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    Complexity of brain signals is associated with outcome in preterm infants. Sortica da Costa Cristine,Placek Michal M,Czosnyka Marek,Cabella Brenno,Kasprowicz Magdalena,Austin Topun,Smielewski Peter Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism A characteristic feature of complex healthy biological systems is the ability to react and adapt to minute changes in the environment. This 'complexity' manifests itself in highly irregular patterns of various physiological measurements. Here, we apply Multiscale Entropy (MSE) analysis to assess the complexity of systemic and cerebral near-infrared spectroscopy (NIRS) signals in a cohort of 61 critically ill preterm infants born at median (range) gestational age of 26 (23-31) weeks, before 24 h of life. We further correlate the complexity of these parameters with brain injury and mortality. Lower complexity index (CoI) of oxygenated haemoglobin (HbO), deoxygenated haemoglobin (Hb) and tissue oxygenation index (TOI) were observed in those infants who developed intraventricular haemorrhage (IVH) compared to those who did not (P = 0.002, P = 0.010 and P = 0.038, respectively). Mean CoI of HbO, Hb and total haemoglobin index (THI) were lower in those infants who died compared to those who survived (P = 0.012, P = 0.004 and P = 0.003, respectively). CoI-HbO was an independent predictor of IVH (P = 0.010). Decreased complexity of brain signals was associated with mortality and brain injury. Measurement of brain signal complexity in preterm infants is feasible and could represent a significant advance in the brain-oriented care. 10.1177/0271678X16687314
    Effects of antenatal magnesium sulfate treatment for neonatal neuro-protection on cerebral oxygen kinetics. Stark Michael J,Hodyl Nicolette A,Andersen Chad C Pediatric research BACKGROUND:The underlying neuro-protective mechanisms of antenatal magnesium sulfate (MgSO(4)) in infants born preterm remain poorly understood. Early neonatal brain injury may be preceded by low cerebral blood flow (CBF) and elevated cerebral fractional tissue oxygen extraction (cFTOE). This study investigated the effect of antenatal MgSO(4) on cerebral oxygen delivery, consumption, and cFTOE in preterm infants. METHODS:CBF and tissue oxygenation index were measured, and oxygen delivery, consumption, and cFTOE calculated within 24 h of birth and at 48 and 72 h of life in 36 infants ≤ 30 wk gestation exposed to MgSO(4) and 29 unexposed infants. RESULTS:Total internal carotid blood flow and cerebral oxygen delivery did not differ between the groups at the three study time-points. Cerebral oxygen consumption and cFTOE were lower in infants exposed to antenatal MgSO(4) (P = 0.012) compared to unexposed infants within 24 h of delivery. This difference was not evident by 48 h of age. Fewer infants in the MgSO(4) group developed P/IVH by 72 h of age (P = 0.03). CONCLUSION:Infants exposed to MgSO(4) had similar systemic and cerebral hemodynamics but lower cFTOE compared to nonexposed. These findings suggest reduced cerebral metabolism maybe a component of the neuro-protective actions of antenatal MgSO(4). 10.1038/pr.2015.96
    EEG maturation and stability of cerebral oxygen extraction in very low birth weight infants. El-Dib M,Govindan R,Aly S,Mohamed M,du Plessis A,Aly H Journal of perinatology : official journal of the California Perinatal Association OBJECTIVE:Fractional cerebral tissue oxygen extraction (FTOE) can be continuously monitored by simultaneous near-infrared spectroscopy (NIRS) and pulse oximetry. The objective of this study is to test the hypothesis that in very low birth weight (VLBW) infants, the more mature EEG activity is, the less variable FTOE is. STUDY DESIGN:A prospective study was conducted on VLBW infants (< 1500 g and ⩽ 34 weeks gestation) without significant brain injury. Simultaneous continuous two-channel electroencephalography (EEG), NIRS and pulse oximetry were recorded. Absolute and relative powers of EEG in the delta, theta, alpha, beta and total frequency bands have been calculated. FTOE variability was calculated on two scales: short scales (3 to 20 s) and long scales (20 to 150 s). FTOE variability was examined against changes in relative spectral power of different EEG bands. RESULT:We evaluated 67 studies performed on 46 VLBW infants. Average study duration was 21.3 ± 5.5 h. Relative power of delta band positively correlated with FTOE short- and long-scale variability (r=0.45, P<0.001; r=0.44, P<0.001, respectively). Relative power of alpha bands negatively correlated with FTOE short- and long-scale variability (r=-0.38, P=0.002; r=-0.42, P<0.001, respectively). These correlations continued to be significant when controlling for sex, small for gestational age, postmenstrual age, being on respiratory support, hemoglobin concentration, systemic oxygen saturation and transcutaneous carbon dioxide tension. CONCLUSION:Increased maturation of EEG activity is associated with decreased variability in cerebral oxygen extraction. The implications of increased variability in FTOE on brain injury in premature infants need further exploration. 10.1038/jp.2015.200
    Brain injury and altered brain growth in preterm infants: predictors and prognosis. Kidokoro Hiroyuki,Anderson Peter J,Doyle Lex W,Woodward Lianne J,Neil Jeffrey J,Inder Terrie E Pediatrics BACKGROUND:To define the nature and frequency of brain injury and brain growth impairment in very preterm (VPT) infants by using MRI at term-equivalent age and to relate these findings to perinatal risk factors and 2-year neurodevelopmental outcomes. METHODS:MRI scans at term-equivalent age from 3 VPT cohorts (n = 325) were reviewed. The severity of brain injury, including periventricular leukomalacia and intraventricular and cerebellar hemorrhage, was graded. Brain growth was assessed by using measures of biparietal width (BPW) and interhemispheric distance. Neurodevelopmental outcome at age 2 years was assessed across all cohorts (n = 297) by using the Bayley Scales of Infant Development, Second Edition (BSID-II) or Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III), and evaluation for cerebral palsy. RESULTS:Of 325 infants, 107 (33%) had some grade of brain injury and 33 (10%) had severe injury. Severe brain injury was more common in infants with lower Apgar scores, necrotizing enterocolitis, inotropic support, and patent ductus arteriosus. Severe brain injury was associated with delayed cognitive and motor development and cerebral palsy. Decreased BPW was related to lower gestational age, inotropic support, patent ductus arteriosus, necrotizing enterocolitis, prolonged parenteral nutrition, and oxygen at 36 weeks and was associated with delayed cognitive development. In contrast, increased interhemispheric distance was related to male gender, dexamethasone use, and severe brain injury. It was also associated with reduced cognitive development, independent of BPW. CONCLUSIONS:At term-equivalent age, VPT infants showed both brain injury and impaired brain growth on MRI. Severe brain injury and impaired brain growth patterns were independently associated with perinatal risk factors and delayed cognitive development. 10.1542/peds.2013-2336
    Comparison of the longitudinal effects of persistent periodic breathing and apnoea on cerebral oxygenation in term- and preterm-born infants. Horne Rosemary S C,Sun Sunjuri,Yiallourou Stephanie R,Fyfe Karinna L,Odoi Alexsandria,Wong Flora Y The Journal of physiology KEY POINTS:Periodic breathing and apnoea were more common in preterm compared to age-matched term-born infants across the first 6 months after term-corrected age. Periodic breathing decreased with age in both term and preterm infants. Apnoea duration was not different between groups; however, the decline in apnoea index with postnatal age observed in the term infants was not seen in the preterm infants. Falls in tissue oxygenation index (brain TOI) associated with apnoeas were greater in the preterm infants at all three ages studied. The clinical significance of falls in brain TOI during periodic breathing and apnoea on neurodevelopmental outcome is unknown and warrants further investigations. ABSTRACT:Periodic breathing and short apnoeas are common in infants, particularly those born preterm, but are thought to be benign. The aim of our study was to assess the incidence and impact of periodic breathing and apnoea on heart rate, oxygen saturation and brain tissue oxygenation index (TOI) in infants born at term and preterm over the first 6 months after term equivalent age. Nineteen term-born infants (38-42 weeks gestational age) and 24 preterm infants (born at 27-36 weeks gestational age) were studied at 2-4 weeks, 2-3 months and 5-6 months post-term-corrected age during sleep. Periodic breathing episodes were defined as three or more sequential apnoeas each lasting ≥3 s and apnoeas as ≥3 s in duration. The mean duration of periodic breathing episodes was longer in term infants than in preterm infants at 2-4 weeks (P < 0.05) and at 5-6 months (P < 0.05); however, the nadir in TOI was significantly less in the term infants at 2-3 months (P < 0.001). Apnoea duration was not different between groups; however, the decline in apnoea index with postnatal age observed in the term infants was not seen in the preterm infants. Falls in TOI associated with apnoeas were greater in the preterm infants at all three ages studied. In conclusion, periodic breathing and short apnoeas were more common in infants born preterm and falls in cerebral oxygenation were greater than in the term group. The clinical significance of this on neurodevelopmental outcome is unknown and warrants further investigations. 10.1113/JP275686
    Cerebral oxygenation in preterm infants receiving transfusion. Jain Deepak,D'Ugard Carmen,Bancalari Eduardo,Claure Nelson Pediatric research BACKGROUND:The influence of severity of anemia and cardiac output (CO) on cerebral oxygenation (CrSO) and on the change in CrSO following packed red blood cell (PRBC) transfusion in preterm infants has not been evaluated. The objectives of the current study were to evaluate the effect of pre-transfusion hemoglobin (Hb) and CO-weighted oxygen delivery index (ODI) on CrSO and on the post-transfusion CrSO change. METHODS:Preterm infants of <32 weeks gestational age (GA) receiving PRBC transfusion were enrolled. Infants received 15 ml/kg PRBC over 3 h. CrSO by near-infrared spectroscopy and CO by electrical velocimetry were recorded for 1 h pre-ransfusion and post transfusion. ODI was defined as pre-transfusion Hb × CO. RESULTS:Thirty infants of 26.6 ± 2.0 weeks GA were studied at 19 ± 12 days. Pre-transfusion Hb was 9.8 ± 0.6 g/dl. Pre-transfusion CrSO correlated with pre-transfusion ODI (R = 0.1528, p = .044) but not with Hb level. The pre-transfusion to post-transfusion CrSO change correlated with pre-transfusion ODI (R = 0.1764, p = .029) but not with Hb level. CrSO increased from 66 ± 6% to 72 ± 7% post transfusion (p < .001), while arterial oxygen saturation, heart rate, and CO did not change. CONCLUSION:In these infants, the pre-transfusion ODI was a better indicator of brain oxygenation and its improvement post transfusion than Hb alone. The role of CO and tissue oxygenation monitoring in assessing the need for transfusion should be evaluated. 10.1038/s41390-018-0266-7
    Bayley-III scales at 12 months of corrected age in preterm infants: Patterns of developmental performance and correlations to environmental and biological influences. Velikos Konstantinos,Soubasi Vasiliki,Michalettou Irene,Sarafidis Kosmas,Nakas Christos,Papadopoulou Vasiliki,Zafeiriou Dimitrios,Drossou Vasiliki Research in developmental disabilities BACKGROUND AND AIMS:Premature infants are at high risk for neurodevelopmental impairment (NDI) even in the absence of known brain complications of prematurity. Evaluation of the effectiveness of therapeutic interventions in association to neurodevelopmental outcome is required to improve or prevent the neurodevelopmental consequences of prematurity. The Bayley-III is currently the most commonly applied measurement tool for assessing early development both in clinical practice and research settings. OBJECTIVE:To evaluate the relationship between known risk factors and early performance on the Bayley Scales of Infant Development-Third Edition at 12 months adjusted age in premature infants. METHODS:Prospective study in a cohort of premature infants with gestational age ≤32 weeks, who underwent comprehensive developmental assessment using the five domains of Bayley Scales, cognitive, language, motor, social emotional and adaptive behavior at 12 months corrected age. Developmental scores were evaluated in relation to environmental influences, therapeutic interventions or practices and complications of prematurity. RESULTS:Composite and Subscale scores for the cognitive, language and motor scales were below the 50th percentile, with no significant differences among them. Scores for the social-emotional and adaptive behavior, which are derived from the parent-report questionnaires, were near the average and significantly higher than the scores derived by the examiners. Multiple regression analyses showed that blood transfusions, apart from severely abnormal head ultrasound, gender, being small for gestational age and duration of invasive mechanical ventilation and oxygen administration were consistently related to neurodevelopmental outcome. CONCLUSIONS:Bayley-III assessments are important for getting early information about development following premature birth. Parents may overestimate children's performance. Neurodevelopmental outcome is related to several environmental, biological or medical conditions associated with prematurity. Adoption of therapeutic strategies targeting known neonatal risk factors could positively affect neurodevelopmental outcome. 10.1016/j.ridd.2015.07.014
    Early prediction of cognitive deficits in very preterm infants using functional connectome data in an artificial neural network framework. He Lili,Li Hailong,Holland Scott K,Yuan Weihong,Altaye Mekibib,Parikh Nehal A NeuroImage. Clinical Investigation of the brain's functional connectome can improve our understanding of how an individual brain's organizational changes influence cognitive function and could result in improved individual risk stratification. Brain connectome studies in adults and older children have shown that abnormal network properties may be useful as discriminative features and have exploited machine learning models for early diagnosis in a variety of neurological conditions. However, analogous studies in neonates are rare and with limited significant findings. In this paper, we propose an artificial neural network (ANN) framework for early prediction of cognitive deficits in very preterm infants based on functional connectome data from resting state fMRI. Specifically, we conducted feature selection via stacked sparse autoencoder and outcome prediction via support vector machine (SVM). The proposed ANN model was unsupervised learned using brain connectome data from 884 subjects in autism brain imaging data exchange database and SVM was cross-validated on 28 very preterm infants (born at 23-31 weeks of gestation and without brain injury; scanned at term-equivalent postmenstrual age). Using 90 regions of interests, we found that the ANN model applied to functional connectome data from very premature infants can predict cognitive outcome at 2 years of corrected age with an accuracy of 70.6% and area under receiver operating characteristic curve of 0.76. We also noted that several frontal lobe and somatosensory regions, significantly contributed to prediction of cognitive deficits 2 years later. Our work can be considered as a proof of concept for utilizing ANN models on functional connectome data to capture the individual variability inherent in the developing brains of preterm infants. The full potential of ANN will be realized and more robust conclusions drawn when applied to much larger neuroimaging datasets, as we plan to do. 10.1016/j.nicl.2018.01.032
    Brain and renal oxygenation measured by NIRS related to patent ductus arteriosus in preterm infants: a prospective observational study. Navikiene Jurate,Virsilas Ernestas,Vankeviciene Ramune,Liubsys Arunas,Jankauskiene Augustina BMC pediatrics BACKGROUND:Patent ductus arteriosus (PDA) is common among preterm neonates. Haemodynamically significant ductus arteriosus (hsPDA) can cause ductal steal and contribute to poor outcomes. Our aim was to evaluate ductus arteriosus patency and significance using two-site near-infrared spectroscopy (NIRS) measurements in preterm infants older than 72 h as a supplemental tool to echocardiography. METHODS:In this prospective observational study, 123 preterm infants (gestational age (GA) < 32 weeks, birth weight < 1500 g) were enrolled. Sixty-four newborns had closed ductus arteriosus (noPDA), and 41 and 18 patients were assigned to the PDA and hsPDA groups, respectively, per predefined echocardiographic criteria. Cerebral and renal oxygenation were assessed during NIRS monitoring. RESULTS:A higher renal mean (±SD) regional tissue oxygen saturation (rSpO) (76.7 (±7.64)) was detected in the noPDA group than in the PDA (71.7 (±9.02)) and hsPDA (67.4 (±13.48)) groups (p < 0.001). Renal fractional tissue oxygen extraction (FTOE) (0.18 (±0.079)) was lower in the noPDA group than in the PDA (0.23 (±0.092)) and hsPDA (0.24 (±0.117))0.117 groups (p = 0.002). Cerebral oxygenation was significantly lower in the hsPDA group (77.0 (±5.16)) than in the noPDA (79.3 (±2.45)) and PDA (79.7 (±2.27)) groups (p = 0.004). There was no significant difference in cerebral fractional tissue oxygen extraction (FTOE) between any of the groups. CONCLUSIONS:Our results suggest that renal oxygenation is affected by ductus patency in preterm infants older than 72 h. Significant differences in cerebral oxygenation were observed between the hsPDA group and the PDA and noPDA groups. TRIAL REGISTRATION:ClinicalTrials.gov Identifier: NCT04295395. Registration date: 4 March 2020. This study was retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04295395 . 10.1186/s12887-021-03036-w
    Carbon Dioxide Fluctuations Are Associated with Changes in Cerebral Oxygenation and Electrical Activity in Infants Born Preterm. Dix Laura Marie Louise,Weeke Lauren Carleen,de Vries Linda Simone,Groenendaal Floris,Baerts Willem,van Bel Frank,Lemmers Petra Maria Anna The Journal of pediatrics OBJECTIVES:To evaluate the effects of acute arterial carbon dioxide partial pressure changes on cerebral oxygenation and electrical activity in infants born preterm. STUDY DESIGN:This retrospective observational study included ventilated infants born preterm with acute fluctuations of continuous end-tidal CO (etCO) as a surrogate marker for arterial carbon dioxide partial pressure, during the first 72 hours of life. Regional cerebral oxygen saturation and fractional tissue oxygen extraction were monitored with near-infrared spectroscopy. Brain activity was monitored with 2-channel electroencephalography. Spontaneous activity transients (SATs) rate (SATs/minute) and interval between SATs (in seconds) were calculated. Ten-minute periods were selected for analysis: before, during, and after etCO fluctuations of ≥5  mm Hg. RESULTS:Thirty-eight patients (mean ± SD gestational age of 29 ± 1.8 weeks) were included, with 60 episodes of etCO increase and 70 episodes of etCO decrease. During etCO increases, brain oxygenation increased (regional cerebral oxygen saturation increased, fractional tissue oxygen extraction decreased; P < .01) and electrical activity decreased (SATs/minute decreased, interval between SATs increased; P < .01). All measures recovered when etCO returned to baseline. During etCO decreases, brain oxygenation decreased (regional cerebral oxygen saturation decreased, fractional tissue oxygen extraction decreased; P < .01) and brain activity increased (SATs/minute increased, P < .05), also with recovery after return of etCO to baseline. CONCLUSION:An acute increase in etCO is associated with increased cerebral oxygenation and decreased brain activity, whereas an acute decrease is associated with decreased cerebral oxygenation and slightly increased brain activity. Combining continuous CO monitoring with near-infrared spectroscopy may enable the detection of otherwise undetected fluctuations in arterial carbon dioxide partial pressure that may be harmful to the neonatal brain. 10.1016/j.jpeds.2017.04.043
    Oxygen radical disease in the newborn, revisited: Oxidative stress and disease in the newborn period. Perez Marta,Robbins Mary E,Revhaug Cecilie,Saugstad Ola D Free radical biology & medicine Thirty years ago, there was an emerging appreciation for the significance of oxidative stress in newborn disease. This prompted a renewed interest in the impact of oxygen therapy for the newborn in the delivery room and beyond, especially in premature infants. Today, the complexity of oxidative stress both in normal regulation and pathology is better understood, especially as it relates to neonatal mitochondrial oxidative stress responses to hyperoxia. Mitochondria are recipients of oxidative damage and have a propensity for oxidative self-injury that has been implicated in the pathogenesis of neonatal lung diseases. Similarly, both intrauterine growth restriction (IUGR) and macrosomia are associated with mitochondrial dysfunction and oxidative stress. Additionally, reoxygenation with 100% O in a hypoxic-ischemic newborn lamb model increased the production of pro-inflammatory cytokines in the brain. Moreover, the interplay between inflammation and oxidative stress in the newborn is better understood because of animal studies. Transcriptomic analyses have found a number of genes to be differentially expressed in murine models of bronchopulmonary dysplasia (BPD). Epigenetic changes have also been detected both in animal models of BPD and premature infants exposed to oxygen. Antioxidant therapy to prevent newborn disease has not been very successful; however, new therapeutic principles, like melatonin, are under investigation. 10.1016/j.freeradbiomed.2019.03.035
    Impact of bradycardia and hypoxemia on oxygenation in preterm infants requiring respiratory support at birth. Bresesti Ilia,Avian Alexander,Bruckner Marlies,Binder-Heschl Corinna,Schwaberger Bernhard,Baik-Schneditz Nariae,Schmölzer Georg,Pichler Gerhard,Urlesberger Berndt Resuscitation AIM OF THE STUDY:Analysis of the impact of bradycardia and hypoxemia on the course of cerebral and peripheral oxygenation parameters in preterm infants in need for respiratory support during foetal-to-neonatal transition. METHODS:The first 15 min after birth of 150 preterm neonates in need for respiratory support born at the Division of Neonatology, Graz (Austria) were analyzed. Infants were divided into different groups according to duration of bradycardia exposure (no Bradycardia, brief bradycardia <2 min, and prolonged bradycardia ≥2 min) and to systemic oxygen saturation (SpO) value at 5 min of life (<80% or ≥80%). Analysis was performed considering the degree of bradycardia alone (step 1) and in association with the presence of hypoxemia (step 2). RESULTS:In step 1, courses of SpO differed significantly between bradycardia groups (p = 0.002), while courses of cerebral regional oxygen saturation (crStO) and cerebral fractional tissue oxygen extraction (cFTOE) were not influenced (p = 0.382 and p = 0.878). In step 2, the additional presence of hypoxemia had a significant impact on the courses of SpO (p < 0.001), crStO (p < 0.001) and cFTOE (p = 0.045). CONCLUSION:Our study shows that the degree of bradycardia has a significant impact on the course of SpO only, but when associated with the additional presence of hypoxemia a significant impact on cerebral oxygenation parameters was seen (crStO, cFTOE). Furthermore, the additional presence of hypoxemia has a significant impact on FiO delivered. Our study emphasizes the importance of HR and SpO during neonatal resuscitation, underlining the relevance of hypoxemia during the early transitional phase. 10.1016/j.resuscitation.2021.05.004
    The effects of short time hyperoxia on glutamate concentration and glutamate transporters expressions in brain of neonatal rats. Zhao Yuwei,Liang Lei,Liu Guanghui,Liu Yongqing,Zheng Hong,Dai Liying Neuroscience letters Preterm infants often suffer from impaired postnatal brain development, and glutamate excitotoxicity is identified as a pivotal mechanism of hyperoxia-induced neurological abnormality. We aimed to investigate the effect of short time hyperoxia on glutamate homeostasis and glutamate transporters expressions in immature brain. Six-day-old (P6) rat pups were exposed to 80% oxygen for 24 h (the hyperoxia group) or placed in atmospheric air (the control group). The concentrations of glutamate and γ-aminobutyric acid (GABA) in immature cerebrum and cerebellum at P7, P14 and P21 were determined by ELISA. The mRNA levels of glutamate transporters including excitatory amino acid transporter 1 (EAAT1), EAAT2, EAAT3, vesicular glutamate transporter 1 (VGLUT1) and VGLUT2 in brain were determined by qPCR. Glutamate accumulation was induced by hyperoxia both in immature cerebrum and cerebellum at P7 but got gradually attenuated at P14 and P21, as evidenced by the changes of glutamate and GABA concentrations. Hyperoxia also induced sustained glutamatic oxidative stress in both cerebrum and cerebellum, as GSH (reduced glutathione) levels in the hyperoxia group were constantly higher than the control group at three examined time-points. Furthermore, at P7, the expressions of all glutamate transporters decreased in both cerebrum and cerebellum except that of EAAT1. At P21, VGLUT2 in cerebrum and EAAT1, EAAT3 and VGLUT2 in cerebellum still displayed significant decrease in expression levels upon hyperoxia stimulation. Taken together, our results indicate that hyperoxia induces glutamate accumulation in brain of rat pups, which is associated with increased oxidative stress and decreased expressions of glutamate transporters. 10.1016/j.neulet.2021.136013
    A neonatal mouse model of intermittent hypoxia associated with features of apnea in premature infants. Cai Jun,Tuong Chi Minh,Gozal David Respiratory physiology & neurobiology A neonatal mouse model of intermittent hypoxia (IH) simulating the recurring hypoxia/reoxygenation episodes of apnea of prematurity (AOP) was developed. C57BL/6 P2 pups were culled for exposure to either intermittent hypoxia or intermittent air as control. The IH paradigms consisted of alternation cycles of 20.9% O2 and either 8.0% or 5.7% O2 every 120 or 140s for 6h a day during daylight hours from day 2 to day 10 postnatally, i.e., roughly equivalent to human brain development in the perinatal period. IH exposures elicited modest to severe decrease in oxygen saturation along with bradycardia in neonatal mice, which were severity-dependent. Hypomyelination in both central and peripheral nervous systems was observed despite the absence of visible growth retardation. The neonatal mouse model of IH in this study partially fulfills the current diagnostic criteria with features of AOP, and provides opportunities to reproduce in rodents some of the pathophysiological changes associated with this disorder, such as alterations in myelination. 10.1016/j.resp.2011.06.003
    Preterm infants with severe brain injury demonstrate unstable physiological responses during maternal singing with music therapy: a randomized controlled study. Epstein Shulamit,Bauer Sofia,Levkovitz Stern Orly,Litmanovitz Ita,Elefant Cochavit,Yakobson Dana,Arnon Shmuel European journal of pediatrics Preterm infants with severe brain injury are at high risk for poor outcomes and, therefore, may benefit from developmental care modalities such as music therapy (MT). In this prospective, randomized intervention, preterm infants with severe brain injury (grade 3 or 4 intraventricular hemorrhage or periventricular leukomalacia) who underwent skin-to-skin contact (SSC) with or without maternal singing during MT were evaluated for physiological responses, including autonomic nervous system stability (low frequency (LF)/high frequency (HF) power), heart rate, respiratory rate, oxygen saturation, and behavioral state. Maternal anxiety state and physiological data were also evaluated. A total of 35 preterm infants with severe brain injuries were included in the study analysis. Higher mean ± standard deviation (SD) LF/HF ratio (1.8 ± 0.7 vs. 1.1 ± 0.25, p = 0.01), higher mean ± SD heart rate (145 ± 15 vs. 132 ± 12 beats per minute, p = 0.04), higher median (interquartile range) infant behavioral state (NIDCAP manual for naturalistic observation and the Brazelton Neonatal Behavioral Assessment) score (3 (2-5) vs. 1 (1-3), p = 0.03), and higher mean ± SD maternal anxiety (state-trait anxiety inventory) score (39.1 ± 10.4 vs. 31.5 ± 7.3, p = 0.04) were documented in SSC combined with maternal singing during MT, as compared to SSC alone.Conclusion: Maternal singing during MT for preterm infants with severe brain injury induces physiological and behavioral instability and increases maternal anxiety during NICU hospitalization. A unique MT intervention should be designed for preterm infants with severe brain injury and their mothers. What is Known: • Preterm infants with severe brain injury are at high risk for poor outcomes. • Music therapy benefits brain development of preterm infants without severe brain injury, however it is unknown whether maternal singing during music therapy for preterm infants with severe brain injury is beneficial. What is New: • Maternal singing during music therapy for preterm infants with severe brain injury induces physiological and behavioral instability and increases maternal anxiety during NICU hospitalization. • A unique music therapy intervention should be designed for preterm infants with severe brain injury and their mothers. 10.1007/s00431-020-03890-3
    Perinatal Hyperoxia and Developmental Consequences on the Lung-Brain Axis. Obst Stefanie,Herz Josephine,Alejandre Alcazar Miguel A,Endesfelder Stefanie,Möbius Marius A,Rüdiger Mario,Felderhoff-Müser Ursula,Bendix Ivo Oxidative medicine and cellular longevity Approximately 11.1% of all newborns worldwide are born preterm. Improved neonatal intensive care significantly increased survival rates over the last decades but failed to reduce the risk for the development of chronic lung disease (i.e., bronchopulmonary dysplasia (BPD)) and impaired neurodevelopment (i.e., encephalopathy of prematurity (EoP)), two major long-term sequelae of prematurity. Premature infants are exposed to relative hyperoxia, when compared to physiological in-utero conditions and, if needed to additional therapeutic oxygen supplementation. Both are associated with an increased risk for impaired organ development. Since the detrimental effects of hyperoxia on the immature retina are known for many years, lung and brain have come into focus in the last decade. Hyperoxia-induced excessive production of reactive oxygen species leading to oxidative stress and inflammation contribute to pulmonary growth restriction and abnormal neurodevelopment, including myelination deficits. Despite a large body of studies, which unraveled important pathophysiological mechanisms for both organs at risk, the majority focused exclusively either on lung or on brain injury. However, considering that preterm infants suffering from BPD are at higher risk for poor neurodevelopmental outcome, an interaction between both organs seems plausible. This review summarizes recent findings regarding mechanisms of hyperoxia-induced neonatal lung and brain injury. We will discuss common pathophysiological pathways, which potentially link both injured organ systems. Furthermore, promises and needs of currently suggested therapies, including pharmacological and regenerative cell-based treatments for BPD and EoP, will be emphasized. Limited therapeutic approaches highlight the urgent need for a better understanding of the mechanisms underlying detrimental effects of hyperoxia on the lung-brain axis in order to pave the way for the development of novel multimodal therapies, ideally targeting both severe preterm birth-associated complications. 10.1155/2022/5784146
    Cerebral Oxygenation and Perfusion when Positioning Preterm Infants: Clinical Implications. Jani Pranav R,Lowe Krista,Perdomo Aldo,Wakefield Lorraine,Hinder Murray,Galea Claire,Goyen Traci-Anne,Halliday Robert,Waters Karen Ann,Badawi Nadia,Tracy Mark The Journal of pediatrics OBJECTIVES:To evaluate cerebral tissue oxygenation (cTOI) and cerebral perfusion in preterm infants in supine vs prone positions. STUDY DESIGN:Sixty preterm infants, born before 32 weeks of gestation, were enrolled; 30 had bronchopulmonary dysplasia (BPD, defined as the need for respiratory support and/or supplemental oxygen at 36 weeks of postmenstrual age). Cerebral perfusion, cTOI, and polysomnography were measured in both the supine and prone position with the initial position being randomized. Infants with a major intraventricular hemorrhage or major congenital abnormality were excluded. RESULTS:Cerebral perfusion was unaffected by position or BPD status. In the BPD group, the mean cTOI was higher in the prone position compared with the supine position by a difference of 3.27% (P = .03; 95% CI 6.28-0.25) with no difference seen in the no-BPD group. For the BPD group, the burden of cerebral hypoxemia (cumulative time spent with cTOI <55%) was significantly lower in the prone position (23%) compared with the supine position (29%) (P < .001). In those without BPD, position had no effect on cTOI. CONCLUSIONS:In preterm infants with BPD, the prone position improved cerebral oxygenation and reduced cerebral hypoxemia. These findings may have implications for positioning practices. Further research will establish the impact of position on short- and long-term developmental outcomes. 10.1016/j.jpeds.2021.04.008
    Coupled oxygenation oscillation measured by NIRS and intermittent cerebral activation on EEG in premature infants. Roche-Labarbe N,Wallois F,Ponchel E,Kongolo G,Grebe R NeuroImage Electroencephalography of premature neonates shows a physiological discontinuity of electrical activity during quiet sleep. Near infrared spectroscopy (NIRS) shows spontaneous oscillations of hemoglobin oxygenation and volume. Similar oscillations are visible in term neonates and adults, with NIRS and other functional imaging techniques (fMRI, Doppler, etc.), but are generally thought to result from vasomotion and to be a physiological artifact of limited interest. The origin and possible relationship to neuronal activity of the baseline changes in the NIRS signal have not been established. We carried out simultaneous EEG-NIRS recordings on six healthy premature neonates and four premature neonates presenting neurological distress, to determine whether changes in the concentration of cerebral oxy- and deoxy- and total hemoglobin were related to the occurrence of spontaneous bursts of cerebral electric activity. Bursts of electroencephalographic activity in neonates during quiet sleep were found to be coupled to a transient stereotyped hemodynamic response involving a decrease in oxy-hemoglobin concentration, sometimes beginning a few seconds before the onset of electroencephalographic activity, followed by an increase, and then a return to baseline. This pattern could be either part of the baseline oscillations or superimposed changes to this baseline, influencing its shape and phase. The temporal patterns of NIRS parameters present an unique configuration, and tend to be different between our healthy and pathological subjects. Studies of physiological activities and of the effects of intrinsic regulation on the NIRS signal should increase our understanding of these patterns and EEG-NIRS studies should facilitate the integration of NIRS into the set of clinical tools used in neurology. 10.1016/j.neuroimage.2007.04.002
    Cerebral oxygenation in preterm infants during maternal singing combined with skin-to-skin care. Meder Unoke,Tarjanyi Eszter,Kovacs Kata,Szakmar Eniko,Cseko Anna Judit,Hazay Timea,Belteki Gusztav,Szabo Miklos,Jermendy Agnes Pediatric research BACKGROUND:Our aim was to investigate the effect of music therapy in combination with skin-to-skin care (SSC) on regional cerebral oxygenation (rSO) measured with near-infrared spectroscopy (NIRS) in premature infants and to study physiological stability during the interventions. METHODS:This was a prospective single-center observational cohort study conducted in a tertiary neonatal intensive care unit. The study consisted of four phases: (1) baseline measurements in an incubator for 30 min; (2) quiet SSC for 30 min (SSC-Pre); (3) SSC with live maternal singing accompanied by live guitar music for 20 min (SSC-Music); (4) final quiet SSC for another 30 min (SSC-Post). RESULTS:The primary outcome measure of mean rSO for the 31 preterm infants analyzed showed a significant increase from baseline during SSC-Music (76.87% vs 77.74%, p = 0.04) and SSC-Post (76.87% vs 78.0%, p = 0.03) phases. There were no significant changes observed in heart rate (HR), peripheral oxygen saturation (SpO), and cerebral fractional tissue oxygen extraction (cFTOE). The coefficient of variation (CV) of rSO and SpO decreased during each intervention phase. CONCLUSION:Combining music therapy with SSC appears to be safe in preterm neonates. The impact of the small increase in rSO and reduced variability of SpO and rSO warrants further investigation. IMPACT:Music therapy combined with skin-to-skin care (SSC) is safe in clinically stable premature infants and could be encouraged as part of developmental care. This is the first report where near-infrared spectroscopy (NIRS) was used to detect the simultaneous effect of music therapy and SSC on cerebral rSO in preterm infants. Music therapy with SSC caused a modest increase in rSO and decreased the coefficient of variation of rSO and peripheral oxygen saturation (SpO), which suggest short-term benefits for preterm infants. 10.1038/s41390-020-01235-2
    The Effect of Antenatal Neuroprotective Magnesium Sulfate Treatment on Cerebral Oxygenation in Preterm Infants. Ozer Bekmez Buse,Oğuz Yüksel,Kutman Hayriye Gözde Kanmaz,Uygur Dilek,Canpolat Fuat Emre,Oğuz Serife Suna,Tayman Cüneyt American journal of perinatology OBJECTIVE:Antenatal magnesium sulfate (MgSO) treatment is associated with reduced risk of cerebral palsy in preterm infants. We aimed to investigate whether this treatment leads to any alterations on cerebral hemodynamics which could be detected by near-infrared spectroscopy (NIRS) readings in early postnatal life. STUDY DESIGN:Infants with gestational ages (GAs) ≤ 32 weeks were divided into two groups regarding their exposure to antenatal neuroprotective MgSO treatment or not. NIRS monitoring was performed to all infants, and readings were recorded for 2 hours each day during the first 3 days of life. The primary aim was to compare regional cerebral oxygen saturation (rcSO) and cerebral fractional tissue oxygen extraction (cFTOE) between the groups. RESULTS:Sixty-six infants were exposed to antenatal MgSO, while 64 of them did not. GA and birth weight were significantly lower in the treatment group ( < 0.01). No difference was observed in rcSO and cFTOE levels in the first, second, and the third days of life ( > 0.05). An insignificant reduction in severe intraventricular hemorrhage rates was observed (8 vs. 15%,  = 0.24). CONCLUSION:We could not demonstrate any effect on cerebral oxygenation of preterm infants in early postnatal life that could be attributed to antenatal neuroprotective MgSO treatment. Future studies are warranted to clarify the exact underlying mechanisms of neuroprotection. 10.1055/s-0040-1705148
    Splanchnic-Cerebral Oxygenation Ratio Decreases during Enteral Feedings in Anemic Preterm Infants: Observations under Near-Infrared Spectroscopy. Braski Katherine,Weaver-Lewis Kimberlee,Loertscher Manndi,Ding Qian,Sheng Xiaoming,Baserga Mariana Neonatology BACKGROUND:Anemia is common in premature infants. Due to risks with red blood cell transfusions, many anemic infants are not transfused. The implications of this pathophysiologic status, especially at times of increased metabolic demand (enteral feedings), is not well understood. Near-infrared spectroscopy (NIRS) allows for the noninvasive determination of regional oxygen saturations (rSO2) in tissues such as the brain and mesentery, giving insight into their oxygen sufficiency. OBJECTIVE:We tested the hypothesis that during enteral feedings very low birth weight (VLBW) infants with a hematocrit ≤28% will experience a decrease in splanchnic rSO2 and splanchnic-cerebral oxygenation ratio (SCOR). METHODS:This prospective, observational, 2-centered study included VLBW infants receiving full enteral feedings with a hematocrit ≤28%. Cerebral and splanchnic rSO2 were monitored via NIRS for 24 h. Average values were calculated for periods immediately preceding, during, and after each feeding. SCOR was calculated from these values (rSO2 splanchnic/rSO2 cerebral), and data were analyzed using a linear mixed effect model. RESULTS:Fifty neonates with a median gestational age of 28 weeks (range 23-32), a birth weight of 1,118 ± 284 g (mean ± SD), and a hematocrit of 26 ± 2% (mean ± SD) were studied. During feedings, SCOR decreased significantly from baseline (0.72 ± 0.17 to 0.69 ± 0.17, p = 0.043). With feedings, there was a trend of decreased splanchnic rSO2 (47 ± 11 to 45 ± 10, p = 0.057) and no change in cerebral rSO2 (66 ± 8 to 66 ± 7, p = 0.597). CONCLUSIONS:VLBW infants with a hematocrit ≤28% had a decrease in SCOR and a trend towards decreased splanchnic rSO2 with enteral feedings. 10.1159/000481396
    Cerebral and splanchnic oxygenation during automated control of inspired oxygen (FiO ) in preterm infants. Pediatric pulmonology OBJECTIVES:Our aim in this study was to assess the effect of the Predictive Intelligent Control of Oxygenation (PRICO ) system on cerebral (rSO C) and splanchnic (rSO S) oxygenation in a cohort of preterm infants with frequent desaturations. METHODS:Twenty infants with gestational age <32 weeks (n = 20) were assigned in random sequence to 12 h of automated or manual adjustment of FiO . Over this period, they were studied continuously by near-infrared spectroscopy (NIRS). RESULTS:We found that rSO C [68.0% (60.5%-74.7%) vs. 68.5% (62%-72%); p = .824] and rSO S [27.0% (17.3%-45.7%) vs. 27.0% (15%-53%); p = .878] were similar during automatic and manual control of FiO . Time spent with SpO 90%-95% was higher during the automatic than manual control of FiO , while time spent with SpO <80% or >95% was lower. CONCLUSIONS:Automated control of FiO with PRICO system did not improve brain and splanchnic oxygenation in comparison with manual control in a cohort of preterm infants, but it significantly decreased SpO fluctuations and limited the duration of both hypoxemia and hyperoxemia. 10.1002/ppul.25379
    Reference Value of Brain Tissue Oxygen Saturation in Newborns Immediately After Birth. Kato Ryota,Hosono Shigeharu,Takahashi Syori Advances in experimental medicine and biology The Consensus on Resuscitation Science and Treatment Recommendations indicate the target SpO2 values during the first 10 min of life. There are a few studies of values of brain regional saturation of oxygen (rSO2) in newborns, conventional instruments are large and not suitable for measuring in the delivery room. The purpose of this study was to develop reference values for brain rSO2 up to 10 min after birth and to review the changes in cerebral oxygenation in late preterm and term newborn infants immediately after birth. METHOD:We evaluated both brain rSO2 and SpO2 at 1, 3, 5 and 10 min after birth in 100 neonates. rSO2, was measured at the forehead using a finger-mounted oximeter. This is 1/100 the size of conventional NIRS and can be carried. To measure SpO2, a Radical-7 was used. This study was approved by the institutional review board at our hospital. RESULTS:The gestational age and birth weight were 37.9 ± 1.2 weeks and 2825 ± 429 g, respectively. Eighty-seven infants and 13 infants were term and late preterm infants, respectively, and there were 21 vaginal deliveries and 79 cesarean sections. In all cases, rSO2 levels were measured at 1, 3, 5, and 10 min after birth. For the SpO2 measurements, nine cases at 1 min, 40 cases at 3 min, 81 cases at 5 min and 93 cases at 10 min were available. The median rSO2 level was 43% at 1 min after birth, 48% at 3 min, 52% at 5 min and 57% at 10 min. CONCLUSION:We used a finger-mounted oximeter to observe changes in brain rSO2 values of 100 normal transition infants. It was easier to detect rSO2 in comparison to the peripheral oxygen saturation monitored by our pulse oximeter. Brain rSO2 values might be useful to evaluate oxygenation immediately after birth. 10.1007/978-3-030-34461-0_3
    Changes in cerebral tissue oxygenation and fractional oxygen extraction with gestational age and postnatal maturation in preterm infants. Mohamed Mohamed A,Frasketi Michael J,Aly Safwat,El-Dib Mohamed,Hoffman Heather J,Aly Hany Journal of perinatology : official journal of the California Perinatal Association OBJECTIVE:This study examined the correlation of cerebral tissue oxygen saturation (SctO) and cerebral tissue fractional oxygen extraction (cFTOE) with gestational age (GA) and postnatal age over the first 28 days of life. STUDY DESIGN:Preterm infants with birth weight (BW) <1500 g were monitored with near-infrared spectroscopy (NIRS) during the first 28 days of life. SctO and cFTOE measurements were analyzed using a linear mixed model. RESULTS:A total of 70 preterm infants were included. Mean SctO decreased with increasing GA; SctO was 76.4% and 74.6% in the first 24 h for infants 24 and 28-week GA, respectively. For infants born at 24 and 28 it decreased to 52.9% and 58.4% at 28 days of life, respectively. cFTOE increased with increasing GA and postnatal age. CONCLUSIONS:There is an inverse relationship between SctO and gestational age and postnatal age but a direct relationship between cFTOE with GA and postnatal age. 10.1038/s41372-020-00794-w
    Lower versus higher oxygen concentrations titrated to target oxygen saturations during resuscitation of preterm infants at birth. The Cochrane database of systematic reviews BACKGROUND:Initial resuscitation with air is well tolerated by most infants born at term. However, the optimal fractional inspired oxygen concentration (FiO - proportion of the breathed air that is oxygen) targeted to oxygen saturation (SpO - an estimate of the amount of oxygen in the blood) for infants born preterm is unclear. OBJECTIVES:To determine whether lower or higher initial oxygen concentrations, when titrated according to oxygen saturation targets during the resuscitation of preterm infants at birth, lead to improved short- and long-term mortality and morbidity. SEARCH METHODS:We conducted electronic searches of the Cochrane Central Register of Controlled Trials (13 October 2017), Ovid MEDLINE (1946 to 13 October 2017), Embase (1974 to 13 October 2017) and CINAHL (1982 to 13 October 2017); we also searched previous reviews (including cross-references), contacted expert informants, and handsearched journals. SELECTION CRITERIA:We included randomised controlled trials (including cluster- and quasi-randomised trials) which enrolled preterm infants requiring resuscitation following birth and allocated them to receive either lower (FiO < 0.4) or higher (FiO ≥ 0.4) initial oxygen concentrations titrated to target oxygen saturation. DATA COLLECTION AND ANALYSIS:Two review authors independently assessed the eligibility of studies for inclusion, extracted data and assessed methodological quality. Primary outcomes included mortality near term or at discharge (latest reported) and neurodevelopmental disability. We conducted meta-analysis using a fixed-effect model. We assessed the quality of the evidence using GRADE. MAIN RESULTS:The search identified 10 eligible trials. Meta-analysis of the 10 included studies (914 infants) showed no difference in mortality to discharge between lower (FiO < 0.4) and higher (FiO ≥ 0.4) initial oxygen concentrations targeted to oxygen saturation (risk ratio (RR) 1.05, 95% confidence interval (CI) 0.68 to 1.63). We identified no heterogeneity in this analysis. We graded the quality of the evidence as low due to risk of bias and imprecision. There were no significant subgroup effects according to inspired oxygen concentration strata (FiO 0.21 versus ≥ 0.4 to < 0.6; FiO 0.21 versus ≥ 0.6 to 1.0; and FiO ≥ 0.3 to < 0.4 versus ≥ 0.6 to 1.0). Subgroup analysis identified a single trial that reported increased mortality from use of lower (FiO 0.21) versus higher (FiO 1.0) initial oxygen concentration targeted to a lowest SpO of less than 85%, whereas meta-analysis of nine trials targeting a lowest SpO of 85% to 90% found no difference in mortality.Meta-analysis of two trials (208 infants) showed no difference in neurodevelopmental disability at 24 months between infants receiving lower (FiO < 0.4) versus higher (FiO > 0.4) initial oxygen concentrations targeted to oxygen saturation. Other outcomes were incompletely reported by studies. Overall, we found no difference in use of intermittent positive pressure ventilation or intubation in the delivery room; retinopathy (damage to the retina of the eyes, measured as any retinopathy and severe retinopathy); intraventricular haemorrhage (any and severe); periventricular leukomalacia (a type of white-matter brain injury); necrotising enterocolitis (a condition where a portion of the bowel dies); chronic lung disease at 36 weeks' gestation; mortality to follow up; postnatal growth failure; and patent ductus arteriosus. We graded the quality of the evidence for these outcomes as low or very low. AUTHORS' CONCLUSIONS:There is uncertainty as to whether initiating post birth resuscitation in preterm infants using lower (FiO < 0.4) or higher (FiO ≥ 0.4) oxygen concentrations, targeted to oxygen saturations in the first 10 minutes, has an important effect on mortality or major morbidity, intubation during post birth resuscitation, other resuscitation outcomes, and long-term outcomes including neurodevelopmental disability. We assessed the quality of the evidence for all outcomes as low to very low. Further large, well designed trials are needed to assess the effect of using different initial oxygen concentrations and the effect of targeting different oxygen saturations. 10.1002/14651858.CD010239.pub2
    Effects of Single Loading Dose of Intravenous Caffeine on Cerebral Oxygenation in Preterm Infants. Ilhan Ozkan,Bor Meltem American journal of perinatology OBJECTIVE:The aim of this study was to evaluate the effects of caffeine on cerebral oxygenation in preterm infants. STUDY DESIGN:This was a prospective study of infants with a gestational age (GA) of < 34 weeks who were treated intravenously with a loading dose of 20 mg/kg caffeine citrate within the first 48 hours of life. Regional cerebral oxygen saturation (rSOC) and cerebral fractional tissue oxygen extraction (cFTOE) were measured using near-infrared spectroscopy before administering caffeine (baseline), immediately after administering caffeine, and 1, 2, 3, 4, 6, and 12 hours after dose completion; postdose values were compared with the baseline values. RESULTS:A total of 48 infants with a mean GA of 29.0 ± 1.9 weeks, birth weight of 1,286 ± 301 g, and postnatal age of 32.4 ± 11.3 hours were included in the study. rSOC significantly decreased from 81.3 to 76.7% soon after administering caffeine, to 77.1% at 1 hour, and to 77.8% at 2 hours with recovery at 3 hours postdose. rSOC was 80.2% at 12 hours postdose. cFTOE increased correspondingly. Although rSOC values were lower and cFTOE values were higher compared with the baseline values at 3, 4, 6, and 12 hours after caffeine administration, this was not statistically significant. CONCLUSION:A loading dose of caffeine temporarily reduces cerebral oxygenation and increases cerebral tissue oxygen extraction in preterm infants. Most probably these changes reflect a physiological phenomenon without any clinical importance to the cerebral hemodynamics, as the reduction in cerebral oxygenation and increase in cerebral tissue oxygen extraction remain well within acceptable range. 10.1055/s-0040-1708490
    The hidden consequence of intraventricular hemorrhage: persistent cerebral desaturation after IVH in preterm infants. Vesoulis Zachary A,Whitehead Halana V,Liao Steve M,Mathur Amit M Pediatric research BACKGROUND:Previous studies describe a short-term decrease in cerebral oxygen saturation (StO2) after intraventricular hemorrhage (IVH) in premature infants; little is known about long-term implications. METHODS:Infants born <30 weeks gestational age (GA) were included. Clinical characteristics, hemoglobin measurements, the highest grade of IVH, and white matter injury (WMI) were noted. NIRS monitoring occurred daily or every other day for 4 weeks; weekly through 36 weeks GA. Recordings were error-corrected before calculation of mean StO2 and fractional tissue oxygen extraction (FTOE). Mean StO2 and FTOE were plotted by postnatal age and injury group (IVH/no IVH; WMI/no WMI). Non-linear regression by locally estimated scatterplot smoothing was used to generate the best-fit line and CI. RESULTS:A total of 1237 recordings from 185 infants were included; mean length = 6.5 h; mean GA = 26.3 w; mean BW = 951 g; overall/severe IVH incidence was 29/8%, WMI incidence was 16%. IVH was independently associated with an acute drop in StO2, which remained lower for 68 d. Severe IVH was associated with lower StO2 values than mild IVH. WMI was associated with early and persistent elevation of FTOE. CONCLUSION:IVH of any grade is associated with a prolonged cerebral desaturation and WMI is associated with prolonged elevation of FTOE. This finding is exacerbated for infants with severe IVH. IMPACT:The longitudinal impact of IVH on cerebral oxygenation has not been previously studied. IVH is associated with persistent cerebral desaturation, months in length, and is independent of anemia. More severe IVH is associated with worsened cerebral hypoxia. Infants later diagnosed with white matter injury have an early and persistent elevation of cerebral oxygen extraction (cFTOE). This cerebral desaturation, below previously identified normative ranges, may provide insight into the mechanistic link between IVH and white matter injury. 10.1038/s41390-020-01189-5
    Changes in Cerebral Oxygenation in Preterm Infants With Progressive Posthemorrhagic Ventricular Dilatation. Kochan Michael,McPadden Jacob,Bass William T,Shah Tushar,Brown Wendy T,Tye Gary W,Vazifedan Turaj Pediatric neurology BACKGROUND:Optimal timing of intervention in neonatal progressive posthemorrhagic hydrocephalus is often a difficult decision. Unchecked hydrocephalus can lead to irreversible brain injury through impaired perfusion, while placement of a shunt is not without long-term morbidity. The purpose of this study was to assess the use of near-infrared spectroscopy to measure changes in regional cerebral oxygen saturation as an indicator of cerebral perfusion in infants with progressive posthemorrhagic ventricular dilatation. METHODS:Near-infrared spectroscopy was used to measure regional cerebral oxygen saturation for more than a one-hour period in infants within 24 hours of cranial ultrasound. Simultaneous pulse oximetry was recorded and oxygen extraction was calculated. Ventricular size was measured by ultrasound using the frontal-occipital horn ratio and compared with average oxygen saturation and oxygen extraction. Statistical analysis was done using the Spearman rank test and analysis of variance. RESULTS:Ventricular measurements were made in 20 very low birth weight premature infants with periventricular-intraventricular hemorrhage and 12 infants with normal ultrasound scans. Ventricular dilatation was associated with lower cerebral oxygen saturation and higher oxygen extraction (P < 0.001). Progressive ventricular dilatation was inversely related to changes in cerebral oxygen saturation (P < 0.001). CONCLUSIONS:Progressive posthemorrhagic ventricular dilatation is associated with a significant decrease in cerebral oxygenation and increase in oxygen extraction suggesting a decrease in cerebral perfusion. Near-infrared spectroscopy could potentially provide additional clinical information to assist in determining optimal timing of surgical intervention in preterm infants with progressive ventricular enlargement. 10.1016/j.pediatrneurol.2017.05.012
    Titration of inspired oxygen in preterm infants with hypoxemic respiratory failure using near-infrared spectroscopy and pulse oximetry: A new approach. Elsayed Yasser N,Dakshinamurti Shyamala Pediatric pulmonology BACKGROUND:Titration of inspired oxygen is a challenge in preterm infants with hypoxemic respiratory failure (HRF). Monitoring of brain oxygen by near-infrared spectroscopy (NIRS) has been proven to minimize the burden of hyperoxia and hypoxemia; with a better understanding of cerebral autoregulation, integrating NIRS and pulse oximetry for titrating inspired oxygen in preterm infants is a novel approach. METHODS:We studied the impact of integrated monitoring of oxygen saturation by pulse oximetry (SpO ) and cerebral regional tissue oxygen (crRTO) by NIRS during a stepwise oxygen reduction test (ORT) on reducing oxygen requirement in preterm infants with HRF. The correlation between SpO with crRTO, and fractional oxygen extraction (FOE) was assessed, concordance levels (r > 0.5) were determined during the assessment period and were considered as a sign of impaired autoregulation. The primary outcome was the achievement of significantly lower FiO at 72 h after the start of the integrated monitoring. RESULTS:A total of 38 preterm infants were included, 27 had normal cerebral autoregulation (CAR) (Group 1) in whom SpO was poorly correlating with crRTO with (r < 0.5) and had a significantly greater percentage of reduction below baseline in FiO (mean: 34%). Eleven infants had impaired CAR (Group 2) with SpO significantly correlating with crRTO (r > 0.5) and had a linear trend of FOE inverse to SpO and crRTO; this was considered as an arterial saturation dependent oxygen delivery (SadDO ). CONCLUSION:Integrated monitoring of preterm infants by SpO and crRTO was associated with easier weaning of oxygen with less burden of both hyperoxia and hypoxemia. 10.1002/ppul.25673
    Is low cerebral near infrared spectroscopy oximetry associated with neurodevelopment of preterm infants without brain injury? Journal of perinatal medicine OBJECTIVES:To evaluate the association between low regional cerebral oxygen saturation (rScO2) and neurodevelopment in preterm infants classified as no brain injury (NBI). METHODS:We retrospectively reviewed data of rScO2 monitoring during the first 3 days of life of infants with a gestational age (GA)<28 weeks or birth weight (BW)<1,000 g, with and without brain injury (BI). BI was defined as intraventricular haemorrhage, cystic periventricular leukomalacia or cerebellar haemorrhage. Univariate and multivariate analyses were used to study the association of rScO2<55% for more than 10 h in the first 3 days of life (NIRS<55%) and the 24 months neurodevelopment. RESULTS:Of the 185 patients who met the inclusion criteria, 31% were classified as BI infants and 69% NBI. BI compared to NBI infants had a significantly lower GA and a higher incidence of complications of prematurity. Mean rScO2 in the first 72 h of life was significantly lower in BI than NBI. NIRS<55% in NBI patients was negatively associated with neurodevelopmental scores both at the univariate and multivariate analysis (p<0.05). NBI infants with NIRS<55% were found to have lower systemic oxygenation than their counterparts with rScO2<55% for less than 10 h. CONCLUSIONS:NIRS<55% in NBI small preterm infants was found to be an independent predictor of neurodevelopment at 24 months and it was associated with low systemic saturation values. 10.1515/jpm-2021-0498
    Regional cerebral and splanchnic tissue oxygen saturation in preterm infants - Longitudinal normative measurements. Howarth Claire N,Leung Terence S,Banerjee Jayanta,Eaton Simon,Morris Joan K,Aladangady Narendra Early human development BACKGROUND:To investigate regional splanchnic and cerebral tissue oxygen saturation in preterm infants <30 weeks gestation. METHODS:Cerebral (cTOI) and splanchnic (sTOI) Tissue Oxygenation Index were measured weekly in 5 min epochs for a total period of 60 min using NIRS (NIRO-300) for the first 8 weeks of life, in 48 appropriately grown preterm infants born at <30 weeks gestation. Infants who developed HPI and/or NEC (n = 12) and those that died (n = 1) were excluded from our main outcome measure of regional gut and cerebral tissue oxygenation in healthy preterm infants <30 weeks gestation. RESULTS:Median birthweight 789 g (460-1486), gestational age 25 weeks (23-29) and 51.4% female. 217 NIRS measurements were completed across the first 8 weeks of life. Mean weekly cTOI ranged from 56.8-65.4% and sTOI ranged from 36.7-46.0%. Mean cTOI was significantly higher than mean sTOI (p < 0.001) throughout the first 8 weeks of life. Mean cTOI decreased significantly with increasing postnatal age [-0.59% each week (-1.26% to -0.07%) p = 0.04]. None of the examined confounding factors had a significant effect. CONCLUSIONS:This is the first report of regional cerebral and splanchnic tissue oxygen saturation ranges during the first 8 weeks of life for preterm infants born at <30 weeks gestation. 10.1016/j.earlhumdev.2022.105540
    The effect of head positioning on brain tissue oxygenation in preterm infants: a randomized clinical trial study. Journal of perinatology : official journal of the California Perinatal Association BACKGROUND:CNS injury in preterm infants is still one of the leading causes of mortality and morbidity. Routine care events might affect the perfusion and cerebral oxygenation of preterm infants. Although positioning the infant's head in a particular condition to improve brain oxygenation is included in many institutions, there is no robust clinical evidence to support this intervention's effectiveness. OBJECTIVE:The present study aimed to determine the effect of head positioning on brain tissue oxygenation in preterm infants. METHODS:This study is a randomized clinical trial. In the first 48 h after birth, 39 infants who met the study inclusion criteria underwent head positioning intervention. In this case, the infants were placed in the supine position, and every 2 h, the head position was changed continuously to one of six randomized modes [using random modes generated by SPSS]. During each head positioning, brain tissue oxygenation was recorded by NIRS. RESULTS:The findings showed a significant difference in brain tissue oxygen saturation among these positions (P < 0.001). Dunn's test showed that the brain tissue oxygen saturation in the third position (head rotates 45-60 degrees from the midline to the right and the head of the bed is zero degrees) was significantly lower than the baseline (P = 0.029; Mean difference = 2.3). Also, in the third position, compared to the first position (P = 0.002; Mean difference = 1.9) and compared to the fourth position (P = 0.003; Mean difference = -2.1), and in the second position compared to the first position (P = 0.046; Mean difference = 1.3), the brain tissue oxygen saturation of the infants was lower. CONCLUSION:Based on the results of the present study, head positioning was effective on brain tissue oxygenation in preterm infants in the first 48 h after birth; Therefore, it is recommended when possible, not to rotate the infant's head during the first 48 h after birth while the head of the bed is at 0°. 10.1038/s41372-022-01366-w
    Cerebral and mesenteric tissue oxygenation by positional changes in very low birth weight premature infants. Demirel Gamze,Oguz Serife Suna,Celik Istemi Han,Erdeve Omer,Dilmen Ugur Early human development AIM:There has been no clear consensus of the appropriate positioning in preterm infants. We aimed to evaluate the changes of cerebral and mesenteric tissue oxygenation in three different positions, by near infrared spectroscopy (NIRS), in stable very low birth weight (VLBW) infants of postnatal >30 days. METHODS:NIRS monitoring of cerebral and mesenteric tissue oxygenation in three different positions was performed in 29 stable preterm newborns in neonatal intensive care unit (NICU). The patients were observed in three different positions consecutively, each lasting for 4h. The demographic features, cerebral and mesenteric tissue oxygenation with positional changes and feeding periods were recorded. RESULTS:Mean gestational age, mean birth weight and mean postnatal age of the patients were 27.6±1.7 weeks, 1046±308 g and 42.4±15.7 days, respectively. There were no statistically significant differences in cerebral and mesenteric tissue regional SO(2) values in each position (p=0.954 and p=0.151, respectively). The values of cerebral and mesenteric tissue regional SO(2) before and after feeding did not show any statistically significant difference in each position. CONCLUSIONS:Clinically stable very low birth weight infants are able to maintain a stable cerebral and mesenteric tissue oxygenation in different positions, both before and after feeding. Positional changes seem to be safe in VLBW stable infants and this influence should be considered in care of these patients in the NICU. Clinical Trials Identification Number: NCT01255189. 10.1016/j.earlhumdev.2011.10.005
    Recording of amplitude-integrated electroencephalography, oxygen saturation, pulse rate, and cerebral blood flow during massage of premature infants. Rudnicki Jacek,Boberski Marek,Butrymowicz Ewa,Niedbalski Paweł,Ogniewski Paweł,Niedbalski Marek,Niedbalski Zbigniew,Podraza Wojciech,Podraza Hanna American journal of perinatology OBJECTIVE:Stimulation of the nervous system plays an important role in brain function and psychomotor development of children. Massage can benefit premature infants, but has limitations. STUDY DESIGN:The authors conducted a study to verify the direct effects of massage on amplitude-integrated electroencephalography (aEEG), oxygen saturation (SaO(2)), and pulse analyzed by color cerebral function monitor (CCFM) and cerebral blood flow assessed by the Doppler technique. RESULTS:The amplitude of the aEEG trend during massage significantly increased. Massage also impacted the dominant frequency δ waves. Frequency significantly increased during the massage and return to baseline after treatment. SaO(2) significantly decreased during massage. In four premature infants, massage was discontinued due to desaturation below 85%. Pulse frequency during the massage decreased but remained within physiological limits of greater than 100 beats per minute in all infants. Doppler flow values in the anterior cerebral artery measured before and after massage did not show statistically significant changes. Resistance index after massage decreased, which might provide greater perfusion of the brain, but this difference was not statistically significant. CONCLUSION:Use of the CCFM device allows for monitoring of three basic physiologic functions, namely aEEG, SaO(2), and pulse, and increases the safety of massage in preterm infants. 10.1055/s-0032-1310529
    Features of cerebral oxygenation detects brain injury in premature infants. O'Toole John M,Kenosi Mmoloki,Finn Daragh,Boylan Geraldine B,Dempsey Eugene M Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference Babies born prematurely can develop brain injury within days after birth. Early identification of high-risk infants enables appropriate clinical care to mitigate potential lifelong disabilities. Near infra-red spectroscopy is an established technology that can provide continuous measurements of cerebral oxygen saturation (rcSO) over this critical period. We develop a feature set of the rcSO signal for the purpose of detecting brain injury. Our feature set contains amplitude, spectral, and fractal dimension features within 5 frequency bands. Features are combined in a support vector machine (SVM) and performance is assessed within a cross-validation procedure. Using a cohort of 47 infants of <;32 weeks of gestation, we find significant (p <; 0.05) features of amplitude in the frequency band 0.9-3.6 mHz and a fractal dimension measure in the frequency band 1.8-3.6 mHz. The SVM has an area-under the receiver operator characteristic (AUC) of 0.75 with sensitivity-specificity values of 67-77%. These moderate results highlight the potential for quantitative analysis of rcSO to detect brain injury and thus enable early identification of high-risk infants. 10.1109/EMBC.2016.7591510
    Changes in Oxygenation Levels Precede Changes in Amplitude of the EEG in Premature Infants. Caicedo Alexander,Thewissen Liesbeth,Smits Anne,Naulaers Gunnar,Allegaert Karel,Van Huffel Sabine Advances in experimental medicine and biology Brain function is supported by an appropriate balance between the metabolic demand and the supply of nutrients and oxygen. However, the physiological principles behind the regulation of brain metabolism and demand in premature infants are unknown. Some studies found that changes in hemodynamic variables in this population precede changes in EEG activity; however, these studies only used descriptive statistics. This paper describes the relationship between changes in cerebral oxygenation, assessed by means of near-infrared spectroscopy (NIRS), and changes in EEG, using mathematical methods taken from information dynamics. In a cohort of 35 neonates subjected to sedation by propofol, we quantified the direction of information transfer between brain oxygenation and EEG. The results obtained indicate that, as reported in other studies, changes in NIRS are likely to precede changes in EEG activity. 10.1007/978-3-319-38810-6_19
    Association of Bolus Feeding With Splanchnic and Cerebral Oxygen Utilization Efficiency Among Premature Infants With Anemia and After Blood Transfusion. Balegar V Kiran Kumar,Jayawardhana Madhuka,Martin Andrew J,de Chazal Philip,Nanan Ralph K H JAMA network open Importance:The pathogenesis of transfusion-associated necrotizing enterocolitis remains elusive. Splanchnic hypoperfusion associated with packed red blood cell transfusion (PRBCT) and feeding has been implicated, but studies of splanchnic tissue oxygenation with respect to feeding plus PRBCT are lacking. Objective:To investigate the oxygen utilization efficiency of preterm gut and brain challenged with bolus feeding during anemia and after transfusion using near-infrared spectroscopy. Design, Setting, and Participants:This prospective cohort study conducted from September 1, 2014, to November 30, 2016, at a tertiary neonatal intensive care unit included 25 hemodynamically stable infants with gestational age less than 32 weeks, birth weight less than 1500 g, and postmenstrual age younger than 37 weeks. Data analysis was performed from August 1, 2017, to October 31, 2018. Exposures:Infants received PRBCT (15 mL/kg for 4 hours) and at least 120 mL/kg daily of second hourly bolus feedings. Main Outcomes and Measures:Splanchnic fractional tissue oxygen extraction (FTOEs) and cerebral fractional tissue oxygen extraction (FTOEc) measures were made during 75-minute feeding cycles that comprised a 15-minute preprandial feeding phase (FP0) and 4 contiguous 15-minute postprandial feeding phases (FP1, FP2, FP3, and FP4; each 15 minutes long). The intraindividual comparisons of feeding-related changes were evaluated during the pretransfusion epoch (TE0: 4 hours before onset of transfusion) and 3 TEs after transfusion (TE1: first 8 hours after PRBCT completion; TE2: 9-16 hours after PRBCT completion; and TE3: 17-24 hours after PRBCT completion). Results:Of 25 enrolled infants (13 [52%] female; median birth weight, 949 g [interquartile range {IQR}, 780-1100 g]; median gestational age, 26.9 weeks [IQR, 25.9-28.6 weeks]; median enrollment weight, 1670 g [IQR, 1357-1937 g]; and median postmenstrual age, 34 weeks [IQR, 32.9-35 weeks]), 1 infant was excluded because of corrupted near-infrared spectroscopy data. No overall association was found between FTOEs and FPs in a multivariable repeated-measures model that accounted for transfusion epochs (primary analysis approach) (FP0: mean estimate, 11.64; 95% CI, 9.55-13.73; FP1: mean estimate, 12.02; 95% CI, 9.92-14.11; FP2: mean estimate, 12.77; 95% CI, 10.68-14.87; FP3: mean estimate, 12.54; 95% CI, 10.45-14.64; FP4: mean estimate, 12.98; 95% CI, 10.89-15.08; P = .16 for the FP association). However exploratory analyses of postprandial changes in FTOEs undertaken for each transfusion epoch separately found evidence of increased postprandial FTOEs during TE1 (mean [SD] FTOEs, 10.55 [5.5] at FP0 vs 13.21 [5.96] at FP4, P = .046). The primary and exploratory analyses found no association between FTOEc and feeding phases, suggesting that cerebral oxygenation may be protected. Conclusions and Relevance:The findings suggest that enteral feeding may be associated with gut ischemia and potentially transfusion-associated necrotizing enterocolitis. The postprandial changes in FTOEs appear to warrant further investigation in larger randomized studies. 10.1001/jamanetworkopen.2020.0149
    The Effects of Rso2 and PI Monitoring Images on the Treatment of Premature Infants Based on Deep Learning. Li Junran,Ma Jing,Liu Sudan,Qiao Yanxia,Shen Cuncun,Qiu Jingjing,Zhang Ming,He Lanlan,Fan Tao Computational and mathematical methods in medicine In recent years, due to the combined effects of individual behavior, psychological factors, environmental exposure, medical conditions, biological factors, etc., the incidence of preterm birth has gradually increased, so the incidence of various complications of preterm infants has also become higher and higher. This article is aimed at studying the therapeutic effects of preterm infants and proposing the application of rSO2 and PI image monitoring based on deep learning to the treatment of preterm infants. This article introduces deep learning, blood perfusion index, preterm infants, and other related content in detail and conducts experiments on the treatment of rSO2 and PI monitoring images based on deep learning in preterm infants. The experimental results show that the rSO2 and PI monitoring images based on deep learning can provide great help for the treatment of preterm infants and greatly improve the treatment efficiency of preterm infants by at least 15%. 10.1155/2022/5671713
    Cerebral regional tissue Oxygen Saturation to Guide Oxygen Delivery in preterm neonates during immediate transition after birth (COSGOD III): an investigator-initiated, randomized, multi-center, multi-national, clinical trial on additional cerebral tissue oxygen saturation monitoring combined with defined treatment guidelines versus standard monitoring and treatment as usual in premature infants during immediate transition: study protocol for a randomized controlled trial. Trials BACKGROUND:Transition immediately after birth is a complex physiological process. The neonate has to establish sufficient ventilation to ensure significant changes from intra-uterine to extra-uterine circulation. If hypoxia or bradycardia or both occur, as commonly happens during immediate transition in preterm neonates, cerebral hypoxia-ischemia may cause perinatal brain injury. The primary objective of the COSGOD phase III trial is to investigate whether it is possible to increase survival without cerebral injury in preterm neonates of less than 32 weeks of gestation by targeting cerebral tissue oxygen saturation (crSO) using specified clinical treatment guidelines during the immediate transition period after birth (the first 15 min) in addition to the routine monitoring of arterial oxygen saturation (SpO) and heart rate (HR). METHODS/DESIGN:COSGOD III is an investigator-initiated, randomized, multi-center, multi-national, phase III clinical trial. Inclusion criteria are neonates of less than 32 weeks of gestation, decision to provide full life support, and parental informed consent. Exclusion criteria are severe congenital malformations of brain, heart, lung, or prenatal cerebral injury or a combination of these. The premature infants will be randomly assigned to study or control groups. Both groups will have a near-infrared spectroscopy (NIRS) device (left frontal), pulse oximeter (right palm/wrist), and electrocardiogram placed immediately after birth. In the study group, the crSO, SpO, and HR readings are visible, and the infant will receive treatment in accordance with defined treatment guidelines. In the control group, only SpO and HR will be visible, and the infant will receive routine treatment. The intervention period will last for the first 15 min after birth during the immediate transition period and resuscitation. Thereafter, each neonate will be followed up for primary outcome to term date or discharge. The primary outcome is mortality or cerebral injury (or both) defined as any intra-ventricular bleeding or cystic periventricular leukomalacia (or both). Secondary outcomes are neonatal morbidities. DISCUSSION:crSO monitoring during immediate transition has been proven to be feasible and improve cerebral oxygenation during immediate transition. The additional monitoring of crSO with dedicated interventions may improve outcome of preterm neonates as evidenced by increased survival without cerebral injury. TRIAL REGISTRATION:ClinicalTrials.gov Identifier: NCT03166722 . Registered March 5, 2017. 10.1186/s13063-019-3258-y
    Brain Maturity and Variation of Oxygen Extraction in Premature Infants. El-Dib Mohamed,Aly Safwat,Govindan Rathinaswamy,Mohamed Mohamed,du Plessis Adre,Aly Hany American journal of perinatology Objectives The ability of the premature brain to extract and use oxygen has not been studied adequately. This study aimed to determine factors that influence fractional tissue oxygen extraction (FTOE) of the brain in premature infants using near-infrared spectroscopy (NIRS) and pulse oximetry. Study Design We prospectively studied FTOE in very low birth weight (BW) infants (< 1,500 g and ≤ 34 weeks' gestation). Factors affecting FTOE and its variability were examined using bivariate and linear regression models. FTOE variability was measured on two scales: short scales (3-20 seconds) and long scales (20-150 seconds). Results We examined 147 simultaneous NIRS and pulse oximetry recordings that were collected from 72 premature infants (gestational age [GA] = 28 weeks and BW = 1,036 g). In regression models, average FTOE correlated negatively with hemoglobin (Hb) and increased significantly in patients with severe intraventricular hemorrhage/periventricular leukomalacia. Both FTOE short- and long-scale variabilities correlated negatively with GA and positively with postnatal age (PNA). Moreover, FTOE long-scale variability was significantly reduced in infants supported with invasive ventilation. Conclusions In premature infants, cerebral oxygen extraction increased with reduced Hb and severe brain injury. Variability in oxygen extraction showed differential changes with GA and PNAs and was affected by invasive ventilation. 10.1055/s-0036-1572542