Cord Blood Collection Research Articles

Intrauterine Transfer of Polyunsaturated Fatty Acids in Mother-Infant Dyads as Analyzed at Time of Delivery.

Polyunsaturated fatty acids (PUFAs) are essential for fetal development, and intrauterine transfer is the only supply of PUFAs to the fetus. The prevailing theory of gestational nutrient transfer is that certain nutrients (including PUFAs) may have prioritized transport across the placenta. Numerous studies have identified correlations between maternal and infant fatty acid concentrations; however, little is known about what role maternal PUFA status may play in differential intrauterine nutrient transfer. Twenty mother–infant dyads were enrolled at delivery for collection of maternal and umbilical cord blood, and placental tissue samples. Plasma concentrations of PUFAs were assessed using gas chromatography (GC-FID). Intrauterine transfer percentages for each fatty acid were calculated as follows: ((cord blood fatty acid level/maternal blood fatty acid level) × 100). Kruskal–Wallis tests were used to compare transfer percentages between maternal fatty acid tertile groups. A p-value < 0.05 was considered significant. There were statistically significant differences in intrauterine transfer percentages of arachidonic acid (AA) (64% vs. 65% vs. 45%, p = 0.02), eicosapentaenoic acid (EPA) (41% vs. 19% vs. 17%, p = 0.03), and total fatty acids (TFA) (27% vs. 26% vs. 20%, p = 0.05) between maternal plasma fatty acid tertiles. Intrauterine transfer percentages of AA, EPA, and TFA were highest in the lowest tertile of respective maternal fatty acid concentration. These findings may indicate that fatty acid transfer to the fetus is prioritized during gestation even during periods of maternal nutritional inadequacy.

1007 Umbilical cord segment collection allows for comprehensive genetic diagnostic testing at delivery

The detection of fetal anomalies frequently prompts women to pursue genetic diagnostic testing. Many patients defer testing until delivery to avoid undergoing an invasive procedure during pregnancy. We aim to describe our experience in the collection of umbilical cord tissue, in lieu of cord blood or neonatal blood, for the genetic work up of prenatally detected fetal anomalies. This was a retrospective cohort analysis of participants who underwent collection of umbilical cord tissue for genetic diagnostic testing. From 2015-2019, our institution offered participation in research trio exome sequencing (ES) to all patients with a fetal anomaly and a normal or non-causative karyotype and chromosomal microarray (CMA). Eligible patients consented to a genetic work up with karyotype, SNP-array, and ES on tissue obtained from either invasive prenatal diagnosis or cord segment collected at delivery. One hundred seven participants, ages 19-43, with a prenatally diagnosed fetal anomaly, elected to have genetic testing performed at delivery. There were 104 livebirths, 1 stillbirth, and 2 fetal demises. Cord segments were collected from 105 participants at delivery. Conventional cytogenetics (CC) was performed in 77.5% of cases and was successful in 88.8%. SNP-Array testing was performed in 77.5% of cases and was successful in 95.5%. Exome sequencing was performed in 98.1% of cases and was successful 99.1% of the time. These success rates are similar to chorionic villus sampling and amniocentesis. The collection of a cord segment, in lieu of cord blood, allowed for successful genetic diagnosis across conventional cytogenetic, SNP-array, and next generation technologies in the majority of cases. In patients who decline prenatal diagnosis via CVS/amniocentesis, or for whom collection of cord blood cannot be facilitated, our experience shows umbilical cord segment is an alternative and acceptable sample available for genetic testing on newborns.

Pandemic-related trends and challenges in adult donor stem cell and cord blood collection, banking, and processing

<div class="authors authors-lg"><div class="author"><div class="author-img"><img src="https://bioinsights.blob.core.windows.net/uploads/Heidi_2_Director_StemCells copy 2.jpg" data-image="1"></div><div class="author-det"> <b>Heidi Elmoazzen</b> is currently the director of Canadian Blood Services’ Stem Cell Program which includes Canadian Blood Services’ Cord Blood Bank, Stem Cell Registry, Stem Cell Manufacturing programs and Cord Blood for Research Program. She has been with Canadian Blood Services for 10 years. Dr Elmoazzen obtained her PhD in Medical Sciences from the University of Alberta with a concentration in cryobiology. She then went on to do a post-doctoral fellowship at Harvard Medical School and Massachusetts General Hospital in Boston, USA. Following her fellowship, she became an instructor at Harvard Medical School and an Assistant in Bio-engineering in the Department of Surgery and Obstetrics and Gynaecology. Her area of research was focused on fertility preservation and developing novel biopreservation techniques for stem cells and reproductive cells. Her main areas of expertise and experience include bio-preservation, stem cell banking and translational medicine. She has published two book chapters on stem cell preservation as well as over 50 journal papers. She has hundreds of contributed and invited presentations at various national and international meetings. </div></div></div>

A protocol for umbilical cord tissue cryopreservation as a source of mesenchymal stem cells.

Mesenchymal stem cells (MSC) differentiate into different cell types and have immunomodulatory and paracrine effects. Cryopreservation of umbilical cord tissue as a source of MSC is very promising for regenerative medicine. We aim to evaluate a protocol for cryopreserving this tissue sectioned into small fragments with viable MSC. A total of 723 samples were frozen, thawed and cultured to obtain primary cultures of MSC. These were followed until 90-100% confluence and flow cytometric analysis were performed to confirm the mesenchymal phenotype. Samples in which protocol alterations at the collection of the samples were reported, were excluded for microbial contamination analysis leaving a total of 634 samples composed of 181 vaginal and 453 cesarean births. All cultures reach confluence with a media of 22.57days and 97% in 28 or fewer days. Evaluated cultures showed low percentage of CD45+ and high of CD73 and CD90. Eight samples were subcultured 4 or 5 times and differentiated to chondrocytes and osteocytes to test differentiation potential with positive results. Umbilical cord tissue collections showed similar microbial profile and risk factors to those reported of umbilical cord blood collections, but with higher contamination frequencies. Cryopreserved tissue samples had viable cells that can be expanded without losing differentiation potential. Higher contamination frequencies compared to umbilical cord blood collection are not surprising, however, microbial load and survival of microorganisms to cryopreservation are expected to be lower.

Feasibility of Umbilical Cord Blood Collection in Neonates at Risk of Brain Damage—A Step Toward Autologous Cell Therapy for a High-risk Population

Evidence for umbilical cord blood (UCB) cell therapies as a potential intervention for neurological diseases is emerging. To date, most existing trials worked with allogenic cells, as the collection of autologous UCB from high-risk patients is challenging. In obstetric emergencies the collection cannot be planned. In preterm infants, late cord clamping and anatomic conditions may reduce the availability. The aim of the present study was to assess the feasibility of UCB collection in neonates at increased risk of brain damage. Infants from four high-risk groups were included: newborns with perinatal hypoxemia, gestational age (GA) ≤30 + 0 weeks and/or birthweight <1,500 g, intrauterine growth restriction (IUGR), or monochorionic twins with twin-to-twin transfusion syndrome (TTTS). Feasibility of collection, quantity and quality of obtained UCB [total nucleated cell count (TNC), volume, sterility, and cell viability], and neonatal outcome were assessed. UCB collection was successful in 141 of 177 enrolled patients (hypoxemia n = 10; GA ≤30 + 0 weeks n = 54; IUGR n = 71; TTTS n = 6). Twenty-six cases were missed. The amount of missed cases per month declined over the time. Volume of collected UCB ranged widely (median: 24.5 ml, range: 5.0–102 ml) and contained a median of 0.77 × 108 TNC (range: 0.01–13.0 × 108). TNC and UCB volume correlated significantly with GA. A total of 10.7% (19/177) of included neonates developed brain lesions. To conclude, collection of UCB in neonates at high risk of brain damage is feasible with a multidisciplinary approach and intensive training. High prevalence of brain damage makes UCB collection worthwhile. Collected autologous UCB from mature neonates harbors a sufficient cell count for potential therapy. However, quality and quantity of obtained UCB are critical for potential therapy in preterm infants. Therefore, for extremely preterm infants alternative cell sources such as UCB tissue should be investigated for autologous treatment options because of the low yield of UCB.

Australian maternity healthcare professionals’ knowledge, attitudes and practices relevant to cord blood banking, donation and clamp timing: A cross-sectional survey

ProblemAustralian health professionals’ knowledge and attitudes towards third stage labour options of cord clamp timing, cord blood banking and donation and their practice of informing parents of these options is unknown. BackgroundParents have several options for the management of their infant’ cord blood during the third stage of labour. Early or deferred cord clamping practices may affect parent choices about physiological transfusion to the neonate and/or cord blood collection for private or public banking or donation. AimTo identify health professionals’ knowledge and attitudes towards third stage labour options of cord clamp timing, cord blood banking and donation and their practice of informing parents of these options. MethodsA total of 129 Australian maternity healthcare professionals responded to the self-administered survey between December 2017 and June 2018. FindingsOccupational differences were revealed in regard to cord clamp timing, cord blood banking and donation knowledge, attitudes and practices. Midwives were more likely to discuss cord clamp timing with parents and to clamp the cord later than obstetricians. Obstetricians were more knowledgeable of cord blood banking and donation options than midwives. Cord blood banking and donation options were discussed by both groups if parents asked. DiscussionIdentification of gaps in knowledge should guide future maternity health professional education that is inclusive of all third stage labour options to ensure that open discussion and informing parents of options is consistent, contemporary and evidence-based. ConclusionTo make informed decisions, parents need evidence-based information on all third stage labour options.

Optimization of the criteria for cord blood unit selection for transplantation in recipients of the different age groups: current view and prospects in Ukraine

Umbilical cord blood has been widely used to treat both malignant and non-malignant hematological diseases for over 30 years. During this time, more than 40,000 successful hematopoietic stem cell (HSC) transplantations of umbilical cord blood have been performed. However, today in Ukraine there is no public umbilical cord blood bank established for unrelated HSC transplantation to patients with oncohematological disorders (both children and adults). In this regard, the HSC units must be purchased abroad or the patients are sent to foreign clinics for high-cost treatment. The organization of a public umbilical cord blood bank in Ukraine would help in a short time to meet the needs of patients with oncohematological disorders for donor HSCs for unrelated transplantation and save significant funds for the treatment of patients abroad. According to the experience of the world's leading oncohematological centers, when it is impossible to find either a related or haploidentical donor or in all available registries – a unrelated transplant, the search continues in the registers of public cord blood banks and an umbilical cord blood unit that matches the criteria is usually found. The optimal choice of umbilical cord blood unit is crucial to maximize the likelihood of successful transplant engraftment and recipient survival after the transplantation, so the criteria for cord blood unit selection for unrelated transplantation are a bit broader than those used when matching donor-recipient pairs. The review presents the main criteria for cord blood unit selection according to the assessment of its quality, cell dose, HLA matching for unrelated transplantation to recipients of different age groups in accordance with international guidelines developed by the National Marrow Donor Program (NMDP), USA Center for International Blood and Brain Transplantation Research (CIBMTR), in collaboration with the NMDP Council Advisory Group, as well as in accordance with the American Society for Transplantation and Cellular Therapy (ASTCT) and the Seventh Edition of the NetCord-FACT International Standards for Cord Blood Collection, Banking, and Release for Administration.

Seroepidemiology of maternally-derived antibody against Group B Streptococcus (GBS) in Mulago/Kawempe Hospitals Uganda - PROGRESS GBS.

Background: Group B Streptococcus (GBS) is a major contributor to the high burden of neonatal and young infant infectious disease in resource- limited settings. As disease protection during the first six months of life is provided via placental transfer of maternal antibodies, a maternal GBS vaccine may provide an effective strategy to reduce infectious death and disability. An efficacy study may be difficult because of the large sample size required and alternative approaches such as serocorrelates of protection based on natural antibody concentration are being considered. Such studies would need to be undertaken in high burden settings such as Uganda. We therefore aim to evaluate the feasibility and acceptability of a GBS sero-epidemiology study in Kampala, Uganda. Methods: This is a prospective cohort and nested case-control study, conducted across two-centres with two entry points. A) consecutive women and their infants at birth, with collection of maternal swab, cord and maternal blood, and follow up by telephone until the infant is 3 months old; B) any infant under 3 months of age, presenting with signs of sepsis to any of the paediatric units, with collection of blood culture, cerebrospinal fluid and nasopharyngeal swabs. Any infants identified as having GBS disease (defined as GBS isolated from a normally sterile site) will be recruited and followed up for two years to assess their neurodevelopment. A nested qualitative study will investigate stakeholder (pregnant women and their families, healthcare workers and community leaders) opinions of sampling for such a study and understanding and potential uptake of vaccines in pregnancy. Discussion: The primary aim is to determine anti-GBS antibody concentration in infants with GBS disease compared to healthy controls. Secondary outcomes include stillbirth and all-cause infection and acceptance of sample methods and vaccination. The findings will inform scalability and sustainability of the programme in Uganda.

Seroepidemiology of maternally-derived antibody against Group B Streptococcus (GBS) in Mulago/Kawempe Hospitals Uganda - PROGRESS GBS

Background: Group B Streptococcus (GBS) is a major contributor to the high burden of neonatal and young infant infectious disease in resource- limited settings. As disease protection during the first six months of life is provided via placental transfer of maternal antibodies, a maternal GBS vaccine may provide an effective strategy to reduce infectious death and disability. An efficacy study may be difficult because of the large sample size required and alternative approaches such as serocorrelates of protection based on natural antibody concentration are being considered. Such studies would need to be undertaken in high burden settings such as Uganda. We therefore aim to evaluate the feasibility and acceptability of a GBS sero-epidemiology study in Kampala, Uganda. Methods: This is a prospective cohort and nested case-control study, conducted across two-centres with two entry points. A) consecutive women and their infants at birth, with collection of maternal swab, cord and maternal blood, and follow up by telephone until the infant is 3 months old; B) any infant under 3 months of age, presenting with signs of sepsis to any of the paediatric units, with collection of blood culture, cerebrospinal fluid and nasopharyngeal swabs. Any infants identified as having GBS disease (defined as GBS isolated from a normally sterile site) will be recruited and followed up for two years to assess their neurodevelopment. A nested qualitative study will investigate stakeholder (pregnant women and their families, healthcare workers and community leaders) opinions of sampling for such a study and understanding and potential uptake of vaccines in pregnancy. Discussion: The primary aim is to determine anti-GBS antibody concentration in infants with GBS disease compared to healthy controls. Secondary outcomes include stillbirth and all-cause infection and acceptance of sample methods and vaccination. The findings will inform scalability and sustainability of the programme in Uganda.

Seroepidemiology of maternally-derived antibody against Group B Streptococcus (GBS) in Mulago/Kawempe Hospitals Uganda - PROGRESS GBS

Background: Group B Streptococcus (GBS) is a major contributor to the high burden of neonatal and young infant infectious disease in resource- limited settings. As disease protection during the first six months of life is provided via placental transfer of maternal antibodies, a maternal GBS vaccine may provide an effective strategy to reduce infectious death and disability. An efficacy study may be difficult because of the large sample size required and alternative approaches such as serocorrelates of protection based on natural antibody concentration are being considered. Such studies would need to be undertaken in high burden settings such as Uganda. We therefore aim to evaluate the feasibility and acceptability of a GBS sero-epidemiology study in Kampala, Uganda. Methods: This is a prospective cohort and nested case-control study, conducted across two-centres with two entry points. A) consecutive women and their infants at birth, with collection of maternal swab, cord and maternal blood, and follow up by telephone until the infant is 3 months old; B) any infant under 3 months of age, presenting with signs of sepsis to any of the paediatric units, with collection of blood culture, cerebrospinal fluid and nasopharyngeal swabs. Any infants identified as having GBS disease (defined as GBS isolated from a normally sterile site) will be recruited and followed up for two years to assess their neurodevelopment. A nested qualitative study will investigate stakeholder (pregnant women and their families, healthcare workers and community leaders) opinions of sampling for such a study and understanding and potential uptake of vaccines in pregnancy. Discussion: The primary aim is to determine anti-GBS antibody concentration in infants with GBS disease compared to healthy controls. Secondary outcomes include stillbirth and all-cause infection and acceptance of sample methods and vaccination. The findings will inform scalability and sustainability of the programme in Uganda.

The transfer and decay of maternal antibodies against enterovirus A71, and dynamics of antibodies due to later natural infections in Chinese infants: a longitudinal, paired mother–neonate cohort study

Since 1997, epidemics of hand, foot, and mouth disease associated with enterovirus A71 (EV-A71) have affected children younger than 5 years in the Asia-Pacific region, including mainland China. EV-A71 vaccines have been licensed for use in children aged 6-71 months in China, but not for infants younger than 6 months. We aimed to assess the dynamics of maternal EV-A71 antibodies to inform choice of potential vaccination strategies to protect infants younger than 6 months, because they have a substantial burden of disease. We did a longitudinal cohort study with mother-neonate pairs in local hospitals in southern China during 2013-18. We collected cord blood from neonates and venous blood from mothers at delivery. We followed up and collected blood samples from the children at ages 2, 4, 6, 12, 24, and 36 months and tested for the presence of neutralising antibodies against EV-A71 with virus neutralisation assays. Seropositivity, or protective titre, was defined as a neutralisation antibody titre of 16 or higher. We estimated the seroprevalence, geometric mean titre (GMT), and transfer ratio of maternal antibodies. We used a binomial distribution to derive the 95% CIs of seroprevalence. Seropositivity between mothers and neonates was compared by use of an agreement (κ), while GMTs were compared by use of paired Student's t tests. Between Sept 20, 2013, and Oct 14, 2015, 1054 mothers with 1066 neonates were enrolled. The EV-A71 GMT was similar among pairs of neonates (22·7, 95% CI 20·8-24·9) and mothers (22·1, 95% CI 20·2-24·1; p=0·20). The mean transfer ratio of maternal antibodies was 1·03 (95% CI 0·98-1·08). Although 705 (66%) of 1066 neonates acquired protective concentrations of EV-A71 antibodies from mothers, these declined rapidly, with a half-life of 42 days (95% CI 40-44). The time to loss of protective immunity was extended to 5 months in neonates with mothers who had titres of 128 or higher. By age 30 months, 28% of children had become seropositive because of natural infection. EV-A71 maternal antibodies were efficiently transferred to neonates, but declined quickly to below the protective threshold, particularly among those whose mothers had low antibody titres. Our findings suggest that maternal vaccination could be explored to provide neonatal protection against EV-A71 through maternal antibodies. Catch-up vaccination between ages 6 months to 5 years could provide protection to the approximately 30-90% of children that have not had natural EV-A71 infection by that age. National Science Fund for Distinguished Young Scholars, National Natural Science Foundation of China.

Maternity health professionals\u2019 perspectives of cord clamp timing, cord blood banking and cord blood donation: a qualitative study

BackgroundParents today have several options for the management of their infant’s cord blood during the third stage of labour. Parents can choose to have their infant’s cord clamped early or to have deferred cord clamping. If the cord is clamped early, cord blood can be collected for private cord blood banking or public cord blood donation for use later if needed. If cord clamping is deferred, the placental blood physiologically transfuses to the neonate and there are physiological advantages to this. These benefits include a smoother cardiovascular transition and increased haemoglobin levels while not interfering with the practice of collecting cord blood for gases if needed. The aim of this study is to explore Australian maternity health professionals’ perspectives towards cord clamp timing, cord blood banking and cord blood donation.MethodsFourteen maternity health professionals (midwives and obstetricians) from both private and public practice settings in Australia participated in semi-structured interviews either in person or by telephone. Interviews were transcribed and data analysed using thematic analysis.ResultsOverall there was strong support for deferred cord clamping, and this was seen as important and routinely discussed with parents as part of antenatal care. However, support did not extend to the options of cord blood banking and donation and to routinely informing parents of these options even when these were available at their birthing location.ConclusionFormalised education for maternity health professionals is needed about the benefits and implications of cord blood banking and cord blood donation so that they have the confidence to openly discuss all options of cord clamp timing, cord blood banking and cord blood donation to facilitate informed decision-making by parents.

Association of antenatal vitamin B complex supplementation with neonatal vitamin B12 status: evidence from a cluster randomized controlled trial.

Evidence about the effect of maternal vitamin B12 supplementation on offspring's vitamin B12 status is limited. The present interventional study sought to evaluate the association of antenatal vitamin B complex supplementation with neonatal vitamin B12 status. In an ongoing cluster randomized controlled trial conducted in three rural counties in northwest China, pregnant women < 20weeks of gestation were randomized to three treatment groups: blank control, iron supplements, or vitamin B complex supplements. All women were administered folic acid supplements during the periconceptional period. In a sub-study, we collected cord blood samples of 331 participants from the control or vitamin B complex groups in the Xunyi county from January 2017 to December 2017. Plasma concentrations of folate, vitamin B12, and homocysteine were measured. Linear mixed models with a random intercept for cluster were used to compare biochemical indexes between groups after controlling for covariates. Compared with newborns whose mothers were in the control group, newborns of the vitamin B complex-supplemented women had significantly higher cord plasma vitamin B12 (P = 0.001) and lower homocysteine concentrations (P = 0.043). The association of antenatal vitamin B complex supplementation with cord blood vitamin B12 concentrations appeared to be more pronounced among newborns with high folate status than those with low folate status (Pinteraction = 0.060). Maternal vitamin B complex supplementation during pregnancy was associated with better neonatal vitamin B12 status in rural northwest China.

Emotional labour and cord blood collection: frontline perspectives

PurposeThis paper aims to examine emotional labour in the work of frontline staff (FLS) of the Canadian Blood Services' Cord Blood Bank (CBB), contributes to understandings of emotional labour by allied healthcare workers and suggests implications for healthcare managers.Design/methodology/approachQualitative interviews with 15 FLS were conducted and analyzed as part of a process evaluation of donor recruitment and cord blood collection in Canada.FindingsEmotional labour with donors and hospital staff emerged as a vital component of FLS' donor recruitment and cord blood collection work. Emotional labour was performed with donors to contribute to a positive birthing experience, facilitate communication and provide support. Emotional labour was performed with hospital staff to gain acceptance and build relationships, enlist support and navigate hierarchies of authority.Research limitations/implicationsThe results indicate that FLS perform emotional labour with women to provide donor care and with hospital staff to facilitate organizational conditions. The findings are based on FLS' accounts of their work and would be enhanced by research that examines the perspectives of donors and hospital staff.Practical implicationsAttention should be paid to organizational conditions that induce the performance of emotional labour and may add to FLS workload. Formal reciprocal arrangements between FLS and hospital staff may reduce the responsibility on FLS and enable them to focus on recruitment and collections.Originality/valueThis paper addresses a gap in the healthcare management literature by identifying the emotional labour of allied healthcare workers. It also contributes to the cord blood banking literature by providing empirically grounded analysis of frontline collection staff.

Association of Methylation-Related Nutrient Intake and Status with Offspring DNA Methylation in Pregnant Women with and Without Gestational Diabetes Mellitus

Abstract Objectives Gestational diabetes mellitus (GDM) is associated with alterations in DNA methylation in the placenta and offspring tissues. Nutrients participating in the methionine cycle (e.g., choline, betaine, folate, vitamin B12, methionine) influence the supply of methyl groups. The objective of this research was to determine whether maternal intake and status of these nutrients during pregnancy may interact with the GDM status to shape the offspring epigenome. Methods We conducted 3-day dietary recalls and collected blood samples from pregnant women with and without GDM (n = 22/group) to quantify methylation-related nutrient intakes and status. At delivery, we collected cord blood samples and measured global DNA methylation. Results GDM was associated with a 25% increase (P = 0.041) in global DNA methylation in the cord blood. Maternal choline intake (r = −0.602, P = 0.006) as well as cord blood methionine (r = −0.553, P = 0.014) and betaine (r = −0.566, P = 0.011) levels were negatively correlated with cord blood DNA methylation only in non-GDM women, while intakes and maternal blood levels of other methylation-related nutrients were not related to cord blood DNA methylation. Conclusions GDM and methyl nutrient intake/status interact to modify offspring DNA methylation in humans. Funding Sources Egg Nutrition Center.

SUN-077 Do Low Sex Hormone Binding Globulin Levels in Newborns Predict Weight Gain in Infancy and Early Childhood?

Background: SHBG levels are low in obesity, and low SHBG levels are a biomarker for the development of T2DM and the metabolic syndrome. We sought to determine whether low SHBG in newborns will predict childhood obesity. Methods: We studied 94 healthy, singleton, full-term newborns, and measured their length, weight (BW), waist circumference, and skinfold thicknesses. We collected cord blood as well as day 2 venous blood samples for the measurement of SHBG and insulin (ALPCO, Salem NH). Maternal age, pre-pregnancy weight, pregnancy weight gain, and glucose screening test results were obtained from obstetrical records. Mothers with chronic diseases were excluded from the study. When babies were 2 years old, we administered a questionnaire to collect information about their eating, sleeping, screen viewing habits, and anthropometric measurements at ages 6, 12, and 24 months (n=47). Overweight was defined as a BMI SDS of ≥1 and <2.0, and obesity as ≥2 SDS. We used the Shapiro-Wilk test to determine if variables were normally distributed. Data were analyzed using the Mann Whitney U and Wilcoxon signed-rank tests, and by Pearson or Spearman correlation analyses. We report non-normally distributed variables as medians and interquartile ranges (IQR). Because of skewed distributions, log 10 transformed values for SHBG were used in the regression analyses. Results: SHBG levels on day 2 were significantly higher than in cord blood [22.0(28.7-16.9) vs. 19.0(24.6-14.5) nmol/L, p<0.001], whereas insulin levels were higher in cord blood than in day 2 samples [3.2(5.3-2.0) vs. 1.5(2.2-0.8) µIU/mL, p<0.001]. SHBG and insulin levels were similar in male (n=44) and female (n=50) babies at all time points. Babies with Ponderal index values in the highest quartile had lower day 2 SHBG [18.2(22.1-16.7) vs. 24.3(30.3-18.2) nmol/L, p=0.02] and higher cord blood insulin levels [5.0(7.4-2.6) vs. 2.9(4.8-1.5) µIU/mL, p=0.04] than the remainder of the cohort. At age 2 years, 32% (15/47) of babies were overweight or obese, 60% (28/47) were breastfeeding, 58% (27/47) were watching TV or iPads, and 55% (26/47) were eating sweet snacks. Toddlers watching TV or iPads (p=0.008), or eating sweet snacks (p=0.04) were heavier than their peers. Neither cord blood nor day 2 SHBG or insulin levels correlated significantly with any of the anthropometric measurements in the newborns. On the other hand, day 2 SHBG levels correlated positively with weight at 6 (r=0.311, p=0.04) and 24 months (r=0.353, p=0.02) of age. These associations remained significant after adjusting for gender, BW, gestational age, breastfeeding status and fruit juice intake at 6 months (R2=0.28, p=0.048) and for gender, BW, gestational age, breastfeeding status, sweet snack intake and screen viewing habits at 24 months (R2=0.33, p=0.046). Conclusion: Although the heaviest babies had lower SHBG levels at birth, low SHBG did not predict overweight at age 2 years.

Phase I Trial of Allogeneic Umbilical Cord Tissue-Derived Mesenchymal Stromal Cells in Neonates with Hypoxic-Ischemic Encephalopathy

Background & Aim Background In neonatal animal models of hypoxic-ischemic brain injury administration of mesenchymal stromal cells (MSCs) improves anatomic and functional outcomes. A prior study suggests potential benefit of autologous cord blood-derived cells for infants with hypoxic-ischemic encephalopathy (HIE) but cord blood collection in this population is challenging. A safe, effective off-the-shelf allogeneic cell product could be a useful alternative. Our aim was to conduct a phase I open-label study of umbilical cord tissue-derived MSCs in infants treated with hypothermia for HIE. Methods, Results & Conclusion Methods Infants >35 weeks gestation treated with hypothermia for HIE based on NICHD hypothermia trial criteria were eligible. Goal enrollment was 6 infants. Allogeneic umbilical cord tissue-derived mesenchymal stromal cells (hCT-MSC) were manufactured in the Robertson GMP Cell Manufacturing Laboratory from a single cord tissue donated to the Carolinas Cord Blood Bank. Cells were expanded to passage 2 and cryopreserved. A representative cryobag was quality-tested for cell count, viability, phenotype, functional assays, gram stain and sterility. For administration cells were thawed and diluted 1:1 and delivered in syringes containing plasmalyte-A, 5% HSA, and residual DMSO. Post thaw samples were tested for cell count, viability (required ≥70%) and sterility. The first 3 infants (cohort 1) received 2 × 106 cells/kg i.v. in the first 48 postnatal hours, the second 3 (cohort 2) received a 2nd dose at 2 months. Primary safety outcomes were occurrence of infusion reactions or infections within 2 weeks of infusion. Results Of 18 eligible infants, 6 were enrolled (Table 1). All cultures obtained from subjects were negative, and no subject had an infusion reaction. Subject #5, had a positive panel reactive antibody (PRA) screen at 6 months. Broth culture from thawed hCT-MSC for subject # 1 grew coagulase-negative staphylococci. The infant remained asymptomatic after re-warming and the infant's blood cultures were sterile. The broth culture was assessed as contaminant via handling post-thaw rather than cell product contamination. There was one protocol deviation (One infant received a study dose at 71 hours. (Table 2)). Conclusions Our results suggest that hCT-MSC, an umbilical cord tissue-derived MSC product, can be prepared and infused safely in infants treated with hypothermia for moderate - severe HIE. Further safety and efficacy studies are warranted.

Autologous transplantation of umbilical cord blood-derived cells in extreme preterm infants: protocol for a safety and feasibility study

IntroductionPreterm brain injury continues to be an important complication of preterm birth, especially in extremely premature infants. Umbilical cord blood-derived cells (UCBCs) are increasingly being evaluated for their neuroprotective and...

Improved access to better HLA-matched hematopoietic cells for allogeneic transplant: analysis of donors and cord blood units selected for Canadian patients in 2018.

Patients undergoing hematopoietic cell transplantation (HCT) often require use of an unrelated donor or cord blood unit (CBU). An understanding of evolving practices in graft selection is needed for optimization of donor recruitment and cord blood collection. Each donor workup (WU) requested in 2018 involving a Canadian (CDN) patient and unique donor product or CBU was reviewed (n = 598). Degree of HLA match; product origin (domestic or international [INT]); and non-HLA factors including donor age, sex, cytomegalovirus (CMV), and ABO compatibility were analyzed for WUs that proceeded to transplant (n = 414). We also analyzed changes compared to a similar analysis performed in 2013. The majority of transplants used matched unrelated donors (MUDs; n = 323; 78%) and were most often young (≤35 years), male, INT donors (n = 136). The proportion of transplants involving MUDs, as opposed to mismatched unrelated donors or CBUs, increased by 12.4% compared with 2013. When young, male, CDN MUDs were identified in patient search reports but not selected, CMV mismatching and ABO incompatibility were most likely to have influenced the decision to use an INT MUD. Consistent with global trends, CBU transplants decreased compared to 2013; however, the degree of HLA matching improved significantly, and 27% of transplanted CBUs were procured from the Canadian Blood Services Cord Blood Bank. Access to MUDs and better HLA-matched CBUs by CDN patients has increased since 2013. Ongoing recruitment of young registrants and cord blood donors with diverse HLA haplotypes will support selection of donors with optimal non-HLA characteristics.

Noninvasive white blood cell quantification in umbilical cord blood collection bags with quantitative oblique back‐illumination microscopy

Umbilical cord blood has become an important source of hematopoietic stem and progenitor cells for therapeutic applications. However, cord blood banking (CBB) grapples with issues related to economic viability, partially due to high discard rates of cord blood units (CBUs) that lack sufficient total nucleated cells for storage or therapeutic use. Currently, there are no methods available to assess the likelihood of CBUs meeting storage criteria noninvasively at the collection site, which would improve CBB efficiency and economic viability. To overcome this limitation, we apply a novel label-free optical imaging method, called quantitative oblique back-illumination microscopy (qOBM), which yields tomographic phase and absorption contrast to image blood inside collection bags. An automated segmentation algorithm was developed to count white blood cells and red blood cells (RBCs) and assess hematocrit. Fifteen CBUs were measured. qOBM clearly differentiates between RBCs and nucleated cells. The cell-counting analysis shows an average error of 13% compared to hematology analysis, with a near-perfect, one-to-one relationship (slope = 0.94) and strong correlation coefficient (r = 0.86). Preliminary results to assess hematocrit also show excellent agreement with expected values. Acquisition times to image a statistically significant number of cells per CBU were approximately 1 minute. qOBM exhibits robust performance for quantifying blood inside collection bags. Because the approach is automated and fast, it can potentially quantify CBUs within minutes of collection, without breaching the CBUs' sterile environment. qOBM can reduce costs in CBB by avoiding processing expenses of CBUs that ultimately do not meet storage criteria.