 asymptomatic patients with one previous CS and inconspicuous ultrasound findings were included. An additional 3 T MRI with either a T2-weighted Turbo-Spin-Echo or a Half Fourier-Acquired-Single-shot-Turbo-spin-Echo sequence in a sagittal orientation was performed. We analyzed categorical image quality, inter- and intra-rater reliability as well as anatomy, morphology and thickness of the LUS. Results were compared to ultrasound and intraoperative findings.Results: MRI provided good to excellent image quality in all patients. The imaged structures presented with a high variability in anatomy and morphology. Image characteristics indicating the uterine scar were only found in 11/25 (44%) patients. LUS thickness measurements with MRI showed good inter- and intra-rater reliability but poor agreement with ultrasound.Conclusions: MRI is appropriate for additional LUS diagnostics in patients with previous CS. The strong individual variability of LUS-anatomy and morphology might explain the difficulties in establishing uniform diagnostic standards after CS. [ABSTRACT FROM AUTHOR]

Purpose: To assess fetal central nervous system (CNS) abnormalities presenting as major findings leading to late termination of pregnancy (late TOP) performed ≥ 24 weeks' gestation.Method: The study population included 2789 pregnant women that underwent late TOP in our institute between the years 1998 and 2015.Results: Fifty-seven cases (2.0%) underwent late TOP because of fetal CNS indications and are the subjects of the current study. Those cases were subdivided into four categories (1) no routine prenatal screening with an incidental finding discovered ≥ 24 weeks' gestation (25 patients, 43.8%); (2) developmental or acquired findings detected during late second and third trimester (22 patients, 38.6%); (3) apparently normal routine screening with abnormal findings that could have been detected earlier (six patients, 10.6%); (4) routine prenatal care raised suspicion of abnormalities, and the final diagnosis was established only following additional tests (four patients, 7.0%).Conclusions: Combining the two categories of CNS abnormalities, i.e., pregnant women who did not undergo any fetal evaluation (group 1) and those that could have been detected earlier (group 3) consists 54% from our cohort in which late TOP could have been avoided. On contrary, 39% fetuses from our study population had CNS developmental findings which could be detected only at advanced stage of gestation. [ABSTRACT FROM AUTHOR]

Purpose: The aim of the present study was to report experiences with invasive prenatal diagnosis of α-thalassemia for the prevention of Hb Bart's hydrops fetalis syndrome in the Guangxi Zhuang Autonomous Region, China.Methods: Pregnant women and their partners who tested positive for α0-thalassemia or were diagnosed with HbH diseases were counseled and suggested to undergo a prenatal diagnostic procedure for α-thalassemia. Fetal material was obtained by chorionic villus sampling (CVS) between 9 and 13 weeks of gestation, by amniocentesis between 16 and 24 weeks of gestation and by cordocentesis after 24 weeks of gestation. The α0-thalassemia gene types were detected by gap polymerase chain reaction (Gap-PCR). All results were finally confirmed by DNA analysis after delivery or termination of pregnancy.Results: An invasive prenatal α-thalassemia diagnosis was performed in 3155 cases at risk for Hb Bart's hydrops fetalis syndrome at our hospital from 2002 to 2016. CVS was performed in 1559 cases (49.4%), amniocentesis in 1240 cases (39.3%) and cordocentesis in 356 cases (11.3%). In total, 786 fetuses were diagnosed as Hb Bart's hydrops fetalis syndrome. Among these cases, the α-thalassemia genotype was --SEA/--SEA in 784 cases and --SEA/--THAI in 2 cases. All affected pregnancies were terminated in time.Conclusions: This extensive experience suggests that carrier screening, molecular diagnostics, genetic counselling, and prenatal diagnosis are effective measures to prevent Hb Bart's hydrops fetalis syndrome. [ABSTRACT FROM AUTHOR]

Purpose: Wolf-Hirschhorn syndrome (WHS) is a contiguous gene syndrome due to terminal chromosome 4p deletions. We explored prenatal diagnosis of WHS by ultrasound as well as karyotype and single nucleotide polymorphism array (SNP array) to characterize the structural variants of WHS prenatally.Methods: Ten prenatal cases of WHS were evaluated for the indication of the invasive testing, the ultrasound features, and cytogenetic and microarray results.Results: Eight cases were diagnosed by karyotyping and SNP array, while two cases were detected only by SNP array. Combining our cases with 37 prenatal cases from the literature, the most common sonographic features were IUGR (97.7%) and typical facial appearance (82.9%). Other less common phenotypes included renal hypoplasia (36.2%), cardiac malformation (29.8%), cleft lip and palate (25.5%), cerebral abnormalities (25.5%), skeletal anomalies (21.3%), and increased nuchal translucency/nuchal fold thickness (NT/NF) (19%).Conclusions: The most common intrauterine phenotypes of WHS were severe IUGR and typical facial appearance with other less consistent ultrasound findings. Noninvasive prenatal testing (NIPT) is one very promising screening tool for WHS. SNP array can improve diagnostic precision for detecting WHS, especially for the cryptic aberrations that cannot be identified by the traditional karyotyping. Ectopic kidney may be a previously unrecognized phenotype of WHS. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the percentage of intrauterine vertical human papillomavirus (HPV) transmission among HPV-positive mothers and the relative risk of intrauterine vertical HPV transmission between cesarean and vaginal delivery among HPV-positive women.Methods: This systematic review was made according to the PRISMA statement. We searched PubMed and Scopus and the final articles were selected by two reviewers. Data from the selected articles were plotted, and the pooled percentage of antenatal vertical HPV transmission among HPV-positive mothers as well as the pooled relative risk of antenatal vertical HPV transmission between cesarean and vaginal delivery among HPV-positive women were calculated.Results: 9 studies including 421 HPV-positive mothers and their offsprings were selected from 434 potential papers. Following meta-analysis, the pooled percentage of antenatal vertical HPV transmission was 4.936% (95% CI 1.651-9.849), with moderate heterogeneity between the studies (I2 = 72.22%). The pooled relative risk of antenatal vertical HPV transmission between cesarean and vaginal delivery among HPV-positive women was 0.912, with no statistical significance (95% CI 0.226-3.674) and homogeneity between the studies (I2 = 24.48%). [ABSTRACT FROM AUTHOR]

Purpose: We studied the efficacy of using pre-cesarean delivery (CD) temporary occlusion of internal iliac arteries with balloon catheters in case of placenta previa-accreta in terms of maternal and neonatal outcomes and to test accuracy of ultrasound (US) and magnetic resonance imaging (MRI) for prenatal diagnosis.Methods: From March 2014 to January 2018, women with an US and/or MRI diagnosis of placenta previa-accreta and a planned delivery were enrolled and divided into two groups: balloon catheterization group (women treated with preoperative catheters and CD) and control group (women candidates to elective CD).Results: 37 patients were enrolled: 16 in balloon catheterization group and 21 in control group. Significant differences were detected in estimated blood loss. Prophylactic balloon catheterization could reduce intraoperative red blood cell transfusion. The incidence of hysterectomy was lower in balloon group. No statistical difference was found for neonatal outcomes. Both US and MRI have showed to be useful and complementary to diagnose placenta previa-accreta.Conclusions: Temporal, perioperative, and prophylactic positioning of balloon vascular catheters is an effective method for managing severe hemorrhage caused by placenta previa-accreta as it reduced intraoperative blood loss, lessened perioperative hemostatic measures and intraoperative red cell transfusions, and reduced hysterectomies. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the impact of genetic counseling (GC) during the third trimester by analyzing changes in pregnancy management and the correlation with postnatal findings.Methods: This was a retrospective study. Pregnancy course and neonatal follow-up were analyzed according to the reason for referral and implementation of recommendations.Results: The records of neonates born to 181 women were retrieved. Fifty-two women (group 1-29%) qualified for pregnancy termination under Israeli guidelines and laws, and 129 (group 2-71%) were not at the time they were referred. By another division: 104 women (group 3-57%) followed the physician's diagnostic recommendations completely after counseling including amniocentesis, fetal MRI, targeted ultrasound scans, fetal echocardiography. Seventy-seven declined amniocentesis (group 4-43%). Additional abnormalities were detected postpartum in all groups without statistically difference: 3/52 (10%) in group 1, 9/129 (7%) in group 2, 6/104 (6%) in group 3, and 6/77 (8%) in group 4).Conclusion: GC in the third trimester of pregnancy provided the couple with a sharper more focused picture and assisted them to perceive the significance of new, significant fetal findings which attest to the value of the GC. [ABSTRACT FROM AUTHOR]