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Just as overweight and obesity may impair immunity, excessive body weight-related parameters of women in the pre-conception period and during pregnancy are possible detrimental factors for fetal programming of the immune system in their offspring. We investigated the relationship of pre-pregnancy body mass index (pBMI) and gestational weight gain (GWG) of mothers with the placental transport rate (PTR) of IgG antibodies and antineutrophil cytoplasmatic antibodies against lactoferrin (Lf-ANCA) and their concentration in umbilical cord blood serum (UCS), verifying the sex-specificity of this relationship. The examined group of this cross-sectional pilot study consisted of 101 pregnant women and their healthy CS-delivered newborn children. The concentration of antibodies in maternal serum (MS) and UCS were determined by ELISA method. PTR was assessed as a ratio of the concentration of antibodies in the UCS and MS. A significantly lower PTR of IgG and their concentration in the UCS were demonstrated in newborns of mothers with an excessive pBMI compared to those with pBMI < 25 and the association was more pronounced in male newborns. The lowest PTR of beneficial IgG and their concentration in the UCS as well as the highest PTR of detrimental Lf-ANCA and their concentration in UCS were observed in newborns born to mothers with co-occurrence of both an excessive pBMI and GWG. It seems that maternal preconception overweight and obesity along with an excessive GWG can be a predictor of unfavorable immune effects in fetuses. Further studies are needed to explain the role of maternal weight-related parameters in the development of immunological health of their offspring. [ABSTRACT FROM AUTHOR]

Background: Night shift work during pregnancy has been associated with differential DNA methylation in placental tissue, but no studies have explored this association in cord blood. We aimed to examine associations of maternal night shift work with cord blood DNA methylation. Methods: A total of 4487 mother–newborn pairs from 7 studies were included. Maternal night shift work during pregnancy was ascertained via questionnaires and harmonized into "any" versus "no". DNA methylation was measured in cord blood using the Illumina Infinium Methylation arrays. Robust linear regression models adjusted for relevant confounders were run in the individual cohorts, and results were meta-analyzed. Results: Maternal night shift work during pregnancy ranged from 3.4% to 26.3%. Three CpGs were differentially methylated in relation to maternal night shift work during pregnancy at a false discovery rate adjusted P < 0.05: cg10945885 (estimate (β) 0.38%, standard error (SE) 0.07), cg00773359 (β 0.25%, SE 0.05), and cg21836426 (β − 0.29%, SE 0.05). Associations of the identified CpGs were found in previous literature for gestational age and childhood and adolescent BMI. In a mouse model of prenatal jet lag exposure, information on offspring DNA methylation of ten homologous genes annotated to the 16 CpGs with P < 1 × 10−5 in our analysis was available, of which eight were associated (enrichment P: 1.62 × 10−11). Conclusion: Maternal night shift work during pregnancy was associated with newborn DNA methylation at 3 CpGs. Top findings overlapped with those in a mouse model of gestational jet lag. This work strengthens evidence that DNA methylation could be a marker or mediator of impacts of circadian rhythm disturbances. [ABSTRACT FROM AUTHOR]

Objective: The expanding field of hematopoietic cell transplantation (HCT) for non-malignant diseases, including those amenable to gene therapy or gene editing, faces challenges due to limited donor availability and the toxicity associated with cell collection methods. Umbilical cord blood (CB) represents a readily accessible source of hematopoietic stem and progenitor cells (HSPCs); however, the cell dose obtainable from a single cord blood unit is frequently insufficient. This limitation can be addressed by enhancing the potency of HSPCs, specifically their capacity to reconstitute hematopoiesis. In our study, we investigated the combined effects of treprostinil, a prostaglandin analog, and cinacalcet, a calcium-sensing receptor modulator, on the reconstitution of hematopoiesis. Methods: A Lineage Cell Depletion Kit was employed to isolate lineage-negative (lin−) HSPCs from mouse bone marrow. A Human CB CD34 Positive Selection Kit was utilized to isolate CD34+ cells from the CB of healthy donors. In vitro , the effects of treprostinil, cinacalcet, and their combination on the migration, adhesion, and differentiation of HSPCs were assessed. In vivo , homing and engraftment were examined. Eight-week-old female and male C57BL/6J, BALB/c, or female NSG mice served as recipient models. Results: When administered concomitantly, treprostinil and cinacalcet exhibited mutual antagonism: the survival of recipient animals was lower when both drugs were administered together compared to either agent alone. Conversely, a sequential regimen involving priming with treprostinil/forskolin followed by cinacalcet treatment in vivo enhanced survival, irrespective of whether hematopoiesis was reconstituted by human or murine HSPCs. In vitro assays demonstrated enhanced migration and adhesion in response to the presence of treprostinil and cinacalcet, suggesting potential synergistic effects. Colony formation confirmed synergism. Conclusion: Augmenting the bone marrow reconstitution potential of HSPCs with treprostinil and cinacalcet shows promise for rescuing patients undergoing HCT. This approach is particularly beneficial for those patients at high risk of transplant failure due to limited numbers of available HSPCs. Furthermore, enhancing the potency of HSPCs has the potential to alleviate the burden and risks associated with HSPC donation, as it would reduce the number of cells needed for collection. [ABSTRACT FROM AUTHOR]

Objectives: Research on neurobehavioral abnormalities in neonates of mothers with subclinical hypothyroidism (SCH) is limited. The link between umbilical cord blood brain-derived neurotrophic factor (BDNF) levels and neurobehavioral outcomes in neonates has not been explored. This study investigates the correlation between alterations in umbilical cord blood BDNF levels and early neurobehavioral abnormalities in neonates born to pregnant women with SCH. Methods: This study recruited 72 pregnant women with SCH and 76 healthy controls (HC). The study collected general information for all subjects, including body mass index, parity, thyroid function assessed during early to late pregnancy, and neonatal birth weight. Neonatal behavioral and neural abilities were evaluated using the Neonatal Behavioral Neurological Assessment (NBNA). BDNF levels in umbilical cord blood were measured using the Enzyme-Linked Immunosorbent Assay method. Results: The results indicated that neonates with SCH during pregnancy had lower total NBNA scores, behavioral ability, passive muscle tone, active muscle tone, primitive reflexes, general assessment, and lower levels of cord blood BDNF compared to healthy controls. The cord blood BDNF of newborns with SCH during pregnancy was positively correlated with total NBNA score, behavioral ability, active muscle tone, and general assessment. Moreover, multiple linear regression analysis demonstrated an association between cord blood BDNF levels in pregnant patients with SCH and multiple measures of newborn health, including total NBNA score, behavioral ability, active muscle tone, and general assessment. Conclusion: Infants born to pregnant women with SCH exhibit reduced behavioral and neural abilities linked to BDNF levels in umbilical cord blood. [ABSTRACT FROM AUTHOR]

Introduction: To determine the threshold of umbilical cord blood procalcitonin for early-onset neonatal infection diagnosis. Method: This prospective study was conducted on 126 neonates in the neonatal care unit of Hue University of Medicine and Pharmacy Hospital, Vietnam, from June 01, 2023 to August 31, 2024. All neonates showed signs at birth or risk factors for early-onset infection (EOI) and were divided into two groups: EOI group and non-EOI group. Umbilical cord blood samples were collected for procalcitonin analysis immediately after birth. Results: The median procalcitonin (PCT) levels in umbilical cord blood were significantly higher in the EOI group (0.154 ng/ml [0.092–0.197]) compared to the non-EOI group (0.097 ng/ml [0.082–0.134]; p < 0.001). Receiver operating characteristic (ROC) curve determined the optimal threshold value of PCT of 0.142 ng/ml with an AUC 0.751 (95% CI: 0.661–0.841, p<0.001) in the total population. At this cut-off, the Se, Sp, PPV, and NPV were 68.2%, 76.8%, 61.2%, and 81.8%, respectively. The optimal cut-off value for preterm neonates was 0.122 ng/ml (AUC: 0.785, 95% CI: 0.658–0.911, p<0.001) corresponding a Se of 79.2%, Sp of 74.1%, PPV of 73.1%, and NPV of 80.0%. In term group, the optimal cut-off value was 0.150 ng/ml (AUC: 0.726, 95% CI: 0.583–0.860, p<0.01), with a Se of 60.0%, Sp of 80.4%, PPV of 52.2%, and NPV of 84.9%. Conclusions: Umbilical cord blood PCT concentration were elevated in neonates with EOI. PCT could be a valuable marker for the early diagnosis of EOI. [ABSTRACT FROM AUTHOR]

Background/Objectives: The DNA methylation of neonatal cord blood can be used to accurately estimate gestational age. This is known as epigenetic gestational age. The greater the difference between epigenetic and chronological gestational age, the greater the association with an inappropriate perinatal fetal environment and development. Maternal vitamin D deficiency is common in Japan. The aim of this study was to investigate the associations between maternal serum vitamin D levels and epigenetic gestational age acceleration at birth in Japan. Methods: The data were obtained from the hospital-based birth cohort study conducted at the National Center for Child Health and Development in Tokyo, Japan. Maternal blood was collected in the second trimester to measure the serum vitamin D concentration. Cord blood was collected at birth to measure serum vitamin D and to extract DNA. DNA methylation was assessed using an Illumina methylation EPIC array. Epigenetic gestational age was calculated using the "methylclock" R package. Linear regression analysis was performed to see associations. Results: Maternal serum vitamin D levels in the second trimester were negatively associated with epigenetic gestational age acceleration at birth when calculated by Bohlin's method (regression coefficient [95% CI]: −0.022 [−0.039, −0.005], n = 157), which was still significant after considering infants' sex (−0.022 [−0.039, −0.005]). Cord blood serum vitamin D levels were not associated with epigenetic age acceleration. Maternal age at delivery and birth height were associated in positive and negative ways with epigenetic gestational age acceleration, respectively (0.048 [0.012, 0.085] and −0.075 [−0.146, −0.003]). Conclusions: Maternal vitamin D deficiency was related to an infant's epigenetic gestational age acceleration at birth. These findings suggest that the association between fetal development and maternal vitamin D levels may involve the fetal epigenetic regulation of the fetus. [ABSTRACT FROM AUTHOR]

The article discusses the biochemical screening of glucose-6-phosphate dehydrogenase (G6PD) deficiency in borderline cases, highlighting the importance of detecting heterozygotes who may have moderately decreased enzyme activities. The study conducted at a reference laboratory in France showed that measuring additional enzymes like pyruvate kinase or hexokinase significantly improved the detection of heterozygotes. The research suggests that using a three-enzyme approach can enhance the sensitivity of G6PD deficiency screening, especially in identifying heterozygotes, while also acknowledging the limitations in detecting certain variants. [Extracted from the article]

Oropouche virus (OROV) is an orthobunyavirus endemic in the Brazilian Amazon that has caused numerous outbreaks of febrile disease since its discovery in 1955. During 2024, Oropouche fever spread from the endemic regions of Brazil into non-endemic areas and other Latin American and Caribbean countries, resulting in 13,014 confirmed infections. Similarly to other orthobunyaviruses, OROV can undergo genetic reassortment events with itself as well as other viruses. This occurred during this current outbreak, resulting in novel strains with increased pathogenicity and levels of transmission. For the first time, pregnant women with Oropouche fever have sustained poor perinatal outcomes, including miscarriage, fetal demise, stillbirths and malformation syndromes including microcephaly. In July 2024, PAHO issued an Epidemiological Alert warning of the association of OROV with vertical transmission. OROV has now been identified in the fetal blood, cerebrospinal fluid, placenta and umbilical cords, and fetal somatic organs including the liver, kidneys, brain, spleen, heart, and lungs using nucleic acid and antigen testing. Perinatal autopsy pathology has confirmed central nervous system infection from OROV in infants with congenital infection including microcephaly, ventriculomegaly, agenesis of corpus callosum, and neuronal necrosis. The latest data from Brazil show 3 confirmed cases of OROV vertical transmission; 2 cases of fetal death; 1 case of congenital malformation; and ongoing investigations into the role of OROV in 15 cases of fetal death, 3 cases of congenital malformations and 5 spontaneous miscarriages. This Commentary discusses the mechanisms and significance of development of novel reassortant strains of OROV during the current outbreak and their recent recognition as causing vertical infection and adverse perinatal outcomes among pregnant women with Oropouche fever. [ABSTRACT FROM AUTHOR]

Sepsis is a risk factor associated with increasing neonatal morbidity and mortality, acute lung injury, and chronic lung disease. While stem cell therapy has shown promise in alleviating acute lung injury, its effects are primarily exerted through paracrine mechanisms rather than local engraftment. Accumulating evidence suggests that these paracrine effects are mediated by mesenchymal stem cell (MSC)-derived small extracellular vesicles (sEVs), which play a critical role in immune system modulation and tissue regeneration. sEVs contain a diverse cargo of mRNA, miRNA, and proteins, contributing to their therapeutic potential. We hypothesize that sEVs derived from three distinct sources, cord blood plasma (CBP), Wharton jelly (WJ), and placental (PL) MSCs, may prevent the cytotoxicity induced by E. coli lipopolysaccharide (LPS) in lung alveolar epithelial cells. Objective: To determine the effects of CBP-, WJ-, and PL-MSCs-derived sEVs on cell viability, apoptosis, and proinflammatory cytokine production in alveolar epithelial cells and monocytes following LPS treatment. sEVs were collected from conditioned media of PL-MSCs, WJ-MSCs, and CBP using 50 nm membrane filters. sEVs were characterized based on nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM), and Western blotting techniques. The protein concentration of isolated sEVs was used to standardize treatment doses. A549 cells and monocyte THP-1 cells were cultured and exposed to LPS in the presence or absence of sEVs for 72 h. Cell viability was measured using CellTiter-Glo 2.0 chemiluminescence-based assay. For cytokine analysis, A549 and THP-1 cells were pre-incubated for 24 h with or without PL- and CBP-sEVs, followed by exposure to LPS or control conditions for an additional 24 h. The conditioned media were collected, and interleukin-6 (IL-6) and interleukin-8 (IL-8) levels were quantified using ELISA. LPS treatment significantly reduced the viability of both A549 and THP-1 cells. The presence of CB- or WJ-sEVs significantly increased cell viability compared to controls. Cells treated with PL-sEVs showed increased cell viability but did not reach statistical significance. LPS-treated cells showed a significant increase in apoptosis and elevated levels of pro-inflammatory cytokines IL-6 and IL-8. All three sEVs types (CBP-, WJ-, and PL-sEVs) significantly reduced LPS-induced apoptosis and IL-6 release. Interestingly, while WJ-sEVs decreased IL-8, both CBP- and PL-sEVs led to an increase in IL-8 compared to their respective controls. CBP-, PL-, and WJ-derived sEVs demonstrated protective effects against LPS-induced injury in alveolar epithelial cells and monocytes, as evidenced by increased cell viability and modulation of pro-inflammatory cytokine release. These findings suggest that placenta-derived sEVs have the potential to modulate the immune response, mitigate inflammation, and prevent end-organ damage in neonatal sepsis. [ABSTRACT FROM AUTHOR]

To ensure the preservation of functional hematopoietic stem cells (HSC) and committed progenitor cells (HPC) at + 4 °C in ex vivo expanded cord blood cell products during worldwide transportation and subsequent infusion—without the need for washing and cell concentration—we developed a conservation medium called Stabilizer of Expanded Cells (SEC), composed exclusively of injectable pharmacological products. The in vivo engraftment assay in immunodeficient mice was used to detect primitive HSCs before and after preservation at + 4 °C. In some experiments, a complex phenotype based on CD34, CD38, and CD133 expression was utilized for this purpose. Committed progenitors (CFU-GM, BFU-E, and CFU-Mix) were detected using methylcellulose culture colony-forming assays. Additionally, in some cases, the energetic metabolism (mitochondrial respiration) was evaluated using Seahorse technology. SEC was able to preserve the functionality of HSCs and HPCs in ex vivo expanded cell populations at + 4 °C for at least 48 h. Furthermore, SEC is also effective in fully preserving HSCs and HPCs in cytapheresis products for at least 72 h. Additionally, SEC enabled the full preservation of HSCs and HPCs for 72 h in freshly collected cord blood, maintaining a normal metabolic profile of CD34+ cells. The SEC medium exhibits a positive effect on the maintenance of both HSCs and HPCs at + 4 °C, regardless of their source. Therefore, SEC can be applied in cell therapy protocols based on HSCs and HPCs with a significant advantage: the product does not need to be washed and concentrated before injection into the patient. [ABSTRACT FROM AUTHOR]

Introduction: Cesarean sections are increasing worldwide and are associated with altered risks of complications for both mother and child. Vaginal birth after cesarean section is associated with lower maternal and neonatal morbidity than in repeat cesarean section. Only a few studies have considered the indication for the previous cesarean section to be of importance for the outcome of subsequent labor. The aim of this study was to evaluate whether the indication for a previous cesarean section affects the outcomes at a subsequent delivery in women with induction of labor. Material and Methods: This retrospective cohort study of the four largest delivery units in Stockholm during 2012–2015 included 1150 women with one previous cesarean section with induction of labor. Inclusion criteria: women with induced labor and a previous cesarean section, singleton pregnancy, cephalic presentation, gestational age of ≥34 weeks. The women were grouped by indication for the previous cesarean section. Primary outcome: mode of delivery (vaginal birth after previous cesarean section or repeat cesarean section). Secondary outcomes: induction to delivery time, postpartum hemorrhage, uterine rupture. Neonatal outcomes: birth weight, Apgar score <7, arterial umbilical cord blood gas pH <7.0. Results: Our study found that the indication of labor dystocia at the previous cesarean section, increased the risk of repeat cesarean section (aOR 5.35; 95% CI: 1.64–17.50) in women with induction of labor. Other risk factors for repeat cesarean section were birth weight >4000 g, maternal BMI ≥30 or if vaginal prostaglandin was used as the method for induction of labor. A previous vaginal delivery and use of oxytocin increased the chance of a vaginal delivery in this group of women. Conclusions: Our study showed that the indication for the previous cesarean section affects the outcome in the subsequent delivery in women with induction of labor. If the indication for the previous cesarean section was labor dystocia, the risk of repeat cesarean section was increased. [ABSTRACT FROM AUTHOR]

Objective Mainstay therapy for fetuses affected by maternal red cell alloimmunization is serial intrauterine transfusion (IUT). Testing to determine when fetal red cells have been replaced with donor cells historically involves the use of the Kleihauer–Betke (KB) test. Hemoglobin (Hgb) electrophoresis testing may be more rapid with a reduced cost of analysis. We aimed to determine the correlation between fetal Hgb electrophoresis versus the traditional KB test. Study Design This is a retrospective analysis of all alloimmunized singleton pregnancies undergoing IUT between January 1, 2021, and July 1, 2023. Maternal and fetal characteristics were collected along with the indication for IUT. A final fetal blood sample was obtained at the conclusion of each transfusion and sent for KB testing and Hgb electrophoresis. The primary outcome was the assessment of these parameters in their ability to predict the replacement of the fetal circulating red cell population with donor cells. Linear regression analysis and repeated measures analysis of variance were performed, and p -values less than 0.05 were considered significant. Results A total of 56 IUTs were performed in 16 patients. There were 39 (69.6%) final KB test values collected and compared with 30 (53.6%) final Hgb electrophoresis values. Hgb electrophoresis when compared with the KB test demonstrated a significant correlation (R2 = 0.93; 95% confidence interval, 0.61–0.76; p < 0.001). This same finding held true when examining the correlation at each individual IUT as well. The final KB test and Hgb electrophoresis values significantly decreased with each transfusion (p = 0.003). A predominance of adult donor blood was noted by the third transfusion for both laboratory indices. Conclusion Fetal Hgb electrophoresis obtained at the time of IUT demonstrates a significant correlation with the traditional KB test. Key Points Fetal Hgb electrophoresis following IUT is underexplored Hgb electrophoresis is an automated evaluation The traditional KB test is a manual evaluation These two tests demonstrate significant correlation [ABSTRACT FROM AUTHOR]

The role of the chorio-allantoic placenta as the critical nutrient- and oxygen-supplying organ to nourish the demands of the fetus has been well recognized. This function relies on the successful establishment of the placental feto-maternal exchange unit, or interhaemal barrier, across which all nutrients as well as waste products must pass to cross from the maternal to the fetal blood circulation, or vice versa, respectively. As a consequence, defects in the establishment of this elaborate interface lead to fetal growth retardation or even embryonic lethality, depending on the severity of the defect. Beyond this essential role, however, it has also emerged that the functionality of the feto-maternal interface dictates the proper development of specific embryonic organs, with tightest links observed to the formation of the heart. In this article, we build on the foundational strength of the mouse as experimental model in which the placental causality of embryonic defects can be genetically proven. We discuss in detail the formation of the interhaemal barrier that makes up the labyrinth layer of the murine placenta, including insights into drivers of its formation and the interdependence of the cell types that make up this essential interface, from in vivo and in vitro data using mouse trophoblast stem cells. We highlight mouse genetic tools that enable the elucidation of cause-effect relationships between defects driven by either the trophoblast cells of the placenta or by embryonic cell types. We specifically emphasize gene knockouts for which a placental causality of embryonic heart defects has been demonstrated. This in-depth perspective provides much-needed insights while highlighting remaining gaps in knowledge that are essential for gaining a better understanding of the multi-facetted roles of the placenta in setting us up for a healthy start in life well beyond nutritional support alone. [Display omitted] • Summary of milestones in mouse placental development. • Mechanistic insights into formation of the interhaemal barrier. • Trophoblast Stem Cells to uncover the molecular basis underpinning these processes. • Mouse genetic tools to identify placental causes of embryonic defects. [ABSTRACT FROM AUTHOR]

Approximately 1 in 200 newborns worldwide are affected by congenital cytomegalovirus (CMV). Most of these cases are asymptomatic due to successful control of the infection by the newborn's immune system. In this issue of the JCI, Semmes et al. characterized the cellular immune response in cord blood of neonates with CMV infection. The authors found that conventional T cells with NK-like features expanded during congenital CMV infection. To exert their antiviral function, these cells relied on Fc receptors, recognizing virus-infected cells bound by IgG. Thereby, the fetal and maternal immune system can optimally cooperate to control CMV infection: maternal IgG crossing the placenta opsonizes virus-infected cells subsequently lysed by neonatal NK-like T cells. This finding suggests that innate-like programming of conventional T cells may have evolved to combat congenital CMV infection, offering insights that could inform the development of future therapies. [ABSTRACT FROM AUTHOR]

Human cytomegalovirus (HCMV) profoundly impacts host T and NK cells across the lifespan, yet how this common congenital infection modulates developing fetal immune cell compartments remains underexplored. Using cord blood from neonates with and without congenital HCMV (cCMV) infection, we identify an expansion of Fcγ receptor III-expressing (FcγRIII-expressing) CD8+ T cells following HCMV exposure in utero. Most FcγRIII+CD8+ T cells express the canonical αβ T cell receptor (TCR), but a proportion express noncanonical γδ TCR. FcγRIII+CD8+ T cells are highly differentiated and have increased expression of NK cell markers and cytolytic molecules. Transcriptional analysis reveals FcγRIII+CD8+ T cells upregulate T-bet and downregulate BCL11B, known transcription factors that govern T/NK cell fate. We show that FcγRIII+CD8+ T cells mediate antibody-dependent IFN-γ production and degranulation against IgG-opsonized target cells, similar to NK cell antibody-dependent cellular cytotoxicity (ADCC). FcγRIII+CD8+ T cell Fc effector functions were further enhanced by IL-15, as has been observed in neonatal NK cells. Our study reveals that FcγRIII+CD8+ T cells elicited in utero by HCMV infection can execute Fc-mediated effector functions bridging cellular and humoral immunity and may be a promising target for antibody-based therapeutics and vaccination in early life. [ABSTRACT FROM AUTHOR]

Our objective is to determine the protein and complements constituents of Cord blood Platelet-rich plasma (CB-PRP), based on the hypothesis that it contains beneficial components capable of arresting or potentially decelerating the advancement of atrophic age-related macular degeneration (dry-AMD), with the support of radiomics. Two distinct pools of CB-PRP were assessed, each pool obtained from a total of 15 umbilical cord-blood donors. One aliquot of each pool respectively was subjected to proteomic analysis in order to enhance the significance of our findings, by identifying proteins that are shared between the two sample pools and gaining insights into the pathways they are associated with. The bioinformatics analysis was developed using Reactome software. Three-hundred-seven (307) distinct proteins were found. Two hundred fifteen (215) of the elements mentioned above are shared by both pools. Seventy (70) elements are exclusive to pool S1, while pool S2 contains 22. We detected 109 representative and statistically significant pathways out of 549. We found proteins related to the immune system, signal transduction, vesicle-mediated transport, cell–cell communication, hemostasis, cellular responses to stimuli, cell cycle, and developmental biology. The analysis showed the presence of P15692-12, representing VEGF factor A, long form. With over 200 proteins, the CB-PRP can increase the immune response, including BCR, CD-22, FCGR, phospholipids, IL-10, FCGR-3A, and others. Discovering crucial trophic and complement-regulating variables is highly significant for potential applications in dry AMD. Our future research will examine the effects of intravitreal CB-PRP on dry-AMD eyes. [ABSTRACT FROM AUTHOR]

We aimed to characterize the metabolomic profiles in preterm small-for-gestational age (SGA) infants using cord blood. We conducted a gestational age (GA)-matched case-control study that included 30 preterm infants who were categorized into two groups: SGA infants, with a birth weight (BW) < 10th percentile for GA (n = 15) and non-SGA infants, with BW ≥ 10th percentile for GA (n = 15). SGA infants with chromosomal or genetic abnormalities were excluded. At birth, the umbilicus was double-clamped, and the cord blood was sampled from the umbilical vein. Metabolomic analyses were performed using capillary electrophoresis time-of-flight mass spectrometry. The median GA at birth was not significantly different between the two groups [SGA, 32 (26–36) weeks; non-SGA, 32 (25–35) weeks; p = 0.661)]. Of the 255 metabolites analyzed, 19 (7.5%) showed significant differences between SGA and non-SGA infants. There were significant reductions in the carnosine, hypotaurine, and S-methylcysteine levels in SGA infants as compared to non-SGA infants (p < 0.05). Carnosine was correlated with gestational age, BMI before pregnancy, body weight gain during pregnancy (p = 0.002, p = 0.023, and p = 0.020, respectively). In conclusion, preterm SGA infants have low levels of cord blood antioxidative- and antiglycation-related metabolites, making them vulnerable to oxidative stress. [ABSTRACT FROM AUTHOR]

Context Serum calcium is frequently measured during the neonatal period, and it is known to be influenced by the vitamin D status. Objective We hypothesized that the 25-hydroxyvitamin D (25OHD) concentration may influence the lower limit of the serum calcium normal range in neonates. Methods We included in our prospective cohort study 1002 mother-newborn pair recruited from April 2012 to July 2014, in 2 centers located in the neighborhoods of Paris, France, whose serum calcium was measured at 3 days of life. We established, after exclusion of outliers, a 95% CI for serum calcium (i) in our whole population of 1002 neonates; (ii) in neonates with a cord blood 25OHD concentration ≥ 30 nmol/L; and (iii) in those with a 25OHD ≥ 50 nmol/L. Results The mean serum total calcium was 2.46 ± 0.13 nmol/L (95% CI: 2.19-2.72 mmol/L), 2.47 ± 0.25 mmol/L (95% CI: 2.22-2.72 mmol/L), and 2.50 ± 0.25 mmol/L (95% CI: 2.25-2.75 mmol/L) in the whole group, in the 514 neonates with 25OHD ≥ 30 nmol/L, and in the 202 neonates with 25OHD ≥ 50 nmol/L respectively. The lower limit of the 95% range was significantly higher in neonates with 25 OHD ≥ 30 nmol/L (P < 0.05) and ≥ 50 nmol/L (P <.001) than in the entire cohort. Conclusion We show that the lower limit of the normal serum calcium range is higher in groups with a higher 25OHD than in unselected subjects. We propose that the reference range for serum calcium in neonates is 2.25 to 2.75 mmol/L. [ABSTRACT FROM AUTHOR]

Objective: We investigated whether prepregnancy BMI (prePregBMI) in women with obesity was associated with differential DNA methylation (DNAm) in cord blood (CB) and whether DNAm may mediate the association of prePregBMI and early childhood BMI z score (BMIz). Methods: From the Treatment of Obese Pregnant Women (TOP) study, 232 mother–child pairs were included. We conducted an epigenome‐wide association study on prePregBMI and CB DNAm (450k array), followed by causal mediation analyses to test whether DNAm may mediate effects of prePregBMI on BMIz at age 36 months (BMIz36). Results: DNAm at 5345 CpG sites annotated to 2842 genes, which were overrepresented in biological processes linked to carbohydrate metabolism and plasma lipoprotein particle clearance, was associated with prePregBMI (false discovery rate < 10%). Causal mediation analyses of 168 methylation sites associated with BMIz36 (p < 0.05) and overlapping with the 5345 prePregBMI‐associated sites identified two sites on SYT7 and DEAF1, partially mediating the effect of prePregBMI on BMIz36 (p ≤ 0.01). After cross‐validation, a methylation risk score including these two sites could predict the highest quartile of BMIz36 and fat mass (in grams) with area under the curve = 0.72 (95% CI: 0.58–0.85) and area under the curve = 0.71 (95% CI: 0.58–0.85), respectively. Conclusions: CB DNAm at birth may partially mediate effects of prePregBMI on early childhood BMIz36, supporting its plausible role in influencing individual future obesity risk. [ABSTRACT FROM AUTHOR]

This study aimed to find whether oral administration of calf bone marrow hydrolysate liposomes (CBMHL) can improve renal anemia. Calf bone marrow was defatted, papain hydrolyzed, liposomalized and lyophilized. Its hematopoietic ability was proved by the colony formation experiment of umbilical cord blood hematopoietic stem cells in vitro. The rat model of renal anemia was established by adenine intragastric administration, and different concentrations of CBMHL were intragastricly administrated. Blood routine and serological indexes, transcription levels of hematopoietic factors and renal pathology were detected. From the appearance, redispersability, water content, liposome indexes and stability of Lyophilized powder of CBMHL, it could be concluded that the quality of freeze-dried CBMHL powder under this freeze-drying process was good. Compared with the control group, the burst forming unit-erythroid (BFU-E) in the CBMHL group was larger and the number of colonies increased significantly in the colony formation experiment (P < 0.05). The results of lyophilized powder of CBMHL co-culture with human adipose mesenchymal stem cells (MSCs) and human cytokine-induced killer (CIK) cells showed that the lyophilized powder of CBMHL had no potential toxicity and allergic reaction in vitro. Compared with the Model Group, the red blood cell (RBC) count, hemoglobin (HB) content and hematokrit (HCT) of rats blood routine in the Model+high doses of CBMHL Group (Model+H-CBMHL Group) increased significantly (P < 0.05). Serum erythropoietin (EPO) and glutathione (GSH) levels increased significantly (P < 0.05), while serum creatinine (Cr) levels decreased significantly(P < 0.05). The transcription level of Epo in kidney increased significantly (P < 0.05), the transcription levels of erythropoietin receptor (Epor) in bone marrow and interleukin 6 (Il6) in spleen were significantly increased (P < 0.01). The fragility of red blood cells decreased significantly, and the pathological structure of kidney improved significantly. It was proved that lyophilized powder of CBMHL could effectively enhance the hematopoietic ability of rats with renal anemia and protect the kidney structure and function. [ABSTRACT FROM AUTHOR]

Objective Methods Results Significance Hypoxic–ischemic brain damage (HIBD) is a leading cause of neonatal mortality, resulting in brain injury and persistent seizures that can last into the late neonatal period and beyond. Effective treatments and interventions for infants affected by hypoxia–ischemia remain lacking. Clinical investigations have indicated an elevation of nuclear factor of activated T cells 5 (NFAT5) in whole blood from umbilical cords of severely affected HIBD infants with epilepsy. Experimental research has demonstrated that NFAT5 has ambivalent effects on neuroprotection and neurologic damage. However, the mechanistic role of NFAT5 in HIBD remains unclear. This investigation aims to further clarify the role of NFAT5 in epilepsy following HIBD insult.We created a neonatal HIBD mouse model through left common carotid artery occlusion. By specifically knocking down astrocytic NFAT5 and its downstream molecule, Nedd4‐2, using hippocampal delivery of adeno‐associated virus 5‐driven targeted shRNA, we investigated the role of astrocytic NFAT5 in epilepsy susceptibility in HIBD mice. This was assessed through electroencephalographic recordings, behavioral observations in vivo, and whole‐cell recordings of hippocampal neuronal activity. In vitro, we evaluated the effects of astrocytic NFAT5 alteration on Kir4.1 expression and IKir4.1 in both brain slices from HIBD mice and cultured astrocytes treated with oxygen–glucose deprivation/reoxygenation.Hypoxia–ischemia‐induced upregulation of hippocampal NFAT5 occurs in astrocytes rather than in neurons. This upregulation leads to increased expression of the ubiquitin ligase Nedd4‐2, resulting in excessive degradation of Kir4.1 in astrocytes. Consequently, astrocytic function in buffering extracellular K+ is impaired, causing depolarization of the resting potential and enhanced neuronal discharge. This disruption ultimately affects local neural network balance and increases susceptibility to epilepsy. In contrast, inhibiting or knocking down astrocytic NFAT5 almost completely reverses these effects.Our findings suggest that manipulating the NFAT5–Nedd4‐2–Kir4.1 axis in astrocytes could provide a potential therapeutic strategy for the epileptic complications of HIBD. [ABSTRACT FROM AUTHOR]

Objective: Gestational diabetes mellitus (GDM) is a common complication during pregnancy and increases the risk of metabolic diseases in offspring. We hypothesize that the poor intrauterine environment in pregnant women with GDM may lead to chromosomal DNA damage and telomere damage in umbilical cord blood cells, providing evidence of an association between intrauterine programming and increased long-term metabolic disease risk in offspring. Methods: We measured telomere length (TL), serum telomerase (TE) activity, and oxidative stress markers in umbilical cord blood mononuclear cells (CBMCs) from pregnant women with GDM (N=200) and healthy controls (Ctrls) (N=200) and analysed the associations of TL with demographic characteristics, biochemical indicators, and blood glucose levels. Results: The length of telomeres in umbilical CBMCs in the GDM group was significantly shorter than that in the Ctrl group (P<0.001), and the shortening of telomeres in male infants in the GDM group was more significant than that in the Ctrl group (P<0.001) after adjustment for Pre-pregnancy body mass index (PBMI), Pregnancy weight gain (PGW), and Triglyceride (TG) as confounding factors. In addition, the TE expression level in the GDM group was lower after adjustment. There was no statistically significant difference in oxidative stress hydroxydeoxyguanosine (8-OHdG), malondialdehyde (MDA) and superoxide dismutase (SOD) between the two groups. TL was positively correlated with TE activity, and both were negatively correlated with blood glucose levels. There was no correlation between TL and Gestational age (GA), PBMI, PGW, or TG levels. Conclusion: The poor intrauterine environment in pregnant women with GDM increases telomere attrition and reduces TE activity, which may be potential genetic risk factors for an increased risk of metabolic diseases in offspring later in life due to intrauterine reprogramming. [ABSTRACT FROM AUTHOR]

Cord blood lipid profile in neonates helps to screen for neonatal dyslipidaemia which is associated with long term morbidity mainly cardiovascular disease. Materials and Methods: The present study done in Dept. of Paediatrics, Mahadevappa Rampure Medical College, klb with 222 term and pre-term small or appropriate for gestational age (AGA) neonates using cord blood lipid profile. Results: In the present study of above mentioned 222 neonates, preterm accounts for 30.1% and term neonates accounts for 69.9%. AGA was 63.1% and SGA was 36.9%. Term AGA was 38.2%, term SGA 31.5%, preterm AGA was 24%, preterm SGA was 5.4%. Conclusions: Preterm AGA had higher cord lipid profile values compared to the term AGA neonates. Preterm SGA neonates had lower cord lipid profile of HDL, and LDL as compared to preterm AGA neonates. SGA neonates had higher total cholesterol, triglycerides and VLDL compared to AGA neonates. SGA neonates had lower LDL and HDL as compared to AGA neonates. [ABSTRACT FROM AUTHOR]

Developmental neurotoxicity (DNT) is a well-established hazard attributed to methylmercury (MeHg) exposure. This evidence is based primarily upon includes studies that measured biomarkers of MeHg exposure in samples of maternal hair and blood, and cord blood. The aim of this review was to investigate which of these prenatal biomarkers is most appropriate for quantifying the DNT effects attributed to MeHg. A comprehensive literature search covered MeHg dose-response literature published 1998–2022. Studies were evaluated for risk of bias and study sensitivity using IRIS approach. Quantitative results of investigations were extracted and statistically compared. Seven studies were identified that measured both maternal hair and cord blood Hg levels. In these investigations, several DNT umbrella tests and their sub-tests results were modeled. Cord blood MeHg was more sensitive, producing larger estimates of MeHg potency, in most of the comparisons (91%) with maternal hair MeHg estimates for the same sub-tests in the same study. When comparing results from cord blood Hg to maternal hair Hg there was a 75% increase in sensitivity (range: 4–583%). In the two domains where results for maternal hair Hg were more sensitive, the rise was only 18% (Range: 7–29%). There were limited data (two studies) that compared maternal blood and maternal hair biomarkers (maternal blood Hg was more sensitive (mean 320% and range 43–855%) and cord blood biomarkers (maternal blood Hg was more sensitive by approximately 30%). Maternal hair Hg remains an appropriate biomarker for exposure monitoring in many populations, but these data suggest that cord blood Hg is more appropriate for dose-response modeling of MeHg DNT effects. [ABSTRACT FROM AUTHOR]

Background: Hemolytic disease of the fetus and newborn (HDFN) is a condition due to maternal blood group antibodies targeting antigens in fetal red blood cells, with significant prenatal/perinatal morbidity and mortality. Severe HDFN cases are often associated with alloimmunization against Rhesus D (RhD) or Kell antigens. Information about HDFN epidemiology and treatment in Latin American countries is limited. This review aims to identify and synthesize the available evidence on the epidemiology and management of HDFN in this region. Methods: In July 2023, EMBASE, PubMed, LILACS, and other databases were searched for articles reporting epidemiology, treatment, prenatal and perinatal outcomes, and patient journey of HDFN cases in Latin American countries. A snowball search of cross-references and gray literature complemented the initial search. Publications in English, Spanish, and Portuguese were reviewed. Data were extracted using a defined template and charted in tables. Results: We reviewed five guidelines and 19 observational studies from Brazil, Chile, Mexico, Argentina, Colombia, Panamá, Paraguay, and Peru. HDFN due to Rh alloimmunization ranged from 0.5 to 5 per 1000 live births, and anti-D remains the most frequent alloantibody type for severe HDFN. The perinatal mortality rate of HDFN is approximately 1.3–1.6 per 100,000 live births, and fetal deaths can reach 30% among patients treated with intrauterine transfusions. Up to 47% of alloimmunized pregnancies were referred to reference centers only during the third trimester. About 60% of eligible pregnancies received anti-D IgG prophylaxis. Conclusions: Although estimates in LATAM countries are scarce and lack standardized measures, we observed that the incidence, morbidity, and mortality of HDFN in this region are problematic. RhD alloimmunization was reported in approximately up to 70% of severe HDFN cases, despite anti D HDFN being largely preventable. [ABSTRACT FROM AUTHOR]

Plain language summary Haemolytic disease of the fetus and newborn (HDFN) is a rare condition that causes a baby to develop anaemia while growing inside the woman; or after birth. Left untreated, this may lead to stillbirth or neonatal death.HDFN is caused when the pregnant woman's antibodies cross the placenta, enter the baby's circulation, and attach to proteins called antigens (inherited from the father) on the baby's haemoglobin containing red blood cells, and cause them to break apart, causing fetal anaemia.Women routinely have their blood tested at the start of pregnancy to assess their ABO blood group and Rh antigens. There are five main Rhesus antigens: D, C, c, E, e; with anti‐D being responsible for most cases of HDFN. If a woman is found to be Rh D negative; a ‘non‐invasive’ blood test is performed to assess if the fetal blood group is the same as the woman's. If a woman is found to be Rh D negative, and the baby is found to be D positive, the baby is at risk. This is because the baby has inherited the D antigen from the father; so‐called Rhesus incompatibility. Other red blood cell antibodies such as anti‐Kell or anti‐Duffy can also cause fetal anaemia. Women at highest risk of developing HDFN are those who have had at least one previous birth or a sensitising event (such as abdominal trauma) in a current or previous pregnancy, causing the woman and baby's blood to mix.Current treatment for haemolytic disease of the fetus involves giving fetal blood transfusions, with a small risk of early labour or pregnancy loss. If anaemia develops later in pregnancy, early delivery of the baby may be recommended; which could lead to complications of prematurity. In cases of mild HDFN, the baby may only require light therapy for neonatal jaundice. However, if the anaemia occurs earlier in pregnancy and is severe, the baby may need blood transfusions while still in the womb ‐ and after birth may require an exchange transfusion, to remove the woman's antibodies from their circulation and to treat the anaemia.Intravenous immunoglobulin (IVIG) is a potential non‐invasive method to prevent or delay the onset of severe anaemia. It is a blood product given intravenously every week to women who have been deemed at very high risk of early onset HDFN. It can be started at the end of the first trimester until birth, or until anaemia develops. This paper will discuss the evidence behind IVIG and other novel therapies during pregnancy, including the risks and the benefits. The developers of the paper include obstetricians, neonatologists and haematologists to provide different opinions on this topic. [ABSTRACT FROM AUTHOR]

The Chinese medicinal plant Thesium chinense Turcz. is the only plant used in the manufacture of Bairui Granules. However, to date, there has been very little research into the cytotoxic activity of active substances derived from Bairui Granules. Using chemical separation and spectroscopic methods, phenolic compounds 1–5 were identified as methyl- p -hydroxycinnamate, vanillin, kaempferol, isorhamnetin-3- O -glucoside, and astragalin, respectively. UPLC-MS/MS analyses revealed that compounds 1–5 were present at concentrations of 0.006 ± 0.002, 1.63 ± 0.87, 3.65 ± 0.83, 26.97 ± 11.41, and 27.67 ± 2.91 μ g/g, respectively in Bairui Granules. Compounds 1, 2, and 4 were detected here for the first time in Bairui Granules. Using co-culture experiments, isorhamnetin-3- O -glucoside (4) was found to be beneficial to the proliferation Chinese hamster ovary (CHO) cells (6.46% ± 0.86% to 38.45% ± 9.04%), natural killer cells from human umbilical cord blood (UCB NK cells) (25.68% ± 0.02% to 70.81% ± 0.26%), and mesenchymal stem cells from human umbilical cord blood (UCB MSC cells) (1.66% ± 0.05% to 27.64% ± 0.51%) when the concentration was similar to that found in Bairui granules. Moreover, vanillin (2) was conducive to UCB NK cells proliferation (28.21% ± 0.44%) at a concentration of 64 μ g/mL, while maintaining cell viability. UCB NK cell proliferation was promoted at rates of 41.03% ± 0.48% to 67.22% ± 0.68% when astragalin (5) was present at low concentrations (8 and 16 μ g/mL). Methyl- p -hydroxycinnamate (1) and vanillin (2) at different concentrations both had an inhibitory effect on the proliferation of natural killer cells from human peripheral blood (PB NK cells), but the inhibitory concentration ranges of these compounds were not equivalent to the concentration ranges of the compounds in Bairui Granules. These results provide a foundation for the safe use of T. chinense preparations. [ABSTRACT FROM AUTHOR]

Summary: Neonatal and adult megakaryocytes differ in proliferative capacity and ploidy levels, and neonatal and adult platelets differ in function, gene expression, and protein content. The mechanisms underlying these differences are incompletely understood. CDK8 and CDK19 are transcriptional kinases part of the CDK‐mediator complex, which regulates gene transcription in a cell‐specific manner. We discovered that cortistatin A, a potent highly selective inhibitor of CDK8/CDK19, significantly reduced cell expansion and increased ploidy in cord blood‐derived megakaryocytes. These phenotypic changes were associated with gene expression changes that partially overlapped developmentally regulated genes. These findings might have relevance for the management of developmental megakaryocyte disorders. [ABSTRACT FROM AUTHOR]

The present study investigates the influence of nitrosamines and etoposide on mesenchymal stromal cells (MSCs) in a differentiation state- and biological age-dependent manner. The genotoxic effects of the agents on both neonatal and adult stem cell populations after treatment, before, or during the course of differentiation, and the sensitivity of the different MSC types to different concentrations of MNU or etoposide were assessed. Hereby, the multipotent differentiation capacity of MSCs into osteoblasts, adipocytes, and chondrocytes was analyzed. Our findings reveal that while all cell types exhibit DNA damage upon exposure, neonatal CB-USSCs demonstrate enhanced resistance to genotoxic damage compared with their adult counterparts. Moreover, the osteogenic differentiation of MSCs was more susceptible to genotoxic damage, whereas the adipogenic and chondrogenic differentiation potentials did not show any significant changes upon treatment with genotoxin. Furthermore, we emphasize the cell-specific variability in responses to genotoxic damage and the differences in sensitivity and reaction across different cell types, thus advocating the consideration of these variabilities during drug testing and developmental biological research. [ABSTRACT FROM AUTHOR]

Platelet‐rich plasma (PRP) promotes the wound‐healing process and reduces pain. Cord blood platelet‐rich plasma (CB‐PRP), which can be easily collected from the umbilical cord and reapplied to a cesarean section wound, has been proposed to have similar effects as PRP. This paper hypothesizes that CB‐PRB would provide beneficial effects in terms of wound healing and pain reduction in women undergoing cesarean section. This study is a randomized controlled trial involving 52 pregnant women who underwent cesarean sections. Participants were assigned to either the intervention group (n = 26) or the control group (n = 26) at the Obstetrics and Gynecology Clinic of Police General Hospital. Cord blood PRP was applied to the subcutaneous layer and the surgical wound immediately following the cesarean section. The efficacy of wound healing was evaluated using the REEDA scale score on days 1 and 3 postoperatively, and the Vancouver Scar Scale (VSS) was assessed in the 8th week postoperation. The efficacy in reducing pain was measured using a Visual Analog Scale on days 1 and 3 postoperatively. The mean REEDA scale on day 1 (mean ± SD: 1.5 ± 0.2561.5 ± 0.256 in the CB‐PRP group and 2.5 ± 0.267 in the control group; p = 0.009) and the mean VSS score at the 8th week (mean ± SD: 2.577 ± 2.003 in the CB‐PRP group and 6.962 ± 2.441 in the control group; p < 0.001) were significantly lower in the CB‐PRP group than those in the control group. However, there were no differences in Visual Analog Scale values between the two groups. The findings indicate that CB‐PRP potentially promotes wound healing following cesarean sections but does not reduce pain. Further research is needed to confirm the beneficial effects of CB‐PRP. [ABSTRACT FROM AUTHOR]

Introduction: Retinoblastoma is the most prevalent intraocular tumor in children, commonly manifesting as leukocoria. Persistent fetal vasculature (PFV) is another cause of leukocoria, resulting from the incomplete regression of fetal eye blood vessels. The simultaneous occurrence of retinoblastoma and PFV in the same eye is extremely uncommon and presents significant diagnostic difficulties. Case Presentation: We present a case involving a 2-year-old girl with leukocoria and esotropia in her left eye. Clinical assessments, including biomicroscopy, ocular ultrasound, and magnetic resonance imaging, identified a retrolental mass with calcifications and a hyperechoic tubular structure, indicating the presence of both retinoblastoma and PFV. Enucleation followed by histopathological analysis confirmed these diagnoses. The histopathology revealed retinoblastoma with Homer-Wright and Flexner-Wintersteiner rosettes and signs of PFV, with persistent large vessels in the retrolental region. Conclusion: The coexistence of retinoblastoma and PFV in a single eye is rare and complicates the diagnosis of leukocoria. Comprehensive multimodal imaging is crucial for accurate diagnosis and effective management, tailored to the distinct needs of each condition. This case highlights the importance of detailed evaluation in pediatric patients with leukocoria to ensure correct diagnosis and appropriate treatment. [ABSTRACT FROM AUTHOR]

Introduction: Exposure to Bisphenol A (BPA) during early development particularly in-utero has been linked to a wide range of pathology. Over the last two decades the importance of vitamin D in maternal and child health has been highlighted. The aim of this pilot study was to examine the relationship of BPA and its naturally occurring metabolite BPA-glucuronide (BPA-g) with 25-hydoxy vitamin D (25OHD) levels in South African mother-child pairs. Methods: Third-trimester serum maternal samples and matching cord blood samples were analyzed for BPA and BPA-g using liquid chromatography tandem mass spectrometry (LC-MS/MS) and 25OHD3 and 25OHD2 using high performance liquid chromatography. A total of 58 maternal and child pairs were analyzed. Results: More than fifty percent of maternal-child pairs were noted to be vitamin D deficient or insufficient using the Endocrine Society Practice guidelines cut-off of 50 nmol/L. Spearman rank correlation and Kruskal Wallis analysis did not show statistically significant relationship between cord 25OHD (total) and maternal and cord BPA-g concentrations. Analysis of covariance after controlling for confounders showed a significant relationship between cord BPA-g levels and cord 25OHD levels (p=0.03) as well as between maternal BPA-g levels (p=0.04) and cord total 25OHD levels (p=0.04). Discussion: The findings of the current study indicate a possible relationship with BPA/BPA-g and fetal/early infant Vitamin D levels that needs to be further investigated in this population. [ABSTRACT FROM AUTHOR]

Background Study Design and Methods Results Discussion Umbilical cord blood (CB) units stored in banks are an important source of hematopoietic stem cells for transplantation and other cell therapies. New applications, such as their use in transfusions, require rapid quality release as cord blood red blood cells (CB‐RBC) have a shorter shelf life.This project aims to investigate the most prevalent microbial contaminants in CB preparations and validate a rapid sterility testing strategy for CB‐RBC based on an automated system (BACT/ALERT®) in tandem with a molecular assay (real‐time PCR) capable of detecting at least 100 CFU/mL of Cutibacterium acnes in CB‐RBC to accelerate the detection of the most common slow‐growing bacteria.Microbial contamination incidence was assessed by reviewing 4696 CB sterility tests, revealing a positivity rate of 3.4%, with C. acnes being the most common slow‐growing pathogen. The BACT/ALERT® system, which was validated according to European Pharmacopeia guidelines, was an appropriate method for sterility testing of CB‐RBC, although it required up to 14 days of culture to detect C. acnes when iFAPlus and iFNPlus bottles were used to neutralize antimicrobials. Interestingly, the BACT/ALERT® method detected C. acnes at 30 CFU/mL within 14 days, while real‐time PCR identified concentrations ≥65 CFU/mL by Day 4.In conclusion, we developed a rapid sterility testing strategy that combines automated culture systems and real‐time PCR for early microbial contamination, enhancing CB‐RBC shelf life for transfusion and emphasizing the importance of combining detection methods. [ABSTRACT FROM AUTHOR]

This study investigates the relationship between the cerebro-placental ratio (CPR) measured at 40+0 weeks’ gestation and perinatal outcomes to determine a CPR cut-off that may justify induction of labor at term in appropriately grown fetuses (AGA). Although CPR is used for monitoring growth-restricted fetuses, its role in guiding labor induction decisions for AGA pregnancies at term remains unclear.A retrospective cohort study was conducted using data from 491 singleton pregnancies with intended vaginal deliveries between 2015 and 2021. CPR was assessed at the actual estimated date of delivery (40+0 weeks’ gestation). Adverse Pregnancy Outcome (APO) as the primary endpoint was defined by admission to neonatal intensive care unit (NICU), umbilical cord blood pH<7.1, 5-min APGAR<7 or interventions-due-to-fetal-distress during labor (IDFD=vaginal-operative delivery or emergency caesarean section).APO nearly doubled (adjOR 1.7; CI 1.007–2.905) when CPR was below our calculated cut-off of 1.269 (18.4 vs. 32.3 %, p=0.002) and NICU admissions (4.8 vs. 11.1 %, p=0.020) and IDFD (12.5 vs. 21.2 %, p=0.027) significantly increased. The positive predictive value for the presence of APO using our cut-off was 32.4 %, and the negative predictive value 81.6 %.Our data confirm a predictive value of a reduced CPR at term with impaired perinatal outcome. The cut-off of CPR<1.269 may guide decision-making regarding induction of labor. Further prospective studies are needed to confirm these findings. [ABSTRACT FROM AUTHOR]

Thalassemia and leukemia and related blood disorders are approved for blood stem cell transplants in India, for a stem cell transplant to be successful, the human leukocyte antigen (HLA) complex located on the arm of chromosome six must be a match between the cord blood donor and the recipient. In the quest to find an exact blood stem cell match for an individual, the HLA becomes the node at the center of community genetics where the HLA match is sought (not necessarily successful) in the extended family, the same caste, language, and ethnic (both national and the diaspora) groups. By considering thalassemia as a case study, how do we understand personalized stem cell therapies within biobanking infrastructures in Chennai? How do social categories get entwined with biological materials like cord blood? [ABSTRACT FROM AUTHOR]

Background: Mesenchymal stromal cells (MSC) have immunomodulatory and hematopoiesis-supporting properties that could potentially benefit hematopoietic stem cell (HSC) engraftment and decrease the incidence and/or severity of graft-versus-host disease (GVHD). Methods: Based on our previous pilot study, we established a multicenter, prospective, randomized, double-blind trial evaluating the efficacy of co-infusing third-party MSC (1.5–3 × 106/kg) versus placebo on the day of HSC transplantation (HCT) to prevent GVHD in recipients of HLA-mismatched unrelated donors after reduced-intensity conditioning. Results: The study planned to include 120 patients to improve 1-year overall survival (OS) from 55 to 77% but was stopped after 9 years for low recruitment (n = 38). One-year OS was 74% in the MSC group and 80% in the placebo group. In multivariate analysis, the incidence of grade II-IV acute GVHD was significantly lower in patients receiving MSC (HR 0.332, 95% CI 0.124–0.890, p = 0.0284). No difference was observed in the incidences of chronic GVHD, infection or relapse, overall or progression-free survival at 1 year or long-term, or hematopoietic and immune reconstitution. Conclusions: Despite premature study closure, the suggested beneficial effect of MSC co-transplantation for the prevention of acute GVHD in HLA-mismatched HCT warrants further investigation. [ABSTRACT FROM AUTHOR]