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1.
Expression network analysis reveals cord blood vitamin D-associated genes affecting risk of early life wheeze.
Mirzakhani, H, Al-Garawi, AA, Carey, VJ, Qiu, W, Litonjua, AA, Weiss, ST
Thorax. 2019;(2):200-202
Abstract
Cord blood 25-hydroxyvitamin D (25OHD) has been reported in association with risk of early life recurrent wheeze. In a subset of infants who participated in the Vitamin D Antenatal Asthma Reduction Trial, we demonstrated that higher cord blood 25OHD at birth (>31 ng/mL) was associated with a reduced risk of recurrent wheeze in the first year of life. We then identified a module of co-expressed genes associated with cord blood 25OHD levels >31 ng/mL. Genes in this module are involved in biological and immune pathways related to development and progression of asthma pathogenesis including the Notch1 and transforming growth factor-beta signalling pathways.
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2.
Small-molecule nicotinamide for ex vivo expansion of umbilical cord blood.
Islam, P, Horwitz, ME
Experimental hematology. 2019;:11-15
Abstract
Umbilical cord blood transplant is an alternative graft source for patients lacking a human leukocyte antigen-matched donor; however, delayed engraftment times have historically resulted in transplant-related morbidity and mortality from complications such as infections and ineffective hematopoiesis. Recent advances in ex vivo expansion techniques have successfully augmented the initial cell dose delivered from an umbilical cord blood graft, leading to improved immune reconstitution, durable hematopoiesis, decreased transplant-related morbidity and mortality, and better outcomes. Herein we review the data for existing and developing ex vivo expansion techniques, with a focus on the preclinical and clinical data for nicotinamide-mediated cord blood expansion across both malignant and benign hematologic indications.
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3.
A Low Glycaemic Index Diet in Pregnancy Induces DNA Methylation Variation in Blood of Newborns: Results from the ROLO Randomised Controlled Trial.
Geraghty, AA, Sexton-Oates, A, O'Brien, EC, Alberdi, G, Fransquet, P, Saffery, R, McAuliffe, FM
Nutrients. 2018;(4)
Abstract
The epigenetic profile of the developing fetus is sensitive to environmental influence. Maternal diet has been shown to influence DNA methylation patterns in offspring, but research in humans is limited. We investigated the impact of a low glycaemic index dietary intervention during pregnancy on offspring DNA methylation patterns using a genome-wide methylation approach. Sixty neonates were selected from the ROLO (Randomised cOntrol trial of LOw glycaemic index diet to prevent macrosomia) study: 30 neonates from the low glycaemic index intervention arm and 30 from the control, whose mothers received no specific dietary advice. DNA methylation was investigated in 771,484 CpG sites in free DNA from cord blood serum. Principal component analysis and linear regression were carried out comparing the intervention and control groups. Gene clustering and pathway analysis were also explored. Widespread variation was identified in the newborns exposed to the dietary intervention, accounting for 11% of the total level of DNA methylation variation within the dataset. No association was found with maternal early-pregnancy body mass index (BMI), infant sex, or birthweight. Pathway analysis identified common influences of the intervention on gene clusters plausibly linked to pathways targeted by the intervention, including cardiac and immune functioning. Analysis in 60 additional samples from the ROLO study failed to replicate the original findings. Using a modest-sized discovery sample, we identified preliminary evidence of differential methylation in progeny of mothers exposed to a dietary intervention during pregnancy.
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4.
25-hydroxyvitamin D correlates with inflammatory markers in cord blood of healthy newborns.
Rosendahl, J, Holmlund-Suila, E, Helve, O, Viljakainen, H, Hauta-Alus, H, Valkama, S, Enlund-Cerullo, M, Hytinantti, T, Tervahartiala, T, Sorsa, T, et al
Pediatric research. 2017;(5):731-735
Abstract
BACKGROUND Vitamin D is a potent immunomodulator and may play a role in the development of the fetal innate immune functions. The aim of our study was to evaluate inflammatory markers in cord blood of healthy newborns in relation to vitamin D status at birth. METHODS We studied the concentrations of inflammatory markers, matrix metalloproteinase 8 (MMP-8) and high sensitivity CRP (hs-CRP), and 25-hydroxyvitamin D (25(OH)D) in cord blood of 939 healthy term infants born to mothers of Caucasian origin. We evaluated perinatal factors that affect the concentrations of MMP-8 and hs-CRP, and further explored associations between cord blood 25(OH)D and these inflammatory biomarkers. RESULTS Majority (99%) of the cohort was vitamin D sufficient (>50 nmol/l or 20 ng/ml). We observed a positive correlation between cord blood 25(OH)D and MMP-8 concentrations, and between 25(OH)D and hs-CRP concentrations. After adjustment for potential confounders (parity, antenatal antibiotic treatment, gestational age, mode of delivery, and maternal prepregnancy BMI), the association of 25(OH)D with MMP-8 and hs-CRP remained significant. CONCLUSION Cord blood 25(OH)D correlates with inflammatory markers MMP-8 and hs-CRP. The findings may reflect the diverse immunomodulatory functions of vitamin D in the innate immune response of the newborn.
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5.
Phase I study of cord blood-derived natural killer cells combined with autologous stem cell transplantation in multiple myeloma.
Shah, N, Li, L, McCarty, J, Kaur, I, Yvon, E, Shaim, H, Muftuoglu, M, Liu, E, Orlowski, RZ, Cooper, L, et al
British journal of haematology. 2017;(3):457-466
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Abstract
Multiple myeloma (MM) is a disease with known immune dysregulation. Natural killer (NK) cells have shown preclinical activity in MM. We conducted a first-in-human study of umbilical cord blood-derived (CB) NK cells for MM patients undergoing high dose chemotherapy and autologous haematopoietic stem cell transplantation (auto-HCT). Patients received lenalidomide (10 mg) on days -8 to -2, melphalan 200 mg/m2 on day -7, CB-NK cells on day -5 and auto-HCT on day 0. Twelve patients were enrolled, three on each of four CB-NK cell dose levels: 5 × 106 , 1 × 107 , 5 × 107 and 1 × 108 CB-NK cells/kg. Ten patients had either high-risk chromosomal changes or a history of relapsed/progressed disease. There were no infusional toxicities and no graft-versus-host disease. One patient failed to engraft due to poor autologous graft quality and was rescued with a back-up autologous graft. Overall, 10 patients achieved at least a very good partial response as their best response, including eight with near complete response or better. With a median follow-up of 21 months, four patients have progressed or relapsed, two of whom have died. CB-NK cells were detected in vivo in six patients, with an activated phenotype (NKG2D+ /NKp30+ ). These data warrant further development of this novel cellular therapy.
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Prenatal high-dose vitamin D3 supplementation has balanced effects on cord blood Th1 and Th2 responses.
Akhtar, E, Mily, A, Haq, A, Al-Mahmud, A, El-Arifeen, S, Hel Baqui, A, Roth, DE, Raqib, R
Nutrition journal. 2016;(1):75
Abstract
BACKGROUND Antenatal vitamin D3 (vitD3) supplementation significantly increases maternal and neonatal 25-hydroxyvitamin D3 (25(OH)D3) concentration, yet the effect of an improvement in maternal-fetal vitamin D status on the neonatal immune response is unclear. METHOD To assess the effect of prenatal vitD3 supplementation on cord blood T cell function, healthy pregnant Bangladeshi women (n = 160) were randomized to receive either oral 35,000 IU/week vitD3 or placebo from 26 to 29 weeks of gestation to delivery. In a subset of participants (n = 80), cord blood mononuclear cells (CBMC) were cultured, non-adherent lymphocytes were isolated to assess T cell cytokine responses to phytohemagglutinin (PHA) and anti-CD3/anti-CD28 (iCD3/iCD28), measured by multiplex assay. In 12 participants, lymphocyte gene expression profiles were analyzed by PCR array. RESULT In supplemented group, increased concentrations of IL-10 (P < 0.000) and TNF-α (P = 0.05) with iCD3/iCD28 stimulation and IFN-γ (p = 0.05) with PHA stimulation were obtained compared to placebo group. No differences in the gene expression profile were noted between the two groups. However, PHA stimulation significantly induced the expression of genes encoding Th1 and Th2 cytokines and down-regulated a number of genes involved in T-cell development, proliferation and differentiation of B cells, signal transduction pathway, transcriptional regulation and pattern recognition receptors (PRRs) in the vitamin D group (vitD group). CONCLUSION Third-trimester high-dose vitD3 supplementation in healthy pregnant women had balanced effects on biomarkers of cord blood Th1 and Th2 responses. TRIAL REGISTRATION ClinicalTrials.gov ( NCT01126528 ).
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The presence of B-cell activating factor (BAFF) in umbilical cord blood in both healthy and pre-eclamptic pregnancies and in human breast milk.
Bienertova-Vasku, J, Zlamal, F, Tomandl, J, Hodicka, Z, Novak, J, Splichal, Z, Ventruba, P, Thon, V, Vasku, A
Journal of reproductive immunology. 2015;:89-93
Abstract
B-cell activating factor (BAFF) is an important immune regulator that was recently reported to be secreted by placenta. The aim of the study was to investigate the presence of BAFF in umbilical cord blood, maternal serum, and breast milk in normal and in pre-eclamptic pregnancies. Pairs of maternal serum/umbilical cord blood were obtained from 12 pre-eclamptic and 34 physiological pregnancies. Another cohort of 10 healthy lactating women was established that was followed up for 6 months following delivery to investigate BAFF levels in breast milk. BAFF levels in maternal peripheral blood were significantly higher in physiological pregnancies than in pre-eclamptic pregnancies (p < 0.03). Furthermore, we observed a consistent presence of BAFF in breast milk during the 6-month post-partum period of breastfeeding. In this study, we demonstrate that BAFF levels are significantly lower in maternal peripheral blood in pre-eclamptic pregnancies. We also report the consistent presence of BAFF in breast milk in healthy women. More research into the role of BAFF in pregnancy, and during breastfeeding, is imperative.
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Thymic size correlates with cord blood zinc levels in low-birth-weight newborns.
Kumar, A, Pandey, M, Basu, S, Shukla, RC, Asthana, RK
European journal of pediatrics. 2014;(8):1083-7
Abstract
UNLABELLED Thymus is essential for immunity as it provides environment for T cell differentiation and maturation. There is limited information on various factors which determine thymic size at birth. We studied the influence of cord blood zinc and copper levels and maternal and neonatal nutritional status on thymic size in term low-birth-weight (LBW) newborns. A prospective observational study on 44 term LBW (<2,500 g) newborns (cases) and 71 gestational age-matched newborns weighing ≥2,500 g (controls). Sonographically determined thymic index was correlated to cord blood zinc and copper levels and maternal and neonatal nutritional status. Thymic index measured 3.74 ± 1.57 cm(3) in LBW newborns compared to 4.90 ± 2.33 cm(3) in normal-birth-weight newborns. Thymic index was significantly correlated to cord blood zinc levels but not to cord blood copper levels and had linear relationship to the maternal body mass index and midarm circumference and neonatal anthropometric parameters. CONCLUSION Thymic index is linearly related to cord blood zinc levels and maternal and neonatal nutritional status. Compared to thymic size in the Western newborns, the thymus is less than half in size in Indian newborns of normal birth weight. Reduced thymic size in Indian newborns in general and LBW infants in particular may have consequences for their immune competence and the risk of infections. Improving nutrition of pregnant women, particularly zinc nutriture might favorably influence thymic size in their offspring.
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Perinatal outcomes of prenatal probiotic and prebiotic administration: an integrative review.
VandeVusse, L, Hanson, L, Safdar, N
The Journal of perinatal & neonatal nursing. 2013;(4):288-301; quiz E1-2
Abstract
The purpose of this integrative review was to identify, critique, and synthesize the maternal and neonatal evidence on the prenatal use of probiotics and prebiotics to inform perinatal health professionals. A comprehensive literature search resulted in 37 studies of prenatal probiotics and 1 on antepartal prebiotics published from 1990 through 2011 that reported maternal, fetal, and/or neonatal outcomes. The methodologic quality of the studies reviewed was high, although investigators used different probiotic combinations and inconsistently reported perinatal clinical outcomes. The extraction of perinatal outcome variables resulted in identification of 9 maternal and 5 neonatal categories. Prenatal probiotics significantly reduced the incidence of bacterial vaginosis, increased colonization with vaginal Lactobacillus and intestinal Lactobacillus rhamnosus, altered immune markers in serum and breast milk, improved maternal glucose metabolism, and reduced the incidence of gestational diabetes and preeclampsia. Antepartally, probiotics were associated with significantly higher counts of Bifidobacterium and Lactococcus lactis (healthy intestinal flora) in neonatal stool. Prenatal prebiotics significantly increased maternal intestinal Bifidobacterium. No adverse events were reported and there was evidence of safety and tolerance of prenatal probiotics and prebiotics in the scientific investigations reviewed. It is recommended that in future investigations of prenatal probiotics researchers explicitly report maternal and neonatal outcomes.