Cerebral autoregulation, brain injury, and the transitioning premature infant

Improvements in clinical management of the preterm infant have reduced the rates of the two most common forms of brain injury, such as severe intraventricular hemorrhage and white matter injury, both of which are contributory factors in the development of cerebral palsy. Nonetheless, they remain a persistent challenge and are associated with a significant increase in the risk of adverse neurodevelopment outcomes. Repeated episodes of ischemia–reperfusion represent a common pathway for both forms of injury, arising from discordance between systemic blood flow and the innate regulation of cerebral blood flow in the germinal matrix and periventricular white matter. Nevertheless, establishing firm hemodynamic boundaries, as a part of neuroprotective strategy, has challenged researchers. Existing measures either demonstrate inconsistent relationships with injury, as in the case of mean arterial blood pressure, or are not feasible for long-term monitoring, such as cardiac output estimated by echocardiography. These challenges have led some researchers to focus on the mechanisms that control blood flow to the brain, known as cerebrovascular autoregulation. Historically, the function of the cerebrovascular autoregulatory system has been difficult to quantify; however, the evolution of bedside monitoring devices, particularly near-infrared spectroscopy, has enabled new insights into these mechanisms and how impairment of blood flow regulation may contribute to catastrophic injury. In this review, we first seek to examine how technological advancement has changed the assessment of cerebrovascular autoregulation in premature infants. Next, we explore how clinical factors, including hypotension, vasoactive medications, acute and chronic hypoxia, and ventilation, alter the hemodynamic state of the preterm infant. Additionally, we examine how developmentally linked or acquired dysfunction in cerebral autoregulation contributes to preterm brain injury. In conclusion, we address exciting new approaches to the measurement of autoregulation and discuss the feasibility of translation to the bedside

Cerebral oximetry monitoring in extremely preterm infants

BACKGROUND: The use of cerebral oximetry monitoring in the care of extremely preterm infants is increasing. However, evidence that its use improves clinical outcomes is lacking. METHODS: In this randomized, phase 3 trial conducted at 70 sites in 17 countries, we assigned extremely preterm infants (gestational age, \u3c28 weeks), within 6 hours after birth, to receive treatment guided by cerebral oximetry monitoring for the first 72 hours after birth or to receive usual care. The primary outcome was a composite of death or severe brain injury on cerebral ultrasonography at 36 weeks\u27 postmenstrual age. Serious adverse events that were assessed were death, severe brain injury, bronchopulmonary dysplasia, retinopathy of prematurity, necrotizing enterocolitis, and late-onset sepsis. RESULTS: A total of 1601 infants underwent randomization and 1579 (98.6%) were evaluated for the primary outcome. At 36 weeks\u27 postmenstrual age, death or severe brain injury had occurred in 272 of 772 infants (35.2%) in the cerebral oximetry group, as compared with 274 of 807 infants (34.0%) in the usual-care group (relative risk with cerebral oximetry, 1.03; 95% confidence interval, 0.90 to 1.18; P = 0.64). The incidence of serious adverse events did not differ between the two groups. CONCLUSIONS: In extremely preterm infants, treatment guided by cerebral oximetry monitoring for the first 72 hours after birth was not associated with a lower incidence of death or severe brain injury at 36 weeks\u27 postmenstrual age than usual care. (Funded by the Elsass Foundation and others; SafeBoosC-III ClinicalTrials.gov number, NCT03770741.)

Investigation of EEG activity compared with mean arterial blood pressure in extremely preterm infants

BackgroundCerebral electrical activity in extremely preterm infants is affected by various factors including blood gas and circulatory parameters.ObjectiveTo investigate whether continuously measured invasive mean arterial blood pressure (BP) is associated with electroencephalographic (EEG) discontinuity in extremely preterm infants.Study designThis prospective observational study examined 51 newborn infants born <29 weeks gestation in the first 3 days after birth. A single channel of raw EEG was used to quantify discontinuity. Mean BP was acquired using continuous invasive measurement and Doppler ultrasound was used to measure left ventricular output (LVO) and common carotid artery blood flow (CCAF).ResultsMedian gestation and birthweight were 25.6 weeks and 760 g, respectively. Mean discontinuity reduced significantly between days 1 and 3. EEG discontinuity was significantly related to gestation, pH and BP. LVO and CCAF were not associated with EEG discontinuity.ConclusionContinuously measured invasive mean arterial BP was found to have a negative relationship with EEG discontinuity; increasing BP was associated with lower EEG discontinuity. This did not appear to be mediated by surrogates of systemic or cerebral blood flow. Infants receiving inotropic support had significantly increased EEG discontinuity on the first day after birth

Predicting mortality risk for preterm infants using deep learning models with time-series vital sign data

Mortality remains an exceptional burden of extremely preterm birth. Current clinical mortality prediction scores are calculated using a few static variable measurements, such as gestational age, birth weight, temperature, and blood pressure at admission. While these models do provide some insight, numerical and time-series vital sign data are also available for preterm babies admitted to the NICU and may provide greater insight into outcomes. Computational models that predict the mortality risk of preterm birth in the NICU by integrating vital sign data and static clinical variables in real time may be clinically helpful and potentially superior to static prediction models. However, there is a lack of established computational models for this specific task. In this study, we developed a novel deep learning model, DeepPBSMonitor (Deep Preterm Birth Survival Risk Monitor), to predict the mortality risk of preterm infants during initial NICU hospitalization. The proposed deep learning model can effectively integrate time-series vital sign data and fixed variables while resolving the influence of noise and imbalanced data. The proposed model was evaluated and compared with other approaches using data from 285 infants. Results showed that the DeepPBSMonitor model outperforms other approaches, with an accuracy, recall, and AUC score of 0.888, 0.780, and 0.897, respectively. In conclusion, the proposed model has demonstrated efficacy in predicting the real-time mortality risk of preterm infants in initial NICU hospitalization

Racial disparities in calculated risk for bronchopulmonary dysplasia: A dataset

Bronchopulmonary dysplasia (BPD) is a severe pulmonary complication of prematurity and is associated with significant morbidity or death. Early use of systemic corticosteroids may alter the trajectory of the disease and improve outcomes. A BPD Outcomes estimator, developed by the NICHD using a large population dataset, can be used to calculate individual risk. Risk above a certain threshold may indicate that the benefits of corticosteroids outweigh the risks. Empiric analysis of this calculator by systematic entry of synthetic patient information reveals a marked racial disparity; black infants have lower risk of moderate/severe BPD due to a higher risk of death despite equivalent severity of illness. Interpretation and analysis of this finding can be found in The challenge of risk stratification of preterm infants in the setting of competing and disparate healthcare outcomes [1]. In this report, we provide the underlying data used in this analysis. Calculator output for 108 example patients, systematically varied by sex, birthweight, race, type of ventilator, and fraction of inspired oxygen (Fi

aEEG in the first 3 days after extremely preterm delivery relates to neurodevelopmental outcomes

OBJECTIVES: Investigate relationships between aEEG in the first 72 h in extremely preterm infants with 1) infant, medical, and environmental factors, and 2) infant feeding and neurobehavioral outcomes at term and school-age. METHODS: Sixty-four preterm infants (≤28 weeks gestation) were enrolled within the first 24-hours of life and had two-channel aEEG until 72 h of life. Standardized neurobehavioral and feeding assessments were conducted at term, and parent-reported outcomes were documented at 5-7 years. RESULTS: Lower aEEG Burdjalov scores (adjusted for gestational age) were related to vaginal delivery (p = 0.04), cerebral injury (p = 0.01), Black race (p \u3c 0.01) and having unmarried parents (p = 0.02). Lower Burdjalov scores related to less NICU Network Neurobehavioral Scale arousal (p = 0.002) at term and poorer BRIEF global executive function (p = 0.004), inhibition (p = 0.007), working memory (p = 0.02), material organization (p = 0.0008), metacognition (p = 0.01), and behavioral regulation (p = 0.02) at 5-7 years. We did not observe relationships of early aEEG to feeding outcomes or sensory processing measures. CONCLUSION: Early aEEG within the first 72 h of life was related to medical and sociodemographic factors as well as cognitive outcome at 5-7 years

Neuro-Behçets in a Child

We describe a case of neuro-Behçet disease diagnosed in a 12-year-old girl. This patient presented with recurrent oral ulcers, incontinence, spastic gait, blurry vision, and asymmetrical lower extremity hypertonia. Extensive testing revealed punctate lesions through the central nervous system, vitritis, papillitis, and uveitis. A thorough infectious and neoplastic workup was negative. She was treated with pulse steroids and azathioprine with gradual improvement in her gait and ophthalmologic findings. Although rare, primary neuro-Behçet should be considered in pediatric patients with neurologic abnormalities and recurrent aphthous ulcers without other explanation. </jats:p