The use of umbilical cord blood (UCB) as a stem cell source in haematopoietic stem cell transplant (HSCT) has greatly declined in recent years. It has largely been replaced by mismatched unrelated and family donors, facilitated by advances in transplant technologies, including post-transplant cyclophosphamide to prevent graft-versus-host disease (GVHD). UCB remains a distinctive source of haematopoietic stem cells (HSCs) with unique immunologic and practical advantages, including for those with malignant and non-malignant diseases. Compared to other cell sources, UCB transplantation (UCBT) offers comparable survival with reduced chronic GVHD (cGVHD) and with a potent graft-versus-leukaemia (GVL) effect. These outcomes likely reflect the biology of cord-derived lymphocytes-particularly naïve, adaptable CD8+ T-cells capable of rapid differentiation and tumour-directed cytotoxicity without sustained alloreactivity. UCB permits greater human leukocyte antigen (HLA) mismatch tolerance, especially when transplant is performed T-cell replete and can be accessed immediately, reducing time to transplant for high-risk leukaemia. In addition, recent advances in ex vivo expansion technologies have overcome historical limitations of low cell dose and delayed engraftment, expanding UCB's applicability to older paediatric and adult recipients. This review discusses the evidence of using UCB as a preferred stem cell source in patients with relapsed/refractory haematological malignancies and how we may interrogate the properties of UCB to improve outcomes in these high-risk cohorts.

Experimental and data modeling approaches of umbilical cord blood allogenic response identify cytokine profiles as potential biomarkers associated with the initial stages of alloreactivity and immunomodulation.

Identification of novel polyhalogenated carbazoles in cord serum and their associations with fetal growth.

Early-life exposure to F-53B remodels the pulmonary immune microenvironment and enhances susceptibility to neutrophil-predominant asthma via dysregulation of arachidonic acid metabolism.

Incomplete genotype-phenotype correlations challenge the management of non-SCID FOXN1 immunodeficiency. We describe the detailed clinical course of three distinct newborns with four novel FOXN1 mutations identified by TRECNBS. For comprehensive immune characterization advanced flow cytometry-based immunophenotyping was employed alongside high-resolution single-cell RNA sequencing. In our cohort, we detected heterozygous FOXN1 mutations in P1 (c.1178delG; p.Gly393Alafs*157) and P2 (c.830+1G>T; p.?), and compound heterozygous FOXN1-mutations in P3 (c.1318C>T; p.Gln440* and c.668T>G; p.?). Despite slow and partial recovery from T-cell lymphocytopenia in P3, clinical signs for classical 'nude SCID` were incomplete. Compared to a healthy cord blood control, a distinct B-cell population was identified in the FOXN1-deficient patients expressing immature B-cell markers and lower HLA-II mRNA levels. In summary, our cohort of three newborns with four novel FOXN1 variants highlights heterogeneous immunological courses and broader thymic dysfunction implications in this rare disease. Structured management strategies are essential for those identified by NBS-programs.

Cord blood natural killer cell-derived extracellular vesicles inhibit Zika virus infectivity through ITGB2/perforin-mediated envelope disruption in vitro and in vivo.

The prevalence of obstructive sleep apnea (OSA) increases during pregnancy and is associated with gestational diabetes mellitus (GDM), although its clinical impact on birth outcomes remains unclear. We aimed to assess the effect of several OSA criteria and intermittent hypoxia in the third trimester on perinatal outcomes in women with GDM. In this prospective study, polysomnography was performed on 89 women with GDM. Insulin resistance indices (HOMA-IR/QUICKI) were calculated, and biomarkers (insulin-like growth factor-1 (IGF-1), resistin, soluble endoglobulin, galectin-3, and free fatty acids) were analysed from women and some cord blood samples using enzyme-linked immunosorbent assay. Whereas OSA did not significantly affect overall perinatal outcomes, specific OSA features-including REM-OSA, supine-position OSA, and an oxygen desaturation index (ODI) ≥ 1 h-1-were linked to adverse effects on neonatal birthweight and length. Moreover, apnea duration was an independent predictor of birthweight, while insulin resistance was more impaired in women with OSA and showed an inverse relationship with sleep and REM time, respectively. IGF-1 was elevated and demonstrated a significant predictive value for OSA, as indicated by the AUC-ROC curve. In summary, although OSA did not adversely affect overall perinatal outcomes in women with GDM, specific OSA characteristics were associated with adverse neonatal growth metrics. Insulin resistance was higher in women with OSA, and IGF-1 may serve as a potential biomarker for OSA in this population. Further prospective studies with attention to REM-stage, supine-position OSA, apnea duration, and hypoxic burden are needed to elucidate the complex interactions between OSA, GDM, and fetal outcomes.

Graves' disease presents unique challenges in pregnancy due to the risk of neonatal morbidity and mortality from maternal TSH Receptor antibodies (TRAb). A maternity hospital in Queensland has implemented a policy to identify at-risk neonates and facilitate follow-up, including cord blood TRAb, thyroid function tests (TFTs), and clinic appointments. To evaluate current neonatal follow-up practices for mothers with Graves' disease, assess missed opportunities for biochemical testing and propose recommendations to improve clinical care. This retrospective audit covered deliveries between 1st January 2018 to 31st December 2022. Baseline characteristics and follow-up were summarised by frequency and percentage. Maternal records were reviewed for demographic data, ultrasound follow up, TRAb titres, TFTs, and treatment details. Corresponding neonatal charts were then reviewed for cord blood TRAb levels, TFTs on days 3-5 and days 10-14, and phone clinic appointments. Neonatal testing was indicated if the mother was positive for thyroid stimulating immunoglobulin (TSI) or if TRAb titres were > 3 times the upper limit of normal. Data from 70 mothers with active or previously treated Graves' disease were analysed; 18 pregnancies met criteria for neonatal testing. Compliance with recommended testing was suboptimal, with variable adherence to TFT testing and only 10% undergoing cord blood TRAb measurement. This audit highlights the importance of standardised protocols and ongoing education to optimise neonatal follow-up and improve outcomes for neonates born to mothers with Graves' disease. Recommendations for education, improved documentation and policy updates have been provided with the aim for further audits to ensure ongoing quality improvement.

In silico modelling of changes in spinal cord blood flow after endovascular aortic aneurysm repair.

Prevalence of group B Streptococcus colonization in pregnant women and serotype specific immunity among mother-newborns dyads in Ghana and Zimbabwe.

We evaluated the diagnostic yield of karyotype (KT) and chromosomal microarray (CMA) with isolated severe FGR diagnosed before 32weeks' gestation. Exome and genome sequencing (ES/GS) level data were available in a subset of this population. We performed a retrospective review of singleton pregnancies (delivered 2022-2025) with estimated fetal weight or abdominal circumference <3rd percentile before 32weeks' gestation, no sonographic structural anomalies, and diagnostic testing (KT, CMA, ES, or GS) via amniocentesis or cord blood. Cases with abnormal cell-free DNA were excluded. Forty cases were included (mean diagnosis 26.8weeks). Testing was performed via amniocentesis in 42% and cord blood in 58%. All KT (27/40) were normal. CMA (39/40) identified one pathogenic CNV (2.5%) and three (7.5%) variants of uncertain significance (VUS). Four (10%) showed ≥ 1 region of absence of heterozygosity (AOH)>10Mb; one revealed maternal uniparental disomy of chromosome 6. Sequencing (N=10) detected one VUS in COL1A1. Acute viral infection was not observed in any of the cases. CMA was diagnostic in 2/39 (5.1%) cases, a pathogenic CNV implicating the SHOX gene, and maternal UPD 6, which were consistent with FGR. There was a remarkable rate (10%) of AOH. Further investigation, including placental studies and genome sequencing, may elucidate whether AOH is a contributing factor for FGR.

F-53B (6:2 Cl-PFESA), a major replacement for perfluorooctanesulfonate (PFOS), is frequently detected in human cord blood, yet its developmental neurotoxicity risks remain poorly characterized. This study establishes a quantitative testing strategy coupling in vitro phenotypic profiling, transcriptomics, and a probabilistic adverse outcome pathway-Bayesian network (AOP-BN) with pregnancy physiologically based pharmacokinetic (PBPK) modeling. Using human embryonic neural stem cells, we found that F-53B induced dose-dependent oxidative stress and mitochondrial dysfunction, resulting in compromised neurogenesis. Transcriptomics supported these phenotypic results. We derived a benchmark dose of 3.26 μmol/g of protein for learning and memory impairment and utilized AOP-BN to quantify the probability of adverse outcomes across exposure gradients. By coupling this framework with a pregnancy PBPK model, we estimated fetal brain concentrations of 0.09-14.66 ng/mL (Q5-Q95) based on human biomonitoring data. While these levels remain below the point of departure for downstream neurogenic defects, the narrow margins of exposure for early molecular events, specifically ROS elevation, indicate potential safety concerns. Consequently, this study identifies oxidative stress as a sensitive trigger for F-53B toxicity and demonstrates a robust, mechanistically anchored framework for human-relevant risk assessment of emerging PFAS.

To examine B cell-activating factor (BAFF) and type I interferon (IFN) activity at the transcriptional and protein levels in blood and placental tissue in SLE compared with healthy pregnancies to assess their relationship and to determine whether BAFF levels are associated with pregnancy outcomes in SLE. In the SLE-Placenta study, we followed women with SLE (n=83) and healthy controls (n=67) throughout pregnancy. Blood samples were collected in all trimesters and at delivery from peripheral blood, placental intervillous blood and cord blood. Postpartum blood samples were obtained from a subset of women with SLE. Bulk messenger RNA (mRNA) sequencing was performed on peripheral blood mononuclear cells (PBMCs) and placental tissue from a subgroup of women with SLE and healthy controls. BAFF concentrations were measured by ELISA and IFNα protein levels by single-molecule array (Simoa). Women with SLE had upregulated BAFF (TNFSF13B) and IFN-stimulated gene expression in PBMCs and placenta compared with controls. BAFF blood levels were consistently and significantly higher in SLE throughout pregnancy and inversely correlated with circulating B cell numbers. SLE pregnancies with IF-ANA or anti-dsDNA positivity displayed higher BAFF levels than antibody-negative pregnancies but BAFF showed no association with disease activity. Both BAFF and IFNα concentrations were higher in placental than peripheral blood in SLE, whereas only BAFF showed additional accumulation in cord blood. Finally, elevated BAFF levels were associated with shorter pregnancy duration in SLE but not in healthy pregnancy. Pregnant women with SLE exhibited persistently elevated BAFF levels, which were associated with lower B cell numbers, SLE-related autoantibody positivity and shorter pregnancy duration. Together with a disease-specific placental enrichment of IFNα, these findings support the presence of an inflammatory and potentially pathogenic IFN-BAFF signature in SLE pregnancy. Further studies are needed to determine the functional consequences of these immunological alterations on maternal-fetal health in SLE.

Autophagy is a crucial cellular degradation pathway that maintains homeostasis during stress. Preterm infants are exposed to significant oxidative and metabolic stress during the perinatal transition. This study aimed to evaluate the levels of autophagy markers (Beclin-1, LC3B-I and LC3B-II) in the umbilical cord blood of preterm infants and investigate their association with neonatal morbidities and mortality. This prospective multicentre cohort study included 60 preterm infants. Umbilical cord blood samples were analysed for Beclin-1, LC3B-I and LC3B-II levels using Western blot. The LC3B-I/LC3B-II ratio was calculated as an indicator of autophagic flux. The relationship between these markers and major neonatal outcomes (respiratory distress syndrome (RDS), intraventricular haemorrhage (IVH), haemodynamically significant patent ductus arteriosus (hsPDA), early neonatal sepsis (ENS) and mortality) was evaluated using Mann-Whitney U tests and multivariable logistic regression adjusted for gestational age. A significant positive correlation was observed between gestational age and Beclin-1 levels (r=0.406, p=0.005). In subgroup analyses, non-survivors exhibited significantly lower median Beclin-1 levels (0.45 vs 0.92, p=0.047) and a depressed LC3B-I/LC3B-II ratio (0.48 vs 1.90, p=0.018) compared with survivors. Similarly, infants with IVH had significantly lower LC3B-I levels (0.07 vs 0.65, p=0.011). However, in multivariable logistic regression analyses adjusted for gestational age, the independent statistical significance of these markers was attenuated, suggesting that the observed autophagic impairment is closely linked to gestational immaturity. No significant associations were found for RDS, hsPDA or ENS. This study identifies lower cord blood Beclin-1 levels and an altered LC3B ratio as potential markers of vulnerability in preterm infants, particularly for mortality and IVH. The findings suggest that autophagic capacity at birth is developmentally regulated, with more immature infants displaying compromised autophagy initiation.

Neonatal uterine bleeding (NUB) has been hypothesized as a relatively common early-life event potentially linked to the later development of endometriosis through retrograde menstruation. However, its true prevalence and biological nature remain uncertain. This study aimed to determine the prevalence, biological features, and maternal-neonatal correlates of reddish diaper staining in newborns, and to evaluate its purported association with endometriosis. A prospective cross-sectional study was conducted between September 2023 and March 2024 at a tertiary obstetric center with postpartum outpatient follow-up. A total of 638 pregnant women with singleton pregnancies (530 female and 108 male fetuses) were enrolled. Participants completed prenatal questionnaires, and neonatal outcomes, including diaper staining, were assessed during follow-up. Diapers with reddish staining were collected and analyzed using light microscopy and biochemical assays to identify the presence and origin of blood. Umbilical cord blood samples from female newborns were analyzed for steroid hormone concentrations. Reddish diaper staining was observed in 22% of female and 13% of male neonates. Only two female samples (2.5%) tested positive for menstrual blood. Most of the reddish diapers contained urate crystals rather than blood. Maternal characteristics, exposure to endocrine-disrupting factors, and cord blood steroid hormone levels did not differ significantly between female neonates with and without reddish diaper staining. These findings indicate that reddish diaper staining in neonates is predominantly due to urate crystal excretion rather than true NUB.By identifying a major and previously unrecognized confounder, this study calls into question a long-standing biological assumption and reshapes current understanding of NUB and its supposed link to endometriosis. Our results provide a substantial paradigm shift in the interpretation of this phenomenon, redefining its clinical and biological significance and opening new perspectives for research in early-life determinants of reproductive health.

Metabolomic signatures of SSRI exposure during neural differentiation and correlation of lysophosphatidylcholines with early symptoms of neurodevelopmental disorders.

To evaluate kidney biopsy findings to clarify renal disease in patients after hematopoietic stem cell transplantation (HSCT) using unrelated umbilical cord blood transplantation (UCBT). We retrospectively examined 14 patients who underwent UCBT at Toranomon Hospital, Tokyo, Japan, from 2015 to 2023 and subsequently developed kidney injury requiring biopsy. At biopsy, median urinary protein was 0.57 g/day (IQR, 0.27-1.67), median serum creatinine was 1.97 mg/dL (IQR, 1.81-2.6), and median eGFR was 25.3 mL/min/1.73 m2 (IQR, 18.1-34.2). In 13 of 14 patients, mesangiolysis, glomerular basement membrane (GBM) duplication, and subendothelial widening without thrombi were observed-lesions defined as glomerular microangiopathy (GMA). Immunofluorescence and electron microscopy revealed no immune deposits typical of membranous nephropathy. Eleven patients showed distinctive arterial and arteriolar changes termed vascular microangiopathy. Nine exhibited severe interstitial fibrosis and tubular basement membrane duplication involving > 50% of the cortex. Human leukocyte antigen (HLA) incompatibility was found in 13 patients (92.9%) and ABO incompatibility in nine (64.2%). C4d positivity in glomeruli or peritubular capillaries was detected in 12 patients (85.7%). The coexistence of glomerular, vascular, and tubulointerstitial microangiopathic lesions was associated with mild proteinuria and renal dysfunction after UCBT. These findings suggest a chronic endothelial injury process distinct from classical thrombotic microangiopathy.

Leptin communicates the body's energy utilisation and maintains a stable body weight. Preterm neonates often show rapid compensatory catch-up growth, which may increase the risk of obesity later in life. Although leptin regulates adiposity, its epigenetic role in the obesity risk of preterm neonates remains unclear. Global and LEP promoter methylation, leptin and IGF1 levels, and expression of LEP and IL6 genes were measured in umbilical cord blood from preterm and term deliveries. Genome-wide and LEP-specific methylation were decreased, while circulatory leptin, LEP, LEPR, IL6, and TNFα expression were increased in preterm cord blood (p < 0.05). Cord blood leptin levels were positively associated with birth weight in preterm (r = 0.288, p = 0.03). LEP methylation was inversely associated (r = -0.506, p = 0.03) with IGF1, while IL6 expression positively correlated with leptin (r = 0.318, p = 0.05), and LEP expression (r = 0.278, p = 0.03) in preterm cord blood. The interplay between LEP methylation and IL6 can influence each other in promoting inflammation, which may increase the risk of obesity in preterm neonates in later life. While leptin's role in adiposity is established, its epigenetic influence on the obesity risk of preterm neonates is unknown. Epigenetic dysregulation of the LEP gene, together with increased expression of IL6 and TNFα, led to a pro-inflammatory state in preterm neonates. This is the first study to report LEP-specific promoter methylation and its association with pro-inflammatory markers, exploring early-life biomarkers for predicting obesity. Predicting early biomarkers of obesity might have implications for the early identification and management of metabolic disorders in preterm neonates. Maternal factors leading to preterm birth and cord blood leptin dysregulation in predicting obesity. Elevated blood pressure, infection, and lower haemoglobin in preterm disrupted epigenetic control of leptin and activated inflammation. Leptin dysregulation may affect satiety and body fat, thereby increasing the risk of obesity. Solid arrows depict present data, and dotted lines indicate potential pathways.

Bronchopulmonary dysplasia (BPD) is the most common respiratory disease in preterm infants born at less than 28 weeks gestation. Most existing clinical prediction models for BPD show limited accuracy in predicting BPD development when validated using external data, stressing the need for novel biomarkers to identify at-risk infants for early and effective interventions. We leveraged existing frozen umbilical cord blood samples from the Northwestern University Cord Blood Biobank (NUCord) to perform parallel transcriptional and DNA methylation profiling in a pilot study. Chorioamnionitis-associated differentially expressed genes (DEGs) in our cohort included markers previously established in clinical and animal BPD studies, such as genes related to NF-κB signaling and immune responses. Importantly, these genes were highly associated with chorioamnionitis infection status specifically in preterm infants. We also identified that BPD development is associated with disrupted methylation signatures in microRNA genes and genes associated with glucose metabolism. Taken together, these exploratory findings suggest that BPD development and chorioamnionitis are associated with distinct transcriptomic and epigenetic signatures when compared with healthy term and preterm infants. These signatures may represent biomarkers measurable at birth that predict BPD development during a time window when preventative or therapeutic interventions could be applied.

Hematopoietic stem and progenitor cells support a lifetime supply of blood and immune cells and constitute a powerful cell therapy platform for hematologic diseases. In this study, we define oxygen-dependent activities of hematopoietic stem and progenitor cells. We found that lineage-defined progenitor cells from umbilical cord blood, bone marrow, and mobilized peripheral blood showed increased expansion in high oxygen, while primitive cells- including those from cord blood with in vivo potency- were maintained at higher frequencies in low physiologic O2. Single cell transcriptomic profiling of hematopoiesis under varying oxygen revealed the expected modulation of molecular hypoxia programs, including HIF and MTORc signaling. Transcriptomics also identified genes that are understudied in the context of oxygen dependency including MDM4 pathway and PRSS2, which we found is an mRNA biomarker for hematopoietic cell potency. Transcriptional changes together with biochemical validation revealed that low oxygen preserves cells with lower metabolic activity in a less proliferative state that exhibit decreased accumulation of stress markers. This likely occurs via dynamic interplay of multiple molecular programs and may drive differences in cell potency. Collectively, these data identify oxygen-sensing pathways as targets to improve cell therapies and suggest that local oxygenation dictates hematopoietic potential in anatomic niches.