Tipos de partos y niveles de oxitocina, cortisol y hormonas tiroideas en plasma del cordón umbilical / Types of deliveries and levels of oxytocin, cortisol and thyroid hormones in umbilical cord plasma

Introducción: La placenta sintetiza y secreta varias hormonas que permiten la regulación del embarazo, el trabajo de parto y la adaptación metabólica materno-fetal. Su comportamiento asociado al tipo de parto puede dar información relevante sobre efectos epigenéticos. Objetivo: Describir el tipo de parto con los niveles de oxitocina, cortisol y hormonas tiroideas en plasma de cordón umbilical al nacer. Método: A 50 mujeres con embarazos principalmente normales se les cuantificaron los niveles neurohormonales en plasma de cordón umbilical, obtenido inmediatamente tras el periodo expulsivo. Los resultados se incorporaron a la base de datos clínicos de cada participante y se analizaron con Stata v.14.0. El protocolo fue aprobado por el comité de ética. Resultados: Hubo 33 partos vaginales (12 espontáneos, 13 acelerados y 8 inducidos) y 17 cesáreas (7 electivas y 10 de urgencia). Se observaron mayores niveles de cortisol en los partos vaginales acelerados; las cesáreas tuvieron menores niveles de cortisol y hormona estimulante de la tiroides. Las intervenciones clínicas, con altos o bajos niveles hormonales, están en directa relación con el tipo de parto. Conclusiones: El cortisol y la hormona estimulante de la tiroides medidos en plasma de cordón umbilical variaron según el tipo de parto. Esto es una primera cuantificación de hormonas en plasma de cordón umbilical y su posible regulación placentaria a propósito del tipo de parto.

Introduction: The placenta synthesizes and secretes several hormones allowing the regulation of pregnancy, labor and maternal-fetal metabolic adaptation. Their behavior associated with the type of delivery, may provide relevant information on epigenetic effects. Objective: To describe the type of delivery with the levels of oxytocin, cortisol and thyroid hormones in umbilical cord plasma at birth. Method: Neurohormonal levels from umbilical cord plasma obtained immediately post expulsion, were quantified in 50 women with mainly normal pregnancies. Results incorporated into the clinical database of each participant, statistically analyzed in Stata v.14.0. Protocol approved by ethics committee. Results: 33 were vaginal deliveries (12 spontaneous, 13 accelerated, 8 induced) and 17 cesarean sections (7 elective and 10 emergency). Higher cortisol levels were observed in accelerated vaginal deliveries, cesarean sections had lower cortisol and thyroid stimulating hormone levels. While clinical interventions, with high or low hormone levels, were related to the type of delivery. Conclusions: Cortisol and thyroid stimulating hormone measured in umbilical cord plasma varied according to the type of delivery. This is a first quantification of hormones in umbilical cord plasma and their possible placental regulation in relation to the type of delivery.

Cord Blood Lipid Profile of Term and Preterm Newborns in a Tertiary Hospital in South East Nigeria: Relationship with Gestational Age and Birth Weight

Background: Early-onset atherosclerosis is a marker of future cardiovascular diseases. However, indicators of early dyslipidemia for primary prevention are generally lacking in sub-Saharan Africa. This study aimed at describing the cord blood lipid profile among apparently healthy newborns in a tertiary hospital in Southeast Nigeria, and its relationship with gestational age and birth weight.Methods: Cross-sectional study of 167 consecutively recruited apparently well newborns in a tertiary hospital whose cord blood lipid profile parameters (total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL ­C), low-density lipoprotein cholesterol (LDL ­C) and very low-density lipoprotein cholesterol (VLDL ­C)) were assessed using an autoanalyzer (BiOLis 24i). Lipid variables were presented with descriptive statistics whereas their relationship with gestational age and birth weight was highlighted using Spearman's rank correlation analysis. Dunnett's T3 Post Hoc analysis was used for pairwise comparisons.Results: The 167 newborns recruited included 15 (9%) moderate preterm, 46 (27.5%) late preterm and 106 (63.5%) term babies of which 79 (47.3%) were males and 88 (52.7%) were females. The number of recruited SGA, AGA and LGA were respectively 13 (7.8%), 142 (85%), 12 (7.2%). Mode of delivery was majorly vaginal delivery (69.5%) while the rest (30.5%) was by caesarean section. The median values (in mg/dL) of TC, TG, HDL ­C, LDL ­C and VLDL ­C were 60.0, 30.5, 29.0, 25.8 and 6.1 respectively, all within the normal international ranges. Triglycerides and VLDL-C had a moderate positive correlation with gestational age (rs = 0.4;p < 0.001) and were significantly higher in small-for-gestational-age newborns. Total cholesterol, HDL ­C, and LDL-C had a weak negative correlation with gestational age and birth weight (spearman rs˂-0.3). Birth weight, gestational age, and paternal age were the common predictors of lipid profile variability.Conclusion: The finding of a significant relationship between lipid variables with gestational age and birth weight underscores the need to clinically interpret these given the relationship. The relationship with paternal age is another interesting finding which needs to be replicated and the mechanism(s) elucidated.

Effect of Hypoxia-Supported Umbilical Cord Mesenchymal Stem Cells on the Expansion of Cord Blood Mononuclear Cells in vitro / 中国实验血液学杂志

OBJECTIVE@#To explore the effect of hypoxia-supported umbilical cord mesenchymal stem cell (UC-MSC) on the expansion of cord blood mononuclear cell （MNC） in vitro.@*METHODS@#The isolated cord blood mononuclear cells were inoculated on the preestablished umbilical cord mesenchymal stem cell layer and cultured under hypoxic conditions (3％ O2) and the experimental groups were normoxia (MNCs were cultured under normoxic conditions), hypoxia (MNCs were cultured under hypoxic conditions), UC-MSC (MNCs were cultured with UC-MSC under normoxic conditions), and UC-MSC+hypoxia (MNCs were cultured with UC-MSC under hypoxic conditions). To further investigate the combinational effect of 3 factors of SCF+FL+TPO (SFT) on expansion of cord blood MNCs in vitro in hypoxia-supported UC-MSC culture system, the experiments were further divided into group A (MNCs were cultured with UC-MSC and SFT under normoxic conditions), group B (MNCs were cultured with UC-MSC under hypoxic conditions), group C (MNCs were cultured with UC-MSC and SFT under hypoxic conditions). The number of nucleated cells (TNC), CD34+ cell, CFU and CD34+CXCR4+, CD34+CD49d+, CD34+CD62L+ cells of each groups were detected at 0, 7, 10 and 14 days, respectively.@*RESULTS@#Compared with group hypoxia and UC-MSC, group UC-MSC+hypoxia effectively promoted the expansion of TNC, CD34+ cell and CFU, and upregulated the expression level of adhesion molecule and CxCR4 of the cord blood CD34+ cell（P<0.05）. After culturing for 14 days, compared with group A and group B, group C effectively promoted the expansion of cord blood MNC at different time points（P<0.05）, and the effect of group A was better than that of group B at 7 and 10 days（P<0.05）.@*CONCLUSION@#Hypoxia-supported UC-MSC efficiently promoted the expansion and expression of adhesion molecule and CXCR4 of cord blood CD34+ cell, and the effect of expansion could be enhanced when SFT 3 factors were added.

A nested case-control study on the association of neonatal cord blood selenium, iron and copper with congenital heart disease / 中华预防医学杂志

Objective: To investigate the relationship between the levels of selenium, iron and copper in cord blood of neonates and the risk of congenital heart disease (CHD), and analyze their interaction effects. Methods: The subjects were obtained from the birth cohort in Lanzhou area established from 2010 to 2012. A baseline survey was conducted in the first trimester, and the follow-up was conducted in the second trimester, third trimester and 42 days after delivery. The umbilical vein blood was collected from newborns at delivery, and information on their birth outcomes was extracted from medical records. A nested case-control study was used to select 97 neonates with CHD newly diagnosed by echocardiography as the case group, and 194 neonates were selected as the control group by 1∶2 matching according to their mother's age, block and CHD onset time. Inductively coupled ion mass spectrometry was used to detect the concentrations of selenium, iron and copper in neonatal cord blood. The element exposure was categorized into three groups, the low, medium and high concentrations, according to the quartiles Q1 and Q3 of selenium, iron and copper concentrations in the control group. The association between cord blood selenium, iron and copper concentrations and CHD was analyzed by conditional logistic regression model using medium concentration as the reference standard. The association of their interactions with CHD was analyzed by a phase multiplication model. Results: The M (Q1, Q3) concentration of neonatal cord blood copper was 746.12 (467.48, 759.74) μg/L in the case group and 535.69 (425.21, 587.79) μg/L in the control group, with a statistically significant difference between the two groups (P<0.05). After adjustment for confounders, logistic regression models showed that the risk of CHD development was increased in neonates with either high copper in cord blood (OR=4.062, 95%CI: 2.013-8.199) or high copper combined with high iron (OR=3.226, 95%CI: 1.343-7.750). No correlation was observed between selenium and iron concentrations and the development of CHD in neonates. There was a multiplicative interaction between copper and iron in cord blood on the risk of developing CHD (OR=1.303, 95%CI: 1.056-1.608). Conclusion: There is a multiplicative interaction between iron and copper elements. The high copper and the high copper combined with high iron in umbilical cord blood are risk factors for neonatal CHD.

Comparative Study of the Two High-Efficient Strategies for in vitro Generation of Human Umbilical Cord Blood-derived Natural Killer Cells / 中国实验血液学杂志

OBJECTIVE@#To explore the similarities and variations of biological phenotype and cytotoxicity of human umbilical cord blood natural killer cells (hUC- NK) after human umbilical cord blood-derived mononuclear cells (hUC-MNC) activated and expanded by two in vitro high-efficient strategies.@*METHODS@#Umbilical cord blood mononuclear cells (MNC) from healthy donor were enriched by Ficoll-based density gradient centrifugation. Then, the phenotype, subpopulations, cell viability and cytotoxicity of NK cells derived from Miltenyi medium (denoted as M-NK) and X-VIVO 15 (denoted as X-NK) were compared using a "3IL" strategy.@*RESULTS@#After a 14-day's culture, the contents of CD3-CD56+ NK cells were elevated from 4.25%±0.04% (d 0) to 71%±0.18% (M-NK) and 75.2%±1.1% (X-NK) respectively. Compared with X-NK group, the proportion of CD3+CD4+ T cells and CD3+CD56+ NKT cells in M-NK group decreased significantly. The percentages of CD16+, NKG2D+, NKp44+, CD25+ NK cells in X-NK group was higher than those in the M-NK group, while the total number of expanded NK cells in X-NK group was half of that in M-NK group. There were no significant differences between X-NK and M-NK groups in cell proliferation and cell cycle, except for the lower percentage of Annexin V+ apoptotic cells in M-NK group. Compared with X-NK group, the proportion of CD107a+ NK cells in M-NK group were higher under the same effector-target ratio (E∶T) (P<0.05).@*CONCLUSION@#The two strategies were adequate for high-efficient generation of NK cells with high level of activation in vitro, however, there are differences in biological phenotypes and tumor cytotoxicity.

Expansion of cord blood stem cells in fibronectin-coated microfluidic bioreactor

ABSTRACT Background: Hematopoietic stem/progenitor cell transplantation is the main treatment option for hematological malignancies and disorders. One strategy to solve the problem of low stem cell doses used in transplantation is pre-transplant expansion. We hypothesized that using fibronectin-coated microfluidic channels would expand HSPCs and keep self-renewal potential in a three-dimensional environment, compared to the conventional method. We also compared stem cell homing factors expression in microfluidic to conventional cultures. Materials and methods: A microfluidic device was created and characterized by scanning electron microscopy. The CD133+ cells were collected from cord blood and purified. They were subsequently cultured in 24-well plates and microfluidic bioreactor systems using the StemSpan serum-free medium. Eventually, we analyzed cell surface expression levels of the CXCR4 molecule and CXCR4 mRNA expression in CD133+ cells cultured in different systems. Results: The expansion results showed significant improvement in CD133+ cell expansion in the microfluidic system than the conventional method. The median expression of the CXCR4 in the expanded cell was lower in the conventional system than in the microfluidic system. The CXCR4 gene expression up-regulated in the microfluidic system. Conclusion: Utilizing microfluidic systems to expand desired cells effectively is the next step in cell culture. Comparative gene expression profiling provides a glimpse of the effects of culture microenvironments on the genetic program of HSCs grown in different systems.

Oxidative stress in maternal milk and cord blood in gestational diabetes mellitus: a prospective study

ABSTRACT BACKGROUND: Reduced antioxidant defenses may reflect a poor protective response against oxidative stress and this may be implicated in progression of gestational diabetes mellitus (GDM). Oxidative stress induced by hyperglycemia plays a major role in micro and macrovascular complications, which imply endothelial dysfunction. OBJECTIVE: Our aim in this study was to investigate the association between GDM and oxidative stress markers measured in plasma, with regard to revealing changes to total antioxidant capacity (TAC) and total oxidant status (TOS) among mothers showing impairments in oral glucose tolerance tests (OGTTs). DESIGN AND SETTING: Prospective study at a university hospital in Turkey. METHODS: The study group consisted of 50 mothers with GDM, and 59 healthy mothers served as controls. Umbilical cord blood samples were taken from all mothers during delivery and breast milk samples on the fifth day after delivery. TAC, TOS, thiol and disulfide levels were measured. RESULTS: No statistically significant relationship between the blood and milk samples could be found. An analysis on correlations between TAC, TOS and certain parameters revealed that there were negative correlations between TOS and total thiol (r = -0.386; P < 0.001) and between TOS and disulfide (r = -0.388; P < 0.001) in milk in the control group. However, these findings were not observed in the study group. CONCLUSION: Our findings suggested that a compensatory mechanism of oxidative stress was expected to be present in gestational diabetes mellitus and that this might be ameliorated through good glycemic regulation and antioxidant supplementation.

Validation of the single-platform ISHAGE protocol for enumeration of CD34+ hematopoietic stem cells in umbilical cord blood in a Brazilian center

Abstract Background This study aims to validate the single-platform method for enumeration of CD34+ cells, by comparing the performance of two different commercial kits, as well as to evaluate the efficiency of the AccuriTM C6 cytometer in providing direct counts of absolute cell numbers. Method We evaluated 20 samples from umbilical cord blood (UCB), comparing the two different methodologies for enumeration of CD34+ cells: single and dual-platform. For the assessment of the single-platform, Procount and SCE kits were used, both of which use fluorescent beads as a counting reference to obtain absolute CD34+ cells numbers. Moreover, after the acquisition of samples in flow cytometer AccuriTM C6, following the protocol established for each kit, the number of CD34+ cells was recalculated, considering the cell count provided by the AccuriTM C6. Main Results In our analysis, the results showed a strong correlation between the number of CD34+ cells/μL (r2 = 0.77) when comparing the SCE kit and the current dual-platform method. On the other hand, the comparison between Procount kit and dual-platform results showed a moderate correlation for the number of CD34+/μL cells (r2 = 0.64). Conclusion Our results showed that the AccuriTM C6 flow cytometer can be used safely, applying both the dual and single platform analysis strategy. Considering the ISHAGE protocol-based single-platform approach, as the most appropriate methodology for CD34+ cells enumeration, our results demonstrated that the SCE kit has great potential for national standardization of UCB samples analysis methodology.

Relación entre el consumo materno de carne vacuna durante el embarazo y los niveles de ferritina en el cordón umbilical / Relationship between maternal beef consumption during pregnancy and umbilical cord ferritin concentration / Relação entre o consumo materno de carne bovina durante a gravidez e os níveis de ferritina no cordão umbilical

Antecedentes: la nutrición durante el embarazo impacta en la salud del recién nacido, con efectos a nivel epigenético determinando consecuencias neurológicas a largo plazo. Las necesidades de hierro durante el embarazo se estiman en 27 mg/día. El hierro hemo que se absorbe mejor se encuentra en la carne. La determinación de ferritina en sangre de cordón umbilical permite evaluar los depósitos de hierro alcanzados durante la etapa fetal. Sus niveles se asociaron con efectos a largo plazo sobre el desarrollo infantil. Objetivos: el objetivo de este estudio de carácter exploratorio es determinar la relación entre el consumo de carnes rojas durante el tercer trimestre de gestación y el nivel de ferritina en el cordón umbilical. Métodos: se realizó un estudio observacional descriptivo con datos recolectados prospectivamente durante un año en el Departamento de Neonatología del Centro Hospitalario Pereira Rossell (CHPR) en Montevideo, Uruguay. Un total de 188 pacientes cumplieron los criterios de inclusión. Se extrajo sangre del cordón umbilical después de un pinzamiento estricto del cordón pasado un minuto de vida. La ferritina se midió utilizando el método de quimioinmunofluorescencia. Se aplicó una encuesta nutricional materna (cualitativo-cuantitativa) que midió la frecuencia de consumo de alimentos con fuente de hierro y las cantidades aproximadas consumidas durante el último trimestre del embarazo. Esta encuesta se centró en el consumo materno de carne vacuna como principal fuente de hierro hemínico en Uruguay. Se analizó la relación entre estas variables. Resultados: el déficit latente de hierro (ferritina en el cordón umbilical <100 ng/ml) se asoció con un menor consumo de carne vacuna durante el embarazo. Valor p de Fisher: 0,0133, OR: 3,71, IC del 95% (1,25-11,05). Conclusiones: este estudio considera adecuada la evidencia que relaciona que los niveles bajos de consumo total de hierro y de carne vacuna durante el tercer trimestre de gestación determinarán un mayor riesgo de déficit latente de hierro y de ferritina medido en el cordón umbilical. Los niveles descendidos de ferritina en cordón umbilical se asocian con un mayor riesgo de efectos adversos a largo plazo sobre la mielinización y el desarrollo neurocognitivo.

Background: nutrition during pregnancy impacts the foetus and the newborn health, it has consequences at the epigenetic level and determines long-term neurological consequences. Iron requirements during pregnancy are estimated at 27 mg/day. Iron is blood absorption from is most efficient from beef. Umbilical cord blood ferritin levels can be used to assess iron deposits reached during the foetal stage. Ferritin levels are linked to the child's long-term development. Objective: this exploratory study's objective is to determine the relationship between beef consumption during the first quarter of pregnancy and ferritin levels in the umbilical cord. Methods: we carried out a descriptive, observational study with prospectively collected data for one-year at the Neonatology Department of the Pereira Rossell Hospital Center (CHPR) in Montevideo, Uruguay. A total of 188 patients met the inclusion criteria. We extracted umbilical cord blood after a strict cord clamping after one minute of life. Ferritin was measured using the chemoimmunofluorescence method. We carried out a maternal nutritional survey using a qualitative-quantitative method and measured the frequency and approximate quantity of iron source food consumption during the last quarter of pregnancy. This survey was focused on maternal beef consumption as the major heme iron source in Uruguay. We analyzed the relationship between these variables. Results: latent iron deficiency (ferritin in the umbilical cord <100 ng / ml) was associated with lower beef consumption during pregnancy. Fisher p-value: 0.0133, OR: 3.71, 95% CI (1.25 - 11.05). Conclusions: this study agrees with the evidence that shows that low levels of total iron and beef consumption during pregnancy determine an increased risk of latent iron deficiency and lower levels of ferritin in newborns, and therefore, greater risk of long-term adverse effects on myelination and neurocognitive development.

Contexto: a nutrição durante a gravidez tem impacto sobre a saúde do recém-nascido, com efeitos no nível epigenético, determinando consequências neurológicas a longo prazo. As necessidades de ferro durante a gravidez são estimadas em 27 mg / dia. O ferro heme de melhor absorção e aquele encontrado na carne vacuna. A determinação da ferritina no sangue do cordão umbilical permite avaliar os depósitos de ferro atingidos na fase fetal. Seus níveis foram associados a efeitos de longo prazo no desenvolvimento das crianças. Objetivos: o objetivo deste estudo exploratório é determinar a relação entre o consumo de carne vermelha durante o terceiro trimestre de gestação e o nível de ferritina no cordão umbilical. Métodos: foi realizado um estudo observacional descritivo com dados coletados prospectivamente durante um ano no Departamento de Neonatologia do Centro Hospitalar Pereira Rossell (CHPR) em Montevidéu, Uruguai. Um total de 188 pacientes cumpriram os critérios de inclusão. O sangue do cordão umbilical foi coletado após clampeamento estrito do cordão após um minuto de vida da criança. A ferritina foi medida pelo método de quimioimunofluorescência. Aplicamos um inquérito nutricional materno (qualitativo-quantitativo) que mediu a frequência de consumo de alimentos com fonte de ferro e as quantidades aproximadas consumidas durante o último trimestre da gravidez. Esta pesquisa enfocou o consumo materno de carne bovina como principal fonte de ferro heme no Uruguai. A relação entre essas variáveis foi analisada. Resultados: a deficiência latente de ferro (ferritina no cordão umbilical <100 mg / ml) foi associada ao menor consumo de carne bovina durante a gestação. Valor de p de Fisher: 0,0133, OR: 3,71, IC 95% (1,25-11,05). Conclusões: este estudo concorda com as evidências que relacionam que os baixos níveis de ferro total e consumo de carne bovina durante o terceiro trimestre de gestação determinam um maior risco de déficit de ferro latente e ferritina mensurado no cordão umbilical. A redução dos níveis de ferritina no cordão umbilical está associada a um risco aumentado de efeitos adversos de longo prazo na mielinização e no desenvolvimento neurocognitivo.

Cord blood bilirubin and prediction of neonatal hyperbilirubinemia and perinatal infection in newborns at risk of hemolysis

Abstract Objective To assess the accuracy of umbilical cord bilirubin values to predict jaundice in the first 48 h of life and neonatal infection. Method Newborn infants treated at a regional well-baby nursery born at ≥36 weeks of gestation were included in this retrospective cohort study. All infants born in a 3-year period from mothers with O blood type and/or Rh-negative were included and had the umbilical cord bilirubin levels measured. Hyperbilirubinemia in the first 48 h was defined as bilirubin levels above the phototherapy threshold. Neonatal infection was defined as any antibiotic treatment before discharge. Results A total of 1360 newborn infants were included. Two hundred and three (14.9%) newborn infants developed hyperbilirubinemia in the first 48 h of life. Hyperbilirubinemic infants had smaller birth weight, higher levels of umbilical cord bilirubin, a higher rate of infection and were more often direct antiglobulin test positive. Umbilical cord bilirubin had a sensitivity of 76.85% and a specificity of 69.58% in detecting hyperbilirubinemia in the first 48 h, with the cut-off value at 34 µmol/L. The area under the receiver operating characteristic curve was 0.80 (95% CI: 0.78-0.82). Umbilical cord bilirubin had a sensitivity of 27.03% and specificity of 91.31% in detecting perinatal infection. The area under the receiver operating characteristic (ROC) curve was 0.59 (95% CI: 0.57-0.63). Conclusions A positive correlation was found between umbilical cord bilirubin and hyperbilirubinemia in the first 48 h of life. Umbilical cord bilirubin is a poor marker for predicting neonatal infection.

Células madre mesenquimatosas y sus diferentes usos / Mesenchymal stem cells and their different uses

Introducción: las células madre mesenquimatosas (CMM) se diferencian de diversos tipos celulares para la regeneración de tejidos, esta característica sumada con la versatilidad del antígeno leucocitario humano (HLA) representan una eficaz alternativa para el tratamiento de enfermedades con tejidos deteriorados. Se pueden obtener a partir de médula ósea, cordón umbilical (CU) y sangre fetal. Objetivo: analizar los tipos de diferenciación de las CMM, sus métodos de extracción y su relación con bancos de sangre de cordón umbilical (BSCU), a fin de demostrar la eficacia de las CMM, en patologías que impliquen alteración de algún tejido u órgano. Metodología: se revisaron varias publicaciones en español e inglés en Pubmed, Clinicalkey y Science Direct; desde 2013 hasta 2020. Se usaron los términos sangre fetal, células madre mesenquimatosas, trasplante de Células Madre de Sangre del Cordón Umbilical y bancos de sangre. Con dicha información se redactó un panorama amplio sobre las células mesenquimales y como estas participan en diversas áreas de la salud, con un énfasis importante en sus usos terapéuticos y lo referente a de donde provienen. Conclusión: a través de la pluripotencialidad de las CMM, se han podido emplear en múltiples patologías pues reestablece tejidos o líneas celulares exitosamente. Así mismo, los recursos para su obtención son claves en la tolerancia de los pacientes, por lo cual una gran opción para su obtención es el CU, que actualmente cuenta con bancos exclusivos para esto. (AU)

Introduction: mesenchymal stem cells (MSC) differentiate into multiple cell types for tissue regeneration, this characteristic added with the versatility of human leukocyte antigen (HLA) represent an effective alternative for the treatment of diseases with damaged tissues. They can be obtained from bone marrow, umbilical cord (UC), and fetal blood. Objetive: analyze the types of differentiation of MSC, their extraction methods and their relationship with umbilical cord blood banks (UCBB), in order to demonstrate the efficacy of MSC, in pathologies that involve alteration of a tissue or organ. Methodology: several publications in Spanish and English in Pubmed, Clinicalkey and Science Direct were reviewed; from 2013 to 2020. The terms fetal blood, mesenchymal stem cells, Umbilical Cord Blood Stem Cell transplantation and blood banks were used. With this information, a broad overview of mesenchymal cells and how they participate in various areas of health was drawn up, with an important emphasis on their therapeutic uses and where they come from. Conclusion: through the pluripotentiality of MSC, they have been used in multiple pathologies as it successfully re-establishes tissues or cell lines. Also, the resources for obtaining it are key in the tolerance of patients, which is why a great option for obtaining it is the UC, which currently has exclusive banks for this.

Optimización de unidades formadoras de colonias y detección del virus de papiloma humano en sangre de cordón umbilical / Colony-forming units optimization and human papillomavirus detection in umbilical cord blood

Resumen Introducción: Se requiere analizar diversos parámetros para el control de calidad adecuado de las unidades de sangre de cordón umbilical (USCU) cuando se utilizan con fines terapéuticos. Objetivo: Optimizar las unidades formadoras de colonias (UFC) de cultivos clonogénicos y detectar el genoma del virus del papiloma humano (VPH) en USCU. Métodos: Se incluyeron 141 muestras de sangre de cordón umbilical (SCU), de segmento y de UFC de cultivos clonogénicos de USCU. Se realizó extracción de ADN, cuantificación y amplificación por PCR del gen endógeno GAPDH. Se detectó el gen L1 del VPH con los oligonucleótidos MY09/MY11 y GP5/GP6+; los productos de PCR se migraron en electroforesis de agarosa. El ADN purificado de las UFC se analizó mediante electroforesis de agarosa y algunos ADN, con la técnica sequence specific priming. Resultados: La concentración de ADN extraído de UFC fue superior comparada con la de SCU (p = 0.0041) y la de segmento (p < 0.0001); así como la de SCU comparada con la de segmento (p < 0.0001). Todas las muestras fueron positivas para la amplificación de GAPDH y negativas para MY09/MY11 y GP5/GP6+. Conclusiones: Las USCU criopreservadas fueron VPH netativas; además, es factible obtener ADN en altas concentraciones y con alta pureza a partir de UFC de los cultivos clonogénicos.

Abstract Introduction: Analysis of several markers is required for adequate quality control in umbilical cord blood units (UCBU) when are used for therapeutic purposes. Objective: To optimize colony-forming units (CFU) from clonogenic cultures and to detect the human papillomavirus (HPV) genome in UCBU. Methods: One hundred and forty-one umbilical cord blood (UCB), segment or CFU samples from UCBU clonogenic cultures were included. DNA extraction, quantification and endogenous GAPDH gene PCR amplification were carried out. Subsequently, HPV L1 gene was detected using the MY09/MY11 and GP5/GP6+ oligonucleotides. PCR products were analyzed with electrophoresis in agarose gel. CFU-extracted purified DNA was analyzed by electrophoresis in agarose gel, as well as some DNAs, using the SSP technique. Results: CFU-extracted DNA concentration was higher in comparison with that of UCB (p = 0.0041) and that of the segment (p < 0.0001), as well as that of UCB in comparison with that of the segment (p < 0.0001). All samples were positive for GAPDH amplification and negative for MY09/MY11 and GP5/GP6+. Conclusions: Cryopreserved UCBUs were HPV-negative. Obtaining CFU DNA from clonogenic cultures with high concentrations and purity is feasible.

Hokkaido birth cohort study on environment and children's health: cohort profile 2021

BACKGROUND@#The Hokkaido Study on Environment and Children's Health is an ongoing study consisting of two birth cohorts of different population sizes: the Sapporo cohort and the Hokkaido cohort. Our primary objectives are to (1) examine the effects that low-level environmental chemical exposures have on birth outcomes, including birth defects and growth retardation; (2) follow the development of allergies, infectious diseases, and neurobehavioral developmental disorders, as well as perform a longitudinal observation of child development; (3) identify high-risk groups based on genetic susceptibility to environmental chemicals; and (4) identify the additive effects of various chemicals, including tobacco.@*METHODS@#The purpose of this report is to provide an update on the progress of the Hokkaido Study, summarize recent results, and suggest future directions. In particular, this report provides the latest details from questionnaire surveys, face-to-face examinations, and a collection of biological specimens from children and measurements of their chemical exposures.@*RESULTS@#The latest findings indicate different risk factors of parental characteristics on birth outcomes and the mediating effect between socioeconomic status and children that are small for the gestational age. Maternal serum folate was not associated with birth defects. Prenatal chemical exposure and smoking were associated with birth size and growth, as well as cord blood biomarkers, such as adiponectin, leptin, thyroid, and reproductive hormones. We also found significant associations between the chemical levels and neuro development, asthma, and allergies.@*CONCLUSIONS@#Chemical exposure to children can occur both before and after birth. Longer follow-up for children is crucial in birth cohort studies to reinforce the Developmental Origins of Health and Disease hypothesis. In contrast, considering shifts in the exposure levels due to regulation is also essential, which may also change the association to health outcomes. This study found that individual susceptibility to adverse health effects depends on the genotype. Epigenome modification of DNA methylation was also discovered, indicating the necessity of examining molecular biology perspectives. International collaborations can add a new dimension to the current knowledge and provide novel discoveries in the future.

The Value of Umbilical Cord Blood Erythrocyte Index in the Screening of Neonatal Thalassemia / 中国实验血液学杂志

OBJECTIVE@#To investigate the relationship between umbilical cord blood erythrocyte index and thalasse-mia, and reveal its clinical value in the screening of thalassemia in neonates.@*METHODS@#2 919 cases of umbilical cord blood from neonatal who were born in Boai Hospital of Zhongshan Affiliated with Southern Medical University from July 2017 to December 2018 were collected, the routine blood tests were preformed to detect the umbilical cord blood. Thalassemia gene in peripheral blood of neonates was collected. The cut-off values of cord blood indexes were determined, and the sensitivity, specificity and other evaluation indexs were calculated.@*RESULTS@#Among the cord blood in 2 919 neonates, 314 cases were detected out as thalassemia(positive rate: 10.76%). The average level of RBC and RDW in 2 605 children with non-thalassemia was lower than those with 314 children with thalassemia. The levels of Hb, MCV, MCH, MCHC, HCT, Hb/RBC and MCV/RBC in children with non-thalassemia were higher than those with thalassemia, and there were significant differences in the neonates between the two groups. The RBC and RDW levels of neonates in the α-thalassemia group were higher than those in the non-thalassemia group, while the levels of Hb, MCV, MCH, MCHC, HCT, Hb/RBC and MCV/RBC of neonates were lower than those in the non-thalassemia group. The levels of MCV, MCH and Hb/RBC of neonates in the β-thalassaemia group were lower than those in the non-thalassaemia group. The levels of MCV, MCH, Hb/RBC, and MCV/RBC of neonates in the complex thalassemia group were lower than those in the non-thalassemia group. When the cut-off value of MCV was set to 106.05 fl, the sensitivity was 0.548, and the specificity was 0.907, the specificity was the highest among all indexes. The area under the ROC curve of the combined diagnosis of MCH+MCV/RBC was the largest(0.807), the sensitivity was 0.710, the specificity was 0.841, the positive predictive value was 0.348, and the negative predictive value was 0.960.@*CONCLUSION@#The single indicator of umbilical cord blood red blood cells has advantages and disadvantages for the screening of thalassemia, but the combination of MCH+MCV/RBC can improve the accuracy of the screening or diagnosis of thalassemia, it also has a positive effect to the reduction of the birth rate of children with thalassemia major, which showed a high popularization value in primary hospitals.

Influence of maternal and infant factors on CD34 / 中国当代儿科杂志

OBJECTIVE@#To study the association of different maternal and infant factors with the number of total nucleated cells and CD34@*METHODS@#A prospective study was performed for the umbilical cord blood samples of 130 neonates who were born in Dalian Women and Children's Medical Center from June 2019 to January 2020, with a male/female ratio of 1:1. Related perinatal information was collected, including maternal age and blood type, presence or absence of gestational diabetes or gestational hypertension, pregnancy method, mode of delivery, singleton pregnancy/twin pregnancy, body weight and sex of neonates, Apgar score after birth, and the conditions of placenta, amniotic fluid, and umbilical cord.@*RESULTS@#The neonates were grouped according to maternal blood type, gestational diabetes, gestational hypertension, pregnancy method, mode of delivery, singleton pregnancy/ twin pregnancy, sex of neonates, Apgar score after birth, placental morphology, meconium staining of amniotic fluid, and umbilical cord around the neck. The comparison between groups showed no significant differences in the numbers of total nucleated cells and CD34@*CONCLUSIONS@#The number of CD34

Histone Deacetylase Inhibitors in the in Vitro Expansion of Hematopoietic Stem Cells / 中国医学科学院学报

The self-renewal and differentiation of hematopoietic stem cells(HSCs)are highly regulated by epigenetic modification,in which histone acetylation can activate or silence gene transcription.Histone deacetylase inhibitors(HDACIs)can inhibit the activity of histone deacetylase in HSCs to increase histone acetylation.A variety of HDACIs,such as trichostatin A and valproic acid,are used to expand HSCs in vitro,especially cord blood HSCs,combined with cytokines in serum-free culture to obtain more long-term repopulating cells.HDACIs promote the transcription of pluripotent genes related to stem cell self-renewal and inhibit the expression of genes related to differentiation,so as to promote the expansion and inhibit differentiation of HSCs.The expansion of cord blood HSCs by small molecular HDACIs in vitro is expected to improve the quantity of cord blood HSCs.The further research will focus on high-throughput screening for the most powerful HDACIs and the highly selective HDACIs,exploring the combination of epigenetic modifiers of different pathways.

Trisomía 9, trisomía 13 y trisomía 18: resultados del análisis citogenético prenatal, Hospital Clínico Universidad de Chile, años 2000-2017 / Trisomy 9, trisomy 13 and trisomy 18: results of the prenatal cytogenical analysis, Hospital Clínico Universidad de Chile, years 2000-2017

INTRODUCCIÓN: En Chile, la norma técnica de la Ley N° 21.030 de 2017 considera tres aneuploidías como letales; las trisomías 9, 13 y 18, cuyo diagnóstico se confirma con un cariograma. No existe a la fecha registro nacional de frecuencia prenatal de estas patologías. OBJETIVO: Determinar la frecuencia de trisomías 9, 13 y 18 en los estudios citogenéticos prenatales en muestras de células obtenidas con amniocentesis y cordocentesis, procesados en el Laboratorio de Citogenética del Hospital Clínico Universidad de Chile. MATERIALES Y MÉTODOS: Estudio descriptivo y retrospectivo de los resultados de cariograma de líquido amniótico (LA) y sangre fetal (SF), procesados desde enero de 2000 a diciembre de 2017. RESULTADOS: Se incluyeron 2.305 muestras (402 de SF y 1.903 de LA), de ellas 442 (19%) fueron trisomías letales (TL), dentro de ellas fueron TL libres 416 (95%), TL estructurales 15 (2,7%) y mosaicos 11 (2,3%). La trisomía 18 fue en ambos tipos de muestra la más frecuente (73,5%), seguida de trisomía 13 (24,2%) y trisomía 9 (2,3%). Se desglosan resultados conforme al tipo de TL, muestra, motivo de derivación, edad materna y edad gestacional. CONCLUSIONES: El cariograma confirma el diagnóstico de aneuploidías y aporta datos relevantes para el consejo genético. La cromosomopatía letal más frecuente fue la trisomía 18. Se observó que uno de cada cinco cariogramas referidos por anomalías congénitas y/o marcadores de aneuploidía revelaban una TL.

INTRODUCTION: In Chile, the technical standard of Law No. 21,030 of 2017 considers three aneuploidies as lethal; trisomies 9, 13 and 18, whose diagnosis is confirmed with a Karyotype. To date there is not a national registry of prenatal frequency of these pathologies. OBJECTIVE: To determine the frequency of trisomies 9, 13 and 18 in prenatal cytogenetic studies in samples of cells obtained with amniocentesis and cordocentesis, processed in the Cytogenetics Laboratory of the Universidad de Chile Clinical Hospital. MATERIALS AND METHODS: Descriptive and retrospective study of the results of karyotypes of amniotic fluid (LA) and fetal blood (SF) processed from January 2000 to December 2017. Results: 2,305 samples (402 of SF and 1,903 of LA) were included, of which 438 (19%) were lethal trisomies (TL), corresponding to free TL 416 (95%), structural TL 12 (2,7%) and mosaics 10 (2.3%). Trisomy 18 was the most frequent in both types of sample (73,5 %), followed by trisomy 13 (24,2%) and trisomy 9 (2.3%). RESULTS are shown according to the type of TL, sample, reason for referral, maternal age and gestational age. CONCLUSIONS: The karyotype confirms the diagnosis of aneuploidies and provides relevant data for genetic counseling. The most frequent lethal chromosomopathy was trisomy 18. It was observed that one in five karyotypes referred for congenital anomalies and / or aneuploidy markers revealed a TL.

Effects of intrauterine latent iron deficiency on auditory neural maturation in full-term newborns / Efeitos da deficiência de ferro latente intrauterino na maturação neural auditiva em recém-nascidos a termo

Abstract Objective: This study analyzed the relationship between latent iron deficiency evaluated by ferritin, and the myelination of the central nervous system evaluated through the brainstem evoked response audiometry test. Method: A total of 109 full-term newborns, born without anemia and risk factor for hearing deficiency, were enrolled. After delivery, umbilical cord blood was collected to determine ferritin and hematocrit levels. The brainstem evoked response audiometry test was carried out in the first 28 days of life. Analysis was performed between the control group (n = 71) with ferritin greater than 75 ng/mL, and the latent iron deficiency group (n = 38) with ferritin between 11 and 75 ng/mL. Results were presented as mean ± standard deviation. Statistical analysis was performed using GraphPad prism7 and SPSS with a significance level of 5%. Results: A significant higher V-wave (p = 0.02) and interpeak intervals I-III (p = 0.014), I-V (p = 0.0003), and III-V (p = 0.0002) latencies were found in the latent iron deficiency group, as well as a significant inversely proportional correlation between ferritin and the same wave and intervals (p = 0.003, p = 0.0013, p = 0.0002, p = 0.009, respectively). Multiple correlation analysis showed a significant correlation of latent iron deficiency with all interpeak intervals, even taking into account newborn gestational age. Conclusion: Iron deficiency anemia is a prevalent pathology; this study showed auditory delayed maturation associated to intrauterine iron deficiency, even in its latent form. This reinforces the importance of adopting effective measures, on a global scale, to prevent and treat this pathology in different life periods, especially in the most vulnerable population.

Resumo Objetivo Este estudo analisou a relação entre deficiência de ferro latente avaliada pela ferritina e a mielinização do sistema nervoso central avaliada pelo teste de Potenciais Evocados Auditivos de Tronco Encefálico. Método Foram incluídos no estudo 109 recém-nascidos a termo, nascidos sem anemia e fator de risco para deficiência auditiva. Após o parto, o sangue do cordão umbilical foi coletado para determinar os níveis de ferritina e hematócrito. O teste de Potenciais Evocados Auditivos de Tronco Encefálico foi realizado nos primeiros 28 dias de vida. A análise foi realizada entre o grupo controle (n = 71) com ferritina acima de 75 ng/mL e o grupo com deficiência de ferro latente (n = 38) com ferritina entre 11 e 75 ng/mL. Os resultados foram apresentados como média ± desvio-padrão. A análise estatística foi realizada utilizando o software GraphPad prism7 e SPSS com nível de significância de 5%. Resultados Latências significativamente maiores da onda V (p = 0,02) e dos intervalos interpicos I-III (p = 0,014), I-V (p = 0,0003) e III-V (p = 0,0002) foram encontradas no grupo de deficiência de ferro latente, assim como uma correlação significativa inversamente proporcional entre a ferritina e a mesma onda e intervalos (p = 0,003, p = 0,0013, p = 0,0002, p = 0,009, respectivamente). A análise de correlação múltipla mostrou uma correlação significativa da deficiência de ferro latente com todos os intervalos interpicos, mesmo se levarmos em consideração a idade gestacional do recém-nascido. Conclusão A anemia ferropriva é uma patologia prevalente e este estudo demonstrou maturação auditiva tardia associada à deficiência intrauterina de ferro, mesmo em sua forma latente. Isso reforça a importância da adoção de medidas efetivas, em escala global, para prevenir e tratar essa patologia em diferentes períodos da vida, principalmente na população mais vulnerável.

Donación dirigida de sangre de Cordón Umbilical de Hermano Compatible en el Sistema de Salud Público de Chile / Directed sibling donor cord blood donation in the Chilean Public Health System

Resumen: Introducción: La sangre de cordón umbilical (SCU) como fuente para trasplante de células proge- nitoras hematopoyéticas (TPH) está bien establecida. Internacionalmente, menos del 10% de los TPH de SCU corresponde a donantes hermanos compatibles. Dentro de la red del Programa Infantil Nacional de Drogas Antineoplásicas (PINDA), existe desde enero 2004 un programa de donación dirigida de SCU para TPH. Pacientes y Método: Se diseñó un estudio observacional, retrospectivo, descriptivo, se revisaron el número y características de las unidades de SCU recolectadas en el PINDA y el número, características y evolución de los pacientes trasplantados con esas unidades entre enero de 2004 y octubre de 2018. Resultados: Sesenta unidades de SCU han sido recolectadas, de ellas 55 con registro completo. La mediana de volumen de las unidades almacenadas fue 74,8 ml (30,0-170,8), la mediana de células nucleadas totales 7,6 x 10e8 (2,0-21,1), mediana de células CD34+ 1,6 x 10e6 (0,2-11,6). Cuatro pacientes con leucemias de alto riesgo fueron trasplantados; mediana de segui miento es de 8 años. Todos desarrollaron complicaciones severas post TPH, uno de ellos falleció de recaída y los tres actualmente vivos presentan un Karnofsky/Lansky 100%. Conclusión: El programa ha permitido el trasplante de 4 pacientes que de otro modo no habrían tenido acceso a un donante. Este programa de donación dirigida puede ser considerado una primera etapa para el desarrollo de un banco público de sangre de cordón umbilical en Chile.

Abstract: Introduction: Cord blood (CB) as a source of Hematopoietic Stem Cells for Transplantation (HSCT) is well established. Worldwide, nonetheless, less than 10% of the CB HSCTs are performed with a match sibling donor. Since 2004, the Chilean National Childhood Cancer Program (PINDA) net work, has established a CB directed donation program for HSCT. Patients and Method: An obser vational, descriptive and retrospective study was designed to assess the number and characteristics of the CB units collected in the program as well as the number, clinical characteristics and follow-up of the patients who received an HSCT from those CB units between January 2004 and October 2018. Results: Sixty CB units have been collected; 55 of them with full records and stored. The median volume collected was 74.8 ml (30.0-170.8), the median number of total nucleated cells was 7.6 x 10e8 (2.0-21.1), and the median of CD34+ cells was 1.6 x 10e6 (0.2-11.6). Four high-risk leukemia patients received HSCT, all of them developed severe complications after transplantation and one patient died due to relapse. Those patients currently alive have a 100% Karnofsky/Lansky score. The median follow-up time was 8 years. Conclusion: The PINDA program has allowed 4 patients to be transplan ted who otherwise would not have had access to a donor. This directed donation program could be seen as a model for the development of a public cord blood bank in Chile.