Five-year follow-up outcomes after phase 1 trial of mesenchymal stromal cells for periventricular hemorrhagic infarction in preterm infants.

Periventricular hemorrhagic infarction (PVHI), commonly referred to as grade 4 intraventricular hemorrhage, is a serious neurological disorder in premature infants with no established disease-modifying therapy. This study evaluated the long-term safety and outcomes of intraventricular administration of mesenchymal stromal cells (MSCs) in premature infants with PVHI who previously participated in a phase I trial, with follow-up through a corrected age (CA) of 5 years. Nine infants were included, of whom four had a PVHI score of 2 and five had a score of 3. No significant short-term or long-term adverse events, including tumorigenicity, were observed. Infants with higher PVHI severity (score 3) showed more frequent long-term adverse outcomes, including a mental development index <70 on the Bayley Scales of Infant and Toddler Development II at a CA of 2 years, developmental impairment as assessed by the Korean Developmental Screening Test, and cerebral palsy (CP) with Gross Motor Function Classification System (GMFCS) ≥3 at both CA 2 and 5 years. Lower intact brain volume ratio strongly correlates with the presence of CP with GMFCS ≥3. Intraventricular MSC administration appeared safe and feasible over 5 years; however, baseline PVHI severity remained the strongest predictor of long-term neurodevelopmental outcomes. These findings support the need for larger, controlled trials to further evaluate the therapeutic potential of MSCs for PVHI. ClinicalTrials.gov Identifier: NCT02673788.