Early Neurodevelopment of Extremely Preterm Infants Administered Autologous Cord Blood Cell Therapy: Secondary Analysis of a Nonrandomized Clinical Trial.

IMPORTANCE

Umbilical cord blood-derived cells (UCBCs) are increasingly being evaluated for neuroprotective properties in perinatal brain injury.

OBJECTIVE

To report early neurodevelopmental outcomes of extremely preterm infants who received autologous UCBCs in the CORD-SaFe study.

DESIGN, SETTING, AND PARTICIPANTS: This study reports early follow-up on the preplanned secondary aims of a phase 1 safety and feasibility nonrandomized clinical trial conducted between May 2021 and November 2023, with early follow-up completed in August 2024. Participants were infants born at less than 28 weeks' completed gestation who received autologous UCBCs in the CORD-SaFe study at Monash Children's Hospital, Australia. A contemporaneous cohort of noninfused infants born during the study period was included for comparison. Data were analyzed from October to December 2024.

INTERVENTION

Autologous UCBC administered intravenously in the second postnatal week of life.

MAIN OUTCOMES AND MEASURES

Infants underwent brain magnetic resonance imaging to assess structure and injury (Kidokoro score) at term-equivalent age. Assessments at 52 to 54 weeks postmenstrual age included General Movements Assessment, Hammersmith Infant Neurological Examination score, and clinical examination to diagnose risk of cerebral palsy.

RESULTS

A total of 23 infants (median [IQR] gestation, 26 [25-27] weeks; median [IQR] birth weight, 748 [645-981] grams; 17 [73.9%] male) were administered UCBCs at a median (IQR) dose of 42.3 (31.1-63.2) million cells/kg. The contemporaneous cohort included 93 infants (median [IQR] gestation, 26 (24-27) weeks; median [IQR] birth weight, 769 [660-1017] grams; 39 [41.9%] male). Median (IQR) Kidokoro score was 2 (1-3) for the UCBCs group and 3 (2-5) for the contemporaneous cohort, with no statistically significant difference observed between the groups (adjusted median difference, 0 [95% CI, -1.78 to 1.78]). No infants in the UCBC group were assessed as high risk for cerebral palsy compared with 6 of 87 assessed infants (6.8%) in the contemporaneous group; however, the difference was not statistically significant (adjusted log odds, 0.31 [95% CI, -0.76 to 1.38]). No differences in Hammersmith Infant Neurological Examination score (adjusted log odds, -1.50 [95% CI, -5.78 to 2.78]) and absent fidgety movements (adjusted odds ratio, 0.24 [95% CI, 0.20 to 3.04]) were observed between groups.

CONCLUSIONS AND RELEVANCE

This phase 1 nonrandomized clinical trial assessing the safety and feasibility of autologous UCBCs in extremely preterm infants did not find significant differences in brain imaging parameters and early neurodevelopmental outcomes between the cell therapy and contemporaneous untreated groups. It was encouraging to note no infants who received UCBCs were assessed as high risk for cerebral palsy at 52 to 54 weeks postmenstrual age, and the absence of high risk for CP merits further study.

TRIAL REGISTRATION

ANZCTR.org.au Identifier: ACTRN12619001637134.