Prenatal Diagnosis Research Articles

Genetic analysis of a fetus with with 45,X/46,X,idic(Y)(q11.2) mosaicism

To explore the genetic characteristics of a fetus with sex chromosome abnormality indicated by non-invasive prenatal testing (NIPT) at 25+ gestational weeks. A pregnant woman who was admitted to the Taizhou Hospital for abnormal NIPT result on January 6, 2023 was selected as the study subject. Relevant clinical data was collected. The fetus was subjected to chromosomal karyotyping analysis, copy number variation sequencing (CNV-seq), fluorescence in situ hybridization (FISH), and multiplex PCR assays. NIPT had suggested monosomy of X chromosome. The fetus was found to have a chromosomal karyotype of 45,X[59]/46,X,del(Y)(q11.2)[17] at 30+ weeks of gestational age. CNV-seq suggested the presence a 7.98 Mb deletion at Yq11.222q12 and a mosaicism 16.92 Mb deletion. FISH suggested that the fetus harbored two SRY genes and a mosaicism sex chromosomal abnormality, and multiplex PCR revealed that its AZF b+c region was completely deleted. C-banded karyotyping showed darkly stained dense mitotic granules at both ends of the Y chromosome. The fetus was ultimately determined as a 45,X/46,X,idic(Y)(q11.2) mosaicism. Following elected abortion, testing of the fetal tissue confirmed the presence of 45,X/46,XY mosaicism, and CNV-seq result of the placental tissue was compatible with that of NIPT. CNV-seq analysis of the couple revealed no obvious abnormality. With combined NIPT, karyotyping, CNV-seq, FISH and multiplex PCR assays, the fetus was diagnosed as a 45,X/46,X,idic(Y)(q11.2) mosaicism with deletion of the AZF b+c region. Above finding has enabled prenatal diagnosis for the fetus.

Prenatal diagnosis of a fetus with Rubinstein-Taybi syndrome

To explore the clinical characteristics and variant of CREBBP gene in a fetus with Rubinstein-Taybi syndrome (RSTS). A fetus with RSTS diagnosed at the Third Affiliated Hospital of Zhengzhou University in August 2022 was selected as the study subject. Clinical data, amniotic fluid sample of the fetus and peripheral blood samples of its parents were collected for whole exome sequencing (WES). Candidate variant was verified by Sanger sequencing. Foot malformation, cerebellar vermis agenesis, brain agenesis, polysyndactyly of the big toes and other phenotypes were found by prenatal ultrasound. WES revealed that the fetus has harbored a heterozygous c.4684G>T (p.E1562*) variant in exon 28 of the CREBBP gene (NM_004380.3), which was de novo in origin. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was predicted to be pathogenic (PVS1+PS2_Moderate+PM2_Supporting). After genetic counseling, the couple had opted to terminate the pregnancy and refused autopsy of the fetus. The c.4684G>T (p.E1562*) variant of the CREBBP gene probably underlay the RSTS in this fetus. The newly discovered variant has enriched the mutational spectrum of the CREBBP gene and illustrated that WES is an efficient tool for the prenatal diagnosis of RSTS.

Whole exome sequencing analysis of 37 fetuses with cardiac abnormalities

To explore the genetic etiology of fetuses with congenital heart disease (CHD) through whole exome sequencing (WES). Thirty seven fetuses identified with CHD by prenatal ultrasonography but with negative results by chromosomal microarray analysis (CMA) at Jinhua Maternal and Child Health Care Hospital from January 2020 to June 2022 were selected as the study subjects, for whom WES was carried out. WES and Sanger sequencing had detected 6 pathogenic or likely pathogenic variants, and 6 variants with unknown clinical significance. The variants had involved 15 loci within 11 genes, in addition with one copy number variation. WES can increase the detection rate for genetic abnormalities among fetuses with CHD, which can facilitate the prenatal diagnosis, evaluation of prognosis and genetic counseling for the couples.

Cytogenetically Balanced Reciprocal Translocation Could Hide Molecular Genomic Unbalances: Implications for Foetal Phenotype Correlation.

When an increased nuchal translucency (>3.00 mm) is observed during the echographic examination of a foetus in the first trimester of pregnancy, an increased risk of chromosomopathy is considered, and the pregnant woman is offered the possibility of an invasive investigation. Here, we focused our attention on prenatal diagnosis issues in cases of foetuses with cytogenetically balanced reciprocal translocations. We report the finding of a cytogenetically balanced, de facto genomically unbalanced translocation that poses a challenge in a case of prenatal diagnosis, changing the risk of Down syndrome in a Zellweger syndromic spectrum risk (PEX3 deletion). At term, a healthy baby was born. This case teaches that prenatal diagnosis in cases of foetuses at increased risk of chromosomal abnormality imperatively requires molecular investigation in addition to a morphological karyotype.

The prevalence of low birth weight and its associated maternal factors among women of reproductive age who gave birth to live babies within five years preceding the survey in Tanzania: an analysis of data from the 2015-16 Tanzania Demographic and Health Survey and Malaria Indicators Survey

BackgroundInfant survival is an important factor in any community’s health. Low birth weight affects babies not only during their infancy but also has long-term consequences for their health as adults. Unfortunately, Sub-Saharan Africa as a region is still dealing with the burden of Low birth weight (LBW), and Tanzania as a part of this region is no exception. So this study aimed to determine the Magnitude of Low Birth Weight and Its Associated Maternal Factors among Women of Reproductive Age who gave birth to live babies.MethodsThe study used analytical cross-sectional study design to analyze secondary data from the Tanzania Demographic and Health Survey and Malaria Indicators Survey 2015–2016. A total of 4,644 women of reproductive age who gave birth to live babies within five years preceding the survey were included in the study. Both bivariate and multivariable logistics regression analyses were used to assess maternal factors associated with low birth weight.ResultsThe prevalence of LBW was 262(6.2%). After adjusting for confounders, the maternal factors associated with LBW were Age group of a pregnant woman [Less than 20 years (aOR = 1.907 CI = 1.134–3.205) in reference to those aged more than 34years], Number of ANC visits made [Inadequate visits (aOR = 1.612 CI = 1.266–2.05)], parity [para 2–4 (aOR = 0.609 CI = 0.453–0.818), para 5+ (aOR = 0.612 CI = 0.397–0.944)] and area of residence [Unguja (aOR = 1.981 CI = 1.367–2.87).ConclusionThe prevalence of low birth weight in Tanzania remains high. Women’s age, parity, number of Antenatal care visits (ANC), and area of residence were found to be maternal factors associated with LBW. Thus, early prenatal diagnosis of risk factors for low birth weight in high-risk pregnant women may help to reduce the LBW burden in Tanzania and its detrimental effects.

Clinical characteristics, laboratory features and genetic profile of hemoglobin E (HBB:c.79 G > A)/β (nucleotide -28 A > G) (HBB:c.-78 A > G) -thalassemia subjects identified from community- and hospital-recruited cohorts

Despite several existing laboratory-based studies of hemoglobin (Hb) E (HBB:c.79 G > A)/ β (nucleotide (NT) -28 A > G) (HBB:c.-78 A > G) -thalassemia, no reports have ever provided clinical severity information as well as dependency of blood transfusion. Previously, a comparative study of community- and hospital-recruited Hb E/β-thalassemia subjects was conducted in the lower northern Thailand between June 2020 and December 2021. A mobile medical team visited each community hospital on-site, collecting clinical severity parameters, and conducting Hb and DNA analyses. The control included Hb E/β-thalassemia patients undergoing transfusions. Subgroup study of adult Hb E/β (NT -28 A > G) -thalassemia subjects was subsequently conducted. Additional pediatric individuals were recruited from prenatal diagnosis databases. Twenty adult and nine pediatric subjects were enrolled; all were classified as having mild disease severity. Twenty-two individuals (75.9 %) were asymptomatic. Six adults (20.7 %) required blood transfusion. The mean Hb level of subjects without transfusion (23 [79.3 %]) was 10.77 ± 1.10 g/dL. Hb analysis revealed a distinct EFA pattern with low Hb F fraction. The positive impact of genetic modifiers could not be statistically demonstrated except rs7482144-XmnI. These findings could provide essential information for parents carrying fetuses with Hb E/β (NT -28 A > G) -thalassemia.

Clinical predictive value of pre-pregnancy tests for unexplained recurrent spontaneous abortion: a retrospective study.

Early prediction and intervention are crucial for the prognosis of unexplained recurrent spontaneous abortion (uRSA). The main purpose of this study is to establish a risk prediction model for uRSA based on routine pre-pregnancy tests, in order to provide clinical physicians with indications of whether the patients are at high risk. This was a retrospective study conducted at the Prenatal Diagnosis Center of Henan Provincial People's Hospital between January 2019 and December 2022. Twelve routine pre-pregnancy tests and four basic personal information characteristics were collected. Pre-pregnancy tests include thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), free thyroxine thyroid (FT4), thyroxine (TT4), total triiodothyronine (TT3), peroxidase antibody (TPO-Ab), thyroid globulin antibody (TG-Ab), 25-hydroxyvitamin D [25-(OH) D], ferritin (Ferr), Homocysteine (Hcy), vitamin B12 (VitB12), folic acid (FA). Basic personal information characteristics include age, body mass index (BMI), smoking history and drinking history. Logistic regression analysis was used to establish a risk prediction model, and receiver operating characteristic (ROC) curve and decision curve analysis (DCA) were employed to evaluate the performance of prediction model. A total of 140 patients in uRSA group and 152 women in the control group were randomly split into a training set (n = 186) and a testing set (n = 106). Chi-square test results for each single characteristic indicated that, FT3 (p = 0.018), FT4 (p = 0.048), 25-(OH) D (p = 0.013) and FA (p = 0.044) were closely related to RSA. TG-Ab and TPO-Ab were also important characteristics according to clinical experience, so we established a risk prediction model for RSA based on the above six characteristics using logistic regression analysis. The prediction accuracy of the model on the testing set was 74.53%, and the area under ROC curve was 0.710. DCA curve indicated that the model had good clinical value. Pre-pregnancy tests such as FT3, FT4, TG-Ab, 25-(OH)D and FA were closely related to uRSA. This study successfully established a risk prediction model for RSA based on routine pre-pregnancy tests.

"A Retrospective Evaluation of the Impact of Prenatal Diagnosis of Facial Clefts. Does Prenatal Diagnosis Matter?"

With the advent of improved prenatal detection, some patients with facial clefting are diagnosed prenatally while others are diagnosed postnatally. There is limited data regarding the utility of prenatal diagnosis and how this affects care of patients with facial clefts. A retrospective chart review was performed. Children with incomplete demographic data and those with syndromic conditions were excluded. The data were analyzed via Fisher's exact tests and Kruskal-Wallis tests (p < 0.05). 106 patients met inclusion criteria. Facial clefting was diagnosed prenatally at different frequencies depending on type of facial cleft- patients with cleft palate alone were less likely to be identified prenatally (p < 0.0001). Patients diagnosed prenatally were seen by craniofacial specialists at an earlier age compared to those diagnosed after birth (0.27 months vs 0.7 months, p < 0.001). Similarly, those with prenatal diagnosis underwent surgery at a younger age compared to those who were diagnosed postnatally (median: 3.6 months vs 10.67 months, p < 0.001) and experienced shorter lag time (median: 3.4 months vs 8.4 months, p = 0.027) from consultation to surgery. Importantly, prenatal diagnosis resulted in pre-surgical therapy more often than in children diagnosed postnatally (86% vs 22.2%, p < 0.001). Our data suggests that patients with prenatal diagnosis of facial clefts were more likely to undergo pre-surgical therapy, presented to a craniofacial specialist at an earlier age, underwent surgery at an earlier age, and experienced less lag time between initial visit and surgery. More study is warranted to improve protocols for prenatal diagnoses to improve surgical outcomes.

Hepatitis B clinical care provision in pregnancy: A whole-of-population linkage study in Victoria, Australia.

Pregnancy is a key setting for engagement in chronic hepatitis B (CHB) care, due to the implications for transmission to the infant and antenatal diagnosis representing an opportunity for ongoing follow-up. This study aimed to identify the coverage and predictors of clinical care for women with CHB during and after pregnancy in a population-level cohort. Notified CHB cases in Victoria, Australia, were linked with hospitalizations, medical services, and prescribing data, covering the period 1991-2018. Women with an admission for a live birth were identified and services provided during pregnancy were assessed, including general practitioner (GP) or specialist visits, viral load and serology testing, and antiviral treatment. Viral load and serology testing coverage ware also assessed for the 2-year period following pregnancy. Demographic and clinical predictors of viral load testing during pregnancy were assessed. A total of 11015 birth events occurred for 6090 women with CHB. During pregnancy most had a GP consultation (91.6%); however, only 39.5% had viral load testing and 41.4% had a gastroenterology or infectious diseases specialist consultation. Viral load testing and serology testing in the 2years after pregnancy occurred in approximately half (47.9% and 52.2%, respectively) with increases over time. Viral load testing was more likely in those born overseas, those with more than one previous birth, and those living in Melbourne. Despite improvements over time, key gaps were identified in the provision of CHB clinical care during and after pregnancy, with implications for ongoing transmission and adverse outcomes.

A novel de novo synonymous variant in GREB1L impacts the mRNA splicing associated with aplasia of the urogenital system.

GREB1-like retinoic acid receptor coactivator (GREB1L) gene is associated with autosomal dominant renal hypodysplasia/aplasia 3 (RHDA3) and deafness, autosomal dominant 80 (DFNA80). Among the GREB1L variants reported, most of them are missense or frameshift, while no pathogenic synonymous variants have been recorded. Classical theory paid little attention to synonymous variants and classified it as nonpathogenic; however, recent studies suggest that the variants might be equally important. Here, we report a 7-year-old girl with new symptoms of clitoromegaly, uterovaginal, and ovarian agenesis as well as right kidney missing. A novel de novo GREB1L synonymous variant (NM_001142966: c.4731C>T, p.G1577=) was identified via whole exome sequencing. The variant was predicted to be disease-causing through in silico analysis and was classified as likely pathogenic. Minigene splicing assays confirmed a 6 bp deletion in mutant cDNA comparing with the wild type, leading to two amino acids lost in GREB1L protein. Secondary and tertiary structure modeling showed alterations in protein structure. Our finding reveals a novel GREB1L variant with a new phenotype of urogenital system and is the first to report a pathogenic synonymous variant in GREB1L which affects mRNA splicing, suggesting synonymous variants cannot be ignored in prenatal diagnosis and genetic counseling.

Clinical and genetic spectrum of Ataxia Telangiectasia Tunisian patients: Bioinformatic analysis unveil mechanisms of ATM variants pathogenicity

Ataxia Telangiectasia (AT) is a rare multisystemic neurodegenerative disease caused by biallelic mutations in the ATM gene. Few clinical studies on AT disease have been conducted in Tunisia, however, the mutational landscape is still undefined. Our aim is to determine the clinical and genetic spectrum of AT Tunisian patients and to explore the potential underlying mechanism of variant pathogenicity.Sanger sequencing was performed for nine AT patients. A comprehensive computational analysis was conducted to evaluate the possible pathogenic effect of ATM identified variants. Genetic screening of ATM gene has identified nine different variants from which six have not been previously reported. In silico analysis has predicted a pathogenic effect of identified mutations. This was corroborated by a structural bioinformatics study based on molecular modeling and docking for novel missense mutations. Our findings suggest a profound impact of identified mutations not only on the ATM protein stability, but also on the ATM-ligand interactions.Our study characterizes the mutational landscape of AT Tunisian patients which will allow to set up genetic counseling and prenatal diagnosis for families at risk and expand the spectrum of ATM variants worldwide. Furthermore, understanding the mechanism that underpin variant pathogenicity could provide further insights into disease pathogenesis.

Prenatal diagnosis and genetic counseling of a de novo 10q11.21q11.23 duplication associated with a normal phenotype.

Copy number variants (CNVs) are an important source of normal and pathogenic genome variations. Unbalanced chromosome abnormalities are either gains or losses of large genomic regions that do not or only minimally clinically affect the individual. Noninvasive prenatal testing (NIPT) is widely used in the screening of common fetal chromosome aneuploidy. One example is the duplication of 10q11.21q11.23, which includes the 10q11.2 region. This region contains a complex set of low-copy repeats that may lead to various genomic alterations through non-allelic homologous recombination. In this report, we present a case of a de novo 10q11.21q11.23 duplication with a normal phenotype. This case may be helpful for prenatal diagnosis and genetic counseling. A combination of NIPT, prenatal ultrasound, karyotype analysis, copy number variation sequencing, and genetic counseling is helpful for the prenatal diagnosis of CNVs.

Nonimmune Hydrops Fetalis.

Nonimmune hydrops fetalis (NIHF) poses a significant challenge in perinatal care due to its high mortality rates and diverse etiologies. This comprehensive review examines the pathophysiology, etiology, antenatal diagnosis and management, postnatal care, and outcomes of NIHF. NIHF arises from numerous underlying pathologies, including genetic disorders, cardiovascular causes, and fetal infections, with advances in diagnostic techniques improving identification rates. Management strategies include termination of pregnancy for severe cases and fetal therapy for selected treatable etiologies, and neonatal care involves assessing and treating fluid collections and identifying underlying causes. Prognosis depends on factors such as gestational age at diagnosis and the extent of resuscitation needed, with challenges remaining in improving outcomes for affected infants.

Malformative uropathies in children: epidemiological, clinical, therapeutic and evolutive aspects in an ivoirian hospital setting

Congenital anomalies of the kidney and the urinary tract are a major cause of chronic kidney failure in children. Prevalence in paediatrics varies according to studies. The data being rare in the ivorian context, this study aims to describe these defects' epidemiological, clinical, therapeutic and evolutionary aspects in children in a reference hospital setting. We performed a retrospective and descriptive study held in the Yopougon's Teaching Hospital Pediatric Nephrology Unit from December 1st 2008 to December 31st 2020. It involved 152 children aged 0 to 15 years, admitted to the unit, with a congenital anomaly of the kidney and the urinary tract diagnosed with radiology. Socio-demographic characteristics: congenital anomalies of the kidney and urinary tract's prevalence was 11%. The median age at admission was 36 months. The median age at diagnosis of malformative uropathy was 17.5 months. The sex ratio (M/F) was 2.3. Clinical characteristics: posterior urethra valves were the most common malformative uropathy (38%). Malformative uropathy was associated with other defects in 4% of cases. The antenatal diagnosis involved 24% of patients. The average gestational age of discovery was 32 weeks of amenorrhea. In the postnatal period, abdominal pain was the main circumstance for discovery (39%). Therapeutic characteristics: surgery was indicated in 58% of patients and performed in 64% of cases. Evolutionary characteristics: evolution was better in patients who had received surgical treatment (asymptomatic in 83% of cases, occurrence of urinary tract infection in 35% of cases and chronic renal failure in 23% of cases). 72% of the study population was lost. In Côte d'Ivoire, malformatives uropathies are late-discovered and are dominated by posterior urethra valves. Knowledge and management of these renal and urinary tract defects deserve to be improved through the development of antenatal diagnosis and training of practitioners in early recognition of clinical signs. The high rate of lost patients must be reduced by the implementation of an active patients' follow-up system.

Population-based prevalence of congenital defects in a routine sentinel site-based surveillance system in the Western Cape, South Africa.

Lack of data on the burden and scope of congenital disorders (CDs) in South Africa undermines resource allocation and limits the ability to detect signals from potentially teratogenic pregnancy exposures. We used routine electronic data in the Western Cape Pregnancy Exposure Registry (PER) to determine the overall and individual prevalence of CD identified on neonatal surface examination at birth in the Western Cape, South Africa, 2016-2022. CD was confirmed by record review. The contribution of late (≤24 months) and antenatal diagnoses was assessed. We compared demographic and obstetric characteristics between women with/without pregnancies affected by CD. Women with a viable pregnancy (>22 weeks gestation; birth weight ≥ 500 g) (n = 32,494) were included. Of 1106 potential CD identified, 56.1% were confirmed on folder review. When internal and minor CD were excluded the prevalence of major CD identified on surface examination at birth was 7.2/1000 births. When missed/late diagnoses on examination (16.8%) and ultrasound (6.8%) were included, the prevalence was 9.2/1000 births: 8.9/1000 livebirths and 21.5/1000 stillbirths. The PER did not detect 21.5% of major CD visible at birth. Older maternal age and diabetes mellitus were associated with an increased prevalence of CD. Women living with/without HIV (or the timing of antiretroviral therapy, before/after conception), hypertension or obesity did not significantly affect prevalence of CD. A surveillance system based on routine data successfully determined the prevalence of major CD identified on surface examination at birth at rates slightly higher than in equivalent studies. Overall rates, modeled at ~2%, are likely underestimated. Strengthening routine neonatal examination and clinical record-keeping could improve CD ascertainment.

Open distal ureteroureterostomy for non-refluxing duplicated collecting system in children: Multicentric study and mid-term outcomes

When indicated, ureteroceles and ectopic ureters in duplicated collecting systems can be managed via upper or lower urinary tract surgical approaches, or a combination of both. Open ureteroureterostomy (UU) has been described to address these conditions in the absence of lower pole (LP) vesicoureteral reflux (VUR). We report outcomes from multiple centers worldwide with mid-term follow-up. Our study consists of a retrospective review of records and imaging of children who underwent open distal UU via inguinal incision for duplicated collecting system without lower pole VUR in institutions from North America, South America, and the Caribbean. Descriptive statistics and univariate analysis were utilized. The records of 127 patients who underwent open distal UU for double collecting system between 2009 and 2022 were reviewed. Of those, 65% were female (n=82), with a mean age at operation of 18 months (range 3-180). Main presentation at surgery included prenatal hydronephrosis (64%, n=81), followed by febrile urinary tract infections (28%, n=36), and urinary incontinence or other (8%, n=10). The patients with antenatal or incidental diagnosis of hydronephrosis were classified as preoperative Society for Fetal Urology (SFU) grade 3 (n=64) and 4 (n=54) (96%). Those who were classified with SFU grade 0-2 (4%) had symptomatic clinical presentations including febrile urinary tract infections (UTIs) (n=3), urinary incontinence (n=3), and a 12-year-old patient with recurrent abdominal pain (n=1). Mean operative time from skin incision to skin closure was 86min (range 45-240). Mean hospital stay was estimated at 1.1 days (range 0.5-4). In our cohort of 127 patients, 3 (2%) developed Clavien-Dindo grade I (2 with ureteral stent displacement and 1 with a urine leak/managed conservatively), 6 (5%) with grade II (3 febrile and 3 non-febrile UTIs managed with oral antibiotics), and 2 (2%) with grade IIIb complications (urine leaks requiring surgical management), which were appropriately treated. None presented grade IV or V complications. A double J stent was used in 56 patients (44%), and a Penrose drain was left in 10 (8%). A total of 125 children (98%, n=125/127) showed sonographic improvement of hydronephrosis, or resolution of symptoms with stable ultrasound findings. Successful outcome was similar for both ureterocele and ectopic ureter subgroups: 49/49 patients with ureterocele showed 100% improvement, 76/78 children with ectopic ureter showed improvement in 97% of the cases. On univariate analysis, outcomes were similar regardless of the use of ureteral stents (p=0.11). Mean follow-up was 28.2 months (range 12-85). Open distal UU is a good alternative for the definitive surgical management of ectopic ureters and ureteroceles without LP VUR. This multicentric and mid-term follow-up study demonstrates that open distal UU offers high success rates, low morbidity, short operative times and hospital stays, and satisfactory aesthetic outcomes. Additionally, the surgery is performed extra-peritoneally and may not require the use of stents or drains, depending on surgeon preference. Further investigations are being conducted to determine the role of UU in the settings of double collecting systems associated with ipsilateral LP VUR.

Isolated posterior urethral valves (PUV) and anterior urethral valves (AUV) with and without concomitant PUV: Matched cohort study at a high-risk pediatric center

ObjectivesTo compare postnatal outcomes of AUV and PUV patients to evaluate for potential differences between these conditions, given that anterior urethral valves (AUV) with or without concomitant posterior urethral valves (PUV) is a rare congenital anomaly leading to lower urinary tract obstruction (LUTO). MethodsWe reviewed our LUTO database and included patients with AUV or concomitant AUV+PUV, managed at our institution between 2003 and 2023 matching them to comparable PUV cases. Assessed variables included prenatal diagnosis, gestational age (GA) at birth, initial management, kidney function, presence and degree of hydronephrosis (HN), and need for renal replacement therapy (RRT). ResultsThe AUV ± PUV group (AUV: n=11, concomitant PUV: n=2) and PUV group (n=26) had similar presenting ages and follow-up times (p>0.05). Only 15.4% of AUV cases presented prenatally compared to 72.0% of PUV cases (p=0.0016), leading to delayed postnatal management in AUV patients (p=0.0260). Findings at presentation included UTI, weak stream or a palpable penile mass. PUV patients demonstrated significantly higher creatinine levels at the initial visit and at last follow-up (p=0.0120 and p=0.0302) than the AUV ± PUV group, with only one patient requiring RRT (p>0.05). At the last follow-up, no patient in the AUV ± PUV group required clean intermittent catheterization compared to 37.5% in the PUV group (p=0.0331) which also demonstrated more patients with persistent HN (p=0.0039). ConclusionAUV with or without concomitant PUV is a rare finding that should be considered in patients presenting with weak stream, UTI, and penile swelling. Our data suggests potential differences in presentation and less severe postnatal outcomes in AUV compared to PUV patients.

Phenotypic and genotypic analysis of 11 fetal cases with Bardet-Biedl syndrome.

To present the prenatal sonographic features and genomic spectrum of pregnancies with fetal Bardet-Biedl syndrome (BBS). This was a retrospective study of 11 cases with BBS diagnosed by prenatal ultrasound and confirmed by genetic testing. Clinical and laboratory data were collected and reviewed for these cases, including maternal demographics, prenatal sonographic findings, molecular testing sequencing results, and pregnancy outcomes. All cases had unremarkable first-trimester ultrasound scans without reporting limb malformations. All had second-trimester abnormal ultrasounds: postaxial polydactyly in nine cases (9/11), renal abnormalities in seven (7/11), reduced amniotic fluid volume in two (2/11), central nervous system anomalies in two (2/11), and ascites in three (3/11). Ten fetuses presented with at least two-system anomalies, and one (Case 11) presented with only postaxial polydactyly. Variants were detected in five genes, including BBS2, ARL6/BBS3, BBS7, CEP290/BBS14 and IFT74/BBS22. Ten pregnancies were terminated in the second trimester, while one continued to term. Enlarged hyperechogenic kidneys and postaxial polydactyly are the two most common sonographic features of fetal BBS. Prenatal diagnosis of BBS can be done with ultrasound and genetic testing although the diagnosis may be made in the second trimester.

Inconsistencies between prenatal diagnostic and genetic testing laboratories on variant validation of rare monogenic diseases.

The advent of next-generation sequencing (NGS) has enhanced the diagnostic efficacy for monogenic diseases, while presenting challenges in achieving consistent diagnoses. We retrospectively analyzed the concordance rate and reasons for the inconsistency between the original diagnostic result from the genetic testing laboratory and the variant validation result from the prenatal diagnostic center. The validation procedure comprised three stages: validation of variant detection, reevaluation of variant classification, and assessment of recurrence risk, which involved verifying the mode of inheritance and parental carriage. In total, 17 (6%) of the 286 families affected by rare monogenic diseases showed different results during the variant validation procedure. These cases comprised four (23.5%) with variant detection errors, 12 (70.5%) with inconsistent interpretation, and one (6%) with non-Mendelian inheritance patterns. False-positive NGS results confirmed by Sanger sequencing were related to pseudogenes and GC-rich regions. The classification of the 17 variants was altered in the 12 cases owing to various factors. The case with an atypical inheritance pattern was originally considered autosomal recessiveinheritance, but was diagnosed as maternal uniparental disomy after additional genetic analysis. We underscored the significance of variant validation by prenatal diagnostic centers. Families affected by monogenic diseases with reproductive plans should be referred to prenatal genetic centers as early as possible to avoid different results that may postpone subsequent prenatal diagnosis.

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

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