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Background: Despite therapeutic hypothermia (TH) and neonatal intensive care, 45–50% of children affected by moderate-to-severe neonatal hypoxic-ischemic encephalopathy (HIE) die or suffer from long-term neurodevelopmental impairment. Additional neuroprotective therapies are sought, besides TH, to further improve the outcome of affected infants. Allopurinol — a xanthine oxidase inhibitor — reduced the production of oxygen radicals and subsequent brain damage in pre-clinical and preliminary human studies of cerebral ischemia and reperfusion, if administered before or early after the insult. This ALBINO trial aims to evaluate the efficacy and safety of allopurinol administered immediately after birth to (near-)term infants with early signs of HIE. Methods/design: The ALBINO trial is an investigator-initiated, randomized, placebo-controlled, double-blinded, multi-national parallel group comparison for superiority investigating the effect of allopurinol in (near-)term infants with neonatal HIE. Primary endpoint is long-term outcome determined as survival with neurodevelopmental impairment versus death versus non-impaired survival at 2 years. Results: The primary analysis with three mutually exclusive responses (healthy, death, composite outcome for impairment) will be on the intention-to-treat (ITT) population by a generalized logits model according to Bishop, Fienberg, Holland (Bishop YF, Discrete Multivariate Analysis: Therory and Practice, 1975) and."will be stratified for the two treatment groups. Discussion: The statistical analysis for the ALBINO study was defined in detail in the study protocol and implemented in this statistical analysis plan published prior to any data analysis. This is in accordance with the Declaration of Helsinki and the International Conference on Harmonization Good Clinical Practice guidelines. Trial registration: ClinicalTrials.gov NCT03162653. Registered on 22 May 2017. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effect of fetal growth restriction (FGR) on cerebrovascular autoregulation in preterm neonates during the first 3 days of life.Design: Case-control study.Setting: Neonatal intensive care unit of the Wilhelmina Children's Hospital, The Netherlands.Patients: 57 FGR (birth weight <10th percentile) and 57 appropriate for gestational age (AGA) (birth weight 20th-80th percentiles) preterm neonates, matched for gender, gestational age, respiratory and blood pressure support.Methods: The correlation between continuously measured mean arterial blood pressure and regional cerebral oxygen saturation was calculated to generate the cerebral oximetry index (COx). Mean COx was calculated for each patient for each postnatal day. The percentage of time with impaired autoregulation (COx>0.5) was also calculated.Results: FGR neonates had higher mean COx values than their AGA peers on day 2 (0.15 (95% CI 0.11 to 0.18) vs 0.09 (95% CI 0.06 to 0.13), p=0.029) and day 3 (0.17 (95% CI 0.13 to 0.20) vs 0.09 (95% CI 0.06 to 0.12), p=0.003) of life. FGR neonates spent more time with impaired autoregulation (COx value >0.5) than controls on postnatal day 2 (19% (95% CI 16% to 22%) vs 14% (95% CI 12% to 17%), p=0.035) and day 3 (20% (95% CI 17% to 24%) vs 15% (95% CI 12% to 18%), p=0.016).Conclusion: FGR preterm neonates more frequently display impaired cerebrovascular autoregulation compared with AGA peers on days 2 and 3 of life which may predispose them to brain injury. Further studies are required to investigate whether this impairment persists beyond the first few days of life and whether this impairment is linked to poor neurodevelopmental outcome. [ABSTRACT FROM AUTHOR]

Background: Animal models suggest that neuroprotective effects of therapeutic hypothermia (TH) after perinatal asphyxia are reduced in infants with early-onset sepsis., Objectives: To assess the outcome of infants with perinatal asphyxia, neonatal encephalopathy, and TH in the presence of early-onset sepsis., Methods: In a retrospective cohort of 1,084 infants with perinatal asphyxia and TH, the outcome of 42 infants (gestational age 36.1-42.6 weeks and birth weight 2,280-5,240 g) with proven sepsis (n = 14) and probable sepsis (n = 28) was analyzed. Death, cerebral palsy, or a delayed development at 2 years was considered an adverse outcome., Results: Sepsis was caused mostly by group B streptococci (n = 17), other Gram-positive bacteria (n = 5), and Candida albicans (n = 1). Of the 42 infants, 9 (21.4%) died, and 5 (11.9%) showed impairments on follow-up. The outcome is comparable to the previously reported outcome of infants with TH without early-onset sepsis., Conclusion: A good outcome was reported in the majority of infants with perinatal asphyxia, TH, and early-onset sepsis. Cooling should not be withheld from these infants., (© 2018 The Author(s) Published by S. Karger AG, Basel.)

Background: Therapeutic hypothermia was introduced in the Netherlands and Flanders, Belgium, in 2008. Since then, an increasing number of patients has been treated - up to 166 in 2010. Complications and outcome were registered in an online database., Objectives: The aim of this study was to analyse complications and outcome after implementation., Methods: Data were retrieved from an online database to which all centres had contributed., Results: In 3 years, 332 patients were treated. Excluding 24 patients with congenital abnormalities or metabolic disorders, mortality was 31.8%. Of the 210 survivors without congenital malformations, 21 had cerebral palsy, another 19 a developmental delay of more than 3 months at the age of at least 24 months, and 2 had severe hearing loss. The total adverse outcome, combining death and adverse neurodevelopment, in 308 patients without congenital malformations is 45.5%, which is similar to that of the large trials., Conclusions: The introduction of therapeutic hypothermia for neonates with perinatal asphyxia in the Netherlands and Flanders has been rapid and successful, with results similar to findings in the randomised controlled trials., (Copyright © 2013 S. Karger AG, Basel.)