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Background: Niemann-Pick disease type C poses a significant challenge within the landscape of rare genetic disorders, marked by its connection to variants in the NPC1 or NPC2 genes. This autosomal recessive lipid storage disorder unfolds with a relentless progression of neurological deterioration and a distinctive hallmark of hepatosplenomegaly. Case presentation: This case report delves into the intricate presentation of a 9-year-old Iraqi boy exhibiting heightened walking instability and speech slurring. His medical history unfolds a series of challenges, including neonatal hyperbilirubinemia, hepatosplenomegaly, and recurrent nasal bleeding. A comprehensive physical examination reveals motor and neurological abnormalities such as an inability to squat and rise, vertical gaze palsy, and dysdiadochokinesia. Further investigations, encompassing laboratory tests and imaging studies, coupled with the identification of foamy cells in bone marrow smears, raise significant concerns about Niemann-Pick disease type C. By utilizing whole exome sequencing, we pinpointed a previously unreported homozygous variant—c.2925_2928delCTGC; p.Cys976PhefsTer6—found within exon 20 (NM_000271.5) of the proband's NPC1 gene. Conclusions: This study significantly advances our understanding of the c.2925_2928del (C976Ffs*6) variant in the NPC1 gene, shedding light on the complexities of Niemann-Pick disease type C. Beyond its scientific significance, the findings provide crucial insights for familial genetic counseling and prenatal diagnoses. This research expands our knowledge of the variant's genetic landscape, making it a valuable resource in both academic and clinical settings, particularly for families dealing with Niemann-Pick disease type C. [ABSTRACT FROM AUTHOR]

Background: For women in the first trimester, amniocentesis or chorionic villus sampling is recommended for screening. Machine learning has shown increased accuracy over time and finds numerous applications in enhancing decision-making, patient care, and service quality in nursing and midwifery. This study aims to develop an optimal learning model utilizing machine learning techniques, particularly neural networks, to predict chromosomal abnormalities and evaluate their predictive efficacy. Methods/ design: This cross-sectional study will be conducted in midwifery clinics in Mashhad, Iran in 2024. The data will be collected from 350 pregnant women in the high-risk group who underwent screening tests in the first trimester (between 11-14 weeks) of pregnancy. Information collected includes maternal age, BMI, smoking habits, history of trisomy 21 and other chromosomal disorders, CRL and NT levels, PAPP-A and B-HCG levels, presence of insulin-dependent diabetes, and whether the pregnancy resulted from IVF. The study follows up with the women during their clinic visits and tracks the results of amniocentesis. Sampling is based on Convenience Sampling, and data is gathered using a checklist of characteristics and screening/amniocentesis results. After preprocessing, feature extraction is conducted to identify and predict relevant features. The model is trained and evaluated using K-fold cross-validation. Discussion: There is a growing interest in utilizing artificial intelligence methods, like machine learning and deep learning, in nursing and midwifery. This underscores the critical necessity for nurses and midwives to be well-versed in artificial intelligence methods and their healthcare applications. It can be beneficial to develop a machine learning model, specifically focusing on neural networks, for predicting chromosomal abnormalities. Ethical code: IR.MUMS.NURSE.REC. 1402.134 Plain English Summary: Approximately 3% of newborns are affected by congenital abnormalities and genetic diseases, leading to disability and death. Among live births, around 3000 cases of Down syndrome (trisomy 21) can be expected based on the country's birth rate. Pregnant women carrying fetuses with Down syndrome face an increased risk of pregnancy complications. Artificial intelligence methods, such as machine learning and deep learning, are being used in nursing and midwifery to improve decision-making, patient care, and research. Nurses need to actively participate in the development and implementation of AI-based decision support systems. Additionally, nurses and midwives should play a key role in evaluating the effectiveness of artificial intelligence-based technologies in professional practice. [ABSTRACT FROM AUTHOR]

Objectives: To assess the diagnostic accuracy of two‐dimensional ultrasound at 11–14 weeks' gestation as a screening test for individual fetal anomalies and to identify factors impacting on screening performance. Methods: This was a systematic review and meta‐analysis that was developed and registered with PROSPERO (CRD42018111781). MEDLINE, EMBASE, Web of Science Core Collection and the Cochrane Library were searched for studies evaluating the diagnostic accuracy of screening for 16 predefined, non‐cardiac, congenital anomalies considered to be of interest to the early anomaly scan. We included prospective and retrospective studies from any healthcare setting conducted in low‐risk, mixed‐risk and unselected populations. The reference standard was the detection of an anomaly on postnatal or postmortem examination. Data were extracted to populate 2 × 2 tables and a random‐effects model was used to determine the diagnostic accuracy of screening for the predefined anomalies (individually and as a composite). Secondary analyses were performed to determine the impact on detection rates of imaging protocol, type of ultrasound modality, publication year and index of sonographer suspicion at the time of scanning. Post‐hoc secondary analysis was conducted to assess performance among studies published during or after 2010. Risk of bias assessment and quality assessment were undertaken for included studies using the Quality Assessment of Diagnostic Accuracy Studies‐2 tool. Results: From 5684 citations, 202 papers underwent full‐text review, resulting in the inclusion of 52 studies comprising 527 837 fetuses, of which 2399 were affected by one or more of the 16 predefined anomalies. Individual anomalies were not equally amenable to detection on first‐trimester ultrasound: a high (> 80%) detection rate was reported for severe conditions, including acrania (98%), gastroschisis (96%), exomphalos (95%) and holoprosencephaly (88%); the detection rate was lower for open spina bifida (69%), lower urinary tract obstruction (66%), lethal skeletal dysplasias (57%) and limb‐reduction defects (50%); and the detection rate was below 50% for facial clefts (43%), polydactyly (40%) and congenital diaphragmatic hernia (38%). Conditions with a low (< 30%) detection rate included bilateral renal agenesis (25%), closed spina bifida (21%), isolated cleft lip (14%) and talipes (11%). Specificity was > 99% for all anomalies. Secondary analysis showed that detection improved with advancing publication year, and that the use of imaging protocols had a statistically significant impact on screening performance (P < 0.0001). Conclusions: The accurate detection of congenital anomalies using first‐trimester ultrasound is feasible, although detection rates and false‐positive rates depend on the type of anomaly. The use of a standardized protocol allows for diagnostic performance to be maximized, particularly for the detection of spina bifida, facial clefts and limb‐reduction defects. Highlighting the types of anomalies amenable to diagnosis and determining factors enhancing screening performance can support the development of first‐trimester anomaly screening programs. © 2024 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Noninvasive prenatal testing (NIPT) has become widely available in recent years. While initially used to screen for trisomies 21, 18, and 13, the test has expanded to include a range of other conditions and will likely expand further. This paper addresses the ethical issues that arise from one particularly controversial potential use of NIPT: screening for adult‐onset conditions (AOCs). We report data from our quantitative survey of Australian NIPT users' views on the ethical issues raised by NIPT for AOCs. The survey ascertained support for NIPT for several traits and conditions including AOCs. Participants were then asked about their level of concern around implications of screening for AOCs for the future child and parent(s). Descriptive and comparative data analyses were conducted. In total, 109 respondents were included in data analysis. The majority of respondents expressed support for NIPT screening for preventable (70.9%) and nonpreventable AOCs (80.8%). Most respondents indicated concern around potential harmful impacts associated with NIPT for AOCs, including the psychological impact on the future child and on the parent(s). Despite this, the majority of participants thought that continuation of a pregnancy known to be predisposed to an AOC is ethically acceptable. The implications of these data are critically discussed and used to inform the normative claim that prospective parents should be given access to NIPT for AOCs. The study contributes to a body of research debating the ethical acceptability and regulation of various applications of NIPT as screening panels expand. [ABSTRACT FROM AUTHOR]

Introduction: Vasa previa (VP), defined as unprotected fetal vessels traversing the membranes over the cervix, is associated with a high perinatal mortality when undiagnosed prenatally. Conversely, prenatal diagnosis with ultrasound and cesarean delivery before the membranes rupture is associated with excellent outcomes. However, controversy exists regarding screening for VP. In the UK, routine screening for VP is not recommended. The objective of this study was to report the incidence of VP and our experience in the detection of VP with a universal screening protocol at the time of the second‐trimester fetal anomaly scan with third‐trimester confirmation in an unselected population of pregnancies. Material and methods: We performed a single‐center historical cohort study of all pregnant women who underwent routine second‐trimester anomaly screening scans at West Middlesex University Hospital, London, UK, between 2012 and 2016. Over 5 years, every patient undergoing routine anomaly screening was evaluated for VP using a systematic protocol during their 20‐week anomaly scan. Suspected cases of VP were rescanned in the third trimester by specialist sonographers with an interest in VP. The primary outcomes were the incidence and detection of VP. Results: During the study period, 24 690 anatomy scans were performed. A total of 64 patients were identified as having potential VP at the second‐trimester anomaly screening scan, of which 19 were confirmed by the specialist sonographer in the third trimester and at delivery. The screen positive rate was 0.26% (95% confidence interval [CI] 0.20%–0.32%). VP at birth was found in 19/24690 births (1:1299 [95% CI: 1:832–1:2030] births). Universal screening for VP using our protocol had a sensitivity of 100% and a specificity of 99.78% (95% CI: 99.72%–99.84%). The false‐positive rate of the second‐trimester screen was 0.18% (95% CI: 0.13–0.24). There were no false positives or false negatives at delivery. Of the 19 patients with confirmed VP, 17 had scheduled cesarean deliveries, and two required emergency deliveries due to antepartum hemorrhage. One baby died, giving a perinatal mortality of 5%. Conclusions: VP complicates approximately 1:1300 pregnancies. Routine screening for VP yielded a 100% detection rate. We suggest the inclusion of structured VP assessment in standard fetal anomaly screening programs. [ABSTRACT FROM AUTHOR]

Aim: To examine whether antenatal diagnosis modifies relationships between neonatal brain volumes and 18‐month neurodevelopmental outcomes in children with transposition of the great arteries (TGA). Method: In a retrospective cohort of 139 children with TGA (77 antenatally diagnosed), we obtained total brain volumes (TBVs) on pre‐ (n = 102) and postoperative (n = 112) magnetic resonance imaging. Eighteen‐month neurodevelopmental outcomes were assessed using the Bayley Scales of Infant and Toddler Development, Third Edition. Generalized estimating equations with interaction terms were used to determine whether antenatal diagnosis modified associations between TBVs and neurodevelopmental outcomes accounting for postmenstrual age at scan, brain injury, and ventricular septal defect. Results: Infants with postnatal diagnosis had more preoperative hypotension (35% vs 14%, p = 0.004). The interactions between antenatal diagnosis and TBVs were significantly related to cognitive (p = 0.003) outcomes. Specifically, smaller TBVs were associated with lower cognitive scores in infants diagnosed postnatally; this association was attenuated in those diagnosed antenatally. Interpretation: Antenatal diagnosis modifies associations between neonatal brain volume and 18‐month cognitive outcome in infants with TGA. These findings suggest that antenatal diagnosis may be neuroprotective, possibly through improved preoperative clinical status. These data highlight the need to improve antenatal diagnosis rates. What this paper adds: Antenatal diagnosis of transposition of the great arteries modified relationships between neonatal brain volume and neurodevelopment.Smaller brain volumes related to poorer cognitive scores with postnatal diagnosis only.There was more preoperative hypotension in the postnatal diagnosis group. [ABSTRACT FROM AUTHOR]

Objectives: Congenital diaphragmatic hernia (CDH) is defined as organ protrusion from the abdominal to the thoracic cavity. The Hadlock formula is the most commonly used tool for calculating estimated fetal weight (EFW). The anatomical nature of CDH usually leads to underestimation of the abdominal circumference, resulting in underestimation of fetal weight. Accurate weight estimation is essential before birth for counselling, preparation before surgery and ECMO. The research is made to compare the accuracy of Hadlock's formula and Faschingbauer's formula for fetal weight estimation in CDH fetuses population. Methods: In our study, we investigated differences between EFW and actual birthweight in 42 fetuses with CDH as compared to 80 healthy matched controls. EFW was calculated using the Hadlock formula and a recently introduced formula described by Faschingbauer et al., which was tailored for fetuses with CDH. Additionally, both of the formulas were adjusted for the interval between the ultrasound and delivery for both of the groups. Results: The majority of hernias were left-sided (92.8% vs. 7.2%). EFW adjusted for the interval between the ultrasound and delivery had the highest correlation with the actual birthweight in both, study group and controls. We compared the results for both tools and found the Hadlock formula to predict birthweight in CDH children with a 7.8 ± 5.5% error as compared to 7.9 ± 6.5% error for the Faschingbauer's formula. Conclusions: The Hadlock formula adjusted for the interval between the ultrasound and delivery is a more precise method of calculating EFW in fetuses with CDH. Routine biometry scan using Hadlock's formula remains reliable for predicting birthweight. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the potential connections between marginal cord insertion during the first trimester and furcate cord insertion later in pregnancy. Methods: This is a prospective study of screening data on the cord insertion site in 3178 singleton pregnancies. The cord insertion site was examined in two stages. The first stage was screening for the cord insertion site between 10–13 weeks of gestation, the purpose is to determine the category of umbilical cord insertion. The second stage, performed at 22–28 weeks of gestation, was to follow up on the relationship between the cord insertion site and the placenta and to identify any changes in the category of umbilical cord insertion. This was performed to diagnose or exclude furcate cord insertion by identifying whether the umbilical cord trunk separated or branched before it reached the placenta. Factors influencing progression to furcate cord insertion and perinatal complications were assessed. Results: Fourteen cases (0.44%) with progression to furcate cord insertion, all of which showed marginal cord insertion on ultrasound in the first trimester (p < 0.001). without progression to furcate cord insertion, there were no changes in the category of umbilical cord insertion in 3050 cases (96.40%) compared to the early pregnancy. 114 cases (3.60%) with changes in the category of umbilical cord insertion that was not consistent with furcate cord insertion. A total of 14 cases progressed to furcate cord insertion, all showed the cord insertion site were in close proximity, and 11 (78.57%) cases showed a low insertion site (p < 0.001). Regarding the choice of mode of delivery, elective caesarean delivery was done in 8/14 (57.14%). The incidences of spontaneous vaginal delivery were 5/14 (35.71%) (p < 0.001). One (7.14%) case of progression to furcate cord insertion due to haematoma at the root of the umbilical cord ended with an emergency caesarean section. In terms of perinatal complications, marginal cord insertion that progressed to furcate cord insertion had higher incidences of SGA infants, abnormal placental morphology, retention of the placenta, and cord-related adverse pregnancy outcomes than not progressed to furcate cord insertion (p < 0.05). Conclusions: Marginal cord insertion in the first trimester has the potential to progress to furcate cord insertion. We suggest that ultrasound-diagnosed marginal cord insertion in the first trimester should be watched carefully in the second trimester, which is clinically useful to accurately determine the category of cord insertion and to improve the rate of prenatal diagnosis of furcate cord insertion. [ABSTRACT FROM AUTHOR]

Mosaicism for autosomal trisomy is uncommon in clinical practice. However, despite its rarity among both prenatally and postnatally diagnoses, there are a large number of characterized and published cases. Surprisingly, in contrast to regular trisomies, no attempts at systematic analyses of mosaic carriers' demographics were undertaken. This is the first study aimed to address this gap. For that, we have screened more than eight hundred publications on mosaic trisomies, reviewing data including gender and clinical status of mosaic carriers, maternal age and reproductive history. In total, 596 publications were eligible for analysis, containing data on 948 prenatal diagnoses, including true fetal mosaicism (TFM) and confined placental mosaicism (CPM), and on 318 cases of postnatally detected mosaicism (PNM). No difference was found in maternal age between normal pregnancy outcomes with appropriate birth weight and those with intrauterine growth restriction. Unexpectedly, a higher proportion of advanced maternal ages (AMA) was found in normal outcomes compared to abnormal ones (abnormal fetus or newborn) and fetal losses, 73% vs. 56% and 50%, p = 0.0015 and p = 0.0011, correspondingly. Another intriguing finding was a higher AMA proportion in mosaic carriers with concomitant uniparental disomy (UPD) for chromosomes 7, 14, 15, and 16 compared to carriers with biparental disomy (BPD) (72% vs. 58%, 92% vs. 55%, 87% vs. 78%, and 65% vs. 24%, correspondingly); overall figures were 78% vs. 48%, p = 0.0026. Analysis of reproductive histories showed a very poor reporting but almost two-fold higher rate of mothers reporting a previous fetal loss from PNM cohort (in which almost all patients were clinically abnormal) compared to mothers from the TFM and CPM cohorts (with a large proportion of normal outcomes), 30% vs. 16%, p = 0.0072. The occurrence of a previous pregnancy with a chromosome abnormality was 1 in 13 in the prenatal cohort and 1 in 16 in the postnatal cohort, which are five-fold higher compared to published studies on non-mosaic trisomies. We consider the data obtained in this study to be preliminary despite the magnitude of the literature reviewed since reporting of detailed data was mostly poor, and therefore, the studied cohorts do not represent "big data". Nevertheless, the information obtained is useful both for clinical genetic counseling and for modeling further studies. [ABSTRACT FROM AUTHOR]

Celocentesis is a new sampling tool for prenatal diagnosis available from 7 weeks in case of couples at risk for genetic diseases. In this study, we reported the feasibility of earlier prenatal diagnosis by celocentesis in four cases of cystic fibrosis and one case of cystic fibrosis and β-thalassemia co-inherited in the same fetus. Celomic fluids were aspired from the celomic cavity between 8+2 and 9+3 weeks of gestation and fetal cells were picked up by micromanipulator. Maternal DNA contamination was tested and target regions of fetal DNA containing parental pathogenetic variants of CFTR and HBB genes were amplified and sequenced. Four of the five fetuses resulted as being affected by cystic fibrosis and, in all cases, the women decided to interrupt the pregnancy. In the other case, the fetus presented a healthy carrier of cystic fibrosis. The results were confirmed in three cases on placental tissue. In one case, no abortive tissue was obtained. In the last case, the woman refused the prenatal diagnosis to confirm the celocentesis data; the pregnancy is ongoing without complications. This procedure provides prenatal diagnosis of monogenic diseases at least four weeks earlier than traditional procedures, reducing the anxiety of patients and providing the option for medical termination of the affected fetus at 8–10 weeks of gestation, which is less traumatic and safer than surgical termination in the second trimester. [ABSTRACT FROM AUTHOR]

Aim To develop a non-invasive prenatal test for beta-hemoglobinopathies based on analyzing maternal plasma by using next generation sequencing. Methods We applied next generation sequencing (NGS) of maternal plasma to the non-invasive prenatal testing (NIPT) of autosomal recessive diseases, sickle cell disease and beta-thalassemia. Using the Illumina MiSeq, we sequenced plasma libraries obtained via a Twist Bioscience probe capture panel covering 4 Kb of chromosome 11, including the beta-globin (HBB) gene and >450 genomic single-nucleotide polymorphisms (SNPs) used to estimate the fetal fraction (FF). The FF is estimated by counting paternally transmitted allelic sequence reads present in the plasma but absent in the mother. We inferred fetal betaglobin genotypes by comparing the observed mutation (Mut) and reference (Ref ) read ratios to those expected for the three possible fetal genotypes (Mut/Mut; Mut/Ref; Ref/ Ref ), based on the FF. Results We bioinformatically enriched the FF by excluding reads over a specified length via in-silico size selection (ISS), favoring the shorter fetal reads, which increased fetal genotype prediction accuracy. Finally, we determined the parental HBB haplotypes, which allowed us to use the read ratios observed at linked SNPs to help predict the fetal genotype at the mutation site(s). We determined HBB haplotypes via Oxford Nanopore MinION sequencing of a 2.2 kb amplicon and aligned these sequences using Soft Genetics' NextGENe LR software. Conclusion The combined use of ISS and HBB haplotypes enabled us to correctly predict fetal genotypes in cases where the prediction based on variant read ratios alone was incorrect. [ABSTRACT FROM AUTHOR]

Background: The protein kinase domain containing cytoplasmic (PKDCC) gene (OMIM#618821) is associated with bone development. Biallelic variants in the PKDCC gene can cause rhizomelic limb shortening with dysmorphic features. Case Report: A fetus was found to be rhizomelic limb shortening at 16 weeks of gestation and amniocentesis was performed at 19 weeks of gestation. Genomic DNA extracted from the amniotic fluid was subjected to chromosomal microarray analysis (CMA), and Trio‐total whole‐exome sequencing (Trio‐WES). Sanger sequencing was used to verify the candidate pathogenic variants. CMA was normal, while Trio‐WES identified two compound heterozygous variants in the PKDCC gene, namely c.417_c.423delCGGCGCG insTCATGGGCTCAGTACAC(p.G140fs*35) and c.345G>A (p.W115*,379). Then the fetus was aborted and the development of its bone cells were compared with that of a normal fetus of similar gestational age by histopathological examination. Clinical findings of the fetus were shortening humerus and femur, synophrys, much hair on the side face, simian line on the right palm, etc. Histopathological examination showed that the affected fetus had increased proliferative chondrocytes, widened proliferative bands, and delayed bone mineralization. Conclusions: We reported a prenatal case of rhizomelic shortening of limbs caused by compound heterozygous variants in the PKDCC gene, which emphasized the important role of Trio‐WES for diagnosis of skeletal dysplasia in fetuses. [ABSTRACT FROM AUTHOR]

Multiple congenital contractures (MCC) due to fetal akinesia manifest across a broad spectrum of diseases, ranging from mild distal arthrogryposis to lethal fetal akinesia deformation sequence. We hereby present a series of 26 fetuses displaying severe MCC phenotypes from 18 families and describe detailed prenatal ultrasound findings, postmortem clinical evaluations, and genetic investigations. Most common prenatal findings were abnormal facial profile (65%), central nervous system abnormalities (62%), polyhydramnios (50%), increased nuchal translucency (50%), and fetal hydrops (35%). Postmortem examinations unveiled additional anomalies including facial dysmorphisms, dysplastic skeletal changes, ichthyosis, multiple pterygia, and myopathy, allowing preliminary diagnosis of particular Mendelian disorders in multiple patients. Evaluation of the parents revealed maternal grip myotonia in one family. By exome sequencing and targeted testing, we identified causative variants in ACTC1, CHST14, COG6, DMPK, DOK7, HSPG2, KLHL7, KLHL40, KIAA1109, NEB, PSAT1, RAPSN, USP14, and WASHC5 in 15 families, and one patient with a plausible diagnosis associated with biallelic NEB variants. Three patients received a dual diagnosis. Pathogenic alterations in newly discovered genes or in previously known genes recently linked to new MCC phenotypes were observed in 44% of the cohort. Our results provide new insights into the clinical and molecular landscape of lethal MCC phenotypes. [ABSTRACT FROM AUTHOR]

This article discusses a case study involving the prenatal detection and neonatal surgical resection of a giant aneurysm in the left atrial appendage of a fetus. The study highlights the feasibility of prenatal diagnosis and emphasizes the importance of timely assessment and treatment in the early postpartum period. The use of multimodal imaging is also emphasized for accurate characterization of the appendage and optimal surgical planning. The article concludes by noting that giant aneurysms in the left atrial appendage are rare and potentially associated with thromboembolism. [Extracted from the article]

This is a single tertiary population-based study conducted at a center in southwest Romania. We retrospectively compared data obtained in two periods: January 2008–December 2013 and January 2018–December 2023. The global incidence of the transposition of great arteries in terminated cases, in addition to those resulting in live-born pregnancies, remained almost constant. The live-birth incidence decreased. The median gestational age at diagnosis decreased from 29.3 gestational weeks (mean 25.4) to 13.4 weeks (mean 17.2). The second trimester and the overall detection rate in the prenatal period did not significantly change, but the increase was statistically significant in the first trimester. The proportion of terminated pregnancies in fetuses diagnosed with the transposition of great arteries significantly increased (14.28% to 75%, p = 0.019). [ABSTRACT FROM AUTHOR]

Background: Deep learning (DL) is a new technology that can assist prenatal ultrasound (US) in the detection of congenital heart disease (CHD) at the prenatal stage. Hence, an economic-epidemiologic evaluation (aka Cost-Utility Analysis) is required to assist policymakers in deciding whether to adopt the new technology. Methods: The incremental cost-utility ratios (CUR), of adding DL assisted ultrasound (DL-US) to the current provision of US plus pulse oximetry (POX), was calculated by building a spreadsheet model that integrated demographic, economic epidemiological, health service utilization, screening performance, survival and lifetime quality of life data based on the standard formula: CUR = Increase in Intervention Costs - Decrease in Treatment costs Averted QALY losses of adding DL to US & POX US screening data were based on real-world operational routine reports (as opposed to research studies). The DL screening cost of 145 USD was based on Israeli US costs plus 20.54 USD for reading and recording screens. Results: The addition of DL assisted US, which is associated with increased sensitivity (95% vs 58.1%), resulted in far fewer undiagnosed infants (16 vs 102 [or 2.9% vs 15.4%] of the 560 and 659 births, respectively). Adoption of DL-US will add 1,204 QALYs. with increased screening costs 22.5 million USD largely offset by decreased treatment costs (20.4 million USD). Therefore, the new DL-US technology is considered "very cost-effective", costing only 1,720 USD per QALY. For most performance combinations (sensitivity > 80%, specificity > 90%), the adoption of DL-US is either cost effective or very cost effective. For specificities greater than 98% (with sensitivities above 94%), DL-US (& POX) is said to "dominate" US (& POX) by providing more QALYs at a lower cost. Conclusion: Our exploratory CUA calculations indicate the feasibility of DL-US as being at least cost-effective. [ABSTRACT FROM AUTHOR]

Background: Non-invasive prenatal testing (NIPT) is a widely adopted maternal blood test that analyses foetal originating DNA to screen for foetal chromosomal conditions, including Down's syndrome (DS). The introduction of this test, which may have implications for important decisions made during pregnancy, requires continual monitoring and evaluation. This systematic review aims to assess the extent of NIPT introduction into national screening programmes for DS worldwide, its uptake, and impact on pregnancy outcomes. Methods and findings: The study protocol was published in PROSPERO (CRD42022306167). We systematically searched MEDLINE, CINAHL, Scopus, and Embase for population-based studies, government guidelines, and Public Health documents from 2010 onwards. Results summarised the national policies for NIPT implementation into screening programmes geographically, along with population uptake. Meta-analyses estimated the pooled proportions of women choosing invasive prenatal diagnosis (IPD) following a high chance biochemical screening result, before and after NIPT was introduced. Additionally, we meta-analysed outcomes (termination of pregnancy and live births) amongst high chance pregnancies identified by NIPT. Results demonstrated NIPT implementation in at least 27 countries. Uptake of second line NIPT varied, from 20.4% to 93.2% (n = 6). Following NIPT implementation, the proportion of women choosing IPD after high chance biochemical screening decreased from 75% (95% CI 53%, 88%, n = 5) to 43% (95%CI 31%, 56%, n = 5), an absolute risk reduction of 38%. A pooled estimate of 69% (95% CI 52%, 82%, n = 7) of high chance pregnancies after NIPT resulted in termination, whilst 8% (95% CI 3%, 21%, n = 7) had live births of babies with DS. Conclusions: NIPT has rapidly gained global acceptance, but population uptake is influenced by healthcare structures, historical screening practices, and cultural factors. Our findings indicate a reduction in IPD tests following NIPT implementation, but limited pre-NIPT data hinder comprehensive impact assessment. Transparent, comparable data reporting is vital for monitoring NIPT's potential consequences. [ABSTRACT FROM AUTHOR]

(1) Background: Non-invasive prenatal testing (NIPT) is a screening test for fetal aneuploidy using cell-free fetal DNA. The fetal fragments (FF) of cell-free DNA (cfDNA) are derived from apoptotic trophoblast of the placenta. The level of fetal cfDNA is known to be influenced by gestational age, multiple pregnancies, maternal weight, and height. (2) Methods: This study is a single-center retrospective observational study which examines the relationship between the fetal fraction (FF) of cell-free DNA in non-invasive prenatal testing (NIPT) and adverse pregnancy outcomes in singleton pregnancies. A total of 1393 samples were collected between 10 weeks and 6 days, and 25 weeks and 3 days of gestation. (3) Results: Hypertensive disease of pregnancy (HDP) occurred more frequently in the low FF group than the normal FF group (5.17% vs. 1.91%, p = 0.001). Although the rates of small for gestational age (SGA) and placental abruption did not significantly differ between groups, the composite outcome was significantly higher in the low FF group (7.76% vs. 3.64%, p = 0.002). Furthermore, women who later experienced complications such as HDP or gestational diabetes mellitus (GDM) had significantly lower plasma FF levels compared to those without complications (p < 0.001). After adjustments, the low FF group exhibited a significantly higher likelihood of placental compromise (adjusted odds ratio: 1.946). (4) Conclusions: Low FF in NIPT during the first and early second trimesters is associated with adverse pregnancy outcomes, particularly HDP, suggesting its potential as a predictive marker for such outcomes. [ABSTRACT FROM AUTHOR]

Vasa previa is a pregnancy complication that occurs when unprotected fetal blood vessels traverse the cervical os, placing the fetus at high risk of exsanguination and fetal death. These fetal vessels may be compromised by fetal movement and compression, leading to poor oxygen distribution and asphyxiation. Diagnostic tools for vasa previa management and preterm labor (PTL) include transvaginal ultrasound, cervical length (CL) surveillance and use of fetal fibronectin (FFN) testing. These tools can prove to be quite useful as they allow for lead time in the prediction of PTL and spontaneous rupture of membranes which can result in devastating outcomes for pregnancies affected by vasa previa. We conducted a literature review on vasa previa management and the usefulness of FFN and CL surveillance in predicting PTL and found 36 related papers. Although there is limited research available to show the impact of FFN and CL surveillance in the management of vasa previa, there is sufficient evidence to support FFN and CL surveillance in predicting the onset of PTL, which can have devastating consequences for the pregnancies affected. It can be extrapolated that these tools, by helping to determine pregnancies at risk for PTL, could improve management and outcomes in patients with vasa previa. Future studies investigating the management of vasa previa with FFN and CL surveillance to reduce the burden of PTL and its associated comorbidities are warranted. [ABSTRACT FROM AUTHOR]

Background: Non-invasive prenatal testing (NIPT) has been clinically available in Australia on a user-pays basis since 2012. There are numerous providers, with available tests ranging from targeted NIPT (only trisomies 21, 18, and 13 +/- sex chromosome aneuploidy) to genome-wide NIPT. While NIPT is being implemented in the public health care systems of other countries, in Australia, the implementation of NIPT has proceeded without public funding. The aim of this study was to investigate how NIPT has been integrated into antenatal care across Australia and reveal the successes and challenges in its implementation in this context. Methods: An anonymous online survey was conducted from September to October 2022. Invitations to participate were sent to healthcare professionals (HCPs) involved in the provision of NIPT in Australia through professional society mailing lists and networks. Participants were asked questions on their knowledge of NIPT, delivery of NIPT, and post-test management of results. Results: A total of 475 HCPs responded, comprising 232 (48.8%) obstetricians, 167 (35.2%) general practitioners, 32 (6.7%) midwives, and 44 (9.3%) genetic specialists. NIPT was most commonly offered as a first-tier test, with most HCPs (n = 279; 60.3%) offering it to patients as a choice between NIPT and combined first-trimester screening. Fifty-three percent (n = 245) of respondents always offered patients a choice between NIPT for the common autosomal trisomies and expanded (including genome-wide) NIPT. This choice was understood as supporting patient autonomy and informed consent. Cost was seen as a major barrier to access to NIPT, for both targeted and expanded tests. Equitable access, increasing time demands on HCPs, and staying up to date with advances were frequently reported as major challenges in delivering NIPT. Conclusions: Our findings demonstrate substantial variation in the clinical implementation of NIPT in Australia, including in the offers of expanded screening options. After a decade of clinical use, Australian clinicians still report ongoing challenges in the clinical and equitable provision of NIPT. [ABSTRACT FROM AUTHOR]

Objective: This study aims to perform a prenatal genetic diagnosis of a high-risk fetus with trisomy 7 identified by noninvasive prenatal testing (NIPT) and to evaluate the efficacy of different genetic testing techniques for prenatal diagnosis of trisomy mosaicism. Methods: For prenatal diagnosis of a pregnant woman with a high risk of trisomy 7 suggested by NIPT, karyotyping and chromosomal microarray analysis (CMA) were performed on an amniotic fluid sample. Low-depth whole-genome copy number variation sequencing (CNV-seq) and fluorescence in situ hybridization (FISH) were used to clarify the results further. In addition, methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) was performed to analyze the possibility of uniparental disomy(UPD). Results: Amniotic fluid karyotype analysis revealed a 46, XX result. Approximately 20% mosaic trisomy 7 was detected according to the CMA result. About 16% and 4% of mosaicism was detected by CNV-seq and FISH, respectively. MS-MLPA showed no methylation abnormalities. The fetal ultrasound did not show any detectable abnormalities except for mild intrauterine growth retardation seen at 39 weeks of gestation. After receiving genetic counseling, the expectant mother decided to continue the pregnancy, and follow-up within three months of delivery was normal. Conclusion: In high-risk NIPT diagnosis, a combination of cytogenetic and molecular genetic techniques proves fruitful in detecting low-level mosaicism. Furthermore, the exclusion of UPD on chromosome 7 remains crucial when NIPT indicates a positive prenatal diagnosis of trisomy 7. [ABSTRACT FROM AUTHOR]

Background: This study aims to evaluate the outcomes of fetal sacrococcygeal teratoma (SCT) submitted to prenatal interventions. Methods: We performed a systematic literature review of fetal SCT patients and compared the outcomes between open fetal surgery and percutaneous intervention. In addition, we also compared the results of SCT fetuses who did not undergo any surgical intervention (NI). Results: We identified 16 cases of open fetal surgery (OS), 48 cases of percutaneous fetal intervention (PI), and 93 NI patients. The survival rate was 56.2% in OS, 45.8% in PI (p = 0.568), and 71.0% in NI patients. The gestational age at delivery was earlier in cases where there was no survival compared to cases where the fetuses did survive across all evaluated cohorts (OS: p = 0.033, PI: p < 0.001, NI: p < 0.001). The gestational weeks at delivery in OS and PI fetuses were more similar; however, OS tended to be performed later on in pregnancy, and the affected fetuses had more severe presented findings. In our evaluation, we determined that the presence of fetal hydrops and cardiac failure had no significant impact on survival in SCT cases. In NI patients, polyhydramnios was much higher in fetuses who did not survive compared to their surviving cohorts (p < 0.001). Conclusions: In conclusion, gestational age at delivery can affect the short-term prognosis of fetuses affected with sacrococcygeal teratomas. Regardless of the mode of delivery or the necessity for intervention during the fetal period, monitoring for complications, including polyhydramnios, can prevent premature delivery. [ABSTRACT FROM AUTHOR]

Fryns syndrome (FS) is a multiple congenital anomaly syndrome with different multisystemic malformations. These include congenital diaphragmatic hernia, pulmonary hypoplasia, and craniofacial dysmorphic features in combination with malformations of the central nervous system such as agenesis of the corpus callosum, cerebellar hypoplasia, and enlarged ventricles. We present a non-consanguineous northern European family with two recurrent cases of FS: a boy with multiple congenital malformations who died at the age of 2.5 months and a female fetus with a complex developmental disorder with similar features in a following pregnancy. Quad whole exome analysis revealed two likely splicing-affecting disease-causing mutations in the PIGN gene: a synonymous mutation c.2619G>A, p.(Leu873=) in the last nucleotide of exon 29 and a 30 bp-deletion c.996_1023+2del (NM_176787.5) protruding into intron 12, with both mutations in trans configuration in the affected patients. Exon skipping resulting from these two variants was confirmed via RNA sequencing. Our molecular and clinical findings identified compound heterozygosity for two novel splice-affecting variants as the underlying pathomechanism for the development of FS in two patients. [ABSTRACT FROM AUTHOR]

Objective: To investigate the diagnostic yield of trio whole‐genome sequencing (WGS) in fetuses with various congenital malformations referred to a tertiary center for prenatal diagnosis. Methods: In this prospective study, 50 pregnancies with different congenital malformations, negative for trisomies and causative copy‐number variants, were analyzed further with fetal–parental trio WGS analysis. Parents were eligible for inclusion if they accepted further investigation following the detection of isolated or multiple malformations on prenatal ultrasound. Cases with isolated increased nuchal translucency, gamete donation or multiple pregnancy were excluded. WGS with the Illumina Inc. 30× polymerase‐chain‐reaction‐free short‐read sequencing included analysis of single‐nucleotide variants, insertions and deletions, structural variants, short tandem repeats and copy‐number identification of SMN1 and SMN2 genes. Results: A molecular diagnosis was achieved in 13/50 (26%) cases. Causative sequence variants were identified in 12 genes: FGFR3 (n = 2), ACTA1 (n = 1), CDH2 (n = 1), COL1A2 (n = 1), DHCR7 (n = 1), EYA1 (n = 1), FBXO11 (n = 1), FRAS1 (n = 1), L1CAM (n = 1), OFD1 (n = 1), PDHA1 (n = 1) and SOX9 (n = 1). The phenotypes of the cases were divided into different groups, with the following diagnostic yields: skeletal malformation (4/9 (44%)), multisystem malformation (3/7 (43%)), central nervous system malformation (5/15 (33%)) and thoracic malformation (1/10 (10%)). Additionally, two cases carried variants that were considered potentially clinically relevant, even though they were assessed as variants of uncertain significance, according to the guidelines provided by the American College of Medical Genetics and Genomics. Overall, we identified a causative or potentially clinically relevant variant in 15/50 (30%) cases. Conclusions: We demonstrate a diagnostic yield of 26% with clinical WGS in prenatally detected congenital malformations. This study emphasizes the benefits that WGS can bring to the diagnosis of fetal structural anomalies. It is important to note that causative chromosomal aberrations were excluded from our cohort before WGS. As chromosomal aberrations are a well‐known cause of prenatally detected congenital malformations, future studies using WGS as a primary diagnostic test, including assessment of chromosomal aberrations, may show that the detection rate exceeds the diagnostic yield of this study. WGS can add clinically relevant information, explaining the underlying cause of the fetal anomaly, which will provide information concerning the specific prognosis of the condition, as well as estimate the risk of recurrence. A genetic diagnosis can also provide more reproductive choice for future pregnancies. © 2024 The Authors. 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 Vivanti et al. Click here to view the Correspondence. Linked article: There is a comment on this article by Wei and Li. Click here to view the Correspondence. [ABSTRACT FROM AUTHOR]

Objective: Antenatal growth assessment using ultrasound aims to identify small fetuses that are at higher risk of perinatal morbidity and mortality. This study explored whether the association between suboptimal fetal growth and adverse perinatal outcome varies with different definitions of fetal growth restriction (FGR) and different weight charts/standards. Methods: This was a retrospective cohort study of 17 261 singleton non‐anomalous pregnancies at ≥ 24 + 0 weeks' gestation that underwent routine ultrasound at a tertiary referral hospital. Estimated fetal weight (EFW) and Doppler indices were converted into percentiles using a reference standard (INTERGROWTH‐21st (IG‐21)) and various reference charts (Hadlock, Fetal Medicine Foundation (FMF) and Swedish). Test characteristics were assessed using the consensus definition, Society for Maternal–Fetal Medicine (SMFM) definition and Swedish criteria for FGR. Adverse perinatal outcome was defined as perinatal death, admission to the neonatal intensive care unit at term, 5‐min Apgar score < 7 and therapeutic cooling for neonatal encephalopathy. The association between FGR according to each definition and adverse perinatal outcome was compared. Multivariate logistic regression analysis was used to test the strength of association between ultrasound parameters and adverse perinatal outcome. Ultrasound parameters were also tested for correlation. Results: IG‐21, Hadlock and FMF fetal size references classified as growth‐restricted 1.5%, 3.6% and 4.6% of fetuses, respectively, using the consensus definition and 2.9%, 8.8% and 10.6% of fetuses, respectively, using the SMFM definition. The sensitivity of the definition/chart combinations for adverse perinatal outcome varied from 4.4% (consensus definition with IG‐21 charts) to 13.2% (SMFM definition with FMF charts). Specificity varied from 89.4% (SMFM definition with FMF charts) to 98.6% (consensus definition with IG‐21 charts). The consensus definition and Swedish criteria showed the highest specificity, positive predictive value and positive likelihood ratio in detecting adverse outcome, irrespective of the reference chart/standard used. Conversely, the SMFM definition had the highest sensitivity across all investigated growth charts. Low EFW, abnormal mean uterine artery pulsatility index (UtA‐PI) and abnormal cerebroplacental ratio were significantly associated with adverse perinatal outcome and there was a positive correlation between the covariates. Multivariate logistic regression showed that UtA‐PI > 95th percentile and EFW < 5th percentile were the only parameters consistently associated with adverse outcome, irrespective of the definitions or fetal growth chart/standard used. Conclusions: The apparent prevalence of FGR varies according to the definition and fetal size reference chart/standard used. Irrespective of the method of classification, the sensitivity for the identification of adverse perinatal outcome remains low. EFW, UtA‐PI and fetal Doppler parameters are significant predictors of adverse perinatal outcome. As these indices are correlated with one other, a prediction algorithm is advocated to overcome the limitations of using these parameters in isolation. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Objectives: The identification of structural variants and single‐nucleotide variants is essential in finding molecular etiologies of monogenic genetic disorders. Whole‐genome sequencing (WGS) is becoming more widespread in genetic disease diagnosis. However, data on its clinical utility remain limited in prenatal practice. We aimed to expand our understanding of implementing WGS in the genetic diagnosis of fetal structural anomalies. Methods: We employed trio WGS with a minimum coverage of 40× on the MGI DNBSEQ‐T7 platform in a cohort of 17 fetuses presenting with aberrations detected by ultrasound, but uninformative findings of standard chromosomal microarray analysis (CMA) and exome sequencing (ES). Results: Causative genetic variants were identified in two families, with an increased diagnostic yield of 11.8% (2/17). Both were exon‐level copy‐number variants of small size (3.03 kb and 5.16 kb) and beyond the detection thresholds of CMA and ES. Moreover, to the best of our knowledge, we have described the first prenatal instance of the association of FGF8 with holoprosencephaly and facial deformities. Conclusions: Our analysis demonstrates the clinical value of WGS in the diagnosis of the underlying etiology of fetuses with structural abnormalities, when routine genetic tests have failed to provide a diagnosis. Additionally, the novel variants and new fetal manifestations have expanded the mutational and phenotypic spectrums of BBS9 and FGF8. © 2023 International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

In our case, the malformation was diagnosed prenatally at 40 weeks of gestation, and at the age of 14 days, the malformation was removed combined with a segmentectomy of the sixth segment of the left lung. Preoperative diagnostics focus on 3D-CT reconstruction and detailing of the anatomical variations of all arterial and venous vessels, as evident from our case. Treatment includes surgical removal or a minimally invasive interventional approach through the embolization of the vessel afferent to the malformation. After the operation, the child was discharged on the 30th day after birth in good condition and is developing normally. Early operative intervention is of great importance for the favorable outcome of the condition. In our case, this was hypoxemia with a saturation of 70-75%. The rare and often missed prenatal diagnosis of fetal AV malformation is significant for the adequate postnatal treatment and development of affected children. [ABSTRACT FROM AUTHOR]

Brachydactyly is a genetic condition leading to shortened or absent digits in hands or feet. It can occur independently or as part of syndromes. This case focuses on Brachydactyly type B, the rarest form. An 8-month-old from the Philippines was referred due to a missing third toe. Examination revealed a hypoplastic left third toe. X-rays confirmed the finding. Treatment options were discussed, including conservative therapy and follow up. Diagnosis involved history, examination, and imaging. Prenatal diagnosis is limited for isolated cases but useful for syndromic forms if a family mutation is known. Prognosis varies depending on the severity and associated syndromes. Currently there is no definitive treatment; management involves genetic counseling and therapy. Due to limited cases, Type B is underreported, highlighting the need for more research into its genetics. [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to assess the visibility of the indusium griseum (IG) in magnetic resonance (MR) scans of the human fetal brain and to evaluate its reliability as an imaging biomarker of the normality of brain midline development. Material and methods: The retrospective observational study encompassed T2‐w 3T MR images from 90 post‐mortem fetal brains and immunohistochemical sections from 41 fetal brains (16–40 gestational weeks) without cerebral pathology. Three raters independently inspected and evaluated the visibility of IG in post‐mortem and in vivo MR scans. Weighted kappa statistics and regression analysis were used to determine inter‐ and intra‐rater agreement and the type and strength of the association of IG visibility with gestational age. Results: The visibility of the IG was the highest between the 25 and 30 gestational week period, with a very good inter‐rater variability (kappa 0.623–0.709) and excellent intra‐rater variability (kappa 0.81–0.93). The immunochemical analysis of the histoarchitecture of IG discloses the expression of highly hydrated extracellular molecules in IG as the substrate of higher signal intensity and best visibility of IG during the mid‐fetal period. Conclusions: The knowledge of developmental brain histology and fetal age allows us to predict the IG‐visibility in magnetic resonance imaging (MRI) and use it as a biomarker to evaluate the morphogenesis of the brain midline. As a biomarker, IG is significant for post‐mortem pathological examination by MRI. Therefore, in the clinical in vivo imaging examination, IG should be anticipated when an assessment of the brain midline structures is needed in mid‐gestation, including corpus callosum thickness measurements. [ABSTRACT FROM AUTHOR]

Objective: Unusual clinical course. Background: Rapidly involuting congenital hemangioma (RICH) of the fetal skull is an extremely rare vascular disease which undergoes proliferation only in utero and progresses with maximal size at birth. RICH can be detected by prenatal imaging but is easily misdiagnose. Case Report: A 28-year-old nulliparous woman was referred at 38 weeks of gestation for routine screening with obstetric ultrasonography. The ultrasonography revealed a female fetus with a previously undetected head tumor (32×22 mm). Certain unusual sonographic features were observed: the lesion was fusiform, with a wide base adjacent to the frontal bone. Tumor growth appeared to be toward the brain parenchyma rather than outwards (ie, toward the skull), which suggested that the mass may have been derived from the skull. The mass may have remained undiagnosed due to its small size or due to the superimposition of the skull in poor quality ultrasound images. On the basis of ultrasound findings, the lesion was diagnosed as an intracranial tumor, but fetal MRI findings led to the suspicion of RICH of the fetal skull. Finally, the patient was followed up until 1 year after birth, by which time the lesion had completely disappeared. Conclusions: Careful evaluation of prenatal ultrasound is necessary to ensure detection of any mass adjacent to the skull, and the ultrasonography technician should carefully examine the features of any suspected mass to diagnose it correctly to avoid affecting the treatment strategy. [ABSTRACT FROM AUTHOR]

Background: Noninvasive prenatal testing (NIPT) is widely used to screen for fetal aneuploidies. However, there are few reports of using NIPT for screening chromosomal microduplications and microdeletions. This study aimed to investigate the application efficiency of NIPT for detecting chromosomal microduplications. Methods: Four cases of copy number gains on the long arm of chromosome 17 (17q12) were detected using NIPT and further confirmed using copy number variation (CNV) analysis based on chromosome microarray analysis (CMA). Results: The prenatal diagnosis CMA results of the three cases showed that the microduplications in 17q12 (ranging from 1.5 to 1.9 Mb) were consistent with the NIPT results. The karyotypic analysis excluded other possible unbalanced rearrangements. The positive predictive value of NIPT for detecting chromosomal 17q12 microduplication was 75.0%. Conclusions: NIPT has a good screening effect on 17q12 syndrome through prenatal diagnosis, therefore it could be considered for screening fetal CNV during the second trimester. With the clinical application of NIPT, invasive prenatal diagnoses could be effectively reduced while also improving the detection rate of fetal CNV. [ABSTRACT FROM AUTHOR]

Deep learning algorithms have demonstrated remarkable potential in clinical diagnostics, particularly in the field of medical imaging. In this study, we investigated the application of deep learning models in early detection of fetal kidney anomalies. To provide an enhanced interpretation of those models' predictions, we proposed an adapted two-class representation and developed a multi-class model interpretation approach for problems with more than two labels and variable hierarchical grouping of labels. Additionally, we employed the explainable AI (XAI) visualization tools Grad-CAM and HiResCAM, to gain insights into model predictions and identify reasons for misclassifications. The study dataset consisted of 969 ultrasound images from unique patients; 646 control images and 323 cases of kidney anomalies, including 259 cases of unilateral urinary tract dilation and 64 cases of unilateral multicystic dysplastic kidney. The best performing model achieved a cross-validated area under the ROC curve of 91.28% ± 0.52%, with an overall accuracy of 84.03% ± 0.76%, sensitivity of 77.39% ± 1.99%, and specificity of 87.35% ± 1.28%. Our findings emphasize the potential of deep learning models in predicting kidney anomalies from limited prenatal ultrasound imagery. The proposed adaptations in model representation and interpretation represent a novel solution to multi-class prediction problems. [ABSTRACT FROM AUTHOR]

18p deletion syndrome constitutes one of the most frequent autosomal terminal deletion syndromes, affecting one in 50,000 live births. The syndrome has un-specific clinical features which vary significantly between patients and may overlap with other genetic conditions. Its prenatal description is extremely rare as the fetal phenotype is often not present during pregnancy. Trisomy 8p Syndrome is characterized by heterogenous phenotype, with the most frequent components to be cardiac malformation, developmental and intellectual delay. Its prenatal diagnosis is very rare due to the unspecific sonographic features of the affected fetuses. We present a very rare case of a fetus with multiple anomalies diagnosed during the second trimester whose genomic analysis revealed a 18p Deletion and 8p trisomy Syndrome. This is the first case where this combination of DNA mutations has been described prenatally and the second case in general. The presentation of this case, as well as the detailed review of all described cases, aim to expand the existing knowledge regarding this rare condition facilitating its diagnosis in the future. [ABSTRACT FROM AUTHOR]

This study had two main objectives. Firstly, we conducted a thorough literature review on the prenatal diagnosis of abdominal congenital arteriovenous fistulas (CAVFs) involving the abdominal aorta and hepatic arteries. Secondly, we aimed to provide detailed descriptions of eight additional cases diagnosed at our medical center and assess the outcome of this anomaly for informed counseling. We conducted a systematic search of online databases using specific keywords like "outcome", "ultrasound", "intrahepatic fistulae", and "fetal venous anomalies", focusing on studies published between 1998 and 2023. We selected 10 relevant articles and analyzed 13 cases. Additionally, we conducted a five-year prospective study in two referral centers, identifying eight CAVF cases with an incidence rate of 0.16%. Among the 21 cases evaluated, 11 resulted in live births, all of which received treatment. However, four cases (36.3%) had poor postnatal outcomes and neonatal demise due to heart failure. Prenatal signs of poor fetal hemodynamics, including cardiomegaly or hydrops, were observed in 52.3% of cases, regardless of outcome. Our findings highlight the rarity of this vascular malformation and emphasize the importance of effective treatment to avoid unfavorable outcomes. The long-term effectiveness of prenatal treatment or postnatal embolization remains uncertain, with liver transplantation being considered the most reliable treatment option. [ABSTRACT FROM AUTHOR]

Large-scale copy number variants (CNVs) are structural alterations in the genome that involve the duplication or deletion of DNA segments, contributing to genetic diversity and playing a crucial role in the evolution and development of various diseases and disorders, as they can lead to the dosage imbalance of one or more genes. Massively parallel sequencing (MPS) has revolutionized the field of genetic analysis and contributed significantly to routine clinical diagnosis and screening. It offers a precise method for detecting CNVs with exceptional accuracy. In this context, a non-invasive prenatal test (NIPT) based on the sequencing of cell-free DNA (cfDNA) from pregnant women's plasma using a low-coverage whole genome MPS (WGS) approach represents a valuable source for population studies. Here, we analyzed genomic data of 12,732 pregnant women from the Slovak (9,230), Czech (1,583), and Hungarian (1,919) populations. We identified 5,062 CNVs ranging from 200 kbp and described their basic characteristics and differences between the subject populations. Our results suggest that re-analysis of sequencing data from routine WGS assays has the potential to obtain large-scale CNV population frequencies, which are not well known and may provide valuable information to support the classification and interpretation of this type of genetic variation. Furthermore, this could contribute to expanding knowledge about the central European genome without investing in additional laboratory work, as NIPTs are a relatively widely used screening method. [ABSTRACT FROM AUTHOR]

Background: Maldevelopment of the fetal bowel can result in the rare condition of intestinal atresia, which results in congenital bowel obstruction. This report describes a case of prenatal diagnosis of fetal ileal atresia at 22 weeks' gestation. Case Report: Here, we present a 24-year old woman who was 22 weeks into her first pregnancy when she underwent routine fetal ultrasound. She was diagnosed with gestational diabetes mellitus. Her body mass index was normal and she had normal weight gain. The ultrasonographic examination performed revealed a hyperechoic bowel and a small dilatation of the bowel. The couple was counselled for possible intestinal atresia and its postnatal implications. At 33 weeks of gestation, polyhydramnios appeared, and the intestinal distension was much more pronounced, with hyperechoic debris in the intestinal lumen (succus-entericus). After birth, surgery was performed and we concluded the patient had type II atresia, which was surgically treated. Conclusions: This report has highlighted the importance of antenatal ultrasound in detecting fetal abnormalities, and has shown that rare conditions such as intestinal atresia can be accurately diagnosed and successfully managed. Surgical correction, if implemented promptly after stabilizing the general condition, can have a relatively good prognosis. Coexisting fetal ileal atresia and gestational diabetes mellitus are rare occurrences, which can make each condition even more difficult to treat. [ABSTRACT FROM AUTHOR]

Background: Accurate prenatal diagnosis of cleft lip and palate is essential to discuss severity prediction, perform appropriate parental counseling, and, at last, establish long-term treatment planning. The aim of this systematic review was to analyze the accuracy of various imaging techniques for the prenatal diagnosis of cleft lip and palate, assess the pregnancy phase for orofacial clefts diagnosis, and study the different cleft types in terms of diagnostic methods, timing, and predictability. Methods: A search of the PubMed, EMBASE, Scopus, and Web of Science databases was conducted to identify potentially relevant studies published until January 2024. The quality of the selected articles was assessed using the Newcastle–Ottawa scale for methodological quality assessment of cohort studies and the QUADAS-2 scale for diagnostic test studies. Results: A total of 18 studies met the eligibility criteria and were included in the review. The findings of this review indicate that the majority of studies showed improved diagnostic accuracy when supplementary techniques, such as 3D ultrasound or magnetic resonance imaging, were added to 2D ultrasound. Conclusions: The implementation of magnetic resonance imaging as a standard procedure could significantly improve the precision of diagnosing cleft lip and palate. Therefore, the diagnostic technique used will play a crucial role in the accuracy of the diagnosis. [ABSTRACT FROM AUTHOR]

Background: Contemporary diagnostic methods aimed at assessing neonatal outcomes predominantly rely on the medical history of pregnant women. Ideally, universal biomarkers indicating an increased risk of delivering infants in poor clinical condition, with a heightened likelihood of requiring hospitalization in a Neonatal Intensive Care Unit (NICU), would be beneficial for appropriately stratifying pregnant women into a high-risk category. Our study evaluated whether biochemical and ultrasonographical markers universally used in first-trimester screenings for non-heritable chromosomal aberrations could serve this purpose. Methods: This study encompassed 1164 patients who underwent first-trimester screening, including patient history, ultrasound examinations, and biochemical tests for pregnancy-associated plasma protein-A (PAPP-A) and the free beta-HCG subunit (fbHCG), from January 2019 to December 2021. The research concentrated on the correlation between these prenatal test results and neonatal outcomes, particularly Apgar scores, umbilical blood pH levels, and the necessity for NICU admission. Results: In our cohort, neonates scoring lower than 8 on the Apgar scale at birth exhibited lower concentrations of PAPP-A in the first trimester, both in raw and normalized values (PAPP-A MoM 0.93 vs. 1.027, p = 0.032). We also observed a higher pulsatility index in the venous duct in the first trimester in full-term neonates born with <8 points on the Apgar scale. Additionally, newborns born with an umbilical blood pH < 7.2 had lower normalized first-trimester PAPP-A concentrations (0.69 vs. 1.01 MoM, p = 0.04). We also noted that neonates requiring NICU hospitalization post-delivery had lower first-trimester bHCG concentrations (0.93 MoM vs. 1.11 MoM, p = 0.03). However, none of the correlations in our study translated into a robust prognostic ability for predicting dichotomous outcomes. All areas under the curve achieved a value < 0.7. Conclusions: Low concentrations of PAPP-A and free bHCG subunit in the first trimester may be associated with poorer clinical and biochemical conditions in neonates post-delivery. However, the relationship is weak and has limited predictive capability. Further research evaluating these relationships is necessary for the appropriate stratification of pregnant women into high-risk categories for neonatological complications. [ABSTRACT FROM AUTHOR]

Objective: To determine the diagnostic accuracy of prenatal ultrasound in detecting coarctation of the aorta (CoA). Methods: An individual participant data meta‐analysis was performed to report on the strength of association and diagnostic accuracy of different ultrasound signs in detecting CoA prenatally. MEDLINE, EMBASE and CINAHL were searched for studies published between January 2000 and November 2021. Inclusion criteria were fetuses with suspected isolated CoA, defined as ventricular and/or great vessel disproportion with right dominance on ultrasound assessment. Individual participant‐level data were obtained by two leading teams. PRISMA‐IPD and PRISMA‐DTA guidelines were used for extracting data, and the QUADAS‐2 tool was used for assessing quality and applicability. The reference standard was CoA, defined as narrowing of the aortic arch, diagnosed after birth. The most commonly evaluated parameters on ultrasound, both in B‐mode and on Doppler, constituted the index test. Summary estimates of sensitivity, specificity, diagnostic odds ratio (DOR) and likelihood ratios were computed using the hierarchical summary receiver‐operating‐characteristics model. Results: The initial search yielded 72 studies, of which 25 met the inclusion criteria. Seventeen studies (640 fetuses) were included. On random‐effects logistic regression analysis, tricuspid valve/mitral valve diameter ratio > 1.4 and > 1.6, aortic isthmus/arterial duct diameter ratio < 0.7, hypoplastic aortic arch (all P < 0.001), aortic isthmus diameter Z‐score of < −2 in the sagittal (P = 0.003) and three‐vessel‐and‐trachea (P < 0.001) views, pulmonary artery/ascending aorta diameter ratio > 1.4 (P = 0.048) and bidirectional flow at the foramen ovale (P = 0.012) were independently associated with CoA. Redundant foramen ovale was inversely associated with CoA (P = 0.037). Regarding diagnostic accuracy, tricuspid valve/mitral valve diameter ratio > 1.4 had a sensitivity of 72.6% (95% CI, 48.2–88.3%), specificity of 65.4% (95% CI, 46.9–80.2%) and DOR of 5.02 (95% CI, 1.82–13.9). The sensitivity and specificity values were, respectively, 75.0% (95% CI, 61.1–86.0%) and 39.7% (95% CI, 27.0–53.4%) for pulmonary artery/ascending aorta diameter ratio > 1.4, 47.8% (95% CI, 14.6–83.0%) and 87.6% (95% CI, 27.3–99.3%) for aortic isthmus diameter Z‐score of < –2 in the sagittal view and 74.1% (95% CI, 58.0–85.6%) and 62.0% (95% CI, 41.6–78.9%) for aortic isthmus diameter Z‐score of < –2 in the three‐vessel‐and‐trachea view. Hypoplastic aortic arch had a sensitivity of 70.0% (95% CI, 42.0–88.6%), specificity of 91.3% (95% CI, 78.6–96.8%) and DOR of 24.9 (95% CI, 6.18–100). The diagnostic yield of prenatal ultrasound in detecting CoA did not change significantly when considering multiple categorical parameters. Five of the 11 evaluated continuous parameters were independently associated with CoA (all P < 0.001) but all had low‐to‐moderate diagnostic yield. Conclusions: Several prenatal ultrasound parameters are associated with an increased risk for postnatal CoA. However, diagnostic accuracy is only moderate, even when combinations of parameters are considered. © 2024 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Objective: To compare the performance of two‐dimensional ultrasound (2D‐US), three‐dimensional ultrasound (3D‐US) and magnetic resonance imaging (MRI) at 36 weeks' gestation in predicting the delivery of a large‐for‐gestational‐age (LGA) neonate, defined as birth weight ≥ 95th percentile, in patients at high and low risk for macrosomia. Methods: This was a secondary analysis of a prospective observational study conducted between January 2017 and February 2019. Women with a singleton pregnancy at 36 weeks' gestation underwent 2D‐US, 3D‐US and MRI within 15 min for estimation of fetal weight. Weight estimations and birth weight were plotted on a growth curve to obtain percentiles for comparison. Participants were considered high risk if they had at least one of the following risk factors: diabetes mellitus, estimated fetal weight ≥ 90th percentile at the routine third‐trimester ultrasound examination, obesity (prepregnancy body mass index ≥ 30 kg/m2) or excessive weight gain during pregnancy. The outcome was the diagnostic performance of each modality in the prediction of birth weight ≥ 95th percentile, expressed as the area under the receiver‐operating‐characteristics curve (AUC), sensitivity, specificity and positive and negative predictive values. Results: A total of 965 women were included, of whom 533 (55.23%) were high risk and 432 (44.77%) were low risk. In the low‐risk group, the AUCs for birth weight ≥ 95th percentile were 0.982 for MRI, 0.964 for 2D‐US and 0.962 for 3D‐US; pairwise comparisons were non‐significant. In the high‐risk group, the AUCs were 0.959 for MRI, 0.909 for 2D‐US and 0.894 for 3D‐US. A statistically significant difference was noted between MRI and both 2D‐US (P = 0.002) and 3D‐US (P = 0.002), but not between 2D‐US and 3D‐US (P = 0.503). In the high‐risk group, MRI had the highest sensitivity (65.79%) compared with 2D‐US (36.84%, P = 0.002) and 3D‐US (21.05%, P < 0.001), whereas 3D‐US had the highest specificity (98.99%) compared with 2D‐US (96.77%, P = 0.005) and MRI (96.97%, P = 0.004). Conclusions: At 36 weeks' gestation, MRI has better performance compared with 2D‐US and 3D‐US in predicting birth weight ≥ 95th percentile in patients at high risk for macrosomia, whereas the performance of 2D‐US and 3D‐US is comparable. For low‐risk patients, the three modalities perform similarly. © 2023 International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Background: Despite recent advances in prenatal genetic diagnosis, medical geneticists still face considerable difficulty in interpreting the clinical outcome of copy‐number‐variant duplications and defining the mechanisms underlying the formation of certain chromosomal rearrangements. Optical genome mapping (OGM) is an emerging cytogenomic tool with proved ability to identify the full spectrum of cytogenetic aberrations. Methods: Here, we report on the use of OGM in a prenatal diagnosis setting. Detailed breakpoint mapping was used to determine the relative orientations of triplicated and duplicated segments in two unrelated foetuses harbouring chromosomal aberrations: a de novo 15q23q24.2 triplication and a paternally inherited 13q14.2 duplication that overlapped partially with the RB1 gene. Results: OGM enabled us to suggest a plausible mechanism for the triplication and confirmed that the RB1 duplication was direct oriented and in tandem. This enabled us to predict the pathogenic consequences, refine the prognosis and adapt the follow‐up and familial screening appropriately. Conclusion: Along with an increase in diagnostic rates, OGM can rapidly highlight genotype–phenotype correlations, improve genetic counselling and significantly influence prenatal management. [ABSTRACT FROM AUTHOR]

Background: To explore the clinical application value of pre‐conception expanded carrier screening (PECS) in the Chinese Han ethnicity population of childbearing age. Methods: The results of genetic testing of infertile parents who underwent PECS in the Reproductive Medicine Center of the Second Affiliated Hospital of Zhengzhou University, China, from September 2019 to December 2021, were retrospectively analyzed. The carrier rate of single gene disease, the detection rate of high‐risk parents, and the clinical outcome of high‐risk parents were statistically analyzed. Results: A total of 1372 Chinese Han ethnicity patients underwent PECS, among which 458 patients underwent the extended 108‐gene test, their overall carrier rate was 31.7%, and the detection rate of high‐risk parents was 0.3%. The highest carrier rates were SLC22A (2.4%), ATP7B (2.4%), MMACHC (2.2%), PAH (1.8%), GALC (1.8%), MLC1 (1.3%), UNC13D (1.1%), CAPN3 (1.1%), and PKHD1 (1.1%). There were 488 women with fragile X syndrome—FMR1 gene detection, and 6 patients (1.2%) had FMR1 gene mutation. A total of 426 patients were screened for spinal muscular atrophy—SMN1, and the carrier rate was 3.5%, and the detection rate of parents' co‐carrier was 0.5%. Conclusion: Monogenic recessive hereditary diseases had a high carrier rate in the population. Pre‐pregnancy screening could provide good prenatal and postnatal care guidance for patients and preimplantation genetic testing for monogenic/single gene disorders (PGT‐M) and prenatal diagnosis could provide more precise reproductive choices for high‐risk parents. [ABSTRACT FROM AUTHOR]

Cervical and oropharyngeal teratomas are rare forms of congenital tumors. External compression of the respiratory tract is the major complication. Due to their high mortality, it is very important to establish prenatal diagnosis using ultrasound and fetal magnetic resonance imaging to plan airway management at birth and its eventual resection. If respiratory obstruction due to the tumor is suspected, an EXIT procedure is performed. We describe a case of a cervical teratoma and another of an oropharyngeal teratoma, along with their imaging studio and a literature review. [ABSTRACT FROM AUTHOR]

Objective: Harlequin ichthyosis (MIM 242500) is a rare autosomal recessive skin disorder caused by a congenital disorder of epidermal keratinization and associated with a mutation in the ABCA12 gene of chromosome 2q35. We report a case of a fetus at 25 weeks of gestation with harlequin ichthyosis and a deletion of chromosome 15q11.2-q12. Case(s): The results of an ultrasound examination at 13 weeks 2 days and 18 weeks of pregnancy showed no pathology. Two previous male children were presumably born with harlequin ichthyosis (genetic diagnosis was not performed due to unavailability at that time) and died on the first day of life. Analysis of amniotic fluid using SNP - array technology at 23 weeks revealed a deletion of 15q11.2-q12. Subsequent ultrasound examination at 25 weeks of pregnancy showed signs of harlequin ichthyosis, including an abnormal flat facial profile, a constantly open large mouth, and a large number of inclusions in the amniotic fluid. Considering the family history, a diagnosis of harlequin ichthyosis was made, leading the family to decide to terminate the pregnancy. A male child was born, weighing 800 g, with a typical harlequin ichthyosis phenotype, and died 2 hours after birth. Conclusion: In case of a suspicion of this disease in a family, prenatal diagnosis of harlequin ichthyosis can be carried out by prenatal chromosomal microarray analysis using tissue obtained from chorionic villus sampling, amniocentesis or cordocentesis in the early terms of pregnancy. Ultrasound signs of the disease typically manifest after 24 weeks of pregnancy. [ABSTRACT FROM AUTHOR]

Key Clinical Message: An encephalocele is a congenital malformation characterized by protrusion of the intracranial contents through a cranial defect. We report that a fetus of a pregnant mother who had two consecutive pregnancies with ultrasound‐detected encephalocele carried compound heterozygous variants in B3GALNT2 NM_152490.5:c.[1423C > T (p.Gln475Ter)]; [261‐2A > G] of maternal and paternal origins, respectively, as confirmed by exome sequencing followed by Sanger sequencing validation. The present case implies that mutations in B3GALNT2, a well‐known dystroglycanopathy causative gene, may result in a phenotype of neural tube defect, providing new insights into the clinical spectrum of B3GALNT2‐related disorders. Our study may contribute to prenatal screening/diagnosis and genetic counseling of congenital brain malformations. [ABSTRACT FROM AUTHOR]

Background: The objective of our study to analyze the data of the prenatal diagnosis of congenital malformations at the maternity and reproductive health hospital "Les Orangers" in Rabat and to identify the main anomalies detected, their percentage and their short-term outcome. Methods: This is a cross-sectional study conducted at the maternity and reproductive health hospital "Les Orangers" in Rabat, Morocco. The data was collected and reported on pre-established sheets and on the register of malformations of the hospital. Results: A total of 245 cases of congenital malformations comprising 470 types of congenital malformations were recorded out of a total of 43,923 births over a period of five and a half years, giving a prevalence of 5.58 per thousand. Prenatal diagnosis was made in a third of cases (33%), essentially during the 2nd-3rd trimester of pregnancy. The anomalies revealed by this antenatal diagnosis were dominated by urinary malformations in 70% and central nervous system anomalies in 67%, followed by other types of congenital anomalies in less than 40% of cases, while genetic problems were detected in 2.5%; this rate is underestimated since chromosomal abnormalities sometimes appear as syndromes, so that in some diseases, genetic changes are not separated from other abnormalities, and since more than half (50.7%) of cases presenting polymalformative syndromes not survived 77% of cases i.e. (48.5% of deaths and 28.5% of FDIU) and an etiological study was not carried out. Conclusion: Antenatal ultrasound allows early detection and monitoring of the evolution of congenital malformations, and thus the possibility of ensuring early and adequate management of these anomalies from birth. In our context, it is necessary to develop a prenatal screening program for congenital anomalies and a network of reference centers for the management of these anomalies in order to improve their prognosis. [ABSTRACT FROM AUTHOR]

This study represents our second investigation into NIPT, involving a more extensive patient cohort with a specific emphasis on the high-risk group. The high-risk group was subsequently divided into two further groups to compare confirmed cases versus unconfirmed via direct methods. The methodology encompassed the analysis of 1400 consecutive cases from a single genetic center in western Romania, where NIPT was used to assess the risk of specific fetal chromosomal abnormalities. All high-risk cases underwent validation through direct analysis of fetal cells obtained via invasive methods, including chorionic villus sampling and amniocentesis. The confirmation process utilized QF-PCR, karyotyping, and SNP-Array methods customized to each case. Results: A high risk of aneuploidy at NIPT was identified in 36 out of 1400 (2.57%) cases and confirmed in 28 cases. The study also detected an increased risk for copy number variations (CNVs) in 1% of cases, confirmed in two instances involving one large microdeletion and one large microduplication. Trisomy 21 was the exclusive anomaly where NIPT confirmed all cases with identified risk. High-risk NIPT results which were not validated by invasive methods, were classified as false positives; parents in these cases determined to continue the pregnancy. In conclusion, NIPT can serve as a screening method for all pregnancies; however, in high-risk cases, an invasive confirmation test is strongly recommended. [ABSTRACT FROM AUTHOR]

Background: Prenatal diagnosis of Berry syndrome, a rare combination of cardiac anomalies including aortopulmonary window (APW), aortic origin of the right pulmonary artery (RPA), interrupted aortic arch (IAA), hypoplastic aortic arch, or coarctation of the aorta (COA), poses a significant challenge. Due to the rarity of the disease, and the limited case reports available to features the complex malformation of Berry syndrome postpartum, this article introduces an innovative approach to visually showcase this unusual disease. The proposed method provides a comprehensive display of the structural deformities, offering valuable insights for clinical practitioners seeking to comprehend this condition. Case presentation: In this report, we present a case where fetal echocardiography aided in diagnosing Berry syndrome, which was later confirmed through postpartum cardiovascular casting. Our experience highlights the importance of using the three-vessel view to diagnose APW and aortic origin of the right pulmonary artery. Additionally, obtaining true cross-sectional and sagittal views by continuously scanning from the three-vessel-trachea view to the long-axis view of the aortic arch is necessary to image IAA or coarctation of the aortic arch. Conclusions: Early and accurate prenatal diagnosis of Berry syndrome is feasible and our cardiovascular cast can perfectly display the microvascular morphology of the fetal heart, which may have great application prospects for postpartum diagnosis and teaching of complex cardiac abnormalities. [ABSTRACT FROM AUTHOR]

Background: Single umbilical artery (SUA) is strongly associated with foetal structural abnormalities; however, the exact pattern of this association has not been described. We aimed to investigate the occurrence of malformations in singleton pregnancies with SUA in China and to study the association between the absent side of the umbilical artery and foetal malformations. Methods: This was a retrospective study of singleton pregnancies for which routine first-trimester anatomical screening was performed at 11+ 0-13+ 6 gestational weeks and, if the pregnancy continued, a second-trimester scan was performed at 20+ 0-24+ 0 weeks. Data were extracted from records at the referral centre, the Obstetrics and Gynecology Hospital of Fudan University, between January 2011 and April 2019 (n = 47,894). Using logistic regression, the odds ratios (OR) with 95% confidence intervals (CIs) were calculated for malformations associated with SUA. Results: The incidence of SUA in our study was 2.0% (970/47,894). Of all foetuses with SUA, 387 (39.9%) had structural malformations. The malformation type varied, with cardiovascular complications being the most common. A robust association was observed between SUA and oesophageal stenosis or atresia (OR: 25.33), followed by cardiovascular (OR: 9.98–24.02), scoliosis (OR: 18.62), genitourinary (OR: 2.45–15.66), and brain malformations (OR: 4.73–9.12). The absence of the left umbilical artery (n = 445, 45.9%) was consistent with that of the right umbilical artery (n = 431, 44.4%). Furthermore, a significantly higher rate of an absent right than the left umbilical artery (p<0.01) was observed in SUA with foetal abnormalities than in SUA with no malformations. Conclusions: Overall, we observed a higher risk of various specific malformations in foetuses with SUA, and a strong association between SUA and oesophageal stenosis or atresia. The absence of the right umbilical artery was most common in foetuses with SUA and structural malformations. This study provides a reference for ultrasonographers in conducting foetal structural screening for pregnant women with SUA. [ABSTRACT FROM AUTHOR]

Background: Neural Tube Defects (NTDs) are congenital malformations of the central nervous system resulting from the incomplete closure of the neural tube during early embryonic development. Neuroinflammation refers to the inflammatory response in the nervous system, typically resulting from damage to neural tissue. Immune-related processes have been identified in NTDs, however, the detailed relationship and underlying mechanisms between neuroinflammation and NTDs remain largely unclear. In this study, we utilized integrated multi-omics analysis to explore the role of neuroinflammation in NTDs and identify potential prenatal diagnostic markers using a murine model. Methods: Nine public datasets from Gene Expression Omnibus (GEO) and ArrayExpress were mined using integrated multi-omics analysis to characterize the molecular landscape associated with neuroinflammation in NTDs. Special attention was given to the involvement of macrophages in neuroinflammation within amniotic fluid, as well as the dynamics of macrophage polarization and their interactions with neural cells at single-cell resolution. We also used qPCR assay to validate the key TFs and candidate prenatal diagnostic genes identified through the integrated analysis in a retinoic acid-induced NTDs mouse model. Results: Our analysis indicated that neuroinflammation is a critical pathological feature of NTDs, regulated both transcriptionally and epigenetically within central nervous system tissues. Key alterations in gene expression and pathways highlighted the crucial role of STATs molecules in the JAK-STAT signaling pathway in regulating NTDs-associated neuroinflammation. Furthermore, single-cell resolution analysis revealed significant polarization of macrophages and their interaction with neural cells in amniotic fluid, underscoring their central role in mediating neuroinflammation associated with NTDs. Finally, we identified a set of six potential prenatal diagnostic genes, including FABP7, CRMP1, SCG3, SLC16A10, RNASE6 and RNASE1, which were subsequently validated in a murine NTDs model, indicating their promise as prospective markers for prenatal diagnosis of NTDs. Conclusions: Our study emphasizes the pivotal role of neuroinflammation in the progression of NTDs and underlines the potential of specific inflammatory and neural markers as novel prenatal diagnostic tools. These findings provide important clues for further understanding the underlying mechanisms between neuroinflammation and NTDs, and offer valuable insights for the future development of prenatal diagnostics. [ABSTRACT FROM AUTHOR]