Absence of neural speech discrimination in preterm infants at term-equivalent age

Children born preterm are at higher risk to develop language deficits. Auditory speech discrimination deficits may be early signs for language developmental problems. The present study used functional near-infrared spectroscopy to investigate neural speech discrimination in 15 preterm infants at term-equivalent age compared to 15 full term neonates. The full term group revealed a significantly greater hemodynamic response to forward compared to backward speech within the left hemisphere extending from superior temporal to inferior parietal and middle and inferior frontal areas. In contrast, the preterm group did not show differences in their hemodynamic responses during forward versus backward speech, thus, they did not discriminate speech from non-speech. Groups differed significantly in their responses to forward speech, whereas they did not differ in their responses to backward speech. The significant differences between groups point to an altered development of the functional network underlying language acquisition in preterm infants as early as in term-equivalent age

Effect of allopurinol in addition to hypothermia treatment in neonates for hypoxic-ischemic brain injury on neurocognitive outcome (ALBINO): Study protocol of a blinded randomized placebo-controlled parallel group multicenter trial for superiority (phase III)

Background: Perinatal asphyxia and resulting hypoxic-ischemic encephalopathy is a major cause of death and long-term disability in term born neonates. Up to 20,000 infants each year are affected by HIE in Europe and even more in regions with lower level of perinatal care. The only established therapy to improve outcome in these infants is therapeutic hypothermia. Allopurinol is a xanthine oxidase inhibitor that reduces the production of oxygen radicals as superoxide, which contributes to secondary energy failure and apoptosis in neurons and glial cells after reperfusion of hypoxic brain tissue and may further improve outcome if administered in addition to therapeutic hypothermia. Methods: This study on the effects of ALlopurinol in addition to hypothermia treatment for hypoxic-ischemic Brain Injury on Neurocognitive Outcome (ALBINO), is a European double-blinded randomized placebo-controlled parallel group multicenter trial (Phase III) to evaluate the effect of postnatal allopurinol administered in addition to standard of care (including therapeutic hypothermia if indicated) on the incidence of death and severe neurodevelopmental impairment at 24 months of age in newborns with perinatal hypoxic-ischemic insult and signs of potentially evolving encephalopathy. Allopurinol or placebo will be given in addition to therapeutic hypothermia (where indicated) to infants with a gestational age 65 36 weeks and a birth weight 65 2500 g, with severe perinatal asphyxia and potentially evolving encephalopathy. The primary endpoint of this study will be death or severe neurodevelopmental impairment versus survival without severe neurodevelopmental impairment at the age of two years. Effects on brain injury by magnetic resonance imaging and cerebral ultrasound, electric brain activity, concentrations of peroxidation products and S100B, will also be studied along with effects on heart function and pharmacokinetics of allopurinol after iv-infusion. Discussion: This trial will provide data to assess the efficacy and safety of early postnatal allopurinol in term infants with evolving hypoxic-ischemic encephalopathy. If proven efficacious and safe, allopurinol could become part of a neuroprotective pharmacological treatment strategy in addition to therapeutic hypothermia in children with perinatal asphyxia. Trial registration: NCT03162653, www.ClinicalTrials.gov, May 22, 2017

Functional maturation in preterm infants measured by serial recording of cortical activity

Minimally invasive, automated cot-side tools for monitoring early neurological development can be used to guide individual treatment and benchmark novel interventional studies. We develop an automated estimate of the EEG maturational age (EMA) for application to serial recordings in preterm infants. The EMA estimate was based on a combination of 23 computational features estimated from both the full EEG recording and a period of low EEG activity (46 features in total). The combination function (support vector regression) was trained using 101 serial EEG recordings from 39 preterm infants with a gestational age less than 28 weeks and normal neurodevelopmental outcome at 12 months of age. EEG recordings were performed from 24 to 38 weeks post-menstrual age (PMA). The correlation between the EMA and the clinically determined PMA at the time of EEG recording was 0.936 (95% CI: 0.932-0.976; n = 39). All infants had an increase in EMA between the first and last EEG recording and 57/62 (92%) of repeated measures within an infant had an increasing EMA with PMA of EEG recording. The EMA is a surrogate measure of age that can accurately determine brain maturation in preterm infants.Peer reviewe

Accent discrimination abilities during the first days of life: An fNIRS study

Humans are biologically endowed with the faculty of language. However, the way neonates can crack this complex communicative code is yet not totally understood. While phonetic discrimination has been widely investigated in neonates, less is known about the role of supra-segments patterns in the recognition of native language. Therefore, the aim of this study was to evaluate accent discrimination abilities in newborns in a sentential prosody paradigm. We used near-infared spectroscopy to investigate accent discrimination in 21 full-term born infants within the first days of life. Sentential prosody was used to investigate: (a) native accent, (b) foreign accent, and (c) flattened accent. Neonates revealed a significantly smaller hemodynamic response to native accent compared to flattened accent and foreign accent, respectively. Cluster-based permutation analysis revealed two clusters with a significant difference between the two conditions native accent and foreign accent. The first cluster covered the middle and superior frontal, middle and superior temporal, central, and parietal areas within the left hemisphere. The second cluster, located in the right hemisphere, covered inferior, middle, and superior frontal, central, middle and superior temporal areas. We therefore conclude that neonates can differentiate prosodic features like accents within the same language a few days after birth

Neonatal seizures—Are we there yet?

Neonatal seizures are the most prevalent and distinctive sign of neurologic dysfunction in early life and pose an immense challenge for clinicians. Improvements in neonatal care have increased the survival rate of extremely premature infants, considerably changing the spectrum of underlying etiologies, and instigating a gradual shift from mortality to morbidity. Recognizing neonatal seizures can be challenging due to variability in presentation but clinical features can often provide valuable clues about etiology. Yet, the majority of neonatal seizures are subclinical. Even though conventional electroencephalography (EEG) with simultaneous video detection of seizures still represents the diagnostic gold standard, continuous monitoring using a one- to two-channel amplitude-integrated EEG with concurrent unprocessed EEG can be crucial for early recognition and intervention. Furthermore, tremendous progress has been made in neuroimaging, and all infants with seizures should have a magnetic resonance imaging (MRI) to help identify the underlying etiology. While the majority of neonatal seizures are caused by hypoxic-ischemic events, stroke, hemorrhage, or infection, approximately 15% of patients will require more sophisticated algorithms for diagnostic workup, including metabolic and genetic screening. These recent developments have led to renew interest in the classification of neonatal seizures, which aim to help identify etiology and guide appropriate therapeutic and prognostic decisions. In this review, we outline recent progress made in the etiology, diagnosis, and treatment of neonatal seizures and highlight areas that deserve further research

A Mixed Lipid Emulsion Containing Fish Oil and Its Effect on Electrophysiological Brain Maturation in Infants of Extremely Low Birth Weight: A Secondary Analysis of a Randomized Clinical Trial

Objective To assess whether parenteral nutrition for infants of extremely low birth weight using a mixed lipid emulsion that contains fish oil influences electrophysiological brain maturation. Study design The study is a prespecified secondary outcome analysis of a randomized controlled trial of 230 infants of extremely low birth weight receiving a mixed (soybean oil, medium-chain triglycerides, olive oil, and fish oil; intervention) or a soybean oil−based lipid emulsion (control). The study was conducted at a single-level IV neonatal care unit (Medical University Vienna; June 2012 to October 2015). Electrophysiological brain maturation (background activity, sleep−wake cycling, and brain maturational scores) was assessed biweekly by amplitude-integrated electroencephalography (birth to discharge). Results A total of 317 amplitude-integrated electroencephalography measurements (intervention: n = 165; control: n = 152) from 121 (intervention: n = 63; control: n = 58) of 230 infants of the core study were available for analysis. Demographic characteristics were not significantly different. By 28 weeks of postmenstrual age, infants receiving the intervention displayed significantly greater percentages of continuous background activity. Total maturational scores and individual scores for continuity, cycling, and bandwidth were significantly greater. Maximum maturational scores were reached 2 weeks earlier in the intervention group (36.4 weeks, 35.4-37.5) compared with the control group (38.4 weeks, 37.1-42.4) (median, IQR; P < .001). Conclusions Using a mixed parenteral lipid emulsion that contains fish oil, we found that electrophysiological brain maturation was accelerated in infants who were preterm