Feasibility of autologous cord blood cells for infants with hypoxic-ischemic encephalopathy.

Abstract

Objective

To assess feasibility and safety of providing autologous umbilical cord blood (UCB) cells to neonates with hypoxic-ischemic encephalopathy (HIE).

Study design

We enrolled infants in the intensive care nursery who were cooled for HIE and had available UCB in an open-label study of non-cyropreserved autologous volume- and red blood cell-reduced UCB cells (up to 4 doses adjusted for volume and red blood cell content, 1-5 × 10(7) cells/dose). We recorded UCB collection and cell infusion characteristics, and pre- and post-infusion vital signs. As exploratory analyses, we compared cell recipients' hospital outcomes (mortality, oral feeds at discharge) and 1-year survival with Bayley Scales of Infant and Toddler Development, 3rd edition scores ≥85 in 3 domains (cognitive, language, and motor development) with cooled infants who did not have available cells.

Results

Twenty-three infants were cooled and received cells. Median collection and infusion volumes were 36 and 4.3 mL. Vital signs including oxygen saturation were similar before and after infusions in the first 48 postnatal hours. Cell recipients and concurrent cooled infants had similar hospital outcomes. Thirteen of 18 (74%) cell recipients and 19 of 46 (41%) concurrent cooled infants with known 1-year outcomes survived with scores >85.

Conclusions

Collection, preparation, and infusion of fresh autologous UCB cells for use in infants with HIE is feasible. A randomized double-blind study is needed.

Type

Journal article

Department

Description

Provenance

Citation

Published Version (Please cite this version)

10.1016/j.jpeds.2013.11.036

Publication Info

Cotten, C Michael, Amy P Murtha, Ronald N Goldberg, Chad A Grotegut, P Brian Smith, Ricki F Goldstein, Kimberley A Fisher, Kathryn E Gustafson, et al. (2014). Feasibility of autologous cord blood cells for infants with hypoxic-ischemic encephalopathy. The Journal of pediatrics, 164(5). pp. 973–979.e1. 10.1016/j.jpeds.2013.11.036 Retrieved from https://hdl.handle.net/10161/24697.

This is constructed from limited available data and may be imprecise. To cite this article, please review & use the official citation provided by the journal.

Scholars@Duke

Cotten

Charles Michael Cotten

Professor of Pediatrics

I am involved in 4 major areas of research:
1) Neuroprotection. Working with colleagues from Cell Therapies, we have added to Duke's experience participating in pivotal trials of hypothermia for term newborns with moderate to severe hypoxic-ischemic encephalopathy (HIE) by completing, with Duke CTSI support,  phase I studies of autologous cord blood cells and allogeneic cord tissue derived mesenchymal stromal cells for these infants.  and developing and currently leading a multicenter, double-blind randomized clinical trial of autologous cord blood cells or placebo in term infants with moderate or severe HIE. 
2) Genomics. We at Duke have been in the NICHD Neonatal Research Network (NRN) since 2001. I led the NRN's development of an Anonymized DNA bank of samples collected from 1,000 extremely low birthweight infants, with phenotype information linked to the samples. This resource has been the basis for multiple candidate gene, and genome wide scan analysis, and has identified variants associated with severe retinopathy of prematurity and necrotizing enterocolitis. We partnered with the Vermont Oxford Network-Rady Genomics collaborative to bring 48 hour turnaround Whole Genome Sequencing to patients in the Duke Intensive Care Nursery, and are continuing work with Medical Genetics faculty to keep Duke at the forefront of testing the effectiveness of applied next-gen sequencing in the NICU. 
3) New Technologies: I  collaborated with Drs. David Millington from Duke and Vamsee Pamula (a Duke Pratt School graduate), from BAEBIES Inc, on prototype new technology devices for use in newborn screening for lysosomal storage disease as well as multiplex chips for screening for hyperbilirubinemia and related conditions, as well as working with Dr. Pamula and Dr. Michael Freemark (Peds Endocrinology) on screening panels for hypoglycemia and hypothyroidism, and with investigators from UAB on an Acute Kidney Injury panel.  I continue active collaborations with Dr. Cynthia Toth and the DARSI lab in pediatric ophthalmology, and Pratt School investigators to develop and apply use of optical coherence tomography (OCT) for retinal imaging that will assess associations between retinal neurovascular development, brain development, and neurodevelopmental outcomes. We continue with a comparative trial of the value and effectiveness of utilization of OCT compared with the current standard indirect ophthalmoscopy for ROP screening in the NICU. 
4)Microbiome in Micropreemies and health outcomes of periviable infants.  I have worked with multiple epidemiology researchers to assess practice variation within our center, and within the Neonatal Research Network centers, to identify how variation in practice can influence outcomes, with a particular focus on antibiotic use. This work demonstrated strong associations between high empirical antibiotic use in infants with sterile cultures and subsequent morbidities and mortality. This discovery has led to strong collaborations and new initiatives by early career faculty leading studies of the evolving microbiome, leading to hypothesis generation re: the microbiome and optimal growth in extremely preterm infants.


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