Perinatal Asphyxia

Hypoxic-ischemic brain injury (HIBI) is a leading cause of death and lifelong disability in near-term and term infants, most often caused by perinatal arterial ischemic stroke (PAIS, incidence approximately 1:5000 live births) or perinatal asphyxia (PA, incidence 1-2:1000 live births). No treatment currently exists to repair or limit HIBI, and many affected infants go on to develop cerebral palsy, cognitive impairment, epilepsy, or visual or hearing deficits. Intranasally administered bone marrow-derived mesenchymal stromal cells (IN-MSC) are a candidate regenerative therapy for HIBI. Preclinical studies show that IN-MSC migrate to injured brain regions, dampen neuroinflammation, and stimulate endogenous neural repair, improving both structural and functional outcomes in animal models of HIBI. A first-in-human phase I trial (PASSIoN) in 10 neonates with PAIS showed that intranasal MSC administration was feasible and well tolerated, with no serious adverse events and promising early efficacy signals at 2-year follow-up. iSTOP-CP is a phase II, single-center (UMC Utrecht, the Netherlands), double-blind, randomized, placebo-controlled trial evaluating whether IN-MSC therapy can prevent or reduce motor and other disabilities in infants with MRI-confirmed HIBI due to PAIS or PA. Eligible infants are born at 35.0 weeks of gestation or later, have HIBI confirmed on brain MRI or MRS in predefined brain regions predictive of poor outcome, and are diagnosed with PAIS or PA, with or without prior therapeutic hypothermia. A total of 162 infants will be randomized 1:1 to IN-MSC or matching placebo, stratified by the cause of HIBI and, within the PAIS group, by stroke territory. Infants with suspected chromosomal, metabolic, or congenital central nervous system anomalies, intracranial hemorrhage as the main injury, or contraindications to intranasal administration are excluded, as are infants for whom the clinical team has decided to withdraw intensive care. Participants receive a single intranasal dose of bone marrow-derived MSC or a visually indistinguishable placebo within 7 days after birth. Participants are followed for 24 months, with neurodevelopmental follow-up visits at 3-4, 6, 9-12, and 24 months of age and a brain MRI at 52 weeks postmenstrual age. The primary endpoint is the motor composite score of the Dutch version of the Bayley Scales of Infant and Toddler Development, 4th edition (Bayley-IV-NL), assessed at 24 months corrected age. Key secondary endpoints include cognitive development, the incidence of sensorineural disability, neuroregenerative imaging biomarkers, safety, health-related quality of life for infants and their parents, and the cost-effectiveness of IN-MSC treatment, evaluated through a health technology assessment.

This retrospective, multicenter, observational study evaluates how well a decision-support algorithm can tell apart mild forms of hypoxic-ischemic encephalopathy (HIE) from moderate or severe forms in full-term newborns born after a lack of oxygen around birth (perinatal asphyxia). The algorithm reads the raw (non-compressed) EEG signal. Its output is compared with the reference reading of the full conventional EEG made by a panel of pediatric neurophysiologists together with the baby's clinical information. The study uses only medical data that already exists and asks nothing of the babies or their families.

The purpose of this study is to identify and analyze suboptimal perinatal (obstetric-pediatric) care in the occurrence and management of severe perinatal asphyxia or death of the newborn at or near term. Perinatal asphyxia is a serious and often unexpected pathology, requiring urgent multidisciplinary care (obstetric - pediatric - intensive care, etc.) with a high level of technical expertise and care coordination. Because of its rarity and complexity, it may be subject to suboptimal care. The aim of this study is to provide feedback within the center itself, coupled in 1/3 of cases with a confidential investigation into the search for and understanding of suboptimal care. Primary endpoint: Frequency of optimal or non-optimal maternal and neonatal management of hypoxic-ischemic encephalopathy (AIE) or neonatal death related to severe perinatal asphyxia.

This is a prospective intervention single center study to evaluate the feasibility and safety of intranasal breast milk in hypoxic-ischaemic encephalopathic neonates receiving therapeutic hypothermia.

This is an open-label prospective single-center randomized controlled trial to evaluate the effect of intranasal breast milk in hypoxic-ischemic encephalopathic neonates receiving therapeutic hypothermia on long term neurodevelopmental outcome compared to standard care.

In this clinical study vascular dynamics in the neonatal brain and kidney will be monitored by CUES and ULM before, during and after hypothermia treatment in neonates with asphyxia.