Cord-blood black carbon burden is associated with coordinated inflammatory and heme-metabolic transcriptional programs at birth in Bradford, United Kingdom.

Prenatal and early-life exposure to micro- and nanoplastics and autism-relevant neurodevelopment: An integrated review of human, experimental, and mechanistic evidence.

Low-dose aspirin (LDA) is an intervention recommended to prevent the development of hypertensive disorders of pregnancy (HDP) in high-risk pregnancies. Maternal conditions such as HDP have been associated with cord blood epigenetic changes including those related to cardiovascular processes; however, it is unclear whether maternal aspirin therapy may impact neonatal epigenetics in otherwise healthy high-risk pregnancy. This study aimed to determine if maternal LDA exposure in utero leads to altered DNA methylation in umbilical cord blood cells in term neonates compared with controls not exposed to aspirin, and to identify if these methylation changes alter key pathways in the development of chronic disease. Umbilical cord blood was collected from 10 neonates without LDA exposure and 13 neonates with LDA exposure in utero. Patients with hypertensive disorders of pregnancy, COVID-19, and chorioamnionitis were excluded. Genomic DNA was isolated from umbilical cord blood cells and genome-wide DNA methylation was performed using Illumina Methylation EPIC assay. A total of 155 differentially methylated loci (81 genes were hypermethylated and 74 were hypomethylated) were identified in LDA-exposed neonatal umbilical cord blood compared with the control group. Important canonical pathways identified by Ingenuity Pathway Analysis (IPA) were related to Th1 and Th2 signaling and classical (M1) macrophage activation. The genes affected by LDA exposure were associated with cardiac and renal systems. LDA exposure led to differential DNA methylation in umbilical cord blood. The differentially methylated genes were related to inflammatory pathways as well as cardiac and renal toxicity pathways. LDA exposure in utero may promote altered health programming in the neonate in areas impacting cardiovascular health. · Maternal aspirin exposure is associated with differential DNA methylation in cord blood.. · Cord blood epigenetic changes associated with maternal aspirin relate to anti-inflammatory pathways.. · Research on potential protective impact of maternal aspirin on neonatal epigenetics is warranted..

Early-life mitochondrial impact of prenatal DL-PCB exposure: A signal from cord blood mtDNA.

The insulin/insulin-like growth factor (IGF) system is a key regulator of fetal growth and placental nutrient regulation. The objective of this study was to investigate associated gene and protein expressions of the insulin/IGF, adiponectin, and peroxisome proliferator-activated receptor (PPAR) pathways in placenta and cord blood from small-, appropriate-, or large-for-gestational-age (SGA, AGA, LGA) infants and corresponding first-trimester maternal blood. A total of 60 SGA, 109 AGA, and 55 LGA term infants (birth weight z scores <-2, -2 to +2, and >2, respectively) were included. Placental mRNA expression of 22 genes was analyzed using RT-qPCR. Immunohistochemistry (IHC) was used to determine the protein localization and abundance of 5 differentially expressed genes in 78 representative placental samples. Cord blood and maternal blood concentrations of related proteins were analyzed by ELISA. Placental gene expression of IGF1, IGF2, IGBP2, IGF2R, and PPARA was significantly lower in the SGA group. A moderate correlation in expression levels was observed among differentially expressed genes, except for IGF2R. In the SGA group, IHC staining for IGF1, IGF2, IGF2R, and PPARα was weaker, while IGFBP2 staining was stronger. In the cord blood, the IGF1 and IGF2 concentrations increased successively from the SGA group to the LGA group, whereas the IGFBP2 concentration decreased successively. No differences in maternal blood were observed between the groups. Placental IGF1, IGF2, and PPARα signaling are positively associated with birth weight, whereas that of IGFBP2 is negatively associated, possibly reflecting a shared upstream regulation by nutrition. Conversely, placental IGF2R signaling may aid in normalizing abnormal fetal growth.

Impact of prenatal manganese and selenium exposure on childhood thyroid hormone parameters up to 4years of age: Japan environment and children's study.

Intermittent preventive treatment during pregnancy (IPTp) for malaria prevention with sulfadoxine-pyrimethamine is contraindicated in pregnant women living with HIV receiving cotrimoxazole prophylaxis. A recent clinical trial showed that dihydroartemisinin-piperaquine (DHA-PPQ) for IPTp is a safe and effective option for malaria prevention in this population. The present study evaluated the impact of monthly IPTp with DHA-PPQ on antiretroviral (ARV) drug concentrations in 105 participants recruited in the aforementioned trial in Mozambique and Gabon between January and November 2021. ARV serum concentrations from maternal venous and cord blood collected at the first antenatal care visit and at the end of pregnancy were measured by ultra-high-performance liquid chromatography-tandem mass spectrometry. At the end of pregnancy, median concentrations of dolutegravir were 835.1 ng/mL (248.1-1,687.6) in maternal and 1,204.2 ng/mL (456.4-1,883.3) in cord blood. For lamivudine (3TC), median concentrations were 108.3 ng/mL (28.8-246.1) in maternal and 186.5 ng/mL (81.9-427.6) in cord blood. No significant differences in ARV concentrations were found between the antimalarial treatment arm and the placebo arm. Furthermore, in multivariate exploratory analysis, no independent associations were found between ARV concentrations and participant characteristics. Our study found similar ARV concentrations in both treatment groups, suggesting that DHA-PPQ for monthly IPTp does not affect ARV concentrations in maternal and cord blood in women living with HIV.CLINICAL TRIALSThis study is registered with ClinicalTrials.gov as NCT03671109.

A function-first legacy in hematopoietic stem cell biology: the scientific impact of Hal E. Broxmeyer.

Introduction: Premature and Low-Birth-Weight (LBW) neonates demonstrate underdeveloped organs, including low nephron counts, rendering them susceptible to renal impairment subsequently. Therefore, early and accurate detection of kidney dysfunction is important for management. Traditionally, serum creatinine is used for estimating Glomerular Filtration Rate (GFR), which maternal levels and neonatal muscle mass may influence. Therefore, cystatin-C, a non protein-bound, lowmolecular-weight marker, is tested for this study for the early detection of renal dysfunction. Aim: To identify creatinine or cystatin-C as a better marker in premature and LBW neonates. Materials and Methods: This case-control study was conducted from June to October 2022 at the SRM Medical College Hospital, Tamil Nadu, India. The participants were from Chengalpattu district, including 63 rural and 47 suburban pregnant women. The primary inclusion criteria were neonates diagnosed as premature and LBW, with a sample size of 53 neonates per group. A 3-5 mL of venous and cord blood samples of neonates were collected, serum was separated and stored at -20°C to estimate creatinine, cystatin-C levels and GFR. The results were expressed as mean values, and statistical significance was assessed using the Student’s t-test, with a p-value &lt;0.05 considered statistically significant. Results: Cystatin-C were found to be 1.9±0.8 mg/dL and significantly higher in cord blood samples in comparison with the control. The cystatin-based eGFR value was found to be 91.4±43.2 mL/min and 149±35.4 mL/min for venous and cord blood samples, respectively. Whereas only cystatin-C was statistically significant in venous blood samples. However, GFR based on creatinine and cystatin-C was significantly decreased in both venous and cord blood samples. Conclusion: The AUC for cystatin-C in cord blood samples was found to be 0.7, indicating its reliability compared to creatinine. Moderate accuracy observed indicates the need for a larger number of samples for the establishment of a diagnostic marker. Thereby, for cystatin-C to be used as a marker for renal dysfunction further validation is required.

Erectile dysfunction (ED) secondary to cavernous nerve injury (CNI), such as that occurring after radical prostatectomy, remains a significant clinical challenge, particularly among patients who do not respond to phosphodiesterase Type 5 inhibitors (PDE5i). Extracellular vesicles (EVs) derived from umbilical cord blood (UCB) have recently emerged as a promising cell-free therapeutic modality owing to their potent regenerative and anti-inflammatory properties. This study aimed to investigate the therapeutic efficacy of UCB-derived EVs (UCB-EVs) in restoring erectile function in a bilateral CNI mouse model. UCB-EVs were isolated and characterized by transmission electron microscopy, nanoparticle tracking analysis, and western blotting. Their neuroregenerative effects were assessed in vitro using Neuro-2a (N2a) cell migration assays and ex vivo by evaluating neurite outgrowth in major pelvic ganglia (MPG) and dorsal root ganglia (DRG). In vivo, fluorescently labeled UCB-EVs were tracked following intracavernous administration, and erectile function was quantified using maximal ΔICP and baseline-corrected total ΔICP during cavernous nerve stimulation. Histological and biochemical analyses were conducted to assess neurovascular integrity, apoptosis, proliferation, oxidative stress, and activation of PI3K/AKT signaling in penile tissues. UCB-EVs significantly enhanced N2a cell migration in vitro and promoted neurite sprouting in MPG and DRG explants ex vivo. In CNI mice, intracavernous administration of UCB-EVs resulted in dose-dependent recovery of erectile function, as demonstrated by significant increases in maximal ΔICP and baseline-corrected total ΔICP during cavernous nerve stimulation. Biodistribution analysis demonstrated preferential localization of UCB-EVs to the penile neurovascular bundle. Histological and molecular evaluations revealed preservation of endothelial and neuronal populations, suppression of apoptosis, enhanced cellular proliferation, attenuation of reactive oxygen species (ROS) accumulation, and activation of PI3K/AKT signaling pathways in UCB-EV-treated mice. UCB-EVs promote neurovascular regeneration, mitigate oxidative stress, and improve erectile function following CNI. These findings suggest that UCB-EVs represent a promising regenerative strategy for postprostatectomy ED, particularly in patients refractory to conventional pharmacotherapy.

Peripheral nerve injuries are a major clinical challenge, interrupting neural connectivity between the central nervous system (CNS) and peripheral organs. Traumatic events, natural disasters, and accidents often cause these complex injuries. Recent studies highlight the neurogenic potential of dexamethasone, retinoic acid, and umbilical cord blood stem cells in promoting nerve regeneration. Therefore, the aim of this study was to design electrospun conduits based on PLCL, gelatin, and collagen, along with dexamethasone, retinoic acid, carboxymethyl chitosan, and umbilical cord blood cells to repair sciatic nerve injuries. The chemical and physical properties of the conduits, in addition to biocompatibility and cytotoxicity, were evaluated with different experiments. Finally, the conduits were implanted into a 10mm defect in the mouse sciatic nerve, and tissue regeneration was assessed after 3 months by related tests. The results showed that the presence of dexamethasone in the conduit designed improved biocompatibility, wettability, degradation rate, tensile strength, and increased cell viability. After seeding the umbilical cord blood cells on the conduit, the results showed good efficacy of the conduit, improving sensory and motor function and increasing nerve regeneration. These results indicate the potential of the resulting conduits as a promising tool for repairing nerve injuries and clinical trials.

Prenatal maternal anxiety and offspring development: Insights from neurobehavioral assessments and cord blood metabolomics.

Levothyroxine is one of the most prescribed drugs during pregnancy. Our aim was to determine levothyroxine treatment-associated changes in the metabolite profiles and link these to the health of the newborn. Metabolite profiles of 118 levothyroxine-treated and 118 healthy control pregnancies were determined with nuclear magnetic resonance-based metabolomics from (1) umbilical cord blood samples, (2) samples collected during the first trimester and (3) during delivery from the pregnant women. There was a modest negative correlation between cord blood thyroid stimulating hormone (CBTSH) concentrations and Apgar scores at the 1 and 5 min time points in levothyroxine-treated pregnancies. Furthermore, the concentrations of cord serum metabolites linked with anaerobic glycolysis, for example, lactate, citrate and glycerol, as well as all measured amino acids were negatively associated with Apgar scores. Moreover, cord serum concentrations of lactate, glycerol and alanine were modestly correlated with CBTSH concentrations in the levothyroxine-treated pregnancies. In the during delivery samples, there was small but significant decrease in cholesteryl esters, cholesterol and phospholipids in small very low-density lipoprotein in the levothyroxine-treated pregnancies. In conclusion, levothyroxine treatment during pregnancy was associated with relatively small alterations in the blood metabolite profiles during pregnancy and labour.

Longitudinal trends of per- and polyfluoroalkyl substances in Chinese children from birth to 7 years of age.

Prenatal exposure to metal mixtures and mitochondrial DNA content and telomere length in newborns: Potential modulation by TERT gene variants.

Sex-specific associations of sedentary behaviour and physical activity with placental and fetal IL-6 in pregnant women with obesity. Impact on neonatal adiposity in the DALI randomised controlled trial.

8-Me-PIQ Expands Cord Blood CD34+ Hematopoietic Stem and Progenitor Cells via Metabolic Suppression and Inhibition of Ribosome Biogenesis.

This study aimed to analyze metabolic characteristics of the umbilical cord blood associated with brain injury in neonates with selective fetal growth restriction (sFGR). A prospective cohort of 30 sFGR twin pairs delivered at Peking University Third Hospital between September 2017 and December 2019 was enrolled. Maternal-fetal clinical data and information on neonatal complications, including brain injury, were collected for both the growth-restricted (sFGR-S) and larger (sFGR-L) fetuses. The mean maternal age at delivery was (30.7±3.9) years, and the mean gestational age at delivery was (32.7±2.2) weeks. Among the 30 sFGR cases, there were 12 cases of type Ⅰ, 11 type Ⅱ, and 7 type Ⅲ. The cohort comprised 30 male and 30 female neonates (50% each). Brain injury occurred in 12 (40%) of the sFGR-S group, including 7 cases of intracranial hemorrhage (IVH), 3 cases of periventricular leukomalacia (PVL), and 2 case with both. In the sFGR-L group, brain injury occurred in 9 (30%) neonates, including 6 cases of IVH, 2 cases of PVL, and 1 case with both. Receiver operating characteristic (ROC) curve analysis for the sFGR-S group yielded an area under the curve (AUC) of 0.853 (95%CI: 0.698-1.000) for tyrosine alone, and an AUC of 0.944 (95%CI: 0.859-1.000) for the combination of tyrosine and myristic acid. For the sFGR-L group, the AUC was 0.880 (95%CI: 0.708-1.000) for S-adenosyl methionine (SAM) alone, and 0.917 (95%CI: 0.749-1.000) for the combination of SAM and trans-vaccenic acid. In conclusion, neonates in the sFGR-S and sFGR-L groups exhibit distinct metabolic profiles, and differential metabolites with their related pathways hold potential predictive value for neonatal brain injury.

Hereditary elliptocytosis (HE) caused by heterozygosity of three common SPTB mutations, namely SPTB Providence (c.6055T>C), SPTB Buffalo (c.6074T>G) and SPTB Chiang Mai (c.6224A>G), is the most prevalent form of red blood cell membranopathy in Thailand. Here, we explored the prevalence of the mutated SPTB-causing HE using molecular screening and demonstrated its impact on the development and severity of jaundice among Thai neonates. This cross-sectional study identified the three common SPTB mutations in cord blood samples from all neonates born at Ramathibodi Hospital from March to November 2024 using a recently developed robust, rapid molecular method. Clinical data related to neonatal jaundice were obtained from medical records and were analysed according to the presence of the SPTB mutations. A total of 1505 neonates with a mean (SD) gestational age of 37.5 (2.3) weeks were enrolled. Thirteen unrelated neonates were identified as having HE caused by the screened SPTB mutations, yielding a prevalence of 0.86%. The analyses revealed the mutated SPTB-causing HE as an independent risk factor for neonatal jaundice requiring phototherapy (risk ratio 5.01, 95% CI 2.56 to 9.79, p<0.001). The mean total bilirubin levels of neonates with the mutated SPTB-causing HE were significantly higher than those of neonates with glucose-6-phosphate dehydrogenase (G6PD) deficiency throughout the first 3 days of life (p=0.009 to 0.049). Most neonates with HE caused by the common SPTB mutations who required phototherapy did not exhibit anaemia and were not diagnosed clinically at birth. Coinheritance of the SPTB mutations and G6PD deficiency likely aggravated anaemia and worsened the degree of jaundice. HE caused by the three common SPTB mutations is associated with the development of significant jaundice requiring treatment among Thai neonates. Given the region's high prevalence, screening for the SPTB mutations is likely beneficial for comprehensive monitoring of neonatal jaundice and for disease counselling.

Bacterial sepsis is a leading cause of neonatal mortality. Pro-inflammatory MR1-restricted T (MR1T) cells may help protect from sepsis by recognizing bacterial pathogens producing the canonical MR1 antigen 5-OP-RU. Most adult MR1T cells are mucosal-associated invariant T (MAIT) cells expressing a semi-invariant TCRα, while neonatal MR1T cells express diverse TCRα chains. Here, we perform combined single-cell RNA-sequencing and TCR repertoire analyses on MR1/5-OP-RU tetramer-positive cells from neonatal cord blood (CB) and adult blood. Compared to adult MR1T cells, CB MR1T cells exhibit greater TCR diversity, reduced cytotoxic and proinflammatory gene expression, diminished bacterial recognition and reduced binding to MR1/5-OP-RU. Structural analysis of a CB MAIT TCR reveals decreased β chain contribution to the TCR-MR1 interface relative to an adult MAIT TCR. These findings demonstrate developmental stage-specific differences in MR1T cell repertoire, function and MAIT TCR structure with implications for neonatal sepsis.