Randomized Trial of Drainage, Irrigation and Fibrinolytic Therapy for Premature Infants with Posthemorrhagic Ventricular Dilatation: Developmental Outcome at 2 years

Whitelaw, Andrew; Jary, Sally; Kmita, Grażyna; Wróblewska, Jolanta; Musialik-Swietlińska, Ewa; Mandera, Marek; Hunt, Linda; Carter, Michael; Pople, Ian

doi:10.1542/peds.2009-1960

Cited by 157 publications

(120 citation statements)

References 16 publications

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“…A pioneering randomized trial for neonatal IVH using drainage, irrigation and fibrinolytic therapy showed severe cognitive disability in survivors and overall death or severe disability, when neurodevelopmental outcome was assessed at 2‐year follow‐up 45. Hence, to prove the safety and efficacy of MSCs as a therapeutic strategy, a double‐blind randomized controlled phase II clinical trial with follow‐up evaluation is necessary.…”

Section: Discussionmentioning

confidence: 99%

Mesenchymal Stem Cells for Severe Intraventricular Hemorrhage in Preterm Infants: Phase I Dose-Escalation Clinical Trial

Ahn

Chang

Sung

et al. 2018

Stem Cells Translational Medicine

121

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We previously demonstrated that transplanting mesenchymal stem cells (MSCs) improved recovery from brain injury induced by severe intraventricular hemorrhage (IVH) in newborn rats. To assess the safety and feasibility of MSCs in preterm infants with severe IVH, we performed a phase I dose‐escalation clinical trial. The first three patients received a low dose of MSCs (5 × 106 cells/kg), and the next six received a high dose (1 × 107 cells/kg). We assessed adverse outcomes, including mortality and the progress of posthemorrhagic hydrocephalus. Intraventricular transplantation of MSCs was performed in nine premature infants with mean gestational age of 26.1 ± 0.7 weeks and birth weight of 808 ± 85 g at 11.6 ± 0.9 postnatal days. Treatment with MSCs was well tolerated, and no patients showed serious adverse effects or dose‐limiting toxicities attributable to MSC transplantation. There was no mortality in IVH patients receiving MSCs. Infants who underwent shunt surgery showed a higher level of interleukin (IL)‐6 in cerebrospinal fluid (CSF) obtained before MSC transplantation in comparison with infants who did not receive a shunt. Levels of IL‐6 and tumor necrosis factor‐α in initially obtained CSF correlated significantly with baseline ventricular index. Intraventricular transplantation of allogeneic human UCB‐derived MSCs into preterm infants with severe IVH is safe and feasible, and warrants a larger, and controlled, phase II study. Stem Cells Translational Medicine 2018;7:847–856

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Section: Discussionmentioning

confidence: 99%

Mesenchymal Stem Cells for Severe Intraventricular Hemorrhage in Preterm Infants: Phase I Dose-Escalation Clinical Trial

Ahn

Chang

Sung

et al. 2018

Stem Cells Translational Medicine

121

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“…Moreover, except for shunt insertion to drain cerebrospinal fluid in infants with posthemorrhagic hydrocephalus and possibly the removal of blood clots in infants with high-grade IVH [18,19], there is no treatment for established IVH and no medical therapies exist to ameliorate the neurodevelopmental sequelae of IVH. …”

Section: Introductionmentioning

confidence: 99%

Erythropoietin for the Repair of Cerebral Injury in Very Preterm Infants (EpoRepair)

et al. 2015

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Background: Preterm infants suffering from intraventricular hemorrhage (IVH) are at increased risk for neurodevelopmental impairment. Observational data suggest that recombinant human erythropoietin (rEPO) improves long-term cognitive outcome in infants with IVH. Recent studies revealed a beneficial effect of early high-dose rEPO on white matter development in preterm infants determined by magnetic resonance imaging (MRI). Objectives: To summarize the current evidence and to delineate the study protocol of the EpoRepair trial (Erythropoietin for the Repair of Cerebral Injury in Very Preterm Infants). Methods: The study involves a review of the literature and the design of a double-blind, placebo-controlled, multicenter trial of repetitive high-dose rEPO administration, enrolling 120 very preterm infants with moderate-to-severe IVH diagnosed by cranial ultrasound in the first days of life, qualitative and quantitative MRI at term-equivalent age and long-term neurodevelopmental follow-up until 5 years of age. Results and Conclusions: The hypothesis generated by observational data that rEPO may improve long-term cognitive outcomes of preterm infants suffering from IVH are to be confirmed or refuted by the randomized controlled trial, EpoRepair.

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“…Despite a decrease in its incidence with routine use of both antenatal steroids and artificial surfactant at delivery, GMH/IVH remains one of the major complications of very preterm birth and brain injury. These neonates have an increased mortality rate (21) and display a high incidence of posthemorrhagic hydrocephalus, cerebral palsy, developmental disabilities, and cognitive impairments (22,23). A recent postmortem study has shown suppressed cell proliferation and decreased numbers of premyelinating oligodendrocytes in the ganglionic eminence following preterm GMH (24), which may have an adverse effect on the premyelinating oligodendrocyte population and myelination.…”

mentioning

confidence: 99%

Microglia activation in the extremely preterm human brain

et al. 2012

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Randomized Trial of Drainage, Irrigation and Fibrinolytic Therapy for Premature Infants with Posthemorrhagic Ventricular Dilatation: Developmental Outcome at 2 years

Abstract: Despite an increase in secondary intraventricular bleeding, DRIFT reduced severe cognitive disability in survivors and overall death or severe disability.

Cited by 157 publications

References 16 publications

Mesenchymal Stem Cells for Severe Intraventricular Hemorrhage in Preterm Infants: Phase I Dose-Escalation Clinical Trial

Mesenchymal Stem Cells for Severe Intraventricular Hemorrhage in Preterm Infants: Phase I Dose-Escalation Clinical Trial

Erythropoietin for the Repair of Cerebral Injury in Very Preterm Infants (EpoRepair)

Microglia activation in the extremely preterm human brain

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