Umbilical Cord Blood In Children Research Articles

Serotonin and cyclic sleep organization in healthy full-term newborns

Relevance: The growth of neuropsychiatric diseases caused by perinatal pathology indicates the need to study the biochemical markers of brain damage in the newborn for the timely prevention of adverse consequences. Serotonin in early ontogenesis provides intensive development of neuronal structures and cortical networks involved in the mechanisms of formation of cyclic sleep organization a fine criterion of morphofunctional development of the brain.
 aim: The aim of the work is to study the content of serotonin in healthy full-term newborns in comparison with the quantitative and qualitative characteristics of the electropoligraphic sleep pattern.
 Material and methods: 84 healthy newborns were examined, which, depending on the gestational age, were divided into 3 groups: I 37 weeks (20 people), II 38 weeks (24 people), III 39-40 weeks (40 people). The content of serotonin in platelet-rich plasma of blood from the umbilical cord vein and in platelet suspension prepared from venous blood taken from mothers and children on the first day of life and again on day 5 was determined by high-performance liquid chromatography with electrochemical detection. A quantitative and qualitative analysis of the sleep electropoligram was performed 7-12 hours after birth.
 Results: The content of serotonin in platelet-rich plasma in umbilical cord blood in children does not depend on the method of birth, is 2 times lower than in the venous blood of mothers (0.379 0.116 microns/l, versus 0.756 0.200 microns/l, but there is a high correlation between the indicators (r = 0.8, p 0.05). At the gestational age of 39-40 weeks, the level of serotonin in platelet-rich plasma and in venous blood platelets is significantly higher than in those born at 37 weeks. In the latter, the increase in the content of serotonin in platelets continues after birth (at day 1, 0.539 0.149 nM/109 Tr, and on day 5 0.846 0.094 nM/109 Tr; p 0.05), whereas the indicators for those born at 39-40 weeks of pregnancy. They do not change (0.797 0.190 nM/109 Tr and 0.749 0.142 nM/109 Tr, respectively). A significant increase in the content of serotonin in the platelet-rich plasma and in the platelets of the child in the period from 37 to 39 weeks, both during intrauterine development and in the first days of life, correlates with an increase in the representation of the orthodox phase in the sleep cycle.
 Conclusion: The general pattern of changes in serotonin content and cyclic sleep organization in the early neonatal period in healthy newborns, depending on gestational age, indicates the possibility of using the obtained standard values of serotonin as a biochemical marker of functional brain development.

Autologous cord blood in children with cerebral palsy: a review.

The aim of this narrative review is to report on the current knowledge regarding the clinical use of umbilical cord blood (CB) based on articles from PubMed and clinical trials registered on ClinicalTrials.gov. An increasing amount of evidence suggests that CB may be used for both early diagnostics and treatment of cerebral palsy. The acidity of CB and its biochemical parameters, including dozens of cytokines, growth factors, and other metabolites (such as amino acids, acylcarnitines, phosphatidylcholines, succinate, glycerol, 3-hydroxybutyrate, and O-phosphocholine) are predictors of future neurodevelopment. In addition, several clinical studies confirmed the safety and efficacy of CB administration in both autologous and allogeneic models, including a meta-analysis of five clinical trials involving a total of 328 participants. Currently, nine clinical trials assessing the use of autologous umbilical CB in children diagnosed with hypoxic-ischemic encephalopathy or cerebral palsy are in progress. The total population assessed in these trials exceeds 2500 patients.

Knowledge, beliefs, and decisions of pregnant Australian women concerning donation and storage of umbilical cord blood: a population-based survey.

Many women giving birth in Australian hospitals can choose to donate their child's umbilical cord blood to a public cord blood bank or pay to store it privately. We conducted a survey to determine the proportion and characteristics of pregnant women who are aware of umbilical cord blood (UCB) banking and who have considered and decided about this option. The survey also sought to ascertain information sources, knowledge, and beliefs about UCB banking, and the effect of basic information about UCB on decisions. Researchers and hospital maternity staff distributed a survey with basic information about UCB banking to 1,873 women of at least 24 weeks' gestation who were attending antenatal classes and hospital clinics in 14 public and private maternity hospitals in New South Wales. Most respondents (70.7%) were aware of UCB banking. Their main information sources were leaflets from hospital clinics, print media, antenatal classes, TV, radio, friends, and relatives. Knowledge about UCB banking was patchy, and respondents overestimated the likelihood their child would need or benefit from UCB. Women who were undecided about UCB banking were younger, less educated, or from ethnic or rural backgrounds. After providing basic information about UCB banking, the proportion of respondents who indicated they had decided whether or not to donate or store UCB more than doubled from 30.0 to 67.7 percent. Basic information for parents about UCB banking can affect planned decisions about UCB banking. Information should be accurate and balanced, should counter misconceptions, and should target specific groups.

Umbilical Cord Blood for Non-Hematopoietic Clinical Applications in Neonates

Umbilical cord blood (UCB) is increasingly used as alternative to bone marrow or mobilized peripheral blood in allogeneic hematopoietic stem cell (HSC) transplantation. This led to the establishment of public cord blood banks providing an inventory of approximately 260000 cord blood units. Whereas the storage of autologous cord blood units in private banks is possible, its use is not advised in HSC transplantation settings. However, there are phase I/II clinical trials evaluating autologous UCB in children with traumatic brain injury, acquired hearing loss, neonatal hypoxic-ischemic encephalopathy, and cerebral palsy. To date, most of the preclinical studies applied the UCB mononuclear cell fraction. This contains a variety of different cell types: lymphocytes including regulatory T cells (Treg), monocytes, HSC, mesenchymal stromal/stem cells (MSC), and endothelial progenitor cells (EPC). Each of these cell populations have been used individually in preclinical settings of neonatal diseases, like neonatal hypoxic-ischemic encephalopathy or hypoxia-induced lung damage. The aim of cell therapy in neonates is to provide a pro-regenerative milieu by direct cellular engraftment and differentiation into endothelial, neuronal or lung cells, by immunomodulation, preventing adverse immune reactions leading to scar formation, and/or by release of trophic factors to facilitate endogenous repair/regeneration responses. Transplantation of UCB mononuclear cells improves impairments on neonatal diseases. The underlying mechanisms, however, are still only poorly understood. Also the contribution of the different cell populations, present at different, but often extremely low frequencies within the mononuclear cell fraction, remains to be determined. MSC which exhibit immunomodulatory potential, release pro-regenerative factors, and show differentiation currently appear as most investigated cell source for treating neonatal diseases.

Herpesvirus Viremia and Engraftment Status of Umbilical Cord Blood in Children Undergoing Allogeneic Hematopoietic Stem Cell Transplant

Abstract 3021Umbilical Cord Blood (UCB) is frequently used as a source of stem cells for children undergoing allogeneic hematopoietic stem cell transplant (HSCT) for both benign and malignant disorders. Despite algorithms using both nucleated cell numbers and HLA typing, the rate of engraftment failure remains higher than rates observed using other stem cell products. We conducted a retrospective review of our centre’s experience with HSCT with UCB to evaluate the impact of herpesvirus viremia on the rate of engraftment. Children who underwent allogeneic HSCT with UCB between 06/2005 and 05/2010 inclusive were identified from the program database. Engraftment was defined as the first day of three consecutive absolute neutrophil counts of > 0.5 × 10[exp 9]/L within 42 days of UCB infusion and evidence of donor DNA on chimerism testing. Blood samples were sent for qualitative herpesvirus polymerase chain reaction (PCR) weekly (HHV-6, HHV-7, EBV, CMV, HSV or VZV). If either CMV or EBV results were positive, a quantitative assay was performed as well. Viremia was considered to have occurred if the qualitative assay became positive. Anti-viral therapy was initiated for measurable amounts of either CMV or EBV DNA or selectively for HHV-6 DNA. Eighty-one HSCT utilizing UCB were performed during this period. One child was unevaluable (NRM at day +15) so the analysis was performed using the remaining 80 patients. Thirty HSCT (37.5%) were performed for non-malignant indications and 50 (62.5%) for malignant disorders. Ninety per cent were performed using unrelated UCB; 27 were 6/6 HLA matched UCB, 42 were 5/6 HLA matches and 11 were 4/6 matches. Four children were recovering counts at day +42 but had not reached the threshold neutrophil value. They were considered as delayed engraftment rather than engraftment failure. Eleven (14%) failed to engraft. Forty-two (52.5%) of the transplants were complicated by the detection of 1 or more herpesviruses (24 for only 1 virus, 15 for 2 viruses and 3 for 3 viruses). None of gender, ABO matching, recipient CMV pre-HSCT serostatus, disease category, use of ATG or TBI in the conditioning regimen, use of methotrexate as GVHD prophylaxis or positivity for any single herpesvirus was associated with engraftment failure. Numbers of viable nucleated cells and CD34+ cells were not different between those that engrafted and those that failed to engraft. Transplants complicated by viremia of more than 1 herpesvirus had a significantly poorer engraftment rate than others (0.667 vs 0.933, P=0.007); more specifically viremia due to CMV and any other herpesvirus was associated with a worse engraftment rate than others (0.643 vs 0.921, P=0.006) (table). Notably viremia due to HHV-6 and others or EBV and others were not related to engraftment failure.PCR resultEngraftedFailed to engraftNo CMV516CMV positive185CMV alone90CMV plus:HHV-632HHV-721EBV22HHV-6 & HHV-710HHV-6 & EBV10 Conclusion:A significantly poorer engraftment rate in children undergoing HSCT using UCB was seen in those with CMV viremia in the presence of another herpesvirus. Further research is needed to define cause and effect and the therapeutic strategies to prevent it. Disclosures:No relevant conflicts of interest to declare.

Comparison of Outcomes Between Transplantation From Unrelated Donor Umbilical Cord Blood and From Unrelated Donor Bone Marrow or Peripheral Blood in Children with Acute Leukemia.

Abstract 4340 IntroductionAlthough umbilical cord blood (UCB) is an accepted alternative to bone marrow or peripheral blood (BM/PB) for transplantation, allele-matched marrow or peripheral blood is generally regarded as the preferred graft source. Our aim is to compare leukemia-free survival after transplantation of unrelated donor UCB and allele-matched BM/PB, and to provide guidelines for selection of an appropriate donor and graft source in children with acute leukemia. Patients and MethodsOutcomes of 22 children with acute leukemia and transplanted with single unit UCB were compared with outcomes of 34 BM/PB recipients. All transplantations were performed in Samsung Medical Center between May 2003 and June 2009. Recipients of UCB were transplanted with grafts that were HLA-matched (n = 3) or HLA-mismatched for one (n = 15) or two antigens (n = 4). BM/PB recipients were transplanted with grafts that were HLA-matched (n = 20) or mismatched (n = 14). While allele-level typing for HLA-A, HLA-B, HLA-DRB1 and antigen-level typing for HLA-C was used for BM/PB transplantation, antigen level typing for HLA-A, HLA-B and HLA-DRB1 was used for UCB transplantation. Myeloablative conditioning regimens were used for both BM/PB and UCB transplantation. ResultsThe median times to neutrophil and platelet recovery were 15 (range 10–21) and 22 (12–29) days after BM/PB transplantation, and 17 (13–44) and 34 (24–148) days after UCB transplantation, respectively. The 4-year probabilities of leukemia-free survival were 58.0% after HLA-matched BM/PB transplants, 65.9% after HLA-mismatched BM/PB transplants, 66.7% after HLA-matched UCB transplants, 67.5% after one-mismatched UCB transplants with high cell dose (NC > 3.0 × 107/kg), 40.0% after one-mismatched UCB transplants with low cell dose (NC < 3.0 × 107/kg), and 33.3% after two-mismatched UCB transplants. The incidence of grade 3-4 acute graft-versus-host disease (GVHD) were 12.1% after BM/PB transplantation and 5.3% after UCB transplantation, respectively (P = 0.64). Rates of extensive chronic GVHD were 53.8% after BM/PB transplantation and 23.1% after UCB transplantation, respectively (P = 0.09). Transplant-related mortality rates were higher after UCB transplantation (21.7%) than BM/PB transplantation (2.9%) (P = 0.03). Relapse rates were similar after BM/PB transplantation (29.4%) and UCB transplantation (21.7%) (P = 0.56). ConclusionThese results support the use of HLA-matched or one-antigen HLA mismatched UCB in children with acute leukemia who need transplantation. Faster identification of a suitable cord blood unit may result in a timely transplantation avoiding delay that could expose the patient to the risk of losing the eligibility for transplant due to relapse or other complications. [Display omitted] Disclosures:No relevant conflicts of interest to declare.

Analysis of Umbilical Cord Blood Stem Cell Therapy for Regenerative Medicine Applications

Over the past 20 years umbilical cord blood (UCB) has become valuable source of hematopoietic stem cells for use in transplantation to treat malignancies, blood disorders and genetic diseases. Cord blood stem cells have shown promising results in animal regenerative medicine studies for the repair of damaged or diseased tissues outside of the hematopoietic lineage. Family UCB banks provide collection and storage services for families to store their child's UCB for clinical use. This study compared the release of UCB units from one family bank (Cord Blood Registry, CBR) for regenerative medicine versus traditional transplantation since the release of its first UCB unit for regenerative medicine in 2005. UCB was collected from the placenta of consenting mothers and transported to the processing facility from all 50 states and over 80 countries. The UCB was separated into a mononuclear cell fraction from the red blood cells and other non-engrafting cells. The processed UCB is stored in vapor-phase liquid nitrogen at −195° C until requested for use. To date, 230,000 units have been stored. Prior to release, viability and percent CD34+ (or CFU) content were assessed by the treating institution. Through July 2008, a total of 82 UCB units were released for clinical use, 47 of these units (57%) have been used for traditional transplantation and 35 (43%) have been used for regenerative medicine. From January 2005 through July 2008, 47 UCB units were released, 12 (26%) were used in traditional transplantation and 35 (74%) were used in regenerative medicine applications. Over this period the bank experienced a mean of 338% percent growth per year in the release of UCB units for regenerative medicine. The indications for regenerative medicine autologous infusions were cerebral palsy (24 units), brain injury (4 units), type 1 diabetes (6 units), and a rare immune disorder (1 unit). All patients in the regenerative medicine category did not receive any myeloablative chemotherapy or radiation. Released UCB units were stored a mean of 37 months prior to use, the mean CD34+ percent of TNC was 0.53% and mean viability was 95.9%. These data indicate that regenerative medicine applications utilizing autologous cord blood stem cells represent a significant and growing percentage of all treatments facilitated by a family cord blood bank. Regenerative medicine treatments for cerebral palsy and type 1 diabetes have the potential to impact many lives given that 10,000 cases of cerebral palsy and 13,000 cases of type 1 diabetes are diagnosed each year which compares to 2,500 cases of childhood leukemia and 650 cases of neuroblastoma, two common indications for pediatric transplantation. Further analysis is needed to assess the clinical outcomes which will provide background for larger clinical trials in the future.

The Selenium Levels of Mothers and Their Neonates Using Hair, Breast Milk, Meconium, and Maternal and Umbilical Cord Blood in Van Basin

The objective of the present study is to calculate linear regressions between a mother and her child with respect to their selenium concentration (ng/g) in the following traits: maternal blood and umbilical cord blood, maternal and child hair, maternal milk and child umbilical cord blood, maternal milk and meconium, maternal blood plasma, and child meconium. The data were collected at Research Hospital of the University of Yüzüncü Yil from 30 pairs of mothers and their newborn baby. The mean maternal serum Se level in 30 mothers was 68.52 +/- 3.57 ng/g and cord plasma level was 119.90 +/- 18.08 ng/g. The Se concentration in maternal and neonatal hair was 330.84 +/- 39.03 and 1,124.76 +/- 186.84 ng/g, respectively. The Se concentration of maternal milk at day 14 after delivery was determined as 68.63 +/- 7.78 ng/g (n = 13) and the concentration of Se was 418.90 +/- 45.49 ng/g (n = 22) for meconium of neonatal. There was no significant difference between maternal blood and milk Se levels. However, hair Se concentration was significantly higher than milk and maternal blood Se level. For each trait comparison, the average absolute difference in log(10)-transformed Se concentration was calculated between a mother and her child. The observed average absolute difference was compared with a test distribution of 1,000 resampled bootstrap averages where the number of samples was maintained but the relationship between a mother and her child was randomized among samples (alpha = 0.05).

Outcomes of transplantation of unrelated donor umbilical cord blood and bone marrow in children with acute leukaemia: a comparison study

Although umbilical cord blood is an accepted alternative to bone marrow for transplantation, allele-matched bone marrow is generally regarded as the preferred graft source. Our aim was to assess leukaemia-free survival after transplantations of these alternatives compared with present HLA-matching practices, and to assess the relative effect of cell dose and HLA match, and their potential interaction on leukaemia-free survival after cord-blood transplantation. Outcomes of 503 children (<16 years) with acute leukaemia and transplanted with umbilical cord blood were compared with outcomes of 282 bone-marrow recipients. All transplantation took place in the USA. Recipients of umbilical cord blood were transplanted with grafts that were HLA-matched (n=35) or HLA-mismatched for one (n=201) or two antigens (n=267) (typing at antigen level for HLA-A and HLA-B, and allele level for HLA-DRB1). Bone-marrow recipients were transplanted with grafts that were matched at the allele level for HLA-A, HLA-B, HLA-C, and HLA-DRB (n=116), or mismatched (n=166). The primary endpoint was 5-year leukaemia-free survival. In comparison with allele-matched bone-marrow transplants, 5-year leukaemia-free survival was similar to that after transplants of umbilical cord blood mismatched for either one or two antigens and possibly higher after transplants of HLA-matched umbilical cord blood. Transplant-related mortality rates were higher after transplants of two-antigen HLA-mismatched umbilical cord blood (relative risk 2.31, p=0.0003) and possibly after one-antigen HLA-mismatched low-cell-dose umbilical-cord-blood transplants (1.88, p=0.0455). Relapse rates were lower after two-antigen HLA-mismatched umbilical-cord-blood transplants (0.54, p=0.0045). These data support the use of HLA-matched and one- or two-antigen HLA-mismatched umbilical cord blood in children with acute leukaemia who need transplantation. Because better HLA matching and higher cell doses significantly decrease the risk of transplant-related mortality after umbilical-cord-blood transplantation, greater investment in large-scale banking is needed to increase HLA diversity.

Umbilical cord blood collection, banking, and transplantation: current status and issues relevant to perinatal caregivers.

As a result of recent media coverage of cord blood transplantation, expectant parents increasingly ask perinatal caregivers about the possibility of collecting and saving their newborn child's umbilical cord blood. Umbilical cord blood has been used as a source of hematopoeitic stem cells for the treatment of human disease since 1988. As a result of these initial successes, cord blood collection, banking, and transplantation has become increasingly used worldwide, giving rise to several controversies. We have reviewed the current status of the indications for cord blood collection, the methods of collection, and safety issues related to the cyropreservation of cord blood units. In addition, the clinical success of cord blood transplants from related and unrelated donors is detailed. We have examined the major issues concerning cord blood transplantation as it exists in the year 2000 to provide insight into this exciting area of clinical investigation.

Decreased interleukin-12 levels in umbilical cord blood in children who developed acute bronchiolitis.

Respiratory syncytial virus (RSV) infection is common in young children, but only a few develop severe bronchiolitis. The relationship between bronchiolitis, asthma, and atopy has been debated for a long time, but the pathogenesis of wheezing remains unclear. A Th1 and Th2-type lymphocyte imbalance seems to be involved in asthma and atopic disease. Serum interleukin-12 (IL-12), IL-10, and soluble CD30 (sCD30) levels were measured by enzyme-linked immunosorbent assay (ELISA) in 23 cord blood samples kept frozen since birth: 11 from normal term newborns who several months later were admitted to the hospital with bronchiolitis, and 12 from newborns who did not develop the disease (controls). The study was also performed on 28 additional children (1-16 months old) suffering an episode of acute bronchiolitis. IL-12 was clearly increased in all cases at birth, but newborns who later developed bronchiolitis showed low IL-12 levels in cord blood compared to newborns who did not develop the disease (median 295 vs. 507 pg/mL; P = 0.001). sCD30 levels were also decreased in the first group (15 vs. 26 U/mL; P = 0.007). During episodes of bronchiolitis, a clear rise of IL-12, IL-10, and sCD30 was observed. None of the factors studied in the acute phase showed statistical differences in children who were later readmitted to the hospital due to repeated wheezing crises. Children who develop acute bronchiolitis with wheezing may have an immunological imbalance that is expressed at the time of delivery by a lower concentration of serum IL-12.