Collection of Umbilical cord blood cells in neonates at increased risk of brain damage – a step towards autologous cell therapy for a high risk population

Introduction:

The aim of this study was to assess feasibility of umbilical cord blood (UCB) collection in high risk pregnancies and newborn infants at increased risk of brain damage and to determine whether treatment options with autologous UCB for these infants exist. Evidence for perinatal cell therapies as a potential intervention for neurological diseases is emerging. The optimal cell source, cell type, dose and timing remain to be clarified. Most existing trials working with umbilical cord blood (UCB) cells involve either autologous UCB from mature neonates or work with allogenic cells. It is unclear whether autologous UCB collection is feasible for other neonatal populations at high risk of brain damage, such as very early preterm gestations. Collection of UCB in this critical risk group is organisationally and technically challenging, late cord clamping and anatomic conditions may reduce the availability of UCB. In emergencies the collection cannot be planed.

Material and Methods:

Candidates for UCB collection were infants born between 12/2017 – 12/2018 from four high-risk groups: Perinatal hypoxemia, gestational age ≤30 weeks of gestation, intrauterine growth restriction (IUGR) and monochorionic twins with twin-to-twin transfusion syndrome (TTTS). Feasibility of the collection, quality of obtained blood (volume, sterility, cell viability) and outcome of the included neonates were assessed.

Results:

UCB collection was successful in 141 of 177 enrolled patients (hypoxemia n = 10; GA ≤30 weeks n = 54; IUGR n = 70; TTTS n = 6). 36 cases were missed due to organisational difficulties or technical reasons/anatomical limitations. Median maternal blood-loss in failed cases was 1400 ml (range 500 – 1800 ml). Volume of UCB collected ranged widely from 5,0 – 102 ml and contained a median of 0,77 108 total nucleated cells (median 0.01 – 13.0 108). The nuclear cell count, median cell viability and stored UCB volume correlated significantly with gestational age (p < 0.001, p<= 0.001, p = 0.04). Eight UCB units were microbiologically contaminated. 11% (19/177) of all included neonates developed brain lesions (n = 9 intraventricular hemorrhage, n = 7 hypoxic ischemic encephalopathy, n = 2 periventricular leukomalacia, n = 1 cerebral palsy).

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Discussion:

Collection and preparation of UCB in neonates at high risk of brain damage is challenging but possible with a multidisciplinary approach that includes extensive preparations, and detailed team-briefings. Due to the high prevalence of brain damage in the included study population, autologous collection of perinatal cells from these neonates is worthwhile. For very preterm infants, Wharton“s jelly from umbilical cord tissue should be considered as an alternative cell source because of the low yield of UCB. Further phase I studies and randomized phase II studies should be performed to provide further safety, feasibility, and efficacy information.