Search Results (254)

IgG Fc binding protein (FcGBP) is a mucin-like protein that binds strongly to IgG and IgG–antigen complexes in intestinal mucus. FcGBP presence and its altered expression levels in meconium accumulating in the fetal intestine and amniotic fluid flowing in the intestine may provide new knowledge of the mechanisms responsible for the immune adaptation of the fetus to extrauterine life. FcGBP concentrations were measured by ELISA in the first-pass meconium and amniotic fluid samples collected from 120 healthy neonates delivered by either vaginal birth (n = 35) or cesarean section (n = 85) at 36 to 41 weeks gestation. The meconium FcGBP concentrations (405.78 ± 145.22 ng/g) decreased (r = −0.241, p = 0.007) over the course of 36 to 41 weeks gestation, but there were no significant changes (p > 0.05) in the amniotic fluid FcGBP (135.70 ± 35.83 ng/mL) in the same period. Both meconium and amniotic fluid FcGBP concentrations were higher (p < 0.05) in neonates delivered by cesarean section. Decreases in the meconium FcGBP concentrations correlated (r = −0.37, p = 0.027) with the gestational age in neonates delivered by vaginal birth but not in those delivered by cesarean section (p > 0.05). No association was found between the FcGBP concentrations in meconium and amniotic fluid and the birth weight (p > 0.05). With the development of the mucosal immune system in the fetal intestine over the course of the third trimester of gestation, the meconium FcGBP concentrations decrease. Increased FcGBP concentrations measured in the meconium and amniotic fluid of neonates delivered by cesarean section may possibly indicate altered intestinal mucosal function. Intrauterine growth is not associated with the intestinal mucosal barrier maturation involving FcGBP. Full article

This study applies Computational Fluid Dynamics (CFD) and mathematical modeling to examine uterine and umbilical arterial blood flow during pregnancy, providing a more detailed understanding of hemodynamic changes across gestation. Statistical analysis of Doppler ultrasound data from a large cohort of more than 200 pregnant women (in the second and third trimesters) reveals significant increases in the umbilical arterial peak systolic velocity ($PSV$) between the 22nd and 30th weeks, while uterine artery velocities remain relatively stable, suggesting adaptations in vascular resistance during pregnancy. By combining the Navier–Stokes equations with Doppler ultrasound-derived inlet velocity profiles, we quantify several key fluid dynamics parameters, including time-averaged wall shear stress ($TAWSS$), oscillatory shear index ($OSI$), relative residence time ($RRT$), Reynolds number ($Re$), and Dean number ($De$), evaluating laminar flow stability in the uterine artery and secondary flow patterns in the umbilical artery. Since blood exhibits shear-dependent viscosity and complex rheological behavior, modeling it as a non-Newtonian fluid is essential to accurately capture pulsatile flow dynamics and wall shear stresses in these vessels. Unlike conventional imaging techniques, CFD offers enhanced visualization of blood flow characteristics such as streamlines, velocity distributions, and instantaneous particle motion, providing insights that are not easily captured by Doppler ultrasound alone. Specifically, CFD reveals secondary flow patterns in the umbilical artery, which interact with the primary flow, a phenomenon that is challenging to observe with ultrasound. These findings refine existing hemodynamic models, provide population-specific reference values for clinical assessments, and improve our understanding of the relationship between umbilical arterial flow dynamics and fetal growth restriction, with important implications for maternal and fetal health monitoring. Full article

Background and Clinical Significance: Tuberous sclerosis complex (TSC) is an autosomal dominant disorder caused by pathogenic variants in TSC1 or TSC2. Cardiac rhabdomyoma is a common prenatal finding and can be associated with severe complications, including pericardial effusion. We administered prenatal sirolimus to mitigate pericardial effusion, which led to postnatal complications. Case Presentation: A 28-year-old pregnant woman with no significant family history underwent routine fetal ultrasound at 28.1 weeks of gestation, which identified a large right ventricular mass consistent with rhabdomyoma. Further fetal brain MRI revealed cortical-subcortical tubers and subependymal nodules, leading to a clinical diagnosis of TSC. At 30.4 weeks, oral sirolimus (3 mg/day) was started due to the significant pericardial effusion. The effusion remained after treatment, requiring pericardiocentesis at 33.6 weeks. The sirolimus dosage was raised to 6 mg/day at 35.6 weeks, reaching a plasma level of 3.76 ng/mL, but there was no discernible improvement because of the continued fluid accumulation. The mother did not experience any adverse side effects from the procedure. Genetic testing confirmed a pathogenic variant in TSC2 (c.1372C>T). After birth, the neonate received a single dose of sirolimus but subsequently developed necrotizing enterocolitis (NEC), highlighting the potential adverse effects and the need for cautious consideration of treatment options. Conclusions: This case illustrates the complexities of managing prenatal tuberous sclerosis complex (TSC). While sirolimus has been explored for fetal cardiac rhabdomyoma and associated complications, its effectiveness in resolving pericardial effusion remains uncertain. Additionally, the development of NEC postnatally raises concerns about the safety of mTOR inhibitors in this context. Further studies are necessary to assess the risks and benefits of this approach in fetal therapy. Full article

Background: Histologic chorioamnionitis (HCA) is a placental inflammatory condition characterized by neutrophilic infiltration of the fetal membranes, often occurring without overt clinical signs or symptoms. Risk factors include prolonged labor, premature rupture of membranes (PROM) exceeding 12 h, nulliparity, labor dystocia, and lower socioeconomic status. Although HCA frequently presents as a subclinical condition, its early diagnosis remains challenging. Nevertheless, HCA is associated with an increased risk of maternal and neonatal morbidity, including early-onset neonatal sepsis, cerebral palsy, and long-term neurodevelopmental impairment. We report the case of a 29-year-old primigravida at 40 + 0 weeks of gestation, admitted for decreased fetal movements. Discussion: Cardiotocographic (CTG) monitoring revealed a “zigzag pattern” in the absence of maternal fever, leukocytosis, or tachycardia. Due to the CTG findings suggestive of possible fetal compromise, in addition to reduced fetal movements, an emergency cesarean section was performed. Intraoperative findings included heavily meconium-stained amniotic fluid, then the examination of the placenta confirmed acute HCA with a maternal inflammatory response, without evidence of fetal inflammatory response. Conclusion: This case highlights the crucial role of CTG abnormalities, particularly the “zigzag pattern,” as an early marker of subclinical intrauterine inflammation. Early recognition of such patterns may facilitate timely intervention and improve perinatal outcomes in cases of histologic chorioamnionitis. Full article

Background: Hypotension following epidural labor analgesia (ELA) is its most common complication, affecting approximately 20% of patients and posing risks to both maternal and fetal health. As digital tools and predictive analytics increasingly shape perioperative and obstetric anesthesia practices, real-world implementation data are needed to guide their integration into clinical care. Current monitoring practices rely on intermittent non-invasive blood pressure (NIBP) measurements, which may delay recognition and treatment of hypotension. The Hypotension Prediction Index (HPI) algorithm uses continuous arterial waveform monitoring to predict hypotension for potentially earlier intervention. This clinical trial evaluated the feasibility, acceptability, and efficacy of continuous HPI-guided treatment in reducing time-to-treatment for ELA-associated hypotension and improving maternal hemodynamics. Methods: This was a prospective randomized controlled trial design involving healthy pregnant individuals receiving ELA. Participants were randomized into two groups: Group CM (conventional monitoring with NIBP) and Group HPI (continuous noninvasive blood pressure monitoring). In Group HPI, hypotension treatment was guided by HPI output; in Group CM, treatment was based on NIBP readings. Feasibility, appropriateness, and acceptability outcomes were assessed among subjects and their bedside nurse using the Acceptability of Intervention Measure (AIM), Intervention Appropriateness Measure (IAM), and Feasibility of Intervention Measure (FIM) instruments. The primary efficacy outcome was time-to-treatment of hypotension, defined as the duration between onset of hypotension and administration of a vasopressor or fluid therapy. This outcome was chosen to evaluate the clinical responsiveness enabled by HPI monitoring. Hypotension is defined as a mean arterial pressure (MAP) < 65 mmHg for more than 1 min in Group CM and an HPI threshold < 75 for more than 1 min in Group HPI. Secondary outcomes included total time in hypotension, vasopressor doses, and hemodynamic parameters. Results: There were 30 patients (Group HPI, n = 16; Group CM, n = 14) included in the final analysis. Subjects and clinicians alike rated the acceptability, appropriateness, and feasibility of the continuous monitoring device highly, with median scores ≥ 4 across all domains, indicating favorable perceptions of the intervention. The cumulative probability of time-to-treatment of hypotension was lower by 75 min after ELA initiation in Group HPI (65%) than Group CM (71%), although this difference was not statistically significant (log-rank p = 0.66). Mixed models indicated trends that Group HPI had higher cardiac output (β = 0.58, 95% confidence interval −0.18 to 1.34, p = 0.13) and lower systemic vascular resistance (β = −97.22, 95% confidence interval −200.84 to 6.40, p = 0.07) throughout the monitoring period. No differences were found in total vasopressor use or intravenous fluid administration. Conclusions: Continuous monitoring and precision hypotension treatment is feasible, appropriate, and acceptable to both patients and clinicians in a labor and delivery setting. These hypothesis-generating results support that HPI-guided treatment may be associated with hemodynamic trends that warrant further investigation to determine definitive efficacy in labor analgesia contexts. Full article

Cardiac disease remains a leading cause of maternal morbidity and mortality, particularly in developed countries where improved survival has increased the number of pregnant patients with congenital heart disease. The physiological changes of pregnancy, such as increased blood volume, cardiac output, and hypercoagulability, can exacerbate preexisting cardiac conditions, posing significant anesthetic challenges during cesarean delivery. This review outlines anesthetic strategies for parturients with structural or functional cardiac disease, emphasizing individualized, multidisciplinary care. We examine general and regional anesthesia approaches, intraoperative monitoring, and hemodynamic goals, including fluid balance, venous return optimization, and myocardial oxygen demand reduction. Preoperative risk stratification and coordination with cardiology and obstetric teams are essential. Future efforts should aim to standardize protocols and improve maternal–fetal outcomes through evidence-based anesthetic planning. Full article

Background/Objectives: Pregnancies complicated by idiopathic polyhydramnios are linked to a heightened risk of numerous maternal and perinatal complications. We aim to study the implications of polyhydramnios in term pregnancies complicated with gestational diabetes mellitus (GDM). Methods: A prospective cohort study including 340 GDM cases was conducted. An ultrasound scan was conducted at term between 37 and 40 weeks and amniotic fluid volume (AFV) was assessed by measuring the amniotic fluid index (AFI) and the single deepest pocket (SDP). Maternal demographics and obstetric and perinatal outcomes were evaluated after delivery. We performed comparisons between groups with normal AFV and polyhydramnios (AFI ≥ 24 cm or SDP ≥ 8 cm), and between groups with normal and increased AFV (AFI or SDP ≥ 75th centile). A multivariate logistic regression analysis was performed to study association between AVF measurements and adverse maternal and perinatal outcomes. Results: We found that women with GDM and polyhydramnios at term had a higher risk of maternal (54.3 vs. 27.5%, p < 0.001) and perinatal adverse outcomes (65.7% vs. 46.5%, p < 0.03). The increased AFV group showed a higher risk of fetal overgrowth (LGA: 21.4% vs. 8.2%, p < 0.001 and macrosomia: 19.8% vs. 5.4%, p < 0.001, respectively) and a lesser risk of delivering an SGA fetus (6.3% vs. 13.6%, respectively). Both AFI and SDP showed a significant correlation with newborn weight (r = 0.27; p < 0.001 and r = 0.28; p < 0.001, respectively) and newborn centile (r = 0.26; p < 0.001 and r = 0.26 for both). Subsequent to conducting a multivariate logistic regression analysis adjusted for pregestational BMI, nulliparity, and insulin treatment, both AFI and SDP were significantly associated with perinatal complications, but AFI showed a stronger association with fetal overgrowth (aOR 1.11; p = 0.004 for a LGA fetus and aOR 1.12; p = 0.002 for macrosomia) and with lower risk of delivering an SGA fetus (aOR 0.89; p = 0.009) or IUGR fetus (aOR 0.86; p = 0.03). ROC analysis showed a poor diagnostic performance of both AFI and SDP for identifying macrosomia (AUC 0.68 for AFI, and 0.65 for SDP). Conclusions: Detection of polyhydramnios at term, whether using AFI or SDP, identifies a subgroup of women with gestational diabetes with higher risks of obstetric and perinatal complications. Cases with increased AFV (AFI ≥ 18 cm or SDP ≥ 6.5 cm) are also associated with an increased risk of fetal overgrowth and may require more intensive monitoring for management and optimal delivery timing, with the aim of improve perinatal outcomes. Full article

Background and Clinical Significance: Prader–Willi syndrome (PWS) is a rare genetic disease caused by imprinted gene dysfunction, typically involving deletion of the chromosome 15q11.2-q13 region, balanced translocation, or related gene mutations in this region. PWS presents with complex and varied clinical manifestations. Abnormalities can be observed from the fetal stage and change with age, resulting in growth, developmental, and metabolic issues throughout different life stages. Case Presentation: We report the prenatal characteristics observed from the second to third trimester of pregnancy in a neonate with PWS. Prenatal ultrasound findings included a single umbilical artery, poor abdominal circumference growth from 26 weeks, normal head circumference and femur length growth, increased amniotic fluid volume after 30 weeks, undescended fetal testicles in the third trimester, small kidneys, and reduced fetal movement. The male infant was born at 38 weeks of gestation with a birth weight of 2580 g. He had a weak cry; severe hypotonia; small eyelid clefts; bilateral cryptorchidism; low responsiveness to medical procedures such as blood drawing; and poor sucking, necessitating tube feeding. Blood methylation-specific multiple ligation-dependent probe amplification (MS-MLPA) showed paternal deletion PWS. Notably, this case revealed two previously unreported prenatal features in PWS: a single umbilical artery and small kidneys. Conclusions: Through literature review and our case presentation, we suggest that a combination of specific sonographic features, including these newly identified markers, may aid clinicians in the early diagnosis of PWS. Full article

In this study, thirty female dogs, aged one to five years and varying in weight, in the last week of gestation were evaluated. The animals were divided into two groups: GC, which comprised twenty-two bitches undergoing elective cesarean section, and GD, which consisted of eight dogs requiring therapeutic cesarean section as a treatment to dystocia. We found that cortisol levels in the amniotic fluid were significantly higher in pups delivered via elective cesareans (mean: 9.86 ng/mL) compared to those from therapeutic c-sections (mean: 4.11 ng/mL). This observation contrasted with previous studies that reported lower cortisol levels in elective procedures, suggesting complexities in the physiological responses to different delivery methods that warrant further investigation. Notably, our study observed no significant association between amniotic fluid meconium presence and other distress markers, indicating that meconium may be more closely associated with fetal maturation rather than distress (p > 0.05). Neonatal viability (Apgar score) revealed that 92.86% of the neonates from elective procedures demonstrated no distress shortly after delivery, contrasting with 56.25% in therapeutic c-section. Fetal distress can be a direct consequence of dystocia caused by various stressors, such as pain and hypoxia. These factors can impair the fetus’ ability to adapt to extrauterine life, often leading to lower Apgar scores. Notably, neonatal weight was directly related to fetal cortisol levels, while no significant associations were noted between the litter size or birth order and cortisol concentrations, irrespective of the delivery type. These findings underscore the need for ongoing investigation into the relationships between cesarean delivery types, maternal and neonatal stress markers, and resultant health outcomes, aiming to enhance care strategies for expectant canine mothers and their puppies. Full article

Antenatal inflammation/infection is a major cause of neonatal apnoea and hypoventilation. Prostaglandin E2 (PGE₂) is a key inflammatory mediator associated with depression of fetal and neonatal breathing. We aimed to determine whether antenatal ibuprofen, a cyclooxygenase inhibitor that reduces synthesis of PGE₂, restores fetal breathing movements (FBM) in late-gestation fetal sheep exposed to systemic lipopolysaccharide (LPS). Fetal sheep (125 days gestation, d; term ~148 d) were instrumentally monitored for continuous measurement of FBM and physiological parameters. At 130 d fetuses were randomly allocated between groups receiving i.v. saline (CTL_SAL, n = 9), escalating doses of LPS (i.v.) over 3 days (LPS_SAL, n = 8), or ibuprofen one hour after each LPS dose (LPS_IBU, n = 8). Regular plasma samples were collected for PGE₂ assessment. At 135 d, cerebrospinal fluid and brainstem tissue were collected at autopsy for assessments of PGE₂ expression, and immunohistochemical quantification of astrocytes and microglia within key brainstem respiratory centres was performed to assess inflammation. LPS exposure increased PGE₂ levels in plasma, cerebrospinal fluid and the RTN/pFRG (p < 0.05) and decreased the incidence, amplitude and amount of the accentuated (>5 mmHg) FBMs. Ibuprofen reduced plasma and RTN/pFRG PGE₂ expression (p < 0.01 and p = 0.031, respectively) but did not restore FBMs. Astrocyte and microglial density increased in the RTN/pFRG, NTS and raphe nucleus in LPS_IBU fetuses, compared to LPS_SAL (p < 0.05). Antenatal ibuprofen treatment did not restore depressed FBM, despite reducing the circulating and brainstem PGE₂ levels in LPS-exposed fetal sheep. Other inflammatory pathways or more specific targeting of PGE₂ may be more effective in preventing apnoea caused by exposure to intrauterine infection/inflammation. Full article

CEA (carcinoembryonic antigen), which belongs to the acidic glycoproteins, is primarily produced during the fetal period. Following this stage, low levels of CEA are considered physiological, while elevated concentrations are associated with a range of both benign and malignant pathologies. The liver plays a key role in CEA metabolism. The most common material used to determine CEA concentrations by various techniques is blood, and measuring CEA in peritoneal fluid holds clinical value. CEA has been found to contribute to carcinogenesis, metastasis, and treatment resistance. Therefore, its serum concentration is widely used in oncology for prognosis, disease monitoring, and recurrence detection, despite its limited sensitivity and specificity, which prevent it from serving as a standalone diagnostic tool. Elevated serum CEA levels are linked to worse outcomes in lung, liver, breast, colorectal, and pancreatic cancers. Imaging and multi-marker panels that include CEA enhance diagnostic accuracy, but its role remains context-dependent and varies by cancer type. CEA levels in peritoneal fluid have been explored as a potential marker for detecting malignancy and predicting recurrence, particularly in gastric, gynecological, and colorectal cancers. Peritoneal fluid CEA has also been proven useful in differentiating the etiology of ascites. While cytology remains the standard for the detection of tumor cells in body fluids, its limited sensitivity provides a strong rationale for incorporating peritoneal fluid CEA measurements as a complementary diagnostic tool, potentially alongside other markers. Additionally, the lack of standardized measurement techniques and cut-off values underlines the methodological challenges that still need to be addressed in future research for both serum and peritoneal CEA levels. Full article

Background/Objectives: The human kallikrein-related peptidase 6 (KLK6), a serine protease with trypsin-like properties, belongs to the 15-member kallikrein (KLK) gene family and is predominantly recognized for its role in oncogenesis, neurodegenerative disorders, and skin conditions. Aquaporins (AQPs) are integral membrane proteins that facilitate water transport across cell membranes. AQP1 is constitutively active in the kidneys and plays a crucial role in reabsorbing filtered water, while AQP2 is regulated by vasopressin and is essential for maintaining body fluid homeostasis. The primary objective of the present study is to investigate the spatio-temporal expression patterns of KLK6, AQP1, and AQP2 throughout normal human nephrogenesis and congenital kidney and urinary tract (CAKUT) abnormalities: duplex kidneys, horseshoe kidneys, and dysplastic kidneys. Methods: An immunofluorescence analysis of KLK6, AQP1, and AQP2 was performed on 37 paraffin-embedded fetal kidney samples. The area percentage of KLK6 in the kidney cortex was calculated in normal developing samples during developmental phases 2, 3, and 4 and compared with CAKUT samples. Results: KLK6 exhibits distinct spatiotemporal expression patterns during human kidney development, with consistent localization in proximal tubules. Its subcellular positioning shifts from the basolateral cytoplasm in early phases to the apical cytoplasm in later stages, which may be strategically positioned to act on its substrate in either the peritubular space or the tubular fluid. KLK6 expression followed a quadratic trajectory, peaking at Ph4. This marked increase in the final developmental phase aligns with its strong expression in mature kidneys, suggesting a potential role in proximal tubule differentiation and functional maturation through facilitating extracellular matrix remodeling and activating proteinase-activated receptors, modulating the signaling pathways that are essential for tubular development. In duplex kidneys, structural abnormalities such as ureteral obstruction and hydronephrosis may upregulate KLK6 as part of a reparative response, while its downregulation could impair epithelial remodeling and cytoskeletal integrity, exacerbating dysplastic phenotypes. Conclusions: These findings highlight the potential of KLK6 involvement in normal kidney development and the pathology of CAKUT. Full article

Background: The importance and etiology of meconium-stained amniotic fluid (MSAF) in preterm pregnancies are still poorly understood. Among other factors, intrauterine inflammation is proposed to be a pathophysiological change associated with MSAF. To study the extent of intrauterine inflammation, histological evaluation represents the “gold standard” of diagnostics. Objectives: To investigate the concomitant occurrence of MSAF and histological chorioamnionitis (HCA) and fetal inflammatory response (FIR). To investigate the incidence of short-term neonatal outcomes in preterm infants born from MSAF. Materials and methods: We conducted a single-center retrospective study in a tertiary neonatal intensive care unit between 2020 and 2022. 237 preterm infants born ≤ 32 weeks or with ≤1500 g birthweight were investigated. The group of infants born from MSAF was compared to the group of infants born from clear amniotic fluid (CAF). The variables measured were the following: HCA, FIR, maternal and fetal vascular malformations (MVM, FVM), maternal clinical and laboratory signs of chorioamnionitis (CA), early neonatal outcomes, neonatal white blood cell count (WBC) in the first day of life, and neonatal c-reactive protein (CRP) level on the second day of life. Histological evaluation of the placenta and the umbilical cord was based on the recommendation of the 2014 Amsterdam Placental Workshop Group Consensus Statement (APWGCS). Results: Out of 237 preterm infants (mean gestational age: 28.6 (95% CI: 28.2; 28.9) weeks, mean birth weight: 1165 (95% CI: 1110; 1218) grams), 22 were born from MSAF. There was no difference between the perinatal characteristics of the two groups. A higher incidence of HCA (54.5% vs. 32.6%; p: <0.001), a higher incidence of stage 3 HCA (45.4% vs. 9.3%), a higher incidence of FIR (50% vs. 16.7%; p: <0.001), and a higher incidence of stage 3 FIR (18.2% vs. 1.9%) were found in the MSAF group in comparison with the CAF group. A higher incidence of elevated (>30 mg/L) maternal CRP level (36.8% vs. 15.3%; p: 0.02) and elevated (>15 mg/L) neonatal CRP level (31.8% vs. 14.4%; p: 0.03) was detected in the MSAF group. Among neonatal complications, severe (Stage III/IV) intraventricular hemorrhage (IVH) had a higher incidence in the MSAF group (22.2% vs. 5.1%; p: 0.005). Conclusion: MSAF in preterm pregnancies is associated with a severe maternal and fetal inflammatory response in the placenta and the umbilical cord. MSAF is also accompanied by elevated systemic inflammatory parameters and a higher incidence of severe neonatal IVH as well. Full article

We introduce an innovative, non-invasive prenatal screening approach for detecting fetal monogenic alterations and copy number variations (CNVs) from maternal blood. Method: Circulating free DNA (cfDNA) was extracted from maternal peripheral blood and processed using the VeriSeq NIPT Solution (Illumina, San Diego, CA, USA), with shallow whole-genome sequencing (sWGS) performed on a NextSeq550Dx (Illumina). A customized gene panel and bioinformatics tool, named the “VERA Revolution”, were developed to detect variants and CNVs in cfDNA samples. Results were compared with genomic DNA (gDNA) extracted from fetal samples, including amniotic fluid and chorionic villus sampling and buccal swabs. Results: The study included pregnant women with gestational ages from 10 + 3 to 15 + 2 weeks (mean: 12.1 weeks). The fetal fraction (FF), a crucial measure of cfDNA test reliability, ranged from 5% to 20%, ensuring adequate DNA amount for analysis. Among 36 families tested, 14 showed a wild-type genotype. Identified variants included two deletions (22q11.2, and 4p16.3), two duplications (16p13 and 5p15), and eighteen single-nucleotide variants (one in CFTR, three in GJB2, three in PAH, one in RIT1, one in DHCR7, one in TCOF1, one in ABCA4, one in MYBPC3, one in MCCC2, two in GBA1 and three in PTPN11). Significant concordance was found between our panel results and prenatal/postnatal genetic profiles. Conclusions: The “VERA Revolution” test highlights advancements in prenatal genomic screening, offering potential improvements in prenatal care. Full article

Background: Antenatal hydronephrosis (ANH) is the most common congenital renal and urinary tract anomaly, and parenchymal damage and renal fibrosis due to pathological hydronephrosis are the main causes of end-stage renal disease in children and chronic kidney disease in adults. At present, there is no validated biomarker for ANH, and diagnostic criteria other than prenatal ultrasonography (US) assessment are lacking. Therefore, we assessed to determine if biomarkers extracted from amniotic fluid small extracellular vesicles (sEVs) might be used as ANH diagnosis. Methods: With congenital ureteropelvic junction obstruction (UPJO) as the ultimate diagnosis, 10 pregnant women with Grade III-IV ANH and 10 normal pregnant women were recruited. The sEVs were extracted from amniotic fluid supernatant of all samples. Transcriptomic sequencing of sEVs in the discovery cohort identified the differential expression profiles for ANH. The known differentially expressed lncRNAs (DE-lncRNAs) were assessed by qRT–PCR in the validation cohort. Results: We explored the global RNA expression in sEVs from amniotic fluid. The differential expression profiles of both mRNAs and lncRNAs were related to fetal kidney development. Six known DE-lncRNAs were identified for ANH, and three of those with high expression were verified in more ANH samples. In particular, the upregulated LINC02863 and its target genes were associated with renal development and morphogenesis. The four predicted novel lncRNAs in high expression were also related to mesenchymal morphogenesis and the STAT3 signaling pathway and may play roles in ANH. Conclusions: We identified differentially expressed RNAs of all species in the sEVs from amniotic fluid, and the validated known DE-lncRNAs might serve as promising diagnostic biomarkers for ANH. Full article