Zhou Lindsay, Razak Abdul, McDonald Courtney A, Yawno Tamara, McHugh David T, Whiteley Gillian, Connelly Kristyn, Sackett Vathana, Miller Suzanne L, Jenkin Graham, Novak Iona, Hunt Rod W, Malhotra Atul
Monash Newborn, Monash Children's Hospital, Melbourne, Australia.
Department of Paediatrics, Monash University, Melbourne, Australia.
JAMA Netw Open. 2025 Jul 1;8(7):e2521158. doi: 10.1001/jamanetworkopen.2025.21158.
Umbilical cord blood-derived cells (UCBCs) are increasingly being evaluated for neuroprotective properties in perinatal brain injury.
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.
Autologous UCBC administered intravenously in the second postnatal week of life.
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.
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.
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.
ANZCTR.org.au Identifier: ACTRN12619001637134.
脐带血来源的细胞（UCBCs）在围产期脑损伤中的神经保护特性正得到越来越多的评估。
报告在CORD-SaFe研究中接受自体UCBCs的极早产儿的早期神经发育结局。
设计、背景和参与者：本研究报告了一项2021年5月至2023年11月进行的1期安全性和可行性非随机临床试验预先计划的次要目标的早期随访情况，早期随访于2024年8月完成。参与者为在澳大利亚莫纳什儿童医院进行的CORD-SaFe研究中出生时孕周小于28周且接受自体UCBCs的婴儿。纳入了同期出生的未接受输注的婴儿队列作为对照。2024年10月至12月对数据进行了分析。
在出生后第二周静脉注射自体UCBCs。
婴儿在足月等效年龄时接受脑磁共振成像以评估结构和损伤（Kidokoro评分）。在月经龄52至54周时进行的评估包括全身运动评估、哈默史密斯婴儿神经学检查评分以及用于诊断脑瘫风险的临床检查。
共有23名婴儿（中位[四分位间距]孕周，26[25 - 27]周；中位[四分位间距]出生体重，748[645 - 981]克；17[73.9%]为男性）接受了UCBCs，中位（四分位间距）剂量为42.3（31.1 - 63.2）×10⁶个细胞/千克。同期队列包括93名婴儿（中位[四分位间距]孕周，26（24 - 27）周；中位[四分位间距]出生体重，769[660 - 1017]克；39[41.9%]为男性）。UCBCs组的中位（四分位间距）Kidokoro评分为2（1 - 3），同期队列的评分为3（2 - 5），两组间未观察到统计学显著差异（调整后的中位差异为0[95%置信区间，-1.78至1.78]）。与同期组87名接受评估的婴儿中的6名（6.8%）相比，UCBCs组中没有婴儿被评估为脑瘫高危；然而，差异无统计学意义（调整后的对数比值为0.31[95%置信区间，-0.76至1.38]）。两组间在哈默史密斯婴儿神经学检查评分（调整后的对数比值为-1.50[95%置信区间，-5.78至2.78]）和无烦躁运动（调整后的优势比为0.24[95%置信区间，0.20至3.04]）方面未观察到差异。
这项评估自体UCBCs在极早产儿中的安全性和可行性的1期非随机临床试验未发现细胞治疗组与同期未治疗组在脑成像参数和早期神经发育结局方面存在显著差异。值得注意的是，在月经龄52至54周时，接受UCBCs的婴儿中没有被评估为脑瘫高危，且未出现脑瘫高危情况值得进一步研究。
ANZCTR.org.au标识符：ACTRN12619001637134。
