Search Results (349)

Mesenchymal stem cells (MSCs) derived from the placenta, fetal membranes, or umbilical cord may be used to study the pathophysiology of gestational diabetes mellitus (GDM). The phenotype of MSCs may reflect fetal programming in response to the maternal milieu of a GDM pregnancy. Altered fetal programming is linked to high rates of obesity and type 2 diabetes mellitus (T2DM) in the offspring of mothers with GDM. This review discusses recent findings characterizing the phenotype of GDM-exposed MSCs (GDM-MSCs) which enhance our understanding of the mechanisms of fetal programming. It also considers how MSCs may be used as markers of long-term offspring health to test the benefit of putative interventions and highlights the need for further translational studies to clearly link the MSC phenotype to clinical parameters and interventions. Full article

Objective: To determine whether a third-trimester drop in insulin requirements in pregnant people with pre-existing diabetes is associated with a subsequent occurrence of adverse pregnancy outcomes. Research Design and Methods: We conducted a retrospective cohort study of patients with type 1 and 2 diabetes who were followed at a tertiary referral center in Toronto, Canada. We collected data on insulin dosing in the third trimester (after 28 weeks of pregnancy) and compared outcomes in those with and without a third-trimester drop of 15% or more in their total insulin requirements. Our primary outcome was a composite of stillbirth, spontaneous preterm birth or preterm premature rupture of membranes, and iatrogenic preterm birth or cesarean birth for fetal wellbeing concerns, occurring following the drop in insulin requirements. We conducted regression analyses controlling for early pregnancy glycosylated hemoglobin, body mass index, and diabetes-related microvascular disease, and presented results as odds ratios (OR) with 95% confidence intervals (95%CI). Results: We included 350 pregnant people—146 with type 1 and 204 with type 2 diabetes. Of these, 54 (15.4%) had a third-trimester drop of 15% or more in their total insulin requirements. There was no difference in the primary outcome between groups (OR 0.97; 95% CI 0.41–2.10). Conclusions: Based on this single-center study, limited by sample size and analytic constraints, in people with pre-existing diabetes, a third-trimester drop of ≥15% in total insulin requirements was not associated with subsequent occurrence of adverse pregnancy outcomes. Larger prospective studies looking at associations between a drop in insulin requirements and subsequent occurrence of adverse pregnancy outcomes are necessary to inform meta-analyses and clinical decision making. Full article

Background: Borrelia burgdorferi, the causative agent of Lyme disease, releases outer membrane vesicles (OMVs) that may contribute to infection and modulate the host immune response. Although interest in OMVs is growing, few studies have systematically compared methods for isolating OMVs from B. burgdorferi. Methods: In this study, we evaluated two OMV isolation techniques—standard ultracentrifugation and an ion-exchange chromatography-based ExoBacteria™ kit—and examined how serum supplements (rabbit serum vs. exosome-depleted fetal bovine serum, ED-FBS) influence Bb-OMV yield and composition. Gene expression profiles were assessed using RT-PCR, and specific protein content was identified by Western blot analyses. To assess the ability of Bb-OMVs to interact with host cells, Bb-OMVs were co-cultured with MDA-MB-231 triple-negative breast cancer cells. Results: Transmission electron microscopy confirmed that both methods produced spherical Bb-OMVs with intact membrane bilayers. Ultracentrifugation generated larger vesicles (15–180 nm), while the ExoBacteria™ kit yielded smaller vesicles (<50 nm) with a higher double-stranded DNA (dsDNA) content, and protein levels were similar across samples. Cultures grown with rabbit serum produced more Bb-OMVs and had cleaner backgrounds in the TEM images than those grown with ED-FBS. All Bb-OMV samples lacked intracellular markers (DnaK and 16S rRNA) and consistently expressed the outer surface protein OspA, confirming high purity. All isolated Bb-OMVs were taken up by the cells, as indicated by OspA expression, without detectable 16S rRNA, confirming vesicle internalization without bacterial contamination. Conclusions: These findings indicate that isolated OMVs are biologically active and capable of interacting with mammalian cells, highlighting their potential role in host–pathogen interactions and the broader relevance of OMVs in studying bacterial modulation of mammalian cell behavior. Overall, both isolation methods produced high-quality OMVs, with ultracentrifugation yielding slightly more pure vesicles, emphasizing the importance of selecting appropriate isolation methods and culture conditions for functional OMV studies. Full article

Background and Clinical Significance: Wolf–Hirschhorn syndrome (WHS, OMIM #194190) is caused by deletion of the distal short arm of chromosome 4. It is characterized by intrauterine growth restriction (IUGR), developmental delay, epilepsy, distinctive facial features, and urinary tract anomalies, particularly renal hypoplasia. However, the histological profile of renal involvement in WHS is rarely documented. Case presentation: We report a case of fetal WHS with renal hypoplasia and histological evidence of oligomeganephronia (OMN). At 21 weeks’ gestation, a prenatal ultrasound revealed oligo/anhydramnios and IUGR. Genetic testing (karyotype and CGH-array) confirmed a de novo 17.92 Mb terminal deletion from 4p16.3 to 4p15.31. The pregnancy was legally terminated at 23 weeks. The autopsy showed characteristic WHS dysmorphisms, growth restriction, and markedly small kidneys. Histology revealed OMN with a thinned renal cortex with reduced glomeruli, mainly hypoplastic, some of which were hypertrophic, and dilated proximal tubules. Scattered medullary tubules were present within the tubulointerstitial compartment, alongside thickened tubular basement membranes highlighted by Collagen IV staining. Conclusions: This case suggests that OMN may be a histological hallmark of renal hypoplasia in WHS, especially in larger 4p deletions. Recognizing this pattern may help with prenatal prognosis and clinical management. Further studies are needed to confirm this association. Full article

Background: Chorioamnionitis is the inflammation of the placenta, amniotic fluid, and fetal membranes and its histological confirmation, histologic chorioamnionitis (HCA) is defined as the diffuse infiltration of neutrophils into the chorioamniotic membranes. Several biomarkers have been evaluated for its early prediction, including interleukin-6 (IL-6), which can be measured in plasma, amniotic fluid, and cervicovaginal fluid (CVF). Aims and Scope: We aimed to systematically review and meta-analyze the role of IL-6 in the prediction of HCA, in several body fluids and among distinct subgroups. Methods: A literature search was conducted in PubMed, Embase, Cochrane Library, and CT.gov between March 2024 and July 2024. Studies that measured IL-6 in AF, CVF, or plasma and conducted a placental examination were included. The Quality Assessment of Diagnostic Accuracy Studies—2 (QUADAS-2) tool was used to assess methodological quality. Bivariate analysis combined with a linear mixed model was used for quantitative synthesis, and summary estimates were calculated. Summary Receiver Operating Characteristic (SROC) curves were constructed to evaluate diagnostic accuracy. The z-test was used for subgroup comparisons. Results: In total, 43 studies were included in this meta-analysis, 23 for amniotic fluid (AF), 9 for plasma, and 11 for CVF. AF IL-6 in the overall population had a very good diagnostic performance with an AUC = 0.82 (95% CI: 0.78–0.85) for HCA prediction, with a sensitivity of 65% (95% CI: 0.55–0.74) and a specificity of 84% (95% CI: 0.76–0.89), performing superiorly for the preterm labor (PTL) group (Area Under Curve (AUC) = 0.88, 95% confidence interval (CI): 0.85–0.91) compared with the Preterm premature rupture of membranes (PPROM) subgroup (AUC = 0.76, 95% CI: 0.72–0.80). Plasma IL-6 in the overall population had a good diagnostic performance with an AUC = 0.79 (95% CI: 0.76–0.83), similar to that for the PTL and PPROM subgroups, with a sensitivity of 72% (95% CI: 0.58–0.83) and a specificity of 79% (95% CI: 0.72–0.84). CVF IL-6 in the PPROM group had an excellent diagnostic accuracy, the highest observed in our research (AUC = 0.91, 95% CI: 0.88–0.93), higher than CVF in the overall population, where diagnostic accuracy remained very good. The QUADAS-2 tool revealed a high risk of bias overall. Conclusions: CVF IL-6 could serve as a valid, non-invasive screening test for pregnant women to stratify risk for HCA, while a combination of AF, CVF, and plasma IL-6 could be a tractable diagnostic tool for clinicians, but large-scale Randomized Control Trials are needed to validate this hypothesis. Full article

The human placenta is a complex organ that supports fetal development and is rich in extracellular matrix proteins and growth factors, making it suitable as a biomaterial in wound care. Placenta-derived amnion-only allografts have traditionally been used in the clinic, but they lack the structural and biochemical complexity of the full three-layer placental membrane, which includes the amnion, intermediate, and chorion layers. Advances in tissue engineering have enabled preservation of multiple layers, giving rise to multilayer placental-based Cellular and Acellular Matrix-like Products (CAMPs) such as Full-Thickness (FT; amnion, intermediate, chorion) and ACA (amnion, intermediate, chorion, amnion). Although these advanced CAMPs are increasingly applied clinically, their molecular composition has not been comprehensively defined. This study presents a global proteomic analysis of FT and ACA, complemented by targeted multiplex analysis of soluble proteins and an in vitro angiogenesis assay. Proteomic profiling identified 8908 structural and bioactive components, with 32.5% of proteins associated with tissue repair and remodeling pathways. Multiplex analysis confirmed accessibility of biologically relevant soluble factors. Endothelial tube formation assays further supported biological relevance, demonstrating that soluble proteins in FT and ACA support angiogenesis. These data provide a molecular characterization of multilayer CAMPs and underscore their potential to deliver durable wound coverage while supporting the local microenvironment. Full article

Background: The definitions and approaches used to diagnose gestational diabetes (GD) are varied. The two-step approach recommended by the American College of Obstetricians and Gynecologists (ACOG) combines the sensitivity of a glucose challenge test (GCT) with the specificity of a 3-hour oral glucose tolerance test (OGTT). We investigated if minor modification of the two-step procedure can provide improved detection of GD by identifying a risk group of pregnant women with high risk of GD. Methods: We conducted a prospective cohort study of pregnant women enrolled early during pregnancy and followed till delivery. All participants underwent the ACOG-recommended two-step procedure for GD diagnosis. Based on GCT and OGTT results, the participants were divided into four risk groups (RGs): GCT-negative (RG0), GCT-positive but OGTT normal (RG1), single abnormal value on OGTT or raised HbA1c (RG2) and diagnosed GD (RG3). Baseline evaluation included dietary history (24 hour recall) and physical activity. A series of multivariable logistic regression analyses were conducted to estimate the odds of maternal and fetal outcomes. Results: A total of 1041 pregnant women were included in the study, of whom 16 (1.6%) were diagnosed as GD. Our two-step approach identified 48 (4.6%) women as GD, while RG2, RG1 and RG0 comprised 75 (7.2%), 218 (20.9%) and 700 (67.2%), respectively. Compared to RG0, RG2 showed a higher likelihood of antepartum complications [odds ratio and 95% confidence interval 2.38 (1.16–4.15)], any adverse outcome without [2.04 (1.17–3.55)] or with cesarean section [2.09 (1.21–3.61)] and primary cesarean section [1.68 (1.01–2.81)] after adjustment for potential confounders. RG2 was also significantly associated with pregnancy-induced hypertension, meconium-stained amniotic fluid and premature rupture of membranes. Conclusions: In the study participants, we identified a subgroup (RG2) at high risk of GD with perinatal outcomes showing profile consistent with that of GD. Full article

Persistent pulmonary hypertension of the newborn (PPHN) results from disrupted fetal–neonatal circulatory transition, characterized by elevated pulmonary vascular resistance (PVR), right-to-left shunting, and refractory hypoxemia. Despite improved perinatal care, PPHN remains a major source of neonatal morbidity and mortality. This review details PPHN phenotypes, pathophysiology, etiology, diagnostics including echocardiography and biomarkers like B-type Natriuretic Peptide (BNP) or N-terminal pro-B-type Natriuretic Peptide (NT-proBNP), and current therapeutic modalities, from lung recruitment and surfactant to targeted vasodilator therapy (iNO, sildenafil, milrinone, bosentan) and extracorporeal membrane oxygenation (ECMO). We emphasize the role of endothelial and molecular mechanisms in precision therapy and outline guidelines for clinical decision-making in diverse care settings. Full article

Background: Pulmonary hypertension (PH) in newborns is a rare but serious condition and potentially life-threatening disorder, often initially confused with congenital heart disease due to overlapping echocardiographic findings in the late third trimester. Evidence on prenatal predictors of postnatal PH is limited. We aimed to describe detailed third-trimester echocardiographic findings associated with postnatal PH in infants with prenatally suspected CoA based on a retrospective case series. Methods: We reviewed 18 years of fetal echocardiography (2004–2022) in a tertiary maternal–fetal–neonatal center. We identified fetuses with suspected coarctation of the aorta (CoA) in late gestation who were delivered at term (≥37 weeks) and had prolonged neonatal hospitalization (>10 days) without cardiac surgery or catheterization. Z-scores for cardiac dimensions were calculated. All examinations were performed by experienced fetal cardiologists. Postnatal evaluations confirmed PH based on echocardiographic and clinical findings. Results: Among 19,836 fetuses examined, 138 were prenatally suspected of CoA. In 70 cases, this diagnosis was not confirmed postnatally (false positives). Of these, eight infants (0.04% of the total cohort) developed postnatal PH. Postnatally, all eight neonates required intensive care. Prenatal features included ventricular/atrial disproportion (7/8), cardiomegaly (8/8), main pulmonary artery dilatation (10.2 ± 2.2 mm; Z-score +2.7 ± 1.3), tricuspid regurgitation (8/8), pulmonary regurgitation (4/8), and interventricular septal hypertrophy (>4.5 mm in 5/8). Postnatal evaluations confirmed PH based on echocardiographic criteria (elevated right ventricular pressure, septal flattening/bowing, right ventricular dilation or dysfunction, and abnormal shunt direction) combined with clinical compromise. All infants received prostaglandin E1 (PGE1) initially; none required extracorporeal membrane oxygenation-ECMO. Three died, while five survived with medical management (oxygen, inhaled nitric oxide, sildenafil). Conclusions: Specific functional abnormalities on late third-trimester echocardiography may indicate impaired pulmonary vascular adaptation and predict postnatal PH, particularly in cases initially suspected of CoA. Recognition and awareness of these findings can guide delivery planning, neonatal surveillance, and timely intervention. Prospective multicenter studies are needed to validate these associations and refine prenatal screening protocols. Full article

Background: Abiogenesis is hypothesized to have occurred in the aquatic environments of the early Earth approximately 3.8–4.0 billion years ago, in oceans containing high concentrations of ions (Na⁺ ≈ 470 mmol/L, Cl⁻ ≈ 545 mmol/L, Mg²⁺ ≈ 51–53 mmol/L, Ca²⁺ ≈ 10 mmol/L, K⁺ ≈ 10 mmol/L, SO₄²⁻ ≈ 28–54 mmol/L, HCO₃⁻ ≈ 2.3 mmol/L). Primitive membranes evolved ion-regulatory mechanisms to sustain electrochemical gradients, enabling metabolic activity. Objectives: This review compares the composition of amniotic fluid (AF) to seawater, framing AF as a “biological ocean” for the fetus, and evaluates the impact of micro- and nanoplastics (MNPs) on this protected milieu. Methods: We synthesized data from published studies on concentrations of and ions and other important substances in AF during pregnancy and compared them with marine values. Reports of MNPs detected in placenta, AF, and human organs were systematically reviewed. Results: AF exhibits high ionic similarity to seawater, although the absolute concentrations of ions are lower, reflecting evolutionary conservation. Recent analytical studies identified MNPs in samples of human placenta (4–10 particles per 1 g of tissue), meconium (median 3–5 particles per g), and AF (detectable in >60% of tested samples). Co-exposure to heavy metals, persistent organic pollutants, and endocrine disruptors were reported in 20–40% of maternal–fetal samples. Conclusions: The analogy between oceans and AF underscores a conserved evolutionary continuum. However, the infiltration of MNPs into intrauterine environments is a novel toxicological challenge with potential implications for neurodevelopment, immune programming, and epigenetic regulation. Within the One Health framework, protecting AF from anthropogenic contaminants is as critical as safeguarding marine ecosystems. Full article

Fine particulate matter (PM2.5) emitted by wood smoke is a significant environmental pollutant associated with oxidative stress and hypoxia. These conditions can disrupt placental function by altering the expression of key nutrient transporters, such as glucose transporter 1 (GLUT1) and sodium-dependent vitamin C transporter 2 (SVCT2), which are essential for fetal development. This study evaluates the effects of pregestational and gestational exposure to PM2.5 on GLUT1 and SVCT2 expression in the rat placenta. Pregnant Sprague–Dawley rats were exposed to either filtered air (FA) or non-filtered air (NFA) containing PM2.5 from wood combustion in a controlled exposure system. Four experimental groups were established: FA/FA (control), FA/NFA (gestational exposure), NFA/FA (pregestational exposure), and NFA/NFA (continuous exposure). Immunofluorescence and confocal microscopy were used to quantify the expression of GLUT1 and SVCT2 in the placental labyrinth zone. Statistical analyses were performed using Kruskal–Wallis and post hoc Dunn’s test (p < 0.05). Gestational exposure to PM2.5 (FA/NFA) significantly reduced GLUT1 and SVCT2 expression, compromising glucose transport and antioxidant protection in the placenta. Pregestational exposure (NFA/FA) induced a compensatory increase in SVCT2 expression, suggesting an adaptive response to oxidative stress. Continuous exposure (NFA/NFA) resulted in GLUT1 redistribution within the syncytiotrophoblast and decreased membrane localization, potentially impairing glucose uptake. PM2.5 exposure disrupts the expression and localization of GLUT1 and SVCT2 in the placenta, with differential effects depending on the timing of exposure. The gestational phase appears to be particularly vulnerable, as reduced GLUT1 and SVCT2 levels may impair fetal nutrition and antioxidant defense. These findings underscore the need for preventive measures to mitigate air pollution-related risks during pregnancy. Full article

Background and Clinical Significance: Left ventricular hypoplasia is often repaired surgically in sequence to a Fontan circulation, which is a physiologic state that presents unique challenges during pregnancy. Although women with Fontan physiology can achieve successful pregnancy outcomes, they remain at elevated risk for cardiac, thrombotic, and obstetric complications. Case Presentation: We describe a 38-year-old woman with Fontan physiology and acquired von Willebrand syndrome (AVWS) who was admitted at 23 weeks gestation for preterm premature rupture of membranes. The patient had history of prior classical cesarean delivery and two previous miscarriages. Her pregnancy was further complicated by abnormal placental vasculature and uterine arteriovenous malformation. Given her bleeding diathesis, hematology advised against anticoagulation or antiplatelet therapy, and she ultimately underwent a successful low transverse cesarean delivery under general anesthesia at 24 weeks. Postpartum hemorrhage was managed with clotting factor replacement and supportive care. Conclusions: This case illustrates how AVWS may mitigate thrombotic risk in Fontan physiology and how early activation of a cardio-obstetrics team can enable tailored planning. As more patients with complex congenital heart disease reach reproductive age, multidisciplinary coordination, shared infrastructure, and individualized birth plans will be essential to achieving optimal maternal–fetal outcomes. Full article

Background and Clinical Significance: Brugada syndrome (BrS) is a rare inherited cardiac channelopathy, often associated with SCN5A loss-of-function mutations. Clinical presentations range from asymptomatic to malignant arrhythmias and sudden cardiac death. Physiological and pharmacological stressors affecting sodium channel function—such as pyrexia, certain medications, and possibly pregnancy—may unmask or exacerbate arrhythmic risk. However, there is limited information regarding pregnancy and obstetric outcomes. Obstetric management remains largely informed by isolated case reports and small case series. A literature review was conducted using OVID Medline and Embase, identifying case reports, case series, and one retrospective cohort study reporting clinical presentation, obstetric management, and outcomes in maternal BrS. A case is presented detailing coordinated multidisciplinary input, antenatal surveillance, and intrapartum and postpartum care to contribute to the growing evidence base guiding obstetric care in this complex setting. Case Presentation: A 30-year-old G2P0 woman with asymptomatic BrS (SCN5A-positive) was referred at 31 + 5 weeks’ gestation for multidisciplinary antenatal care. Regular review and collaborative planning involving cardiology, anaesthetics, maternal–fetal medicine, and obstetrics guided a plan for vaginal delivery with continuous cardiac and fetal monitoring. At 38 + 0 weeks, the woman presented with spontaneous rupture of membranes and underwent induction of labour. A normal vaginal delivery was achieved without arrhythmic events. Epidural block with ropivacaine and local anaesthesia with lignocaine were well tolerated, and 24 h postpartum monitoring revealed no abnormalities. Conclusions: This case adds to the limited but growing literature suggesting that with individualised planning and multidisciplinary care, pregnancies in women with BrS can proceed safely and without complication. Ongoing case reporting is essential to inform future guidelines and optimise maternal and fetal outcomes. Full article

Cell culture models are of central importance for the investigation of cellular metabolism, proliferation and stress responses. In this study, the effects of different concentrations of glucose (1 g/L vs. 4.5 g/L) and fetal bovine serum (FBS; 5%, 10%, 15%) on viability, mitochondrial function and autophagy are investigated in four human cell lines: MRC-5, HeLa, Caco-2 and SW-620. Cells were cultured in defined media for 72 h, and viability was assessed by LDH release, mitochondrial membrane potential using Rhodamine 123, ATP content by luminescence and autophagy activity by dual fluorescence staining. The results showed that HeLa and SW-620 cancer cells exhibited increased proliferation and mitochondrial activity under high glucose conditions, while low glucose media resulted in decreased ATP content and increased membrane permeability in HeLa cells. MRC-5 fibroblasts and Caco-2 cells showed greater resilience to nutrient stress, with minimal changes in LDH release and consistent proliferation. Autophagy was activated under all conditions, with a significant increase only in selected cell-medium combinations. These results highlight the importance of medium composition in influencing cellular bioenergetics and stress responses, which has implications for cancer research, metabolic disease modelling and the development of serum-free culture systems for regenerative medicine. Full article

Choline has been recognized as an essential nutrient involved in various physiological functions critical to human health. Adequate daily intake of choline has been established by the US National Academy of Medicine in 1998, considering choline requirements for different ages, sex differences and physiological states (e.g., pregnancy). By serving as a precursor for acetylcholine and phospholipids, choline is important for cholinergic transmission and the structural integrity of cell membranes. In addition, choline is involved in lipid and cholesterol transport and serves as a methyl donor after oxidation to betaine. Extracellular choline is transported across the cell membrane via various transport systems (high-affinity and low-affinity choline transporters) with distinct features and roles. An adequate dietary intake of choline during pregnancy supports proper fetal development, and throughout life supports brain, liver, and muscle functions, while choline deficiency is linked to disease states like fatty liver. Choline has important roles in neurodevelopment, cognition, liver function, lipid metabolism, and cardiovascular health. While its signaling role has been considered mostly indirect via acetylcholine and phosphatidylcholine which are synthesized from choline, emerging evidence supports a role for choline as an intracellular messenger acting on Sigma-1R, a non-opioid intracellular receptor. These new findings expand the cell signaling repertoire and increase the current understanding of the role of choline while warranting more research to uncover the molecular mechanisms and significance in the context of GPCR signaling, the relevance for physiology and disease states. Full article