Allogeneic Umbilical Cord Blood Red Cell Concentrates: An Innovative Blood Product for Transfusion Therapy of Preterm Infants

Abstract Objective. To characterise the umbilical cord blood immune profile in preterm infants compared to term-born controls and the postnatal immune response following exposure to histologic chorioamnionitis (HCA) in preterm infants. Design. Descriptive, observational cohort study. Setting. Edinburgh, UK. Population. 118 preterm infants (mean gestational age 29+0 weeks, range 23+2 to 32+0) and 59 term-born controls. Methods. Placental histopathology was used to identify reaction patterns indicative of HCA, and a customised immunoassay of 24 inflammatory markers and trophic proteins selected to reflect the perinatal immune response was performed on umbilical cord blood in term and preterm participants and postnatal day 5 blood in the preterm group. Results. The umbilical cord blood immune profile classified gestational age category with 86% accuracy (95% CI 0.78-0.92), p-value=1.242x10-14. Pro-inflammatory proteins IL-6, MCP-1 and CRP were elevated in the cord blood of preterm infants whilst BDNF, C3, C9, IL-18, MMP-9 and RANTES were decreased, compared to infants born at term. In preterm infants, exposure to HCA was associated with elevations in 5 immune proteins on postnatal day 5 (BDNF, C3, IL-8, MIP-1β and MMP-9) when compared to preterm infants who were not exposed. Conclusion. Preterm birth is associated with a distinct immune profile in umbilical cord blood and infants exposed to HCA experience specific alterations in immune function that persist to day 5 of postnatal life.

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Remifentanil Degradation in Umbilical Cord Blood of Preterm Infants

Anesthesiology ◽

10.1097/aln.0b013e318204e043 ◽

2011 ◽

Vol 114 (3) ◽

pp. 570-577 ◽

Cited By ~ 34

Author(s):

Lars Welzing ◽

Sabine Ebenfeld ◽

Verena Dlugay ◽

Martin H. J. Wiesen ◽

Bernhard Roth ◽

...

Keyword(s):

Cord Blood ◽

Preterm Infants ◽

Umbilical Cord ◽

Umbilical Cord Blood ◽

Pharmacokinetic Data ◽

Serum Samples ◽

Term Infants ◽

Very Preterm Infants ◽

Cord Serum ◽

Very Preterm

Background No pharmacokinetic data about remifentanil in preterm infants exist, although remifentanil is increasingly used in this especially vulnerable subgroup of pediatric patients. Unfortunately, ethical restrictions in the volume of blood that can be withdrawn for kinetic sampling nearly prohibit pharmacokinetic studies in preterm infants. Methods Because remifentanil is rapidly metabolized by nonspecific blood esterases, we collected umbilical cord serum of preterm and term infants to investigate whether the activity of nonspecific blood esterases depends on gestational age. Umbilical cord serum, buffer solution, ascorbic acid, and remifentanil were mixed in a glass vial placed in a shaking water bath at 37°C. Subsequently, serum samples were subjected to liquid chromatography-mass spectrometry-based analysis of remifentanil and its metabolite GR90291 after 0, 30, 60, 100, and 150 min. Results We analyzed umbilical cord serum samples of 34 preterm infants (24-36 gestational weeks) and six term infants. The degradation rates of remifentanil to its major metabolite GR90291 were comparable in preterm and term infants. The overall median degradation half-life of remifentanil was 143 ± (interquartile range) 47 min (minimum, 76 min; maximum, 221 min) without significant differences between very preterm infants (less than 28 gestational weeks) and term infants. The remifentanil concentration remained stable in control runs without serum. Conclusions Our study demonstrates that very preterm infants exhibit a high nonspecific esterase activity in umbilical cord blood that is comparable with that of term infants. These results support clinical experiences that remifentanil is rapidly metabolized by preterm infants without prolonged side effects.

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Umbilical Cord Blood Adiponectin, Leptin, Insulin, and Ghrelin in Premature Infants and Their Association With Birth Outcomes

Frontiers in Endocrinology ◽

10.3389/fendo.2021.738964 ◽

2021 ◽

Vol 12 ◽

Author(s):

Luyan Han ◽

Bo Li ◽

Xiaojing Xu ◽

Shufang Liu ◽

Zhenghong Li ◽

...

Keyword(s):

Birth Weight ◽

Cord Blood ◽

Preterm Infants ◽

Umbilical Cord ◽

Fetal Growth ◽

Umbilical Cord Blood ◽

Gestational Age ◽

Metabolic Diseases ◽

Term Infants ◽

Preterm Group

BackgroundPremature/low-birth-weight infants are at significant risk of metabolic diseases in adulthood, which may be related to the levels of fetal adipokine. Here, we investigated the differences in the levels of umbilical cord blood adiponectin, leptin, insulin, and ghrelin in preterm and term infants and sought to elucidate the link between these hormones and fetal growth. We also evaluated the interrelationship among these metabolic hormones in both groups of newborns.MethodsA total of 149 mother–infant pairs (100 in the preterm group and 49 in the term group) were enrolled in the study. The preterm group was further subdivided according to birth weight (≤1,500, 1,501–2,000, 2,001–2,500, and >2,500 g), gestational age (<34 vs. ≥34 weeks), and appropriate for gestational age (AGA) vs. small for gestational age (SGA). The general condition of the mothers and the growth parameters of the newborns at birth were recorded.ResultsThe levels of adiponectin, leptin, and ghrelin were lower in the preterm group than those in the term group (p < 0.05). In the preterm group, the leptin levels of infants with gestational age ≥34 weeks were significantly higher than those of infants with gestational age <34 weeks (mean ln leptin = 0.63 vs. 0.36 ng/ml, p = 0.009). The levels of adiponectin were lower in the SGA group than those in the AGA group (mean ln adiponectin = 2.26 vs. 2.84 µg/ml, p = 0.001), whereas those of ghrelin displayed the opposite trend (mean ln ghrelin = 6.29 vs. 5.71 pg/ml, p < 0.001). Leptin was significantly correlated with insulin both in preterm infants with birth weight (BW) >2,000 g and in term infants. Umbilical cord blood leptin was positively correlated with the BW, birth length, and head circumference of newborns (r = 0.460, 0.311, and 0.310, respectively, all p < 0.05), whereas ghrelin was negatively correlated with the same parameters (r = −0.372, −0.415, and −0.373, respectively, all p > 0.05).ConclusionsThe lack of maturation of adipose tissue and the gastrointestinal tract by the fetus due to prematurity is associated with changes in the levels of cord blood adiponectin, leptin, and ghrelin. The dysregulation of these hormones in preterm infants may be a risk factor for fetal growth and future metabolic diseases.

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One Less Painful Procedure: Using Umbilical Cord Blood as Alternative Source to Admission Complete Blood Count

American Journal of Perinatology ◽

10.1055/s-0037-1601565 ◽

2017 ◽

Vol 34 (12) ◽

pp. 1178-1184 ◽

Cited By ~ 3

Author(s):

Neera Prakash ◽

Joseph Decristofaro ◽

Echezona Maduekwe

Keyword(s):

Blood Cell ◽

Cord Blood ◽

Preterm Infants ◽

Umbilical Cord ◽

Umbilical Cord Blood ◽

Gestational Age ◽

Blood Count ◽

Complete Blood Count ◽

Late Preterm ◽

Late Preterm Infants

Objective This study aims to evaluate the use of umbilical cord blood as an alternative to the admission complete blood count (CBC) in the well-appearing late preterm neonates admitted to the neonatal intensive care unit. Study Design Paired umbilical cord and admission blood CBC samples from well late preterm infants were compared using a two-sample t-test or analysis of variance with an unequal variance for differences in the hemoglobin, platelet counts, white blood cell, and absolute neutrophil counts. Results A total of 100 infants were enrolled in the study. The study included 46 females, 5 Asian, 9 Black, 35 Hispanic, 51 White, with a mean gestational age of 35.3 ± 1 weeks (range: 34–36.5 weeks), and a mean birth weight of 2,347 ± 491 g (range: 1,840–4,260 g). Around 80% were appropriate for gestational age, 5% were large for gestational age, and 15% were small for gestational age. The median difference between the cord and admission blood samples were hemoglobin: 1.1 g/dL, platelet: 7.50 × 103 cells/μL, white blood cell count: 2.3 × 103 cells/μL, and absolute neutrophil count: 0.6 × 103 cells/μL. Conclusion The cord and admission blood testing were not statistically or clinically different when compared. In well late preterm infants, the NICU admission blood CBC may be replaced with an umbilical cord blood CBC.

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Unrelated Donor Umbilical Cord Blood Transplant Following Intrauterine Transfusions for Treatment of Alpha Thalassemia Major.

Blood ◽

10.1182/blood.v108.11.5403.5403 ◽

2006 ◽

Vol 108 (11) ◽

pp. 5403-5403

Author(s):

Angela E. Rivers ◽

Douglas Richard ◽

Neil Harris ◽

David H.K. Chui ◽

William B. Slayton ◽

...

Keyword(s):

Cord Blood ◽

Umbilical Cord ◽

Umbilical Cord Blood ◽

Premature Delivery ◽

Unrelated Donor ◽

Globin Genes ◽

Transfusion Therapy ◽

Cord Blood Transplant ◽

Intrauterine Transfusion ◽

Matched Sibling

Abstract Homozygous α0-thalassemia (deletion of all 4 α-globin genes) results in Hb Bart’s (γ4 tetramers). The high oxygen affinity of Hgb Bart’s leads to severe hypoxia inutero with resulting profound edema (hydrops) and congestive heart failure. Almost universally fetal death occurs prior to diagnosis, therefore not allowing the opportunity for treatment. Advancement of maternal-fetal medicine and neonatal ultrasound has led to the possibility of in utero diagnosis and treatment with inrauterine transfusions. Also, cases of premature infants surviving and undergoing chronic transfusion therapy have been reported. Hematopoietic stem cell transplant (HSCT) has become increasingly used in the cure of beta thalassemia, and provides the potential to cure a0thalassemia as well. To date, 3 reported cases of a0thalassemia have been successfully treated with HSCT. Two children underwent matched sibling bone marrow transplant at 20 and 21 months of age and one underwent a 5/6 HLA matched sibling umbilical cord blood transplant (UCBT). One child had received intrauterine transfusions. We report a case of an infant with a0thalassemia successfully treated with intrauterine transfusion therapy followed by unrelated donor UCBT. The child’s mother, of Cambodian descent, presented to the obstetrician at 23 weeks with concerns of decreased fetal movement. Fetal ultrasound revealed a thickened placenta and hydrops fetalis. Based on the family’s nationality and history of previous fetal loss, the suspicion of a0thalassemia was raised. Umbilical cord blood sampling revealed a hypochromic, microcytic anemia with target cells. The hemoglobin electrophoresis demonstrated Hgb Barts and Portland. Subsequent genotyping confirmed deletion of all 4 α-globin genes. Options presented to the family included termination of pregnancy as well as the option of intrauterine transfusion followed by either chronic transfusion therapy with iron chelation or the possibility of HSCT. The patient received three intrauterine transfusions prior to delivery at 32 weeks gestation. A poor physical profile, non-reassuring heart rate and breech position led to the premature delivery. Apgars were 1 at one minute, 6 at five minutes, and 9 at ten minutes. The baby was admitted to the NICU and required mechanical ventilation for two days. The hospital course was relatively uneventful and included red blood cell transfusion. After discharge, he was maintained with intermittent transfusions until 6 months of age. Following informed consent, he was conditioned for transplant with busulfan, cytoan and rabbit ATG. Since the infant lacked an HLA matched sibling, he received a 5/6 HLA matched unrelated donor umbilical cord blood unit delivering 11.8 × 107 nucleated cells/kg. Neutrophil engraftment (ANC>500) was achieved on day + 15. FK506 and methotrexate 5mg/m2 on days 1, 3 and 6 was utilized for GVHD prophylaxis. His course was complicated by moderate venoocclusive disease, small subdural hemorrhage, and CMV and adenovirus viremia. He has not had any evidence of graft versus host disease. Initial chimerism (RFLP) showed approximately 63% donor derived cells, and subsequent testing showed increasing chimerism and 100% T-cell engraftment. He clinically is doing very well post transplant. This case demonstrates that intrauterine transfusion followed by unrelated donor UCBT is feasible for the treatment of a0thalassemia.

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