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Background: The optimal choice for graft‐versus‐host disease (GVHD) prophylaxis in haploidentical stem cell transplantation (haplo‐SCT) remains debatable. Posttransplant cyclophosphamide (PTCy) and anti‐thymocyte globulin (ATG) are two common strategies, but little is known about their combination. Methods: Using the European Society for Blood and Marrow Transplantation (EBMT) registry, the authors identified 3649 adult patients with acute myeloid leukemia (AML) who underwent haplo‐SCT in complete remission between 2007 and 2021 at 260 EBMT‐participating centers who received either PTCy (n = 2999), ATG (n = 358), or combination prophylaxis (n = 292). Cord blood transplants, combined bone marrow and peripheral grafts, and transplants with ex vivo graft manipulation were excluded. Median follow‐up was 31.8 months. Results: On multivariate analysis, adjusting for patient age and performance status, disease status at transplant, cytogenetic risk, conditioning intensity, stem cell source, female‐to‐male graft, and donor and patient CMV status, we present the following. Compared to PTCy, ATG had a higher risk of nonrelapse mortality (hazard ratio [HR], 1.6; p =.003), worse leukemia‐free survival (HR, 1.4; p =.002), overall survival (HR, 1.49; p =.0009), and GVHD‐free and relapse‐free survival (HR, 1.29; p =.012). The combination of PTCy and ATG, however, led to significantly reduced rates of grade 2–4 (HR, 0.51; p =.0003) and grade 3–4 (HR, 0.5; p =.018) acute GVHD and did not affect any transplant outcomes compared to PTCy without ATG. Conclusion: The authors conclude that ATG alone is a less effective prophylaxis strategy compared to PTCy, however, the combination of PTCy and ATG is superior to either monotherapy. They propose that this combination could be considered a potential new standard of care for GVHD prophylaxis in haplo‐SCT for AML. This study analyzed 3649 adult acute myeloid leukemia (AML) patients undergoing haploidentical stem cell transplantation (haplo‐SCT) with either posttransplant cyclophosphamide (PTCy), anti‐thymocyte globulin (ATG), or their combination, and showed that ATG alone had worse outcomes compared to PTCy, but combining PTCy and ATG significantly reduced acute graft‐vs‐host disease (GVHD) rates without affecting transplant outcomes. This suggests the PTCy and ATG combination could be a superior GVHD prophylaxis strategy in haplo‐SCT for AML. [ABSTRACT FROM AUTHOR]

Background: Premature infants requiring mechanical ventilation and supplemental oxygen for respiratory support are at increased risk for bronchopulmonary dysplasia (BPD), wherein inflammation have been proposed as a driver of hyperoxia-induced injuries, including persistent loss of endothelial progenitor cells (EPCs), impaired vascularization and eventual alveolar simplification in BPD lungs. However, the underlying mechanisms linking these phenomena remain poorly defined. Methods: We used clodronate liposomes to deplete macrophages in a mouse model of neonatal hyperoxia-induced lung injury to evaluate if EPC loss in BPD lungs could be an effect of macrophage infiltration. We further generated in vitro culture systems initiated with cord blood (CB)-derived CD34+ EPCs and neonatal macrophages either polarized from CB-derived monocytes or isolated from tracheal aspirates of human preterm infants requiring mechanical ventilation and oxygen supplementation, to identify EV-transmitted molecular mechanism that is critical for inhibitory actions of hyperoxic macrophages on EPCs. Results: Initial experiments using mouse model identified the crucial role of macrophage infiltration in eliciting significant reduction of c-Kit+ EPCs in BPD lungs. Further examination of this concept in human system, we found that hyperoxia-exposed neonatal macrophages hamper human CD34+ EPC maintenance and impair endothelial function in the differentiated progeny via the EV transmission of miR-23a-3p. Notably, treatment with antagomiR-23a-3p to silence miR-23a-3p in vivo enhances c-Kit+ EPC maintenance, and increases capillary density, and consequently mitigates simplified alveolarization in BPD lungs. Conclusion: Our findings highlight the importance of pulmonary intercellular communication in the pathophysiology of BPD, by identifying a linkage through vesicle transfer of miR-23a-3p from hyperoxic macrophages to EPCs, and thus demonstrating potential for novel therapeutic target in BPD. [ABSTRACT FROM AUTHOR]

Background: Neurodevelopmental performance tasks are often separately analyzed, even when they tap into a similar construct. This may yield mixed findings for associations of an exposure-neurobehavioral outcome. We develop an item response theory (IRT) approach to integrate multiple task variables together to improve measurement precision of the underlying construct. We apply this approach to create an integrative measure of childhood inhibitory control, and study impacts of pre/post-natal lead exposure. Methods: Using data from a prospective cohort based in Mexico (N = 533), we created an inhibitory control scale that integrates accuracy and reaction time information from four inhibitory control tasks (Go/NoGo Letter, Go/NoGo Neutral, Go/NoGo Happy, Delis-Kaplan Executive Function System (D-KEFS) Color-Word Interference Test, Condition 3). Using a generalized partial credit item response theory model, we estimated an inhibitory control index for each participant. We then assessed adjusted associations between umbilical cord blood and 4-year lead and childhood inhibitory control. We developed a resampling approach to incorporate error estimates from the inhibitory control variable to confirm the consistency of the lead-inhibitory control associations. We modeled time-varying associations of lead with each inhibitory control measure separately. Results: Participants had a median age of 9 years; 51.4% were males. Umbilical cord blood [-0.06 (95% CI: -0.11, -0.01)] and 4-year lead [-0.07 (95% CI: -0.12, -0.02)] were associated with inhibitory control index at 8–10 years. A resampling approach confirmed that 4-year lead was consistently associated with childhood inhibitory control index. Umbilical cord blood and 4-year lead were each associated with 3 out of 8 measures in separate models. Conclusion: This is the first application of IRT in environmental epidemiology to create a latent variable for inhibitory control that integrates accuracy and reaction time information from multiple, related tasks. This framework can be applied to other correlated neurobehavioral assessments or other phenotype data. Key messages: We are among the first to use item response theory to create an integrative measure of childhood inhibitory control, using multiple performance-tasks to improve measurement precision and construct validity. We combined information about speed and accuracy on each inhibitory control performance-task using theory driven considerations. We developed a resampling approach using plausible value imputation to account for measurement error of inhibitory control factor scores in estimating associations between lead exposures and inhibitory control. Higher lead exposure at birth, and during preschool age, were both associated with worse childhood inhibitory control. In boys, lead exposure at birth was associated with worse childhood inhibitory control, while in girls, lead exposure during preschool age was associated with worse childhood inhibitory control. [ABSTRACT FROM AUTHOR]

Aim: Autism spectrum disorder (ASD) is associated with abnormal lipid metabolism, such as a high total ratio of omega‐6 to omega‐3 in polyunsaturated fatty acids (PUFAs). PUFAs are metabolized to epoxy fatty acids by cytochrome P450 (CYP); then, dihydroxy fatty acid is produced by soluble epoxide hydrolase. This study examined the association between PUFA metabolites in the cord blood and ASD symptoms and adaptive functioning in children. Methods: This prospective cohort study utilized cord blood to quantify PUFA metabolites of the CYP pathway. The Autism Diagnostic Observation Schedule (ADOS‐2) and Vineland Adaptive Behaviors Scales, Second Edition (VABS‐II) were used to assess subsequent ASD symptoms and adaptive functioning in children at 6 years. The analysis included 200 children and their mothers. Results: Arachidonic acid‐derived diols, 11,12‐diHETrE was found to impact ASD symptom severity on the ADOS‐2‐calibrated severity scores and impairment in the socialization domain as assessed by the VABS‐II (P = 0.0003; P = 0.004, respectively). High levels of 11,12‐diHETrE impact social affect in ASD symptoms (P = 0.002), while low levels of 8,9‐diHETrE impact repetitive/restrictive behavior (P = 0.003). Notably, there was specificity in the association between diHETrE and ASD symptoms, especially in girls. Conclusion: These findings suggest that the dynamics of diHETrE during the fetal period is important in the developmental trajectory of children after birth. Given that the role of diol metabolites in neurodevelopment in vivo is completely uncharacterized, the results of this study provide important insight into the role of diHETrE and ASD pathophysiology. [ABSTRACT FROM AUTHOR]

Background: There are no large studies to define the normal value of glycated haemoglobin (HbA1c) measured in full term pregnant women measured at the time of delivery. Research design and methods: The study was conducted at three government hospitals in South India. Clinical data, maternal blood sample and foetal cord blood sample were collected from women admitted for safe confinement. Mean (± SD) of HbA1c in participants with no known diabetes (gestational or pregestational) or any complications (maternal or fetal) is described, 2.5th–97.5th centile reference range was derived. Results: From 3 centres, 2004 women participated in the study. Data from 1039 participants who had no history of diabetes or any maternal or fetal complication were used to determine the reference range for HbA1c at term pregnancy. The mean HbA1c in subjects devoid of diabetes and its known complications was 5.0 (± 0.39) %. The reference range for normal HbA1c at term in these women was found to be 4.3–5.9%. Maternal HbA1c at term pregnancy in non-diabetic pregnant women is associated with pre-pregnancy BMI, maternal age and 2-h plasma glucose level of 2nd trimester oral glucose tolerance test (OGTT). Conclusions: The mean HbA1c at term pregnancy in non-diabetic women admitted for safe confinement is 5.00 (± 0.39) %. An HbA1c of 5.9% or more at term should be considered abnormal and women with such a value may be kept at a close surveillance for development of diabetes. [ABSTRACT FROM AUTHOR]

Neonate responses to pathogen-associated molecular patterns (PAMPS) differ from adults; such understanding is poor in Indian neonates, despite recognized significant infectious risk. Immune profiling analysis was undertaken of 10 secreted mediators contextualized with cellular source induced by six PAMPs in umbilical cord (CB; n = 21) and adult-blood (PBMC; n = 14) from a tertiary care hospital in South India. Differential cytokine expression analysis (minimum log2-fold difference; adj P-value < 0.05) identified bacterial PAMPs induced higher concentrations of IL-1β, IL-10, TNF-α in adults versus IL-8, GM-CSF, IFN-γ, and IL-2 in CB. CB responded to poly I:C and SARS-CoV-2 lysate with a dominant IL-8 response, whereas in PBMC, CXCL-10 dominated poly I:C, but not SARS-CoV-2, responses, highlighting potential IL-8 importance, in the absence of Type I Interferons, in antiviral CB immunity. Candida albicans was the only PAMP to uniformly induce higher secretion of effectors in CB. The predominant source of IL-8/IL-6/TNF-α/IL-1β in both CB and PBMC was polyfunctional monocytes and IFN-γ/IL-2/IL-17 from innate lymphocytes. Correlation matrix analyses revealed IL-8 to be the most differentially regulated, correlating positively in CB versus negatively in PBMC with IL-6, GM-CSF, IFN-γ, IL-2, consistent with more negatively regulated cytokine modules in adults, potentially linked to higher anti-inflammatory IL-10. Cord and adult blood from India respond robustly to PAMPs with unique effector combinations. These data provide a strong foundation to monitor, explore, mechanisms that regulate such immunity during the life course, an area of significant global health importance given infection-related infant mortality incidence. Immune profiling analysis was conducted on umbilical cord blood (CB; n=21) and adult peripheral blood mononuclear cells (PBMC; n=14) from India. Six pathogen-associated molecular patterns (PAMPs) were used to stimulate immune responses. Differential secreted cytokine expression analysis, relative to no stimulation control, as measured by a multiplex ELISA, revealed PAMP-specific distinct effectors patterns. The predominant cellular source of IL-8/IL-6/TNF-a/IL-1ß in both CB and PBMC, as determined by intracellular cytokine staining, was polyfunctional monocytes and IFN-? /IL-2/IL-17/IL-10 from innate lymphocytes. Graphical Abstract [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to demonstrate the establishment of adrenal sparing in intrauterine growth restricted (IUGR) human fetuses. IUGR fetuses are a subgroup of small for gestational age (SGA) fetuses that are unable to reach their own growth potential because of chronic hypoxia and undernutrition. We hypothesized that in IUGR fetuses the adrenal gland is relatively larger and secretion of noradrenaline (NA), adrenaline (A), and cortisol is increased. Study Design: This is a prospective observational study including 65 singleton pregnancies (42 IUGR and 23 controls). Using two‐dimensional ultrasound, we measured fetal adrenal diameters and adrenal/abdominal circumference (AD/AC) ratio between 25 and 37 weeks. We considered only one measurement per fetus. In 21 pregnancies we also measured NA, A, and cortisol levels in arterial and venous fetal cord blood collected at the time of delivery. Results: The AD/AC ratio was significantly higher in IUGR fetuses than in controls. Cord NA and A levels were significantly higher in IUGR fetuses than in controls. An increase in cortisol secretion in IUGR fetuses was observed but the difference was not statistically significant. Conclusions: Adrenal sparing correlates with a relative increase in adrenal measurements and function. Synopsis: The adrenal gland of intrauterine growth‐restricted fetuses is relatively larger compared with controls and its function is enhanced. [ABSTRACT FROM AUTHOR]

Phaeohyphomycosis is caused by dematiaceous (pigmented) fungi. Most phaeohyphomycosis is non-invasive infections, however, they can lead to invasive infections, including fungemia and disseminated disease, particularly in severely immunocompromised patients. Invasive phaeohyphomycosis has recently emerged, however, the treatment strategy was not determined because of the intrinsic resistance to antifungals and the lack of clinical experience. Here, we describe a novel case of echinocandin-breakthrough Coniochaeta hoffmannii (Lecythophora hoffmannii) fungemia after hematopoietic stem cell transplantation, which was identified using matrix-assisted laser desorption ionization time-of-flight mass spectrometry and ribosomal RNA sequencing. The patient was a female in her 40s who had acute myeloid leukemia refractory to chemotherapy before progressing to cord blood transplantation. Before developing fungemia, the patient was administered multiple broad-spectrum antibiotics and micafungin for recurrent infections and prophylaxis. Clinical and microbiological responses to liposomal amphotericin B were poor but improved after replacement to voriconazole and engraftment. A literature review of the previously reported cases with C. hoffmannii human infections imply that disruption of the cutaneous/mucosal barrier and the use of antimicrobial agents, both antibiotics and antifungals, could incite C. hoffmannii invasive infections. [ABSTRACT FROM AUTHOR]

Mode of birth has been linked to offspring health. Changes in DNA methylation (DNAm) may represent a potential mechanism; however, findings are heterogeneous and limited to early infancy. This preregistered study examined whether mode of birth (vaginal birth compared with elective or emergency cesarean section) affects DNAm at birth, in childhood, and adolescence and whether these effects are modified by the postnatal care environment, specifically by breastfeeding and mother–infant bonding. Using data from 876 mother–infant dyads from the U.K. Avon Longitudinal Study of Parents and Children, we examined differentially methylated cytosine-phosphate-guanine dinucleotides and regions associated with mode of birth. DNAm was quantified using Illumina Infinium Human Methylation 450 K BeadChip in cord blood (at birth) and in peripheral blood (at 7 and 15–17 years). Analyses controlled for maternal age, education, smoking during pregnancy, child sex, gestational week at birth, and batch effects. We also examined interactions of mode of birth with breastfeeding practices and mother–infant bonding. In cord blood, two cytosine-phosphate-guanine dinucleotides (cg05230316; cg13230077) were linked to mode of birth (pFDR <.050). DNAm in childhood or adolescence was not statistically associated with mode of birth (pFDR >.050), and breastfeeding and mother–infant bonding were not moderators (p >.050). Overall, findings suggest mode of birth may have a small effect on cord blood DNAm, but these effects may not persist into later developmental stages. Other postnatal influences should be considered, and further investigation is needed to address study limitations. Public Significance Statement: This study suggests that the mode of birth, whether a child is born vaginally or by emergency or elective cesarean section, has a small effect on how the child's genes are methylated in cord blood cells at birth. DNA methylation in peripheral blood cells during childhood and adolescence was not predicted by mode of birth. Breastfeeding and mother–infant bonding did not buffer the effects of mode of birth, highlighting the necessity to further investigate other postnatal factors as potential determinants of the offspring methylome across development. [ABSTRACT FROM AUTHOR]

Advances in single‐cell level analytical techniques, especially cytometric approaches, have led to profound innovation in biomedical research, particularly in the field of clinical immunology. This has resulted in an expansion of high‐dimensional data, posing great challenges for comprehensive and unbiased analysis. Conventional manual analysis is thus becoming untenable to handle these challenges. Furthermore, most newly developed computational methods lack flexibility and interoperability, hampering their accessibility and usability. Here, we adapted Seurat, an R package originally developed for single‐cell RNA sequencing (scRNA‐seq) analysis, for high‐dimensional flow cytometric data analysis. Based on a 20‐marker antibody panel and analyses of T‐cell profiles in both adult blood and cord blood (CB), we showcased the robust capacity of Seurat in flow cytometric data analysis, which was further validated by Spectre, another high‐dimensional cytometric data analysis package, and conventional manual analysis. Importantly, we identified a unique CD8+ T‐cell population defined as CD8+CD45RA+CD27+CD161+ T cell that was predominantly present in CB. We characterised its IFN‐γ‐producing and potential cytotoxic properties using flow cytometry experiments and scRNA‐seq analysis from a published dataset. Collectively, we identified a unique human CB CD8+CD45RA+CD27+CD161+ T‐cell subset and demonstrated that Seurat, a widely used package for scRNA‐seq analysis, possesses great potential to be repurposed for cytometric data analysis. This facilitates an unbiased and thorough interpretation of complicated high‐dimensional data using a single analytical pipeline and opens a novel avenue for data‐driven investigation in clinical immunology. [ABSTRACT FROM AUTHOR]

Authors have expressed reservations regarding the use of base deficit measured in umbilical artery blood samples to assess fetal well-being during the course of labor and to predict neonatal neurologic morbidity. Despite its integration into clinical practice for more than 50 years, obstetricians and maternal-fetal medicine specialists may not realize that this marker has significant limitations in accurately identifying neonatal metabolic acidosis as a proxy for fetal well-being. In brief, there are 2 large families of base deficit, namely whole blood and extracellular fluid. Both rely on equations that use normal adult acid-base characteristics (pH 7.40 and partial CO 2 pressure of 40 mm Hg) that overlook the specificity of the normal in utero acid-base status of pH 7.27 and partial CO 2 pressure of 54 mm Hg. In addition, it ignores the unique characteristic of the in utero fetal response to acute hypoxia. The dependence on placental circulation for CO 2 elimination may lead to extremely high values (up to 130 to 150 mm Hg) during hypoxic events, a phenomenon that is absent in adults with acute metabolic acidosis who can hyperventilate. The dispute over if to include a correction for high partial CO 2 pressure in the bicarbonate estimation, as presented in the Great Trans-Atlantic Debates, remains unresolved. The key constants computed for adult acid-base physiology in the current base deficit algorithms, without accounting for the impact of high partial CO 2 pressure or other fetal characteristics of buffering capacity (eg, differences in body water content composition, plasma protein, and hemoglobin attributes), may lead to an overestimation of metabolic acidosis, especially in newborns who are experiencing hypercarbia during the early stages of the hypoxic response. These unrecognized limitations impact the base deficit results and may mislead clinicians on fetal well-being assessments when discussing the management of fetal heart rate monitoring and neonatal outcomes. Based on our arguments, we believe that it is prudent to consider an alternative to base deficit for drawing conclusions regarding fetal well-being during the course of birth management. We propose a marker specifically related to the newborn acid-base physiology––the neonatal eucapnic pH correction. This marker can be added to arterial cord blood gas analysis, and we have described how to interpret it as a marker of neonatal metabolic acidosis. [Display omitted] [ABSTRACT FROM AUTHOR]

Hematopoietic stem cell transplants for inherited metabolic disorders performed at Tokai University Hospital between June 5, 1986, and May 28, 2021, were analyzed and compared between the period before 2007 and the period from 2007 onward based on availability of medical resources. Transplants were performed for 38 patients with mucopolysaccharidosis, 33 with adrenoleukodystrophy, and 16 with another disorder. Before 2007, oral busulfan-based regimens were mainly used. From 2007 onward, intravenous busulfan-based regimens or 4 Gy of thoracoabdominal irradiation (TAI), fludarabine, and melphalan (Mel)/treosulfan were adopted. Between 2002 and 2010, adrenoleukodystrophy was treated with 12 Gy of TAI and Mel. HLA-identical sibling bone marrow was used in 43% of cases before 2007 and 15% from 2007 onward, while alternative donors were selected for other transplants. Overall survival and event-free survival (EFS) before 2007 and from 2007 onward were 76% and 62%, and 97% and 85%, respectively (P = 0.006 and 0.017). Transplant era predicted superior overall survival and EFS, while myeloablative conditioning also predicted EFS. The incidence of primary graft failure decreased from 2007 onward, especially in cord blood transplant when 4 Gy of TAI with 150 mg/m2 fludarabine and 180 mg/m2 Mel or 42 g/m2 treosulfan were used as conditioning. [ABSTRACT FROM AUTHOR]

Background: Fetal inflammatory response syndrome (FIRS) is a systemic inflammatory response caused by the activation of the fetal immune system. The serological diagnostic criterion for fetal inflammatory response syndrome is a cord blood interleukin-6 concentration that exceeds 11 pg/mL, while pathologic evidence indicates the presence of funisitis or chorionic vasculitis. It can affect all systems of the fetus. Alterations in patients' hematopoietic system are primarily reflected by changes in peripheral blood leukocyte and neutrophil counts. Case presentation: We performed placental pathology to identify FIRS and showed two cases of neonatal leukemoid reaction caused by FIRS. These two babies' alterations in hematopoietic system resolves spontaneously with the inflammation relief, without specific interventions. During the 16‑month and14- month follow‑up period, their motor and intellectual development was normal. Conclusions:. Neonatal leukemoid reaction is a reactive disease characterized by abnormal blood parameters similar to those of leukemia, but not leukemia. It is an aberrant hematopoietic response that typically resolves spontaneously with cause relief without requiring specific interventions. [ABSTRACT FROM AUTHOR]

Prenatal exposure to toxins can adversely affect long-term health outcomes of the offspring. Though chemotherapeutics are now standard of care for treating cancer patients during pregnancy, certain compounds are known to cross the placenta and harm placental tissue. The consequences for the fetus are largely unexplored. Here we examined the responses of newborn cord blood mononuclear cells in tissue culture to two chemotherapeutic drugs, cyclophosphamide and epirubicin, when either directly exposed to these drugs, or indirectly after crossing a placenta trophoblast bilayer barrier. Cord blood mononuclear cells exposed to the conditioned media obtained from cyclophosphamide-exposed trophoblast barriers showed a significant 2.4-fold increase of nuclear ROS levels compared to direct exposure to cyclophosphamide. Indirect exposure to epirubicine-exposed trophoblast barriers not only enhanced nuclear ROS levels but also significantly increased the fraction of cord blood cells with double strand breaks, relative to directly exposed cells. Neither apoptosis nor proliferation markers were affected in cord mononuclear blood cells upon direct or indirect exposure to cyclophosphamide or epirubicin. Our data suggests that trophoblast cells exposed to cyclophosphamide or epirubicine may induce an indirect 'bystander' effect and can aggravate genotoxicity in the fetal compartment. [ABSTRACT FROM AUTHOR]

Introduction: Dolutegravir (DTG)-based antiretroviral therapy is the World Health Organization's preferred first-line regimen for all persons with HIV, including pregnant women. While DTG has been implicated as an obesogen associated with greater weight gain compared to other antiretrovirals, there is a paucity of data in pregnant women and their children. The Obesogenic oRigins of maternal and Child metabolic health Involving Dolutegravir (ORCHID) study is investigating associations between DTG, weight gain, and metabolic outcomes in the context of HIV. Materials & methods: ORCHID is a prospective observational study taking place in Cape Town, South Africa (NCT 04991402). A total of 1920 pregnant women with and without HIV infection are being followed from ≤18 weeks gestational age to 24 months postpartum with their children. Participants attend eleven study visits: 3 antenatal, delivery, and 7 postnatal visits. Several embedded sub-studies address specific scientific aims. Primary outcome measurements in mothers include anthropometry, blood pressure, body composition, dysglycemia, insulin resistance (IR), and dyslipidemia. Other maternal measures include demographics, resting energy expenditure, viral load, physical activity, dietary intake, hepatic steatosis, and repository specimens. Sub-study measurements include markers of adipose inflammation, gut integrity, and satiety/hunger, subcutaneous adipose tissue morphology and mitochondrial function, and metabolomics. Primary outcome measurements in children include anthropometry, adipose tissue mass, dysglycemia, IR, and dyslipidemia. Other variables include fetal growth, birth outcomes, medical/breastfeeding history, caloric intake, neurodevelopment, and repository specimens. Sub-study measurements include metabolites/lipid subspecies in umbilical cord blood, as well as breast milk composition and DTG exposure. Discussion: ORCHID will play a pivotal role in defining obesogenic mechanisms and clinical consequences of DTG use in pregnancy in women with HIV and their children. It will provide insights into metabolic disease risk reduction in the context of HIV/DTG, identify intervention targets, and inform public health approaches to diminish chronic metabolic co-morbidities for women and children. [ABSTRACT FROM AUTHOR]

Malaria blood‐stage parasite is a critical pathogenic stage responsible for serious adverse outcomes in pregnant women and their neonates. Immunoglobulin G (IgG) antibody responses specific to various asexual blood‐stage antigens were well reported in non‐pregnant individuals. However, little is still known during placental malaria. To assess the antibody responses specific to Plasmodium falciparum‐derived MSP3 and UB05 malaria vaccine candidates in mother‐neonate couples, mother's peripheral blood and neonate's cord blood samples were collected at delivery. After malaria diagnostic, plasma levels of IgG and IgG subclass responses specific to UB05, MSP3 and UB05‐MSP3 were determined using ELISA. As outcomes, both mothers and neonates had significantly higher IgG responses to UB05 and UB05‐MSP3 compared to anti‐MSP3 IgG (p < 0.05), irrespective of malaria status. Significant negative correlations were observed between IgG levels specific to the three antigens and parasitaemia (p < 0.01). Anti‐UB05 and anti‐UB05‐MSP3 IgG levels in neonates showed a significant positive correlation with the corresponding mothers' antibodies (rs = 0.25 with p = 0.04; rs = 0.31 with p = 0.01, respectively). UB05MSP3‐specific IgG3 and IgG1 subclass responses were significantly higher than the IgG4 subclass (p < 0.01). The neonates IgG1 and IgG3 levels positively correlated with the corresponding antibody subclasses of mothers. These findings suggest an association between UB05 and UB05‐MSP3‐specific antibody responses and malaria control during pregnancy. Maternal–foetal transfer of MSP3 and UB05‐specific IgG occurs during pregnancy, suggesting the interest in the future malaria vaccination strategies in pregnant women to generate early protective immunity in baby against malaria. [ABSTRACT FROM AUTHOR]

Background: Maternal smoking has been linked to adverse health outcomes in newborns but the extent to which it impacts newborn health has not been quantified through an aggregated cord blood DNA methylation (DNAm) score. Here, we examine the feasibility of using cord blood DNAm scores leveraging large external studies as discovery samples to capture the epigenetic signature of maternal smoking and its influence on newborns in White European and South Asian populations. Methods: We first examined the association between individual CpGs and cigarette smoking during pregnancy, and smoking exposure in two White European birth cohorts (n=744). Leveraging established CpGs for maternal smoking, we constructed a cord blood epigenetic score of maternal smoking that was validated in one of the European-origin cohorts (n=347). This score was then tested for association with smoking status, secondary smoking exposure during pregnancy, and health outcomes in offspring measured after birth in an independent White European (n=397) and a South Asian birth cohort (n=504). Results: Several previously reported genes for maternal smoking were supported, with the strongest and most consistent association signal from the GFI1 gene (6 CpGs with p<5 × 10-5). The epigenetic maternal smoking score was strongly associated with smoking status during pregnancy (OR = 1.09 [1.07, 1.10], p=5.5 × 10-33) and more hours of self-reported smoking exposure per week (1.93 [1.27, 2.58], p=7.8 × 10-9) in White Europeans. However, it was not associated with self-reported exposure (p>0.05) among South Asians, likely due to a lack of smoking in this group. The same score was consistently associated with a smaller birth size (–0.37±0.12 cm, p=0.0023) in the South Asian cohort and a lower birth weight (–0.043±0.013 kg, p=0.0011) in the combined cohorts. Conclusions: This cord blood epigenetic score can help identify babies exposed to maternal smoking and assess its long-term impact on growth. Notably, these results indicate a consistent association between the DNAm signature of maternal smoking and a small body size and low birth weight in newborns, in both White European mothers who exhibited some amount of smoking and in South Asian mothers who themselves were not active smokers. [ABSTRACT FROM AUTHOR]

Background: Hemolytic disease of the fetus and newborn (HDFN) is caused by maternal antibodies attacking fetal blood cell antigens. Despite routine antenatal anti-D prophylaxis, intrauterine transfusions (IUTs) are still needed in some HDFN cases. Methods: We conducted a retrospective cohort study on newborns with HDFN born in the 1st Department of Obstetrics and Gynecology of the Medical University of Warsaw. We analyzed 274 neonates with HDFN, identifying 46 who required IUT due to fetal anemia and 228 who did not. The laboratory results, management, and outcomes were compared between these groups. Results: Comparative analysis showed that newborns treated with IUT were more likely to have significant anemia, hyperbilirubinemia, and iron overload, indicated by a high ferritin concentration. These neonates more often required top-up transfusions, phototherapy, intravenous immunoglobulin infusions, and exchange transfusions. The length of stay was longer for newborns who received IUT. Conclusions: HDFN requiring IUT is associated with a greater number of complications in the neonatal period and more often requires additional treatment compared to HDFN not requiring IUT. [ABSTRACT FROM AUTHOR]

Galectin-3 belongs to a family of soluble glycan-binding proteins, which are increasingly recognized as modulators of pregnancy-associated processes, including proper placental development. Gestational hypertension and preeclampsia are significant complications of pregnancy, affecting millions of women annually. Despite their prevalence, the underlying pathophysiological mechanisms remain poorly understood. Several theories have been proposed, including inflammation, placental insufficiency, disturbed placental invasion, and angiogenesis. The Scopus and PubMed/MEDLINE databases were utilized until the end of May 2024. In total, 11 articles with 1011 patients, with 558 in the control group and 453 in the preeclampsia group, were included. Seven articles investigated the expression of galectin-3 (Gal-3) in placental tissue samples, eight studies calculated the serum levels of Gal-3 in maternal blood samples, while one study referred to the possible correlation of galectin-3 levels in umbilical cord blood. The results were inconsistent in both the placental tissue and maternal serum; Gal-3 placental expression was found to be statistically increased in five studies compared to that in women without gestational hypertensive disorders, while two studies either mentioned decreased expression or no difference. Similarly, the Gal-3 maternal serum levels, compared to those in women without gestational hypertensive disorders, were found to be statistically increased in five studies, while three studies did not find any statistical difference. Gal-3 can play a crucial role in the pathogenesis of preeclampsia, and its expression is influenced by gestational age and placental insufficiency. A further investigation ought to be conducted to enlighten the correlation of Gal-3 with gestational hypertension and preeclampsia development. [ABSTRACT FROM AUTHOR]

To evaluate the role of brain-derived neurotrophic factor (BDNF)—a crucial modulator of neural development and plasticity—in the association between prenatal maternal anxiety, depression, and perceived stress and child neurodevelopment in a prospective cohort study. We included 526 eligible mother-child pairs from the Shanghai Birth Cohort in the study. Maternal mental health was assessed at mid-pregnancy using Zung's Self-Rating Anxiety Scale, Center for Epidemiologic Studies Depression Scale, and Perceived Stress Scale. The concentration of BDNF in cord blood was measured by ELISA. The offspring neurodevelopment at 24 months of age was assessed using the Bayley Scales. Linear and non-linear regression models were used. The average cord blood BDNF levels were higher in female newborns and those born via vaginal delivery, full term, and normal birth weight. Prenatal maternal anxiety (β = −0.32; 95 % CI: −0.55, −0.09), depression (β = −0.30; 95 % CI: −0.52, −0.08), and perceived stress (β = −0.41; 95 % CI: −0.71, −0.12) scores were negatively associated with social-emotional performance at 24 months of age. However, no significant associations were found between prenatal maternal anxiety, depression, or perceived stress at mid-pregnancy and cord blood BDNF levels, as well as between cord blood BDNF levels and child neurodevelopment. Maternal mental health at different timepoints during pregnancy and generalizability of the results warrant further assessment. Prenatal mental health was not associated with cord blood BDNF level and that BDNF may not be a mediator in the association between prenatal mental health and child neurodevelopment. • No statistically significant correlations were found between prenatal maternal mental health and cord blood BDNF levels. • BDNF was not associated with neurodevelopment in 2-year-olds, except for a non-linear relationship with the cognitive domain. • BDNF may not mediate the link between maternal mental health during pregnancy and early childhood neurodevelopment. [ABSTRACT FROM AUTHOR]

Background: Empirical evidence has demonstrated associations between pre-pregnancy obesity and perinatal maternal depressive symptoms. Omega-3 is an essential fatty acid derived from dietary sources that is critical for fetal brain development. Pre-pregnancy obesity is associated with higher omega-3 intake, but a weaker association between dietary intake and respective maternal and cord blood omega-3 levels. Further, lower intake of omega-3 during pregnancy has been linked to higher depressive symptoms. Yet, prior studies have not examined the interactive effects of pre-pregnancy overweight or obesity (OWOB) and prenatal maternal mental health symptoms on infant cord blood omega-3 levels. Methods: Participants included 394 maternal-infant dyads from the NIH Environmental influences on Child Health Outcomes (ECHO) - Safe Passage Study in South Dakota. A pre-pregnancy body mass index (BMI) > 25 was used to dichotomize participants as OWOB (54%) vs. non-OWOB (46%). Prenatal maternal depressive symptoms were measured using the Edinburgh Postnatal Depression Scale (EPDS) and prenatal maternal anxiety symptoms were measured using the State-Trait Anxiety Inventory (STAI). We implemented linear regression models to examine the interaction term between pre-pregnancy BMI category and prenatal maternal mental health symptoms on cord blood omega-3 levels. Secondary analyses were stratified by pre-pregnancy BMI category. Results: We observed a significant interaction between pre-pregnancy BMI category and prenatal maternal depressive symptoms with cord blood omega-3 (F(4,379) = 6.21, p <.0001, adj. R2 = 0.05). Stratified models revealed an association between prenatal maternal depressive symptoms with lower cord blood omega-3 levels only among individuals with pre-pregnancy OWOB (β = -0.06, 95% CI = -0.11, -0.02; F (2,208) = 4.00, p <.05, adj R2 = 0.03). No associations were observed among non-OWOB participants. Conclusions: Findings suggest maternal-placental transfer of omega-3 may represent one pathway by which maternal metabolic and mental health impacts infant development. [ABSTRACT FROM AUTHOR]

Background: Using natural killer (NK) cells to treat hematopoietic and solid tumors has great promise. Despite their availability from peripheral blood and cord blood, stem cell-derived NK cells provide an "off-the-shelf" solution. Methods: In this study, we developed two CAR-NK cells targeting PD-L1 derived from lentiviral transduction of human umbilical cord blood (UCB)-CD34+ cells and UCB-CD34+-derived NK cells. The transduction efficiencies and in vitro cytotoxic functions including degranulation, cytokine production, and cancer cell necrosis of both resultants PD-L1 CAR-NK cells were tested in vitro on two different PD-L1 low and high-expressing solid tumor cell lines. Results: Differentiated CAR‑modified UCB-CD34+ cells exhibited enhanced transduction efficiency. The expression of anti-PD-L1 CAR significantly (P < 0.05) enhanced the cytotoxicity of differentiated CAR‑modified UCB-CD34+ cells and CAR-modified UCB-CD34+-derived NK cells against PD-L1 high-expressing tumor cell line. In addition, CAR-modified UCB-CD34+-derived NK cells significantly (P < 0.05) restored the tumor-killing ability of exhausted PD-1 high T cells. Conclusion: Considering the more efficient transduction in stem cells and the possibility of producing CAR-NK cell products with higher yields, this approach is recommended for studies in the field of CAR-NK cells. Also, a pre-clinical study is now necessary to evaluate the safety and efficacy of these two CAR-NK cells individually and in combination with other therapeutic approaches. [ABSTRACT FROM AUTHOR]

This document is a commentary on the issue of platelet insecurity and the need for action to address it. It discusses the unpredictable supply of platelets for transfusion and the potential threat to the healthcare system, particularly in cancer care and trauma. A virtual conference was held to discuss this issue, with sessions focusing on factors contributing to platelet insecurity and potential solutions. The commentary includes perspectives from various institutions in the United States and Canada, emphasizing strategies such as increasing platelet donor bases, implementing pathogen reduction technology, and improving platelet inventory management. The text also discusses challenges related to platelet inventory management in hospitals and the military, as well as the need for surge capacity in the blood supply during mass casualty incidents. It highlights the efforts to ensure a safe and adequate blood supply, the challenges in identifying transfusion-transmitted infections, and the importance of rapid deployment of platelet inventory. The document also mentions the limitations of weather forecasting and the potential impact of weather events on the platelet supply. Thrombocytopenia, a condition characterized by low platelet count, is a challenge in cancer therapy, and various approaches have been explored to improve platelet recovery. The demand for platelets is increasing, and efforts are being made to manage limited platelet supplies. The use of cold-stored platelets is being explored as a potential solution, but more research is needed. The document also provides a list of references covering various topics related to blood transfusion and the development of new therapies for [Extracted from the article]

The article offers information on the role of inhibiting immunoglobulin G (IgG) to prevent hemolytic disease of the fetus and newborn (HDFN). Topics discussed include the mechanism of action of the monoclonal antibody nipocalimab; the potential benefits of delaying intrauterine transfusion; and the need for further clinical trials to determine its efficacy and safety.

BACKGROUND In early-onset severe hemolytic disease of the fetus and newborn (HDFN), transplacental transfer of maternal antierythrocyte IgG alloantibodies causes fetal anemia that leads to the use of high-risk intrauterine transfusions in order to avoid fetal hydrops and fetal death. Nipocalimab, an anti--neonatal Fc receptor blocker, inhibits transplacental IgG transfer and lowers maternal IgG levels. METHODS In an international, open-label, single-group, phase 2 study, we assessed treatment with intravenous nipocalimab (30 or 45 mg per kilogram of body weight per week) administered from 14 to 35 weeks' gestation in participants with pregnancies at high risk for recurrent early-onset severe HDFN. The primary end point was live birth at 32 weeks' gestation or later without intrauterine transfusions as assessed against a historical benchmark (0%; clinically meaningful difference, 10%). RESULTS Live birth at 32 weeks' gestation or later without intrauterine transfusions occurred in 7 of 13 pregnancies (54%; 95% confidence interval, 25 to 81) in the study. No cases of fetal hydrops occurred, and 6 participants (46%) did not receive any antenatal or neonatal transfusions. Six fetuses received an intrauterine transfusion: five fetuses at 24 weeks' gestation or later and one fetus before fetal loss at 22 weeks and 5 days' gestation. Live birth occurred in 12 pregnancies. The median gestational age at delivery was 36 weeks and 4 days. Of the 12 live-born infants, 1 received one exchange transfusion and one simple transfusion and 5 received only simple transfusions. Treatment-related decreases in the alloantibody titer and IgG level were observed in maternal samples and cord blood. No unusual maternal or pediatric infections were observed. Serious adverse events were consistent with HDFN, pregnancy, or prematurity. CONCLUSIONS Nipocalimab treatment delayed or prevented fetal anemia or intrauterine transfusions, as compared with the historical benchmark, in pregnancies at high risk for early-onset severe HDFN. (Funded by Janssen Research and Development; UNITY ClinicalTrials.gov number, NCT03842189.) [ABSTRACT FROM AUTHOR]

Background: Production of anti-phosphatidylserine (anti-PS) antibodies has been associated with malaria and can aggravate pathology. How these autoantibodies develop during early childhood in a malaria context is not known. We examined levels of anti-PS IgG and IgM antibodies in a longitudinal cohort of mother-baby pairs during birth, in the infants at 2.5, 6 months, and in mothers and their babies at 9 months postpartum. Results: There was no difference between levels of anti-PS IgG in cord blood and the mothers' peripheral blood at birth. However, anti-PS IgM levels were significantly higher in the mothers compared to the infants' cord blood, and IgM levels were steadily increasing during the first 9 months of the infants' life. In infants that had the highest anti-PS IgM levels at birth, there was a decline until 6 months with a rise at 9 months. Infants that possessed high anti-PS IgG at birth also exhibited a progressive decline in levels. When anti-PS were correlated to different fractions of B-cells, there were several correlations with P. falciparum specific atypical B cells both at birth and at 2.5 months for the infants, especially for anti-PS IgM. Anti-PS also correlated strongly to C1q-fixing antibodies at birth. Conclusion: These results show that anti-PS IgG acquired by mothers could be transferred transplacentally and that IgM antibodies targeting PS are acquired during the first year of life. These results have increased the knowledge about autoimmune responses associated with infections in early life and is critical for a comprehensive understanding of malaria vaccine functionality in endemic areas. [ABSTRACT FROM AUTHOR]

Background: Vitamins A and D are essential for the health of pregnant women and infants. Nevertheless, the relationship between umbilical cord blood vitamins A and D levels and the physical growth of exclusively breastfed infants remains uncertain. Objective: This cohort study aims to examine the relationship between cord blood vitamins A and D levels and the physical growth of exclusively breastfed infants aged 0-6 months. Methods: 140 singleton mother-infant pairs were recruited in total. Questionnaires were used to collect maternal and infant information, and liquid chromatography was utilized to quantify the levels of vitamins A and D in the umbilical cord blood. Anthropometric measurements were conducted at birth, at 3 and 6 months of age, and the weight-for-age z-score (WAZ), length-for-age z-score (LAZ), head circumference-for-age z-score (HAZ), and BMI-forage z-score (BMIZ) were calculated. Univariate and multivariate linear regression models were used for the analysis. Results: The average concentration of vitamins A and D in cord blood was 0.58 ± 0.20 mmol/L and 34.07 ± 13.35 nmol/L, both below the normal range for children. After adjusting for confounding factors, vitamin A levels in cord blood positively correlated with HAZ growth in infants aged 3-6 months (β= 0.75, P < 0.01) while vitamin D levels negatively correlated with LAZ growth (β= -0.01, P = 0.01) and positively correlated with BMIZ growth (β= 0.02, P < 0.01). Conclusion: Higher Vitamin A levels at birth promote HAZ growth in infants aged 3-6 months while higher vitamin D levels at birth promote BMIZ growth in infants aged 3-6 months. [ABSTRACT FROM AUTHOR]

Background: Preterm infants are at high risk for retinopathy of prematurity (ROP), with potential life-long visual impairment. Low fetal hemoglobin (HbF) levels predict ROP. It is unknown if preventing the HbF decrease also reduces ROP. Methods: BORN is an ongoing multicenter double-blinded randomized controlled trial investigating whether transfusing HbF-enriched cord blood-red blood cells (CB-RBCs) instead of adult donor-RBC units (A-RBCs) reduces the incidence of severe ROP (NCT05100212). Neonates born between 24 and 27 + 6 weeks of gestation are enrolled and randomized 1:1 to receive adult donor-RBCs (A-RBCs, arm A) or allogeneic CB-RBCs (arm B) from birth to the postmenstrual age (PMA) of 31 + 6 weeks. Primary outcome is the rate of severe ROP at 40 weeks of PMA or discharge, with a sample size of 146 patients. A prespecified interim analysis was scheduled after the first 58 patients were enrolled, with the main purpose to evaluate the safety of CB-RBC transfusions. Results: Results in the intention-to-treat and per-protocol analysis are reported. Twenty-eight patients were in arm A and 30 in arm B. Overall, 104 A-RBC units and 49 CB-RBC units were transfused, with a high rate of protocol deviations. A total of 336 adverse events were recorded, with similar incidence and severity in the two arms. By per-protocol analysis, patients receiving A-RBCs or both RBC types experienced more adverse events than non-transfused patients or those transfused exclusively with CB-RBCs, and suffered from more severe forms of bradycardia, pulmonary hypertension, and hemodynamically significant patent ductus arteriosus. Serum potassium, lactate, and pH were similar after CB-RBCs or A-RBCs. Fourteen patients died and 44 were evaluated for ROP. Ten of them developed severe ROP, with no differences between arms. At per-protocol analysis each A-RBC transfusion carried a relative risk for severe ROP of 1.66 (95% CI 1.06–2.20) in comparison with CB-RBCs. The area under the curve of HbF suggested that HbF decrement before 30 weeks PMA is critical for severe ROP development. Subsequent CB-RBC transfusions do not lessen the ROP risk. Conclusions: The interim analysis shows that CB-RBC transfusion strategy in preterm neonates is safe and, if early adopted, might protect them from severe ROP. Trial registration: Prospectively registered at ClinicalTrials.gov on October 29, 2021. Identifier number NCT05100212. [ABSTRACT FROM AUTHOR]

Gestational hypertension (PIH), especially pre-eclampsia (PE), is a common complication of pregnancy. This condition poses significant risks to the health of both the mother and the fetus. Emerging evidence suggests that epigenetic modifications, particularly DNA methylation, may play a role in initiating the earliest pathophysiology of PIH. This article describes the relationship between DNA methylation and placental trophoblast function, genes associated with the placental microenvironment, the placental vascular system, and maternal blood and vascular function, abnormalities of umbilical cord blood and vascular function in the onset and progression of PIH, as well as changes in DNA methylation in the progeny of PIH, in terms of maternal, fetal, and offspring. We also explore the latest research on DNA methylation-based early detection, diagnosis and potential therapeutic strategies for PIH. This will enable the field of DNA methylation research to continue to enhance our understanding of the epigenetic regulation of PIH genes and identify potential therapeutic targets. [ABSTRACT FROM AUTHOR]

Summary Rearrangement of NUTM1 gene (NUTM1r) is one of the most frequent aberrations occurring in infants (younger than 1 year at diagnosis) with B‐cell precursor Acute Lymphoblastic Leukaemia (BCP‐ALL). In this study we had the unique opportunity to analyze the umbilical cord blood (UCB) sample from one infant patient with NUTM1r BCP‐ALL. Herein we reported for the first time that NUTM1r infant ALL arise prenatally, as both the patient‐specific CUX1::NUTM1 fusion gene, as well as two IG/TR leukaemic markers were already present and detectable in the patient's UCB at birth. Our results clearly demonstrate the prenatal origin of NUTM1r infant BCP‐ALL. [ABSTRACT FROM AUTHOR]

Background: This study aimed to address the increasing prevalence of cesarean section and the importance of evaluating newborn health through arterial blood gas analysis. Its primary objective was to compare the umbilical cord blood gas levels in newborns delivered through different delivery methods. Method: This retrospective descriptive cross-sectional study included singleton pregnancies with a gestational age between 37 and 42 weeks and infants weighing between 2500 and 4000 g. Newborns with an Apgar score of 7 or higher at 1 and 5 min were included. Umbilical cord blood samples were collected from each newborn for blood gas analysis within 60 min after birth. Result: The study included 340 neonates, with 170 born via caesarean section and 170 born through vaginal delivery. No significant differences were observed in Apgar scores between two groups. ABG analysis showed that vaginally born neonates had lower pH (7.24 ± 0.08 vs. 7.27 ± 0.07, P < 0.001), PCO2 (P = 0.015), and HCO3 (P < 0.001). Cesarean section neonates had higher oxygen saturation (P = 0.007) and pressure of oxygen (P < 0.001), and less negative base excess (P < 0.001). In the subgroup analysis, neonates whose mothers received epidural anesthesia had lower pH (7.23 ± 0.07 vs. 7.25 ± 0.08, P = 0.021) and more negative base excess (P = 0.026). Other parameters of ABG did not differ significantly between the groups (P > 0.05). Conclusion: It has been proven that the mode of delivery, whether it is vaginal or cesarean, as well as the administration of epidural anesthesia during vaginal delivery, have a significant impact on newborns at birth. Newborns delivered vaginally exhibit metabolic acidosis compared to those delivered via cesarean section. Although these differences are statistically significant, they do not have a notable clinical significance, as the average values of the evaluated parameters in both groups fall within the normal range. [ABSTRACT FROM AUTHOR]

Purpose: There are abundant hematopoietic stem cells (HSCs) in cord blood. It is known that HSCs continue to differentiate to CLP, CMP and erythroid progenitor cells (EPC), EPC ultimately differentiated to platelets and erythrocytes. It has been reported that the proportion of HSCs in cord blood was higher than that in healthy pregnant women, so as the incidence of neonatal polycythemia in gestational diabetes mellitus (GDM) patients. We aimed to investigate whether the hyperglycemic and/or hyperinsulin environment in GDM patients has effects on the differentiation of HSCs into erythrocytes in offspring cord blood. Methods: In this study, we collected cord blood from 23 GDM patients and 52 healthy pregnant women at delivery. HSCs, CLP, CMP and EPCs in cord blood of the two groups were identified and quantified by flow cytometry. HSCs were sorted out and treated with glucose and insulin, respectively, and then, the changes of HSCs proliferation and differentiation were detected. Results: Compared to healthy controls, HSCs, CMP and EPC numbers in cord blood from GDM group were significantly increased, while CLP cell number was decreased. The differentiation of HSCs into EPC was promoted after treatment with glucose or insulin. Conclusion: There were more HSCs in the cord blood of GDM group, and the differentiation of HSCs to EPCs was increased. These findings were probably caused by the high-glucose microenvironment and insulin medication in GDM patients, and the HSCs differentiation changes might be influencing factors of the high incidence of neonatal erythrocytosis in GDM patients. [ABSTRACT FROM AUTHOR]

Objectives Methods Results Conclusions We aimed to characterize and investigate the safety and efficacy of Plonmarlimab, a novel anti‐granulocyte‐macrophage colony‐stimulating factor (anti‐GM‐CSF) neutralizing antibody, on the treatment of macrophage activation syndrome (MAS), a life‐threatening systemic inflammatory disease, in pre‐clinical models.The binding affinity was evaluated using Biacore. The neutralizing activity was measured through the blockade of ligand–receptor interaction, inhibition of STAT5 phosphorylation and suppression of TF‐1 cell proliferation. The efficacy of Plonmarlimab was evaluated in a humanized MAS model, which was established by engrafting human umbilical cord blood (UCB) cells into NOG‐EXL mice. Additionally, the safety profile of Plonmarlimab was investigated in cynomolgus monkeys.At the molecular level, Plonmarlimab showed sub‐nanomolar binding affinity with human GM‐CSF and effectively blocked the binding of GM‐CSF to its receptor. At the cellular level, Plonmarlimab dose‐dependently inhibited intracellular STAT5 phosphorylation and suppressed GM‐CSF‐induced TF‐1 proliferation. In the UCB‐engrafted NOG‐EXL MAS mouse model, Plonmarlimab treatment significantly ameliorated disease progression, demonstrated by the improvements in body weight loss, anaemia and some histopathological features. Furthermore, Plonmarlimab was well tolerated up to 150 mg/kg weekly in monkeys with no reported adverse effects.Plonmarlimab is a highly potent GM‐CSF blocking antibody and has demonstrated promising efficacy in a pre‐clinical MAS model with a favourable safety profile, supporting its clinical development. [ABSTRACT FROM AUTHOR]

• Increased pregnancy adiponectin was associated with lower infant negative affect. • Pregnancy Adiponectin mediated the effect of pregnancy adiposity on infant negative affect. • Greater cord blood leptin was associated with increased negative affect. • Pregnancy adipokines may be novel biomarkers of offspring risk for psychopathology. Increased adiposity during pregnancy may be related to offspring risk for mental health disorders, although the biological mechanisms are poorly understood. One promising hypothesis is that factors secreted from adipocytes such as leptin and adiponectin may explain this association. The current study examined whether pregnancy or umbilical cord blood concentrations of leptin and/or adiponectin a) predict elevated infant negative affect at 6 months (an early life marker of risk for psychopathology); and b) help explain the association between pregnancy adiposity and increased infant negative affect. Data came from a prospective cohort (N = 305) of pregnant individuals and their offspring. Second trimester adiposity was assessed using air displacement plethysmography. Concentrations of leptin and adiponectin were measured in second trimester plasma and umbilical cord plasma. Infant negative affect was assessed by standardized observation at 6 months. Second trimester inflammation was assessed using a comprehensive panel of cytokines. Lower second trimester adiponectin was associated with elevated infant negative affect, and mediated the effect of pregnancy adiposity on infant negative affect. This association was independent of the effect of second trimester inflammation. Umbilical cord leptin also predicted higher infant negative affect and mediated the association between pregnancy adiposity and infant negative affect. This is the first study to link pregnancy adiponectin or cord blood leptin to infant markers of risk for psychopathology, and the first to demonstrate that these adipokines mediate the association between pregnancy adiposity and offspring behavioral outcomes, suggesting novel markers of risk and potential mechanisms of effect. [ABSTRACT FROM AUTHOR]

Endocrine-disrupting environmental chemicals are a public health concern, particularly fetal exposure to Bisphenol derivatives. This study aimed to assess fetal exposure to Bisphenol derivatives (BPA, BPF, and BPS) by measuring their levels in cord blood and investigating their association with plastic material used in daily life as well as cord blood TSH and free L-thyroxine (fT4) levels. In this descriptive study, a questionnaire with a face-to-face interview was administered before birth, and cord blood samples were taken immediately after delivery. The mean levels of BPA, BPF, TSH, and fT4 were measured as 10.69 ± 2.39 ng/ml, 3.80 ± 0.58 ng/ml; 2.36 ± 0.23 µIU/ml, and 14.18 ± 0.53 pg/ml, respectively, in a total of 104 cord blood samples. All BPS levels remained below the detection limit. Linear regression analysis revealed a positive association between birth weight and cord blood BPA concentration (β = 0.26; p = 0.02). Further research on maternal exposure during the fetal and neonatal period is critical for public health. [ABSTRACT FROM AUTHOR]

Introduction: Our objective was to investigate the association between the presence of placental anastomoses and intertwin differences in renin‐angiotensin‐aldosterone activation in monochorionic twins using amniotic fluid aldosterone (AF‐ALD) levels. In addition, this study also examined the association between AF‐ALD and the ALD levels in the umbilical cord blood (UCB‐ALD) in monochorionic twins. Material and Methods: This prospective study included monochorionic diamniotic (MD) twin pregnancies that were not complicated by twin‐to‐twin transfusion syndrome (TTTS) at delivery. Amniotic fluid and umbilical cord vein blood samples were collected from each twin at delivery, and the ALD levels were measured subsequently. The MD twins were divided into two groups: those with placental anastomoses and those without anastomoses owing to fetoscopic laser surgery. The differences in the AF‐ALD levels between the larger and smaller twins were analyzed. Results: The AF‐ALD levels showed a strong and significant positive correlation with UCB‐ALD levels in 131 MD twins (r = 0.804, p < 0.001). Intertwin differences were examined in 41 and 28 pairs of MD twins with and without placental anastomoses, respectively. The AF‐ALD levels in the smaller twins were significantly higher than those in the larger twins among the pairs of MD twins with placental anastomoses (p = 0.003); however, no statistically significant intertwin differences were observed among the twins without placental anastomoses (p > 0.05). Conclusions: The AF‐ALD levels reflect the UCB‐ALD levels in MD twins. The presence of placental anastomoses led to intertwin discordance in the ALD levels in MD twins even uncomplicated with TTTS. It was considered that monochorionic twins have this clinical background, and it leads to the development of TTTS. [ABSTRACT FROM AUTHOR]

Background and Objectives: In Japan, cord blood transplantations exceed those done with adult‐sourced unrelated stem cells. This study analyses cord blood (CB) storage criteria to maintain high‐quality CB units. Materials and Methods: The Kanto‐Koshinetsu Cord Blood Bank received 29,795 units from 2014 to 2021, mostly >60 mL, and 5486 (18.4%) were stored as transplantable units. We investigated the mother's gestational period, CB volume, total nucleated cells (TNCs), CD34+ cells, total colony‐forming units (CFUs), time from collection to reception and cryopreservation, cell viability, and the reasons for not storing a unit. Results: The average time from collection to reception of 29,795 units was 18.0 h. The most common reason for not storing a CB unit was low cell numbers (pre‐processing TNC count <1.2 billion), accounting for 67.9% of the units received. There was no correlation between the CB volume and the CD34+ cell count. The shorter the gestational period, the lower the TNC count, but the higher the CD34+ cell count. There was no correlation between the time from collection to cryopreservation, within a 36‐h time limit, and the CD34+ cell recovery rate. Conclusion: We could accept units with a TNC count <1.2 billion and a CB volume <60 mL from a gestational period of 38 weeks or less if we did a pre‐processing CD34+ cell count. This would secure more units rich in CD34+ cells. [ABSTRACT FROM AUTHOR]

Allogeneic natural killer (NK) cell therapy has been effective in treating cancer. Many studies have tested NK cell therapy using human pluripotent stem cells (hPSCs). However, the impacts of the origin of PSC-NK cells on competence are unclear. In this study, several types of hPSCs, including human-induced PSCs (hiPSCs) generated from CD34+, CD3−CD56+, and CD56− cells in umbilical cord blood (UCB), three lines of human embryonic stem cells (hESCs, ES-1. ES-2 and ES-3) and MHC I knockout (B2M-KO)-ESCs were used to differentiate into NK cells and their capacities were analyzed. All PSC types could differentiate into NK cells. Among the iPSC-derived NK cells (iPSC-NKs) and ESC-derived NK cells (ES-NKs), 34+ iPSCs and ES-3 had a higher growth rate and cytotoxicity, respectively, ES-3 also showed better efficacy than 34+ iPSCs. B2M-KO was similar to the wild type. These results suggest that the screening for differentiation of PSCs into NK cells prior to selecting the PSC lines for the development of NK cell immunotherapy is an essential process for universal allotransplantation, including the chimeric antigen receptor (CAR). [ABSTRACT FROM AUTHOR]

Summary Acute myeloid leukaemia (AML) is a heterogeneous disease characterized by complex molecular and cytogenetic abnormalities. Pro‐oxidant cellular redox status is a common hallmark of AML cells, providing a rationale for redox‐based anticancer strategy. We previously discovered that auranofin (AUF), initially used for the treatment of rheumatoid arthritis and repositioned for its anticancer activity, can synergize with a pharmacological concentration of vitamin C (VC) against breast cancer cell line models. In this study, we observed that this drug combination synergistically and efficiently killed cells of leukaemic cell lines established from different myeloid subtypes. In addition to an induced elevation of reactive oxygen species and ATP depletion, a rapid dephosphorylation of 4E‐BP1 and p70S6K, together with a strong inhibition of protein synthesis were early events in response to AUF/VC treatment, suggesting their implication in AUF/VC‐induced cytotoxicity. Importantly, a study on 22 primary AML specimens from various AML subtypes showed that AUF/VC combinations at pharmacologically achievable concentrations were effective to eradicate primary leukaemic CD34+ cells from the majority of these samples, while being less toxic to normal cord blood CD34+ cells. Our findings indicate that targeting the redox vulnerability of AML with AUF/VC combinations could present a potential anti‐AML therapeutic approach. [ABSTRACT FROM AUTHOR]

• Biomarkers to predict outcomes were assessed from the clinico-statistical approach. • A prospective multicenter observational study was performed. • Six promising biomarkers were successfully identified and validated. • C-reactive protein to platelet ratio was a novel biomarker to predict transplant outcomes. Various biomarkers have been developed and evaluated to predict the prognosis and complications of allogeneic hematopoietic cell transplantation (HCT). Most previous studies conducted on different biomarkers evaluated single effects such as those associated with inflammation, immunology, iron metabolism, and nutrition, and only a few studies have comprehensively analyzed markers. The study aimed to survey comprehensive multiple markers prior to HCT and extract those that significantly predict the outcomes. A prospective multicenter observational study was performed. (UMIN000013506) Patients undergoing HCT for hematologic diseases were consecutively enrolled. Besides the usual clinical biomarkers, serum samples for extra-clinical biomarkers were collected and cryopreserved before starting the conditioning regimen. A total of 32 candidate biomarkers were selected, 23 from hematology, biochemistry, immunology, nutrition, and iron metabolism, and 9 from composite markers. Based on the area under the curve (AUC) values for survival, promising biomarkers was extracted. Internal validation for these markers was applied based on bootstrap methods. Setting the cut-off values for them, log-rank test was applied and outcomes including overall survival (OS), relapse, and non-relapse mortality (NRM) were evaluated using multivariate analyses. Furthermore, detailed analysis including transplant-related complications and external validation were conducted focusing on C-reactive protein (CRP) to platelet (Plt) ratio. A total of 152 patients with hematologic malignancies were enrolled from April 2014 to March 2017. CRP, soluble interleukin-2 receptor (IL2R), CRP to albumin (Alb) ratio, CRP to Plt ratio, Plt to IL2R ratio, and IL2R to Alb ratio were identified as promising markers. Internal validation successfully confirmed their reliability of AUC and multivariate analysis demonstrated the statistical significance between the higher and the lower markers. Above all, a higher CRP to Plt ratio was significantly associated with a lower OS (hazard ratio [HR] 2.77; 95% confidence interval [CI] 1.30−5.91; P = 0.008) and higher non-relapse mortality rates (HR 2.79; 95%CI 1.14−6.80; P = 0.024) at 180 days. Furthermore, univariate analysis showed that a higher CRP to Plt ratio was significantly associated with a higher incidence of sinusoidal obstructive syndrome (P < 0.001) and bloodstream infection (P = 0.027). An external validation test confirmed the significance of the CRP to Plt ratio for these outcomes. The multicenter prospective observational study successfully identified significant biomarkers in patients with hematologic malignancies who received HCT. In particular, CRP to Plt ratio was identified as a novel and useful biomarker for predicting transplant outcomes. Further investigations are needed to validate the novel markers, analysis of the pathophysiology, and application to treatment settings other than HCT. [ABSTRACT FROM AUTHOR]

Objective In studies of concomitant arterial–venous umbilical cord blood gases (CAV-UBGs), approximately 10% of technically valid samples have very similar pH and/or pCO 2 values and were probably drawn from the same type of blood vessel. Without a way to objectively determine the source in these cases, it has been argued that most of these same-source CAV-UBGs are venous because the vein is larger and more easily sampled than the artery. This study aimed to calculate the probability of an arterial (ProbAS) or venous source (ProbVS) of same-source CAV-UBGs in the clinically and medicolegally important pH range of 6.70 to 7.25 using a statistical predictive model based on the cord blood gas values. Study Design Starting with a dataset of 56,703 CAV-UBGs, the ProbAS, ProbVS, and respective 95% confidence intervals (CIs) were calculated for the 241 sample pairs with near-identical pH, pCO 2 , and pO 2 values and a pH of 6.70 to 7.25. Using a previously validated generalized additive model, the source was categorized as: Probable Arterial or Highly Probable Arterial if the ProbAS and CIs were >0.5 or >0.8, respectively; Probable Venous or Highly Probable Venous if the ProbVS and CIs were >0.5 or >0.8, respectively; or Indeterminant if the CIs encompassed ProbAS/VS = 0.5. Results A total of 39% of the same-source CAV-UBGs were Probable Arterial, 56% were Probable Venous, and 5% were Indeterminant. However, considering samples with a pH ≤7.19, 80% were Probable Arterial and 16% were Probable Venous. Considering the Highly Probable categories, the more acidemic specimens were 9 times more likely to be arterial than venous. Similarly, CAV-UBGs with pCO 2 > 8.2 kPa (62 mm Hg) or pO 2 ≤ 1.9 kPa (14 mm Hg) were more likely to be in the arterial rather than the venous categories. Conclusion Same-source CAV-UBGs in the more acidemic, hypercarbic, or hypoxemic ranges are more likely to be arterial than venous. Key Points Umbilical cord arterial/venous gases (CAV-UBGs) with similar values are thought to be mainly venous. A validated statistical model was used to predict the probability an arterial or venous source. CAV-UBGs with very similar values and pH > 7.19 are likely venous; however, those with pH ≤ 7.19 and/or pCO 2 > 8.2 kPa and/or pO 2 ≤1.9 kPa are more likely arterial. [ABSTRACT FROM AUTHOR]

Drepanocytosis is a genetic disease relevant for its epidemiological, clinical and socio-economic aspects. In our country the prevalence is highly uneven with peaks in former malaria areas, but migration flows in recent years have led to significant changes. In this document we review the screening programs currently existing in Italy with particular emphasis on newborn screening, which in other countries around the world, including within Europe, is at most universal and mandatory. The essential laboratory issues are reviewed, from sampling aspects (cord blood or peripheral), to the analytical (analytical methods dedicated to neonatal screening and adult carrier detection) and post analytical (reporting, informative) ones. An economic analysis based on data collected in the province of Modena is also proposed, clearly showing that neonatal screening is also beneficial from an economic point of view. [ABSTRACT FROM AUTHOR]

Gestational diabetes mellitus (GDM) is a common pregnancy disorder associated with an increased risk of pre-eclampsia and macrosomia. Recent research has shown that the buildup of excess lipids within the placental trophoblast impairs mitochondrial function. However, the exact lipids that impact the placental trophoblast and the underlying mechanism remain unclear. GDM cases and healthy controls were recruited at Kaohsiung Medical University Hospital. The placenta and cord blood were taken during birth. Confocal and electron microscopy were utilized to examine the morphology of the placenta and mitochondria. We determined the lipid composition using liquid chromatography-mass spectrometry in data-independent analysis mode (LC/MSE). In vitro studies were carried out on choriocarcinoma cells (JEG3) to investigate the mechanism of trophoblast mitochondrial dysfunction. Results showed that the GDM placenta was distinguished by increased syncytial knots, chorangiosis, lectin-like oxidized low-density lipoprotein (LDL) receptor-1 (LOX-1) overexpression, and mitochondrial dysfunction. Lysophosphatidylcholine (LPC) 16:0 was significantly elevated in the cord blood LDL of GDM patients. In vitro, we demonstrated that LPC dose-dependently disrupts mitochondrial function by increasing reactive oxygen species (ROS) levels and HIF-1α signaling. In conclusion, highly elevated LPC in cord blood plays a pivotal role in GDM, contributing to trophoblast impairment and pregnancy complications. [ABSTRACT FROM AUTHOR]

This study aimed to document the safety and efficacy of a single infusion of autologous umbilical cord blood (UCB) in 20 autistic children aged 24–72 months. A pre‐post treatment within‐subjects open label design was used. At T = 0, 6, 12, and 18 months, participants underwent detailed and structured safety evaluations (via caregiver report), Vineland Adaptive Behavior Scale (Vineland‐3), Stanford Binet Intelligence Scale (SB‐5), Expressive One‐Word Picture Vocabulary Test, Brief Observation of Social Communication Change (BOSCC), Pervasive Developmental Disorder‐Behavior Inventory, Repetitive Behavior Scale‐Revised, Sensory Experience Questionnaire (SEQ‐2.1), Child Behavior Checklist, Clinical Global Impression‐Severity and Improvement (CGI‐I) Scales, and eye‐gaze tracking. UCB infusion was conducted at T = 6 months, hence, 0–6 months was the control period, and 6–18 months the follow‐up period. Of 20 children recruited, 19 completed the study and 1 was withdrawn due to UCB not meeting quality control criteria for infusion. There were 15 males and 4 females with an overall mean (SD) age of 4.15 (0.62) years. Mean (SD) cell dose administered was 38.16 (9.82) million cells/kg. None suffered serious adverse events although there were mild behavioral side effects and one unit grew coagulase negative staphylococcus from a post‐thaw sample. There were no significant differences in Vineland‐3, SB‐5, BOSCC, and SEQ‐2.1 scores at T = 12 and T = 18 months. Twelve participants had T = 18 CGI‐I scores of 2–3 (minimally to much improved), seven participants had scores of 4 (no change). Autologous UCB infusion in autistic children is generally safe but not without risks, including that of infection. In this within‐subjects study, some children showed global symptom improvements while others showed no change. Stem cell therapies for autism should only be conducted under strict clinical trial conditions with clear risk discussions. Lay Summary: This open label clinical trial investigated changes in language, social communication, autism symptoms, behavior, and eye‐gaze tracking in 20 autistic children, comparing a period when they were on regular behavioral interventions to a period after they had received an infusion of their own cord blood. Nineteen children completed the study, as one had to be withdrawn due to the cord blood unit not meeting quality control criteria to be safe enough for infusion. Although cord blood infusion was found to be generally safe, some children had mild temporary side effects affecting their behavior (increased repetitive behaviors, aggression/irritability, hyperactivity, mood swings, sleep problems). One child's cord blood unit sample also showed bacterial growth, although that child remained well after the infusion. Some children showed global symptom improvements while others showed no change. Stem cell therapies for autism should therefore only be conducted within clinical trials with clear risk discussions, including that of infection. [ABSTRACT FROM AUTHOR]

Orofacial clefts (OFCs) are the second most common birth defect worldwide. The etiology of OFCs involves complex interactions between genetics and environment. Advances in genomic technologies have identified gene variants associated with OFCs. This study aimed to investigate whether selected SNPs in the MYH9, MTHFR, MAFB, and SUMO1 genes influence the occurrence of non-syndromic OFCs in the Polish population. The study included 209 individuals with non-syndromic OFCs and 418 healthy controls. Saliva and umbilical cord blood samples were collected for DNA extraction. Four SNPs in the MYH9, MTHFR, MAFB, and SUMO1 genes were genotyped using real-time PCR-based TaqMan assays. Statistical analysis was performed using logistic regression to assess the association between SNPs and OFCs. A significant association was found between the rs7078 CC polymorphism and OFCs (OR = 3.22, CI 1.68–6.17, p < 0.001). No significant associations were identified for the rs1081131, rs13041247, and rs3769817 polymorphisms. The research indicates that the rs7078 polymorphism significantly influences the occurrence of orofacial cleft palate in the Polish population, whereas the rs3769817, rs1801131, and rs13041247 SNPs do not show such a correlation. [ABSTRACT FROM AUTHOR]

The review analyzes the results of modern high-tech research on the use of umbilical cord blood serum (plasma) as an additive to culture media for growing cell cultures. Since culture media are a key factor in cell culture, this review examines the composition and properties of the main culture media used in cell biology and regenerative medicine. The authors paid special attention to growth factors; the functional characteristics of the main families of these polypeptides are described (fibroblast growth factors, epidermal growth factors, transforming growth factors, growth differentiation, epidermal growth factors, endothelial cell growth factors, hematopoietic growth factors, etc.). It has been noted that one of the promising sources of growth factors is umbilical cord blood serum (plasma). The review presents the main technologies for obtaining umbilical cord blood, as well as systematizing studies reflecting the content of growth factors, cytokines, exosomes, and mRNA in umbilical cord blood; experimental data on the use of umbilical cord blood serum as an additive to culture media for growing various cultures of animal cells are described. Human cord blood serum, compared to animal sources, is an affordable, safe product containing high levels of bioactive molecules. For its widespread introduction as an additive to culture media, it is necessary to develop standards for the production and testing of this product. [ABSTRACT FROM AUTHOR]

Background: This study explores the potential role of Thioredoxin-interacting protein (TXNIP) silencing in endothelial colony-forming cells (ECFCs) within the scope of age-related comorbidities and impaired vascular repair. We aim to elucidate the effects of TXNIP silencing on vasculogenic properties, paracrine secretion, and neutrophil recruitment under conditions of metabolic stress. Methods: ECFCs, isolated from human blood cord, were transfected with TXNIP siRNA and exposed to a high glucose and β-hydroxybutyrate (BHB) medium to simulate metabolic stress. We evaluated the effects of TXNIP silencing on ECFCs' functional and secretory responses under these conditions. Assessments included analyses of gene and protein expression profiles, vasculogenic properties, cytokine secretion and neutrophil recruitment both in vitro and in vivo. The in vivo effects were examined using a murine model of hindlimb ischemia to observe the physiological relevance of TXNIP modulation under metabolic disorders. Results: TXNIP silencing did not mitigate the adverse effects on cell recruitment, vasculogenic properties, or senescence induced by metabolic stress in ECFCs. However, it significantly reduced IL-8 secretion and consequent neutrophil recruitment under these conditions. In a mouse model of hindlimb ischemia, endothelial deletion of TXNIP reduced MIP-2 secretion and prevented increased neutrophil recruitment induced by age-related comorbidities. Conclusions: Our findings suggest that targeting TXNIP in ECFCs may alleviate ischemic complications exacerbated by metabolic stress, offering potential clinical benefits for patients suffering from age-related comorbidities. [ABSTRACT FROM AUTHOR]

Umbilical cord blood (UCB) is a rich source of beneficial stem and progenitor cells with known angiogenic, neuroregenerative and immune-modulatory properties. Preclinical studies have highlighted the benefit of UCB for a broad range of conditions including haematological conditions, metabolic disorders and neurological conditions, however clinical translation of UCB therapies is lacking. One barrier for clinical translation is inadequate cell numbers in some samples meaning that often a therapeutic dose cannot be achieved. This is particularly important when treating adults or when administering repeat doses of cells. To overcome this, UCB cell expansion is being explored to increase cell numbers. The current focus of UCB cell expansion is CD34+ haematopoietic stem cells (HSCs) for which the main application is treatment of haematological conditions. Currently there are 36 registered clinical trials that are examining the efficacy of expanded UCB cells with 31 of these being for haematological malignancies. Early data from these trials suggest that expanded UCB cells are a safe and feasible treatment option and show greater engraftment potential than unexpanded UCB. Outside of the haematology research space, expanded UCB has been trialled as a therapy in only two preclinical studies, one for spinal cord injury and one for hind limb ischemia. Proteomic analysis of expanded UCB cells in these studies showed that the cells were neuroprotective, anti-inflammatory and angiogenic. These findings are also supported by in vitro studies where expanded UCB CD34+ cells showed increased gene expression of neurotrophic and angiogenic factors compared to unexpanded CD34+ cells. Preclinical evidence demonstrates that unexpanded CD34+ cells are a promising therapy for neurological conditions where they have been shown to improve multiple indices of injury in rodent models of stroke, Parkinson's disease and neonatal hypoxic ischemic brain injury. This review will highlight the current application of expanded UCB derived HSCs in transplant medicine, and also explore the potential use of expanded HSCs as a therapy for neurological conditions. It is proposed that expanded UCB derived CD34+ cells are an appropriate cellular therapy for a range of neurological conditions in children and adults. [ABSTRACT FROM AUTHOR]