About this trial
Moderate-severe intraventricular hemorrhage (msIVH, Grades II-IV) is a significant neurological complication among extremely low gestational age neonates (ELGANs, \<=27+6 weeks) and is associated with long-term neuro-disabilities. In Canada, msIVH affects \~25-30% of the 1300 ELGANs born annually, with little change in incidence over last decade. Typically, it occurs between days 2-7 of age, providing a finite window of opportunity. Instituting therapies at the population level, however, exposes many low-risk infants to side effects, adversely affecting risk-benefit profile and requiring large sample sizes in trials. A targeted preventative approach, though ideal, is currently challenged by our inability to reliably identify at-risk ELGANs early after birth. Near-infrared spectroscopy (NIRS) has emerged as a promising non-invasive bedside neuromonitoring tool. Pilot studies using NIRS, including ours, found lower cerebral saturations (CrSO2) and greater periods of altered cerebral autoregulation in infants who later developed msIVH. However, a systematic planned investigation is needed to establish the predictive characteristics of NIRS-derived markers, using clinically translatable methods (cumulative burden over time-period vs. single time-point values) and identify their relative performance at different time-points during transition. Further, incorporating echocardiographic (ECHO) hemodynamic markers, known to be associated with msIVH, may allow for the establishment of robust multi-model prediction models and the gain of mechanistic hemodynamic insights to inform future management. Hence, our objective is to investigate the utility of multi-modal assessment using NIRS and ECHO for early identification of ELGANs at risk of msIVH, and generate clinically applicable predictive model(s).
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Preterm infants born <=27+6 weeks gestational age
Disqualifiers
Known genetic or congenital anomalies that are likely to affect cardiac or cerebral oxygenation measures
Palliative care plan prior to or immediately following delivery
Trial population
Preterm infants at tertiary NICU admitted to one of four study NICUs: * Mount Sinai Hospital, Toronto (ON) * The Children's Hospital at London Health Sciences Center, London (ON) * Foothills Medical Centre, Calgary (AB) * Royal Alexandra Hospital, Edmonton (AB)
Trial design
Cohort
Prospective
Treatments tested in this trial
Cerebral near-infrared spectroscopy
Diagnostic testContinuous cerebral NIRS will be monitored using the INVOS 5100C or 7100 Cerebral Oximeter (Medtronic, Minneapolis, MN, USA), initiated as early as feasible after birth or postnatal consent and continued until 48 hours of age. Neonatal sensors applied over a light-permeable barrier will be placed on the right or left side of forehead, like the methods used in our pilot study and in line with our clinical protocol. The continuous parameters recorded for this study using cerebral NIRS will include CrSO2 and COIx.
Functional echocardiography
Diagnostic testThe first echocardiogram will be completed as soon as possible after consent and \< 24 hours of age in all cases. This will be to capture markers of early low systemic blood flow and document patent ductus arteriosus and its size, as known to be associated with IVH. The second scan will be performed at the end of the monitoring period, between 48-60 hours of age. This scan is planned to record the change in LVO from baseline (re-perfusion), which has been postulated to relate to development of IVH.
Head Ultrasound
Diagnostic testHUS will be paired with both echocardiograms. The first HUS will document baseline IVH status (paired with the first ECHO). The final HUS will be performed between days 4-7 of age, as per the standard clinical practice by site radiology service and will be used to confirm the final IVH status.
Treatment groups
Trial outcomes
Primary outcomes
Intraventricular hemorrhage (IVH) Status
IVH will be classified using Volpe's classification which is also the clinical standard for IVH classification (Grade I: Blood in germinal matrix with or without IVH less than 10% of ventricular space; Grade II: IVH occupying 10-50% of ventricular space on parasagittal view; Grade III: IVH occupying \>50% of ventricle with or without ventricular echo-densities; Grade IV: periventricular hemorrhagic infarction).
Sponsors and contacts
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Mount Sinai Hospital, Canada
Lead sponsor
London Health Sciences Centre
Collaborator
Foothills Medical Centre
Collaborator
Royal Alexandra Hospital
Collaborator