Dolphin CONTINUE: a multi-center randomized controlled trial to assess the effect of a nutritional intervention on brain development and long-term outcome in infants born before 30 weeks of gestation.

BACKGROUND: Preterm born infants are at risk for brain injury and subsequent developmental delay. Treatment options are limited, but optimizing postnatal nutrition may improve brain- and neurodevelopment in these infants. In pre-clinical animal models, combined supplementation of docosahexaenoic acid (DHA), choline, and uridine-5-monophosphate (UMP) have shown to support neuronal membrane formation. In two randomized controlled pilot trials, supplementation with the investigational product was associated with clinically meaningful improvements in cognitive, attention, and language scores. The present study aims to assess the effect of a similar nutritional intervention on brain development and subsequent neurodevelopmental outcome in infants born very and extremely preterm. METHODS: This is a randomized, placebo-controlled, double-blinded, parallel-group, multi-center trial. A total of 130 infants, born at less than 30 weeks of gestation, will be randomized to receive a test or control product between term-equivalent age and 12 months corrected age (CA). The test product is a nutrient blend containing DHA, choline, and UMP amongst others. The control product contains only fractions of the active components. Both products are isocaloric powder supplements which can be added to milk and solid feeds. The primary outcome parameter is white matter integrity at three months CA, assessed using diffusion-tensor imaging (DTI) on MRI scanning. Secondary outcome parameters include volumetric brain development, cortical thickness, cortical folding, the metabolic and biochemical status of the brain, and product safety. Additionally, language, cognitive, motor, and behavioral development will be assessed at 12 and 24 months CA, using the Bayley Scales of Infant Development III and digital questionnaires (Dutch version of the Communicative Development Inventories (N-CDI), Ages and Stages Questionnaire 4 (ASQ-4), and Parent Report of Children's Abilities - Revised (PARCA-R)). DISCUSSION: The investigated nutritional intervention is hypothesized to promote brain development and subsequent neurodevelopmental outcome in preterm born infants who have an inherent risk of developmental delay. Moreover, this innovative study may give rise to new treatment possibilities and improvements in routine clinical care. TRIAL REGISTRATION: WHO International Clinical Trials Registry: NL-OMON56181 (registration assigned October 28, 2021).

Introduction of ultra-high-field MR brain imaging in infants: vital parameters, temperature and comfort.

Background: Brain MRI in infants at ultra-high-field scanners might improve diagnostic quality, but safety should be evaluated first. In our previous study, we reported simulated specific absorption rates and acoustic noise data at 7 Tesla. Methods: In this study, we included twenty infants between term-equivalent age and three months of age. The infants were scanned on a 7 Tesla MRI directly after their clinically indicated 3 Tesla brain MRI scan. Vital parameters, temperature, and comfort were monitored throughout the process. Brain temperature was estimated during the MRI scans using proton MR spectroscopy. Results: We found no significant differences in vital parameters, temperature, and comfort during and after 7 Tesla MRI scans, compared to 3 Tesla MRI scans. Conclusions: These data confirm our hypothesis that scanning infants at 7 Tesla MRI appears to be safe and we identified no additional risks from scanning at 3 Tesla MRI.

Introduction of Ultra-High-Field MR Imaging in Infants: Preparations and Feasibility.

BACKGROUND AND PURPOSE: Cerebral MR imaging in infants is usually performed with a field strength of up to 3T. In adults, a growing number of studies have shown added diagnostic value of 7T MR imaging. 7T MR imaging might be of additional value in infants with unexplained seizures, for example. The aim of this study was to investigate the feasibility of 7T MR imaging in infants. We provide information about the safety preparations and show the first MR images of infants at 7T. MATERIALS AND METHODS: Specific absorption rate levels during 7T were simulated in Sim4life using infant and adult models. A newly developed acoustic hood was used to guarantee hearing protection. Acoustic noise damping of this hood was measured and compared with the 3T Nordell hood and no hood. In this prospective pilot study, clinically stable infants, between term-equivalent age and the corrected age of 3 months, underwent 7T MR imaging immediately after their standard 3T MR imaging. The 7T scan protocols were developed and optimized while scanning this cohort. RESULTS: Global and peak specific absorption rate levels in the infant model in the centered position and 50-mm feet direction did not exceed the levels in the adult model. Hearing protection was guaranteed with the new hood. Twelve infants were scanned. No MR imaging-related adverse events occurred. It was feasible to obtain good-quality imaging at 7T for MRA, MRV, SWI, single-shot T2WI, and MR spectroscopy. T1WI had lower quality at 7T. CONCLUSIONS: 7T MR imaging is feasible in infants, and good-quality scans could be obtained.

Neonatal stroke: a review of the current evidence on epidemiology, pathogenesis, diagnostics and therapeutic options.

UNLABELLED: Neonatal stroke, including perinatal arterial ischaemic stroke and cerebral sinovenous thrombosis, remains a serious problem in the neonate. This article reviews the current evidence on epidemiology, pathogenesis, diagnostics and therapeutic options. CONCLUSION: Although our understanding of the underlying mechanisms and possible risk factors has improved, little progress has been made towards therapeutic options. Considering the high incidence of neurological sequelae, the need for therapeutic options is high and should be the focus of future research.