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Objective: Uterine fibroids are monoclonal tumors, which are often genetically abnormal and associated with false‐positive genome‐wide cell‐free DNA (cfDNA) screening results, particularly when large. It is plausible that fibroids may also increase the risk of cfDNA failure by affecting fetal fraction or due to their genetic anomalies confounding cfDNA algorithms. We aimed to investigate a possible association between fibroids and cfDNA non‐informative results. Methods: This was a retrospective cohort study of women undergoing cfDNA screening for fetal chromosomal abnormalities between 2013 and 2020, comparing pregnancies with vs without uterine fibroids recorded on any obstetric ultrasound before 24 weeks' gestation. Univariable and multivariable logistic regression models were used to investigate the association between fibroids and cfDNA failure, adjusting for gestational age, maternal age, weight and height at blood sampling, mode of conception, multiple gestation and test platform (chromosome‐selective or genome‐wide). Analyses were stratified according to the number of fibroids and total fibroid volume. The impact of fibroids on fetal fraction was assessed using linear regression, adjusting for the same covariates. Results: Among 19 818 pregnancies undergoing cfDNA screening, fibroids were reported in 2038 (10.28%) and cfDNA failure at the first screening attempt occurred in 228 (1.15%) pregnancies. Non‐informative results occurred in 1.96% of pregnancies with fibroids and 1.06% of pregnancies without fibroids (adjusted odds ratio (aOR), 2.40 (95% CI, 1.65–3.48)). The risk of failure in the first screening attempt increased progressively with the number of fibroids (aOR, 5.05 (95% CI, 2.29–11.13) in women with four or more fibroids) and total fibroid volume, with greater than a 5‐fold and 14‐fold increase in risk among women with fibroid volumes of 100.1–400 mL (aOR, 5.52 (95% CI, 2.30–13.25)) and > 400 mL (aOR, 14.80 (95% CI, 4.50–48.69)), respectively. Although test failure was more common with chromosome‐selective than genome‐wide screening, fibroids similarly increased the risk of failure of both screening platforms. Compared to pregnancies without fibroids, those with fibroids had a fetal fraction on average 0.61% lower (adjusted mean difference, −0.61% (95% CI, −0.77% to −0.45%)). Conclusion: Uterine fibroids are associated with lower fetal fraction and an increased risk of cfDNA screening failure. The strength of this association increases with increasing fibroid number and volume. © 2024 The Author(s). Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology. Linked article: There is a comment on this article by Li. Click here to view the Correspondence. [ABSTRACT FROM AUTHOR]

Objectives: To introduce a two‐dimensional sonographic method to assess the fetal anus, and to evaluate the feasibility of this method to diagnose anal atresia prenatally and identify the presence or absence of anoperineal fistula (in males) and anovestibular fistula (in females). Methods: This was an observational study of suspected cases of anal atresia referred to a single center in Israel between August 2018 and October 2023. In addition to conventional evaluation of the perineum in the axial plane, fetuses referred to our center for suspected malformation were scanned with a new method termed the 'infracoccygeal/transperineal window'. This window consisted of a midsagittal view of the fetal pelvis, including the distal rectum and the anal canal. Normal anatomy was confirmed when the anal canal was continuous with the rectum and terminated at the expected location on the perineum. In female fetuses, the normal anal canal runs parallel to the vaginal canal and diverges posteriorly, terminating at the perineal skin, distant from the vestibule. In male fetuses, the normal anal canal diverges posteriorly in relation to the corpora cavernosa, terminating at the perineal skin, distant from the scrotum. High anal atresia was identified when a blind‐ending rectal pouch was demonstrated in the pelvis without a fistula to the perineum or vestibule. Low anal atresia was determined when a rectal pouch was continuous with an anteriorly deflected fistula. In females, the fistula converges with the vaginal canal, terminating at the vestibule; in males, the fistula deflects anteriorly, terminating at the base of the scrotum. Postnatally, the diagnosis and type of anal atresia were confirmed through physical examination with direct visualization of the fistula, radiographic studies, surgical examination and/or postmortem autopsy. Results: Of the 16 fetuses diagnosed prenatally with anal atresia, eight were suspected to have low anal atresia and eight were suspected to have high anal atresia. The median gestational age at diagnosis was 23 (range, 14–37) weeks. All cases showed additional structural malformation. Eleven patients opted for termination of pregnancy, of which four had low anal atresia and seven had high anal atresia. Postnatal confirmation was not available in four cases due to curettage‐induced mutilation or in‐utero degradation following selective termination of the affected twin, leaving 12 cases for analysis, of which seven were diagnosed with low anal atresia and five with high anal atresia. In these 12 cases, all prenatal diagnoses were confirmed as correct, rendering 100% sensitivity and 100% specificity in this high‐risk fetal population. Conclusions: The infracoccygeal/transperineal window is an effective method to detect and classify the level of anal atresia prenatally. This may improve prediction of postnatal fetal continence and optimize prenatal counseling. © 2024 International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Introduction Material and Methods Results Conclusions The European Working Group for Abnormally Invasive Placenta proposed a checklist of ultrasound features for the antenatal detection of placenta accreta spectrum (PAS). This study aims to assess the performance of the checklist in identifying histopathologically confirmed PAS cases in a cohort with a high pre‐test probability of PAS, and identify if particular features are associated with PAS.This is a prospective multi‐site cohort study conducted between 2018 and 2023. Consecutive patients who underwent ultrasound assessment for suspicion of PAS were included, and the sonographic checklist was completed at the time of ultrasound. Cases were defined as PAS where they had intraoperative findings as described by the International Federation of Gynecology and Obstetrics (FIGO) grading, and histopathological findings for hysterectomy and myometrial resection cases. All non‐PAS cases in this study had placenta previa and at least one prior cesarean delivery.Seventy‐eight participants met inclusion criteria, of whom 63 (80.7%) were diagnosed with PAS. Cesarean hysterectomy was performed in 49 cases (62.8%). Overall, third‐trimester ultrasound performed at a median gestational age of 32 weeks (IQR 30–34 weeks) had a sensitivity of 0.84 (95% CI 0.73 to 0.92) and specificity of 0.73 (95% CI 0.45 to 0.92) for detecting PAS, with a positive and negative likelihood ratio of 3.15 (95% CI 1.35 to 7.35) and 0.22 (95% CI 0.11 to 0.41), respectively. Features most associated with PAS were abnormal placental lacunae (Odds Ratio [OR] 5.40 [95% CI 1.61 to 18.03] and myometrial thinning OR 6.87 [95% CI 1.93 to 24.4]). While many of the ultrasound features seen in PAS were also present in cases of placenta previa with prior Cesarean section, the median (IQR) number of features present in PAS cases was significantly higher than in the non‐PAS placenta previa group (six features [3–8] vs. two features [0–3] p = 0.001). No case of non‐PAS placenta previa had more than five features present.The use of a standardized sonographic checklist had a high sensitivity and good specificity for the detection of PAS in this prospective cohort of well‐classified PAS cases. [ABSTRACT FROM AUTHOR]

Background and aims: Public health concerns regarding pregnant women's health after the enactment of the Cannabis Act in Canada (CAC) (a law that allowed non‐medical cannabis use), and the potential impact of the COVID‐19 pandemic, call for a contemporary assessment of these two events. Our study measured associations between the CAC, the COVID‐19 pandemic and the monthly prevalence rates of cannabis‐, all drug‐ and alcohol‐related diagnosed disorders among pregnant women in the province of Quebec. Design, setting and participants: This was a quasi‐experimental design applying an interrupted time‐series methodology in the province of Quebec, Canada. The participants were pregnant women aged 15–49 years, between January 2010 and July 2022. Measurements: Administrative health data from the Québec Integrated Chronic Disease Surveillance System were used to classify pregnant women according to cannabis‐, all drug (excluding cannabis)‐ and alcohol‐related disorders. The CAC (October 2018) and the COVID‐19 pandemic (April 2020) were evaluated as (1) slope changes and (2) level changes. Cannabis‐, all drug (excluding cannabis)‐ and alcohol‐related disorders were measured by total monthly age‐standardized monthly prevalence rate of each disorder for pregnant women aged 15–49 years. Findings Before the CAC, the prevalence rate of cannabis‐related diagnosed disorders significantly increased each month by 0.5% [95% confidence interval (CI) = 0.3–0.6] in the pregnant population. After the CAC, there were significant increases of 24% (95% CI = 1–53) of cannabis‐related diagnosed disorders. No significant changes were observed for all drug (excluding cannabis)‐ and alcohol‐related diagnosed disorders associated with the CAC. A non‐significant decrease of 20% (95% CI = −38 to 3) was observed during the COVID‐19 pandemic in alcohol‐related disorders. Conclusions: The monthly incidence rates of diagnosed cannabis‐related disorders in pregnant women in Quebec increased significantly following the enactment of the Cannabis Act in Canada. Diagnoses of all drug (excluding cannabis)‐ and alcohol‐related disorders remained relatively stable. [ABSTRACT FROM AUTHOR]

Objective: Noninvasive prenatal testing (NIPT) has increased the number of conditions that can be screened. However, the prevalence of conditions assessed by NIPT has remained stable. The "prevalence threshold," a novel epidemiological concept, uses a test's sensitivity and specificity to determine the prevalence below which a test's positive predictive value declines most sharply relative to disease prevalence. In this article, we calculated the prevalence threshold for common conditions assessed through NIPT and compared the value with the actual prevalence of each condition to best ascertain the reliability of NIPT results. Methods: Six databases and PubMed were searched from January 2010 to March 2023 for sensitivity and specificity parameters of common conditions tested through NIPT. Using an equation previously derived by the authors of the current paper, the prevalence threshold for each condition was calculated. The theoretical number of test iterations required to reach the prevalence threshold was also reported. Results: None of the conditions tested through the NIPT had a prevalence rate that met or exceeded the calculated prevalence threshold. Trisomy 21 had the greatest concordance between the prevalence rate and the prevalence threshold. In contrast, Angelman, Cri‐du‐chat, and Prader‐Willi syndromes had the most significant discordance. Apart from trisomy 21 and XXY, all remaining conditions required more than one test iteration to reach their respective prevalence threshold. Conclusion: We conclude that at the current prevalence levels, the positive predictive value of NIPT remains low, with the prevalence of disease levels significantly lower than the prevalence threshold for each condition tested. Synopsis: The positive predictive value of noninvasive prenatal testing remains low, with the prevalence of disease levels significantly lower than the prevalence threshold for each condition tested. [ABSTRACT FROM AUTHOR]

Objective: To evaluate non‐invasive prenatal testing (NIPT) and expanded non‐invasive prenatal testing (NIPT‐plus) for detecting aneuploidies at different sequencing depths and assess Z‐score accuracy in predicting trisomies 21, 18, 13, 45X, and 47XXX. Methods: Pregnancies with positive NIPT or NIPT‐plus results detected at the prenatal diagnosis center of Nanfang Hospital were included in this retrospective study, between January 2017 and December 2022. Invasive prenatal diagnostic results were collected. Logistic regression analyses were used to study the relationship between Z‐score and positive predictive value (PPV). Optimal cut‐off values were obtained based on receiver operating characteristic analysis, and PPVs were calculated in different groups. Results: We evaluated 1348 pregnant women with positive results, including 930 reported by NIPT and 418 reported by NIPT‐plus. NIPT reported significantly more rare chromosomal aneuploidies (RCAs), and NIPT‐plus had a significantly higher PPV for trisomy 21 (T21). Logistic regression analyses showed a significant association (P < 0.001) between Z‐score and PPVs for T21 and trisomy 18 (T18). A linear relationship was observed between fetal fraction (FF) and Z‐values in the true positive cases of T21 and T18.The high Z‐score group had significantly higher PPVs than the low Z‐score group for T21, T18, trisomy 13, and 47XXX, but not for 45X. Conclusion: The Z‐score is helpful in assessing NIPT or NIPT‐plus results. Therefore, we suggest including the Z‐score and FF in the results. By combining the Z‐score, FF, and maternal age, clinicians can interpret NIPT results more accurately and improve personal counsel to reduce patients' anxiety. Synopsis: NIPT‐plus showed a significantly higher PPV for T21 than NIPT, and it is suggested that Z‐scores and fetal fraction are added to the result report. [ABSTRACT FROM AUTHOR]

Timely detection of congenital anomalies using ultrasound improves neonatal care. As specialist sonographers are often geographically dispersed, they are sometimes requested to provide a second opinion via tele-expertise. The present study aimed to evaluate the economic impact of asynchronous tele-expertise in obstetric ultrasound care in private medical practice through a comparison with face-to-face consultations. We conducted a cost minimization analysis using decision tree modeling in order to determine whether asynchronous tele-expertise or face-to-face consultation had the lowest cost, under the assumption of equivalent effectiveness in terms of prenatal diagnosis. Costs were measured from the societal perspective. The data for the base case of our modeling came from a retrospective analysis of the clinical practice of an expert who had been conducting asynchronous tele-expertise for 4 years in France. The study included 260 patients for whom 322 requests for expert opinions were made by physicians/midwives from January 2016 to January 2020. The expected average total cost for tele-expertise for a patient was €74.45 (95% CI: €66.36–€82.54) compared to €195.02 (95% CI: €183.90–€206.14) for the conventional face-to-face strategy. Accordingly, using tele-expertise led to a statistically significant reduction of €120.57 in the average total cost per patient. A sensitivity analysis confirmed the robustness of the model produced. The results of the present study underline the efficiency of tele-expertise and highlight related economic benefits. Accordingly, they could inform public health policy on the dissemination of tele-expertise in the field of obstetric ultrasound care. [ABSTRACT FROM AUTHOR]

• Prenatal ultrasound diagnosis of complete cryptophthalmos, aphakia, and corneal vascularization. • Fetal ocular malformations are often associated with malformations of other organs. • This case provides a new basis for prenatal diagnosis of this rare eye disease. Complete cryptophthalmos, congenital aphakia, and corneal vascularization are relatively uncommon congenital eye malformations during the fetal period. Herein, we report a case of a fetus with complete cryptophthalmos, congenital aphakia, and corneal vascularization in both eyes and review previous prenatal reports of related cases. The patient was a 27-year-old pregnant woman, gravida 2, para 1, who was referred to our hospital for consultation at 23 weeks of gestation due to a diagnosis of fetal right renal agenesis at an external hospital. The ultrasound system of our hospital diagnosed the fetus with complete cryptophthalmos, congenital aphakia, and corneal vascularization, which was verified under the postnatal water basin test, anatomical and pathological sections. Fetal ocular malformations are often associated with malformations of other organs, and if ultrasound findings are associated with such malformations, attention should be paid to the ocular examination to avoid missing the diagnosis. [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]

Dandy–Walker malformation (DWM) is often sporadic, but there are a growing number of genetic disorders that have been associated with this condition. We present a female individual with a de novo variant in ABL1, c.734A>G (p.Y245), who was diagnosed prenatally with DWM. ABL1‐related neurodevelopmental disorder was recently identified but brain malformations have not been well characterized to date. We reviewed the published literature and identified one additional individual with DWM and ABL1‐related disorder, which suggests a possible association with this malformation. [ABSTRACT FROM AUTHOR]

Background: Thalassemia is a common monogenic disorder, and children with β-thalassemia major require regular blood transfusions and iron removal therapy. Klinefelter syndrome (KS) is a common sex chromosome abnormality, and 48,XXYY is rare. This report is the first to describe a fetus with a karyotype of 48,XXYY in prenatal diagnosis of β-thalassemia major. Methods: Amniotic fluid was collected by puncture for the prenatal diagnosis of thalassemia, and chromosomal karyotyping was also performed. PCR and reverse dot-blot hybridization (PCR-RDB) were used to identify 17 common β-thalassemia mutations in China. Karyotype analysis of amniotic fluid was performed. Results: The results of PCR-RDB revealed that the genotype of the fetus was a homozygote of CDs41-42 (-TTCT) in the HBB gene. The karyotype analysis displayed that the fetus had Klinefelter syndrome (KS), and the karyotype was the rare 48,XXYY. The fetus was diagnosed with β-thalassemia major and KS. Conclusions: An unexpected detection of the rare 48,XXYY in the prenatal diagnosis of a fetus with β-thalassemia major. There is a pitfall of genetic counseling and prenatal diagnosis in China. [ABSTRACT FROM AUTHOR]

Throughout all areas of medical practice, genetic counselors (GCs) occupy a key position in promoting patients' personal autonomy while facilitating informed medical decision‐making. This professional position aligns with the concept of reproductive justice. Previous literature has attempted to define reproductive advocacy in medicine as well as the potential intersection of genetic counseling and reproductive justice advocacy work, yet limited data exist regarding GCs' perceptions of their role and involvement in reproductive justice advocacy work. This study aimed to identify the perceptions and actions of GCs regarding reproductive justice advocacy measures, as well as explore motivating factors influencing their attitudes and behaviors. Family planning providers, who tend to prioritize reproductive justice and advocacy, were surveyed to be a comparison group. We distributed an anonymous online survey within the National Society of Genetic Counselors (NSGC) and the Society of Family Planning (SFP) consisting of a 10‐item personality inventory and Likert scale questions exploring characteristics and behaviors regarding reproductive justice advocacy. Results from 252 eligible respondents were analyzed using descriptive statistics, Chi‐square, and Mann–Whitney U analyses. NSGC members are significantly less involved in several areas of reproductive justice advocacy, including regular participation in advocacy efforts when compared to SFP members (p = 0.04). The most cited barrier to NSGC members' participation was feeling unsure how to become involved, a significant difference compared to SFP members (p = 0.01). Findings from this study, undertaken in the final days of Roe v. Wade, suggest that GCs want to be more involved in reproductive justice advocacy but are uncertain where to begin. Intersociety collaboration and intra‐society promotion of grassroots reproductive justice efforts may reduce this perceived barrier and others like it. [ABSTRACT FROM AUTHOR]

Objective: To analyze the value of prenatal diagnostic genetic testing in cases with isolated aberrant right subclavian artery (ARSA). Methods: This is a retrospective cohort study, conducted between January 2015–January 2022 in a fetal medicine center. Women who had an ultrasound scan and diagnosed with fetal ARSA were included. Ultrasonographic characteristics, genetic, obstetric, and neonatal outcomes were collected and analyzed. Results: A total of 240 fetuses with ARSA were identified and included to the analysis. Eighty‐two of the group had isolated ARSA (34.2%, 82/240), 57 had additional soft markers (23.8%, 57/240) and 101 had additional major ultrasonographic abnormalities (42.1%, 101/240). Genetic results were available in 196 cases (81.7%, 196/240). Seventy‐four of isolated ARSA cases underwent genetic testing (90.2%, 74/82). A chromosomal abnormality was present in 60 cases; 54 (22.5%, 54/240) aneuploidies and 6 (2.5%, 6/240) copy number variants. Five (6.1%) of the isolated ARSA cases had chromosomal abnormalities. All of these five cases had prenatal genetic testing due to high‐risk aneuploidy screening fetuses who had ARSA with at least one additional anomaly had the highest chromosomal abnormality rate (38.6%, 39/101). Seventy‐seven of isolated ARSA cases were liveborn (93.9%, 77/82). Conclusion: Our results supports the evidence from the literature that isolated ARSA confers a very low‐risk for aneuploidy, if the aneuploidy screening tests are low‐risk. Also, chromosomal microarray analysis did not yield any extra information in isolated ARSA. [ABSTRACT FROM AUTHOR]

Background: The aim of this extended review of multicenter case series is to describe the prenatal ultrasound features and pathogenetic mechanisms underlying placental and umbilical cord anomalies and their relationship with adverse perinatal outcome. From an educational point of view, the case series has been divided in three parts; Part 1 is dedicated to placental abnormalities. Methods: Multicenter case series of women undergoing routine and extended prenatal ultrasound and perinatal obstetric care. Results: Prenatal ultrasound findings, perinatal care, and pathology documentation in cases of placental pathology are presented. Conclusions: Our case series review and that of the medical literature confirms the ethiopathogenetic role and involvement of placenta abnormalities in a wide variety of obstetrics diseases that may jeopardize the fetal well‐being. Some of these specific pathologies are strongly associated with a high risk of poor perinatal outcome. [ABSTRACT FROM AUTHOR]

Exploring efficient and easily implementable prenatal screening strategies aims at birth defect prevention and control. However, there have been limited economic evaluations of non-invasive prenatal screening (NIPS) strategies in China. Furthermore, these studies were predominantly confined to local or geographically proximate provinces and lacked universality and representativeness. This study assesses the health economics of current prenatal screening strategies and NIPS as first-line screening programs, analyzing their efficacy to determine an optimal strategy. From the perspective of health economics, cost-effectiveness, cost-benefit, and single-factor sensitivity were conducted for five different screening strategies using a decision tree model. Among pregnant women aged < 35 years who underwent only one screening for foetal Down syndrome (DS), the detection rate, false positive rate and positive predictive value of NIPS for foetuses with DS were superior to those of the other four serological screening methods. Although applying NIPS as first-line screening method yields the highest efficacy and benefits, it currently lacks cost-effectiveness when compared to serological screening and sequential NIPS screening strategies. [ABSTRACT FROM AUTHOR]

Background: Right aortic arch (RAA) is a common congenital aortic arch abnormality. Fetuses with RAA frequently have good outcomes after birth. However, chromosomal abnormalities and genetic syndromes suggest poor prognosis for these patients. So far the underlying genetic etiology is still not identified in most RAA patients based on traditional genetic techniques and a problem is still debated whether fetuses with isolated RAA should be referred for CMA. Our study aims to investigate the genetic etiology of fetuses with right aortic arch (RAA) by chromosomal microarray analysis (CMA) and whole exome sequencing (WES) and evaluate the efficacy of CMA in fetal isolated RAA. Results: Among these 153 fetuses, 99 (64.7%) with isolated RAA and 54 (35.3%) with non-isolated RAA; 25.5% (39/153) with additional intracardiac anomalies (ICA), and 19.0% (29/153) with extracardiac anomalies (ECA). Tetralogy of Fallot (n = 10) and persistent left superior vena cava (n = 11) are the most common ICA and ECA, respectively. CMA detected 15 clinically significant copy number variations (CNVs) in 14 cases (9.2%); microdeletion of 22q11.21 was the most common pathogenic CNVs (7.8%). The chromosomal abnormalities rate was higher in non-isolated RAA and RAA with ICA groups than in isolated RAA group (16.7% vs. 5.1%; 20% vs. 5.1%, both p < 0.05). From five cases further undergoing WES, a diagnostic variant in MTOR gene (c.7255G > A, de novo) was first reported in prenatal, extending the prenatal manifestation of Smith–Kingsmore syndrome (OMIM: 616638); a clinically relevant variant c.3407A > T in STAG2 was identified, being inherited from the healthy mother. Moreover, the premature birth and termination rates were higher in non-isolated RAA group than in isolated RAA group (11.1% vs. 1.0%; 37.0% vs. 2.0%, both p < 0.01). Conclusions: We demonstrate that CMA and WES are useful diagnostic tools for fetal RAA, particularly non-isolated RAA, and all fetuses with RAA should be referred for CMA. The data probably aids in prenatal diagnosis and prenatal counseling of fetal RAA. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Ulnar mammary syndrome (UMS) results from heterozygous variants in the TBX3 gene and impacts limb, tooth, hair, apocrine gland, and genitalia development. The expressivity of UMS is highly variable with no established genotype–phenotype correlations. TBX3 belongs to the Tbx gene family, which encodes transcription factors characterized by the presence of a T‐box DNA‐binding domain. We describe a fetus exhibiting severe upper limb defects and harboring the novel TBX3:c.400 C > T (p.P134S) variant inherited from the mother who remained clinically misdiagnosed until prenatal diagnosis. Literature revision was conducted to uncover the TBX3 clinical and mutational spectrum. Moreover, we generated a Drosophila humanized model for TBX3 to study the developmental consequences of the p.P134S as well as of other variants targeting different regions of the protein.Phenotypic analysis in flies, coupled with in silico modeling on the TBX3 variants, suggested that the c.400 C > T is UMS‐causing and impacts TBX3 localization. Comparative analyses of the fly phenotypes caused by the expression of all variants, demonstrated that missense changes in the T‐box domain affect more significantly TBX3 activity than variants outside this domain. To improve the clinicians' recognition of UMS, we estimated the frequency of the main clinical features of the disease. Core features often present pre‐pubertally include defects of the ulna and/or of ulnar ray, hypoplastic nipples and/or areolas and, less frequently, genitalia anomalies in young males. These results enhance our understanding of the molecular basis and the clinical spectrum of UMS, shedding light on the functional consequences of TBX3 variants in a developmental context. [ABSTRACT FROM AUTHOR]

Background: Neonatal hemochromatosis (NH) is a rare condition that is characterized by severe neonatal liver disease in association with hepatic and extrahepatic excess iron deposition (siderosis), while sparing the reticuloendothelial system. The most common cause of fetal liver injury leading to the NH phenotype (accounting for over 95% of cases) is gestational alloimmune liver disease. This condition is caused by the transfer of maternal IgG antibodies through the placenta, targeting a fetal hepatocyte antigen. Prenatal diagnosis, particularly the identification of iron overload involving both liver and thyroid, is of significant importance and can have a profound impact on patient care. To our knowledge, no case has been reported on prenatal diagnosis of iron overload involving both liver and thyroid. Case presentation: We present an exceptionally rare case of fetal hemochromatosis in a primigravida, a case that significantly contributes to our understanding of this condition. The diagnosis was made with the presence of hepatic and extrahepatic siderosis involving the thyroid using Ultrasonography (USG) and fetal Magnetic Resonance Imaging (MRI) findings. A 23-year-old primigravida was referred to our center in view of oligohydramnios, Intrauterine Growth Restriction (IUGR) and echogenic bowel at 29 weeks of gestation. USG and fetal MRI showed features of coarse liver echotexture and iron overload involving the liver and thyroid; this is the first case describing iron accumulation in the fetal thyroid gland diagnosed in utero. Conclusion: This case underscores the critical importance of performing MRI in suspected cases of fetal hemochromatosis for early diagnosis and intervention, emphasizing the potential to significantly improve patient outcomes. [ABSTRACT FROM AUTHOR]

Objective Methods Results Conclusion The aim of the present study was to evaluate the obstetric complications associated with isolated fetal congenital heart disease (CHD) by comparing pregnancies with and without this condition.In this retrospective matched comparative study at Siriraj Hospital, Thailand, we included 233 postnatally confirmed fetal CHD cases and 466 unaffected fetuses. Controls were selected at a 2:1 ratio, ensuring that they matched the cases in terms of maternal age, parity, and history of preterm deliveries.Fetal CHD was significantly associated with an increased risk of spontaneous preterm labor (30% vs 9.7%; adjusted odds ratio [aOR] 2.42; 95% confidence interval [CI]: 1.35–4.36; P = 0.003), delivery before 34 gestational weeks (11.6% vs 0.6%; aOR 12.33; 95% CI: 3.32–45.78; P < 0.001), and pre‐eclampsia (11.6% vs 2.8%; aOR 2.19; 95% CI: 1.01–4.76; P = 0.047). Newborns with CHD were significantly more likely to be small for gestational age (10.7% vs 5.2%; aOR 2.09; 95% CI: 1.11–3.94; P = 0.022). Intriguingly, a prenatal diagnosis of CHD was associated with a reduced risk of preterm delivery in affected pregnancies (P = 0.002).Pregnancies affected by isolated fetal CHD demonstrated a higher propensity for several adverse outcomes. These findings underscore the importance of prenatal CHD detection and tailored perinatal care to potentially improve both pregnancy outcomes and neonatal health. [ABSTRACT FROM AUTHOR]

Prenatal hydrocolpos is characterized by fluid distension of the vagina. Hydrocolpos can be caused by multiple underlying etiologies and often demonstrates overlapping imaging features compared to other cystic abdominal and pelvic lesions. The purpose of the current pictorial essay is to provide a systematic prenatal magnetic resonance imaging (MRI) approach to differentiating the primary etiologies leading to hydrocolpos. After discussing the fundamental embryological processes involved in vaginal development, the current essay discusses the most common causes of hydrocolpos with their associated prenatal and postnatal imaging features. An approach to distinguishing the more common differential diagnoses is provided. Given the implications of parental counseling and postnatal management, this essay provides an important approach for narrowing differential diagnoses based on prenatal imaging. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: The recurrent 1q21.1 microdeletion syndrome is an autosomal dominant disorder and is characterized by dysmorphic facial features, microcephaly, developmental delay, and congenital defects. However, most studies on the distal deletions in the 1q21.1 region were diagnosed postnatally. This study aimed to provide a better understanding of the ultrasound and molecular findings of fetuses with recurrent 1q21.1 microdeletions in prenatal diagnosis. Methods: In this retrospective study, we reported 21 cases with the recurrent 1q21.1 microdeletion syndrome diagnosed at our prenatal diagnostic center from January 2016 to January 2023. The clinical data were reviewed for these cases, including the maternal demographics, indications for invasive testing, ultrasound findings, CMA results, and pregnancy outcomes. Results: In the study, a total of 21 cases with recurrent 1q21.1 microdeletions were diagnosed prenatally by CMA. Fifteen cases were described with ultrasound indications, and the most common findings are as follows: increased nuchal translucency (NT) (26.7%), intrauterine growth retardation (IUGR) (26.7%), congenital heart defects (CHD) (20%), and congenital anomalies of the kidney and urinary tract (CAKUT) (13.3%). All the cases with the distal 1q21.1 deletions contain the common minimal region (located between BP3 and BP4) and eight OMIM genes. Parental studies to determine the inheritance of the deletion were performed for eight cases, and half of the cases were inherited from one of the parents. Pregnancy outcomes were available for nine cases; eight (88.9%) pregnancies were determined to be terminated and one (11.1%) was fullterm delivery. Conclusion: To our knowledge, this is the largest study to find that fetuses with recurrent 1q21.1 microdeletions were closely associated with increased NT, CHD, IUGR, and CAKUT. In addition, ours is the first study to report that cerebral ventriculomegaly might be associated with recurrent 1q21.1 microdeletions. More comprehensive studies are needed for a better understanding of the prenatal phenotype-genotype relationship of the recurrent 1q21.1 microdeletion syndrome in future. [ABSTRACT FROM AUTHOR]

Background: The 15q11.2 BP1-BP2 microdeletion syndrome is associated with developmental delays, language impairments, neurobehavioral disorders, and psychiatric complications. The aim of the present study was to provide prenatal and postnatal clinical data for 16 additional fetuses diagnosed with the 15q11.2 BP1-BP2 microdeletion syndrome in the Chinese population. Methods: A total of 5,789 pregnancy women that underwent amniocentesis were enrolled in the present study. Both karyotype analysis and chromosomal microarray analysis (CMA) were conducted on these subjects to detect chromosomal abnormalities and copy number variants (CNVs). Whole exome sequencing (WES) was performed to investigate sequence variants in subjects with clinical abnormalities after birth. Results: Sixteen fetuses with 15q11.2 BP1-BP2 microdeletion were identified in the present study, with a detection rate of 0.28% (16/5,789). The 15q11.2 BP1-BP2 microdeletion fragments ranged from 311.8 kb to 849.7 kb, encompassing the NIPA1, NIPA2, CYFIP1, and TUBGCP5 genes. The follow-up results regarding pregnancy outcomes showed that five cases opted for pregnancy termination, while the remaining cases continued with their pregnancies. Subsequent postnatal follow-up indicated that only one case with the 15q11.2 BP1-BP2 microdeletion displayed neurodevelopmental disorders, demonstrating an incomplete penetrance rate of 9.09% (1/11). Conclusion: The majority of fetuses with the 15q11.2 microdeletion exhibit typical features during early childhood, indicating a low penetrance and mild impact. Nonetheless, pregnancies involving fetuses with the 15q11.2 microdeletion require thorough prenatal counseling. Additionally, enhanced supervision and extended postnatal monitoring are warranted for those who choose to proceed with their pregnancies. [ABSTRACT FROM AUTHOR]

Aim Method Results Interpretation To investigate the timing of type 1 myotonic dystrophy (DM1) diagnosis in parents of affected children and describe children's perinatal characteristics and developmental outcomes.This was a descriptive case series of children with congenital myotonic dystrophy (CDM) and childhood‐onset myotonic dystrophy (ChDM). Parental timing of DM1 diagnosis and the perinatal, motor, and cognitive outcomes of paediatric patients were recorded.A total of 139 children followed by 12 highly specialized tertiary care neuromuscular centres in Italy and one tertiary neuromuscular centre in the USA were included: 105 children with CDM and 34 children with ChDM (mean age 8 years 8 months and 12 years 2 months respectively; 49 males and 17 males respectively). Seventy (50%) parents were diagnosed with adult‐onset DM1 after the affected child was diagnosed. Only 12 (17%) of the 69 parents known to be affected had prenatal testing.Of the 105 children with CDM, 98% had maternally inherited CDM, 36% were born preterm, 83% required a stay in the neonatal intensive care unit for more than 48 hours, 84% and 79% had ambulation and speech delay, and 84% had an IQ lower than 70. Of the 34 children with ChDM, 59% had paternally inherited ChDM, 91% were born at term, and 36% had an IQ lower than 70.Delay in diagnosing DM1 affects family planning. The prenatal and perinatal outcomes of the affected offspring emphasize the need for proactive counselling as parents may be reluctant to conduct prenatal testing. [ABSTRACT FROM AUTHOR]

Background/aim: Autosomal recessive polycystic kidney disease is an inherited kidney disease. This study aims to detect rare and common DNA variants of the PKHD1 gene using next-generation sequencing (NGS) and to classify them in terms of being pathogenic according to The American College of Medical Genetics and Genomics. Materials and methods: NGS analysis was performed on the DNA of 304 patients who were referred to Ege University Molecular Medicine Laboratory with suspected polycystic kidney disease. Results: As a result, a total of 82 different DNA variants, 16 of which were novel, were detected. The breakdown of the variants found is as follows: 73 (89.02%) were missense variants, six (7.32%) nonsense variants, two (2.44%) frameshift deletions, and one (1.22%) nonframeshift deletion. According to The American College of Medical Genetics and Genomics classification of these variants, 26 were benign (Class 5), two were likely benign (Class 4), 36 were of uncertain significance (Class 3), and nine were likely pathogenic (Class 2), nine of which are pathogenic variants (Class 1). Heterozygosity was found in 39 (63.9%) patients, homozygosity in six (9.8%) patients, compound heterozygosity in 12 (19.7%) patients, and complex genotype in four (6.6%) patients in which variants in Class 1, Class 2 and Class 3 were determined according to ACMG classification. When the exon distributions of the DNA variants detected in the PKHD1 gene were analyzed, the most common exons of the DNA variant are exon 32 (n = 9), exon 58 (n = 8), exon 67 (n = 6), exon 61 (n = 5), 30 exons (n = 4). Conclusion: This fast and economical molecular diagnostic approach will provide a reliable prenatal diagnostic option, enabling definitive disease diagnosis and the identification of carriers. [ABSTRACT FROM AUTHOR]

Aim: In Japan, noninvasive prenatal testing (NIPT) has been performed by facilities accredited by the Japanese Society of Obstetrics and Gynecology since 2013. However, since 2016, with the implementation of NIPT, which can only be performed by blood sampling, non‐obstetricians have been involved in prenatal testing. Therefore, in July 2022, a new government‐involved NIPT certification system based on Health Sciences Council guidelines was introduced to ensure access to prenatal testing information for pregnant women. Methods: This survey was conducted in February 2023 and was the first survey after the certification system implementation. We conducted a web‐based survey of 1227 pregnant women and nursing mothers who underwent NIPT after July 2022 to evaluate their experiences. Results: Respondents were categorized by certification status as certified (C: 56%), non‐certified (non‐C: 23%), or uncertain (Q: 20%). The C group with a higher mean age at examination (35.0 ± 4.5 years) paid lower examination fees, received longer pre‐ and post‐examination explanations, and underwent more weekday examinations (80%) than the other groups. Most respondents, 67%, 48%, and 53% in the C, non‐C, and Q groups, respectively (p < 0.0001), stated that "NIPT needs to be regulated by the government or academic societies." The non‐C group was more likely to say, "Insufficient post‐test explanations at the laboratory made me more anxious," than the other groups when the testing results were non‐negative (p = 0.015). Conclusions: Despite government regulation, some pregnant women choose convenience over certified facilities, risking inadequate care. The government should ensure that NIPT is a safe option for all pregnant women. [ABSTRACT FROM AUTHOR]

A 31‐year‐old primiparous woman underwent non‐invasive prenatal testing. The result was trisomy 13 (T13) positive. The chromosome 13 t‐statistics (Z‐score) was significantly high. The result of amniocentesis was normal karyotype (46,XX). Detailed ultrasound showed no fetal structural abnormalities. We suspected T13 confined placental mosaicism (CPM) and observed the course naturally. From the late second trimester, severe fetal growth restriction manifested followed by proteinuria and hypertension, diagnosing her with preeclampsia (PE). At 35 + 5 weeks, emergent cesarean section was required, yielding a 1480 g female infant. We sampled five locations of chorionic villi in the placenta. T13 cells dominated cells with normal karyotypes in all parts and the rate of trisomic cells ranged from 57% to 96%, which were generally high rate. None developed PE in reported T13 CPM cases and this is the first case of PE. The dominancy of T13 cells can be associated with PE development. [ABSTRACT FROM AUTHOR]

A 35‐year‐old woman (gravida 1, para 0) was admitted to our hospital at 28 weeks' gestation with vaginal bleeding from placenta previa. Severe fetal bradycardia was observed during fetal heart rate monitoring. Ultrasonography showed widely dilated veins on the fetal surface of the placenta and an extraordinarily low umbilical artery peak systolic velocity in the Doppler study. Umbilical cord torsion was suspected. On the subsequent day, we performed a cesarean section due to worsening fetal heart rate patterns. Umbilical artery blood gas analysis indicated severe acidemia (pH 7.063), and umbilical cord torsion was confirmed at the placental cord insertion site. Diagnosing UCT prenatally is challenging; however, it can be suspected by scanning for the widely dilated veins on the fetal placental surface, termed as the "Sunset Sign," an abnormally low umbilical artery peak systolic velocity, and other fetal Doppler abnormalities. [ABSTRACT FROM AUTHOR]

Introduction: Immune checkpoint inhibitors are extensively used in present-day clinical practice for treating many types of cancers at different stages. To date, there are scarce data on the use of immunotherapy in pregnancy. Immune-related adverse events are a typical consequence of this therapy miming autoimmune diseases. Case Presentation: A 35-year-old woman (G1P0) diagnosed with gastric carcinoma underwent neoadjuvant chemotherapy followed by surgery. During follow-up, axillary metastasis was discovered, radiotherapy failed, and consequently immunotherapy was started. Concurrently, pregnancy ensued. Despite potential risks, the patient opted to continue immunotherapy and the pregnancy. At 31 weeks, fetal bowel dilation was noted. Subsequently, the fetus also developed fetal growth restriction. A cesarean section was performed at 35 weeks. The newborn required repeated bowel resections for necrotizing enterocolitis, necessitating extensive medical intervention. The mother continues pembrolizumab treatment with a positive response. Conclusion: To the best of our knowledge, this might constitute a possible case of a fetal immune-related adverse event after immunotherapy in utero exposure. [ABSTRACT FROM AUTHOR]

Introduction: Congenital microgastria (CM) is a rare condition due to early interruption of stomach development between the 4th and 8th week of gestation, leading to a small midline tubular stomach. Prenatal diagnosis of CM is a challenge with important implications. This study explores the value of biochemical amniotic fluid (AF) analysis and fetal magnetic resonance imaging (MRI) for the prenatal diagnosis of CM in case of nonvisible stomach on fetal ultrasound. Case Presentation: Four cases of CM were retrospectively investigated in terms of fetal ultrasound, MRI findings, and biochemical AF analyses. The patients were referred to the Prenatal Diagnosis Unit of the Hôpital Femme Mère Enfant (Lyon, France) at a mean age of 21 weeks of gestation for absent or small fetal stomach on ultrasound with a suspected diagnosis of esophageal atresia (EA). Ultrasound examination confirmed that the stomach was absent in two of the four fetuses and small in the other two. This feature was associated with a congenital heart defect in two cases and a terminal transverse limb defect in one case. Standard genetic workup (array-CGH) results were normal. Biochemical AF analysis, including the EA index, was not suggestive of EA. Fetal MRI showed a small midline tubular stomach, associated with a dilated esophagus, highly suggestive of CM. Conclusion: If the fetal stomach is absent on ultrasound, CM should be considered if the AF volume is normal, especially during the third trimester, and if the EA index is not suggestive of gastrointestinal obstruction. In these cases, the diagnosis can be confirmed by fetal MRI, through observation of a small midline tubular stomach associated with a dilated esophagus. [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to evaluate the occurrence of clinically relevant (sub)microscopic chromosomal aberrations in fetuses with the nuchal translucency (NT) range from 3.0 to 3.4 mm, which would be potentially missed by cfDNA testing. Methods: A retrospective data analysis of 271 fetuses with NT between 3.0 and 3.4 mm and increased first trimester combined test (CT) risk in five cohorts of pregnant women referred for invasive testing and chromosomal microarray was performed. Results: A chromosomal aberration was identified in 18.8% fetuses (1:5; 51/271). In 15% (41/271) of cases, trisomy 21, 18, or 13 were found. In 0.7% (2/271) of cases, sex chromosome aneuploidy was found. In 1.1% (3/271) of cases, CNV >10 Mb was detected, which would potentially also be detected by genome-wide cfDNA testing. The residual risk for missing a submicroscopic chromosome aberration in the presented cohorts is 1.8% (1:54; 5/271). Conclusion: Our results indicate that a significant number of fetuses with increased CT risk and presenting NT of 3.0–3.4 mm carry a clinically relevant chromosomal abnormality other than common trisomy. Invasive testing should be offered, and counseling on NIPT should include the test limitations that may result in NIPT false-negative results in a substantial percentage of fetuses. [ABSTRACT FROM AUTHOR]

Background: Marfan syndrome (MFS) is a complex genetic systemic connective tissue disorder. It is well known that genetic factors play a critical role in the progression of MFS, with nearly all cases attributed to variants in the FBN1 gene. Methods: We investigated a Chinese family with MFS spanning two generations. Whole exome sequencing, in silico analysis, minigene constructs, transfection, RT‐PCR, and protein secondary structure analysis were used to analyze the genotype of the proband and his father. Results: The main clinical manifestations of the proband and his father were subluxation of the left lens and high myopia with pectus deformity. Whole exome sequencing identified a novel single nucleotide variant (SNV) in the FBN1 gene at a non‐canonical splice site, c.443‐3C>G. This variant resulted in two abnormal mRNA transcripts, leading to a frameshift and an in‐frame insertion. Further in vitro experiments indicated that the c.443‐3C>G variant in FBN1 was pathogenic and functionally harmful. Conclusion: This research identified a novel intronic pathogenic FBN1: c.443‐3C>G gene variant, which led to two different aberrant splicing effects. Further functional analysis expands the variant spectrum and provides a strong indication and sufficient basis for preimplantation genetic testing for monogenic disease (PGT‐M). [ABSTRACT FROM AUTHOR]

Background: There is a growing interest in exploring parents' views on the benefits of early diagnosis and awareness of sex chromosome trisomies. However, only a few studies focus specifically on the experience of parents of children with XYY syndrome. The present study aimed to assess, in parents of individuals with XYY, the perceived severity of their children's condition, their level of satisfaction with the disclosure process and their concerns about their children's present and future condition. Methods: A national online sample of 56 Italian parents of children and young adults diagnosed with XYY syndrome participated in the study. They filled out a specifically developed online survey that assessed their children's areas of concern, their experience with the disclosure process and their worries about their children's condition. Results: Seventy per cent of the parents received a prenatal diagnosis, whereas 30% received a postnatal diagnosis. High individual variability was found in the parent report of their child's condition. The most frequent areas of concern were attention regulation, emotion control and behaviour control. Individuals with a postnatal diagnosis showed more severe profiles. Parents were generally dissatisfied with the disclosure process, with no differences between prenatal and postnatal disclosure. However, more than 50% of the parents who received a prenatal disclosure reported that their child's condition was less severe than they had expected. In contrast, only 11% of the parents with postnatal disclosure reported this situation. Parents' concerns were negatively related to global satisfaction with the disclosure process and the correspondence between current and expected conditions but positively associated with the child's severity level. Conclusions: The results suggest that clear and realistic information during the disclosure process to parents is needed in both prenatal and postnatal communication and may alleviate parents' concerns. [ABSTRACT FROM AUTHOR]

Encephalocele is a rare congenital malformation of the central nervous system. The prevalence is estimated to be about 1 in 5,000-40,000 live births. It can affect various anatomical locations such as the occipital, frontal, temporal, and parietal regions. The fourth and fifth weeks of embryonic development are critical for the development of the head and neck. When there is a failure in the separation of the superficial ectoderm from the neuroectoderm, neural tube defects occur, from which encephaloceles may arise. Genetically it can be explained by the dysembryological theory, which involves certain mutated genes that interfere with important cellular mechanisms in early neuronal development. Currently, thanks to prenatal screening tools such as ultrasound, it is possible to identify them from intrauterine life. It is extremely important to make an early diagnosis to establish protocols and provide individualized treatment, involving a multidisciplinary team will be involved. Even though some cases are usually compatible with life, the expected prognosis of the anatomical site involved as well as timely surgical management. One of the most important sequelae is intellectual deficit. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the clinical features and perinatal outcomes of antenatally diagnosed fetuses with omphalocele and gastroschisis. Material and Methods: This was a retrospective, single-center, cohort study of prenatally diagnosed fetuses with omphalocele and gastroschisis followed-up and delivered at a university hospital. Demographic, pregnancy, birth and perinatal outcomes were compared between gastroschisis and omphalocele. Results: A total of 75 fetuses with omphalocele and 21 cases with gastroschisis were evaluated. The mean maternal age of women carrying a fetus with omphalocele was significantly higher than the women with gastroschisis (p=0.001). Associated structural anomalies were found in 53.3% and 4.7% of fetuses with omphalocele and gastroschisis, respectively (p<0.001). The rate of chromosomal anomaly was 8.3% in pregnancies with omphalocele. In liveborn pregnancies, the mean gestational age at delivery and birth weight did not differ between the study groups. Time to postoperative oral intake, duration of parenteral nutrition and length of hospital stay were significantly longer in babies with gastroschisis than omphalocele (p<0.01). Rates of termination, intrauterine, neonatal and infant death of fetuses with omphalocele were 25.3%, 6.7%, 10.7% and 2.7% respectively. Time to postoperative oral intake, duration of parenteral nutrition and duration of hospitalization were significantly longer in babies with complex compared to simple gastroschisis (p<0.01). Survival rates were 95.2%, 82.9% and 20% in fetuses with gastroschisis, isolated and non-isolated omphalocele, respectively. Conclusion: Associated structural and chromosomal anomalies were significantly more common in fetuses with omphalocele compared to those with gastroschisis. Prognosis of fetuses with omphalocele depended on the associated structural and chromosomal anomalies, whereas bowel compromise was the main determining factor in gastroschisis. [ABSTRACT FROM AUTHOR]

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]

Objective: To estimate the prevalence and trend of congenital eye anomalies (CEAs) and the rate of prenatal diagnosis over a 10‐year period. Design: Retrospective population‐based registry study. Setting: All maternity units in Paris, France, from 2010 to 2020. Population: A cohort of 115 cases of CEA detected among all live births or stillbirths, after 22 weeks of gestation, and terminations of pregnancy. Methods: The total prevalence of CEAs and prevalence of each specific CEA were calculated using 95% Poisson exact confidence intervals. Main outcome measures: The total prevalence of CEAs and the proportion of prenatal diagnosis of CEAs, and their evolution. Results: The prevalence of CEAs was 4.1 (95% CI 3.4–5.0) cases, ranging between 3.1 and 5.7 cases, per 10 000 births. CEAs were prenatally diagnosed in 23.5% of cases. CEAs were bilateral in 51 cases (44.3%), unilateral in 43 cases (37.4%) and missing or unknown in 21 cases (18.3%). Of those with CEAs, 20.9% had genetic anomalies and 53.0% had at least one other extraocular anomaly. When detected prenatally, CEAs were bilateral in 15 cases (55.6%), unilateral in eight cases (29.6%) and missing in the four remaining cases. The prenatal diagnosis rate of CEAs associated with genetic anomalies, CEA cases with at least one other malformation and isolated CEA cases were 29.2%, 26.2% and 13.3%, respectively. Conclusions: In total, 115 cases of CEAs were observed during the study period, representing a total prevalence of 4.1 cases per 10 000 births. The overall prenatal detection rate of CEAs in our population was 23.5%, which dropped to 13.3% for isolated cases of CEAs. [ABSTRACT FROM AUTHOR]

Objective: To identify whether conventional methods of estimating fetal growth (Hadlock's formula), which relies heavily on abdominal circumference measurements, are accurate in fetuses with gastroschisis. Methods: A retrospective cohort study was performed between the period January 1, 2011 and December 31, 2021 in a tertiary referral maternity hospital identifying all pregnancies with a diagnosis of gastroschisis. Projected fetal weight was obtained using the formula (EFW [Hadlock's formula] + 185 g × [X/7]) where X was the number of days to delivery. Results: During the study period 41 cases were identified. The median maternal age was 25. The median BMI was 25 and 63% were primiparous women (n = 26). Median gestation at diagnosis was 21 weeks. Median gestation at delivery was 36 weeks. A total of 4.8% of mothers had a history of drug use (n = 2). The rate of maternal tobacco use was 21.9% (n = 9). A total of 4.8% of fetuses had additional congenital anomalies including amniotic band syndrome and myelomeningocele (n = 2). Estimated fetal weight (EFW) and birth weight data were available for 34 cases. A Wilcoxon signed‐rank test showed projected EFW using Hadlock's formula did not result in a statistically significant different birth weight (Z = −1.3, P = 0.169). Median projected weight and actual birth weight were 2241.35 and 2415 g respectively. Median difference was 0.64 g (95% CI: −148 to −28.5). Conclusion: Our data showed accuracy using standard formulae for EFW in fetuses with gastroschisis. Synopsis: Our study shows accuracy using standard formulae such as Hadlock's formula for estimating fetal weight in fetuses with abdominal wall defects such as gastroschisis. [ABSTRACT FROM AUTHOR]

• The prevalence of prenatal ectopic kidney is quite low. • The most common locations of ectopic kidneys are the iliac fossa and lateral pelvic areas, respectively. • In ectopic kidney cases, both kidneys are equally affected in both genders. • Blood supply to ectopic kidneys is most commonly provided by the iliac artery and then the aorta. • The most common extraurinary anomalies accompanying prenatally diagnosed ectopic kidney are cardiac anomalies. To assess the characteristics, additional structural anomalies and postnatal urinary outcome of the cases diagnosed with fetal ectopic kidneys in the prenatal period. Cases having fetal ectopic kidneys, detected from a total of 14,617 pregnant women examined by routine detailed (Group 1) or indicated (Group 2) obstetric ultrasonography (USG) in a tertiary perinatology unit were analyzed. The prevalence of the cases, time of the diagnosis, sidedness of the affected kidney, anatomical location, origins of blood supply, additional urinary or extraurinary anomalies, and urinary complications during the postnatal follow-up period were investigated. We have detected 33 fetuses with ectopic kidneys in our cohort. The prevalence of fetal ectopic kidney was 0.22 %, with a median (min.-max.) diagnosis time of 21.3 (17.6–34) weeks. In the group in whom indicated USG was performed, the time of diagnosis was later compared to routine detailed USG (p = 0.04) group. There was no difference in terms of gender [male, (n = 14), female (n = 19), p = 0.38] and the sidedness of the ectopic kidneys (p = 0.38). The location of ectopic kidneys was most frequent in the iliac fossa (n = 20, 60.6 %) and in the lateral pelvic areas (n = 13, 39.3 %). The blood supply origin of ectopic kidneys was the common iliac artery in 22 (66.6 %), whereas the aorta in 11 cases (33.3 %). There was an additional urinary anomaly in 8 cases (24 %), an extraurinary structural anomaly, most commonly cardiac, and/or a soft marker for aneuploidy were presented in 16 cases (48 %). The most common urinary complication in the postpartum period was vesicoureteral reflux (n = 5). Ectopic kidney in the prenatal period is a rare structural anomaly that can equally affect both genders and both kidneys. Prenatal diagnosis is important for the diagnosis of additional anomalies and follow-up of postnatal complications. [ABSTRACT FROM AUTHOR]

Multicystic dysplastic kidney (MCDK) is a congenital renal disease characterized by variable-sized noncommunicative cysts, impeding parenchymal development and functionality. Renal capabilities are relative to the functionality of the contralateral kidney and response to management. Unilateral and isolated cases are often asymptomatic with more positive outcomes, while severe bilateral derangements have a high mortality rate. We present a case of left-sided MCDK and right-sided renal dysplasia diagnosed at a nontertiary center. In addition, we offer a review of the epidemiology, epigenetics, and pathophysiology of MCDK. A concise discussion of prenatal, intrapartum, and postnatal renal function surveillance methods is presented to assist neonatal healthcare providers in collaborating with pediatric nephrology and urology specialists. [ABSTRACT FROM AUTHOR]