Unique infrared thermographic profiles and altered hypothalamic neurochemistry associated with mortality in endotoxic shock.

Neonatal sepsis results in significant morbidity and mortality, but early detection is clinically challenging. In a neonatal rat model of endotoxic shock, we characterised unique infrared thermographic (IRT) profiles in skin temperature that could identify risk of later mortality. Ten-day old rats were placed in a thermally stable isolette and IRT images of cranial (T), scapula (T) and rump (T) skin temperature were obtained continuously for 8 h following an intraperitoneal injection of lipopolysaccharide (LPS) or saline.

The effect of early postnatal auditory stimulation on outcomes in preterm infants.

Preterm infants are deprived of in utero sensory stimulation during the third trimester, an important period of central nervous system development. As a result, maturational trajectories are often reduced in infants born preterm. One such system affected is the brain including the auditory and respiratory control pathways.

Highly comparative time series analysis of oxygen saturation and heart rate to predict respiratory outcomes in extremely preterm infants.

Highly comparative time series analysis (HCTSA) is a novel approach involving massive feature extraction using publicly available code from many disciplines. The Prematurity-Related Ventilatory Control (Pre-Vent) observational multicenter prospective study collected bedside monitor data from>700extremely preterm infants to identify physiologic features that predict respiratory outcomes..

Apnea, Intermittent Hypoxemia, and Bradycardia Events Predict Late-Onset Sepsis in Infants Born Extremely Preterm.

Objective: The objective of this study was to examine the association of cardiorespiratory events, including apnea, periodic breathing, intermittent hypoxemia (IH), and bradycardia, with late-onset sepsis for extremely preterm infants (<29 weeks of gestational age) on vs off invasive mechanical ventilation.

Study Design: This is a retrospective analysis of data from infants enrolled in Pre-Vent (ClinicalTrials.gov identifier NCT03174301), an observational study in 5 level IV neonatal intensive care units.

Elevated Urine Hyaluronan Concentrations Are Associated with an Unfavorable Respiratory Outcome in Preterm Neonates at 40 Weeks Postmenstrual Age.

Introduction: Hyaluronan (HA) is a major component of the extracellular matrix. Increased pulmonary HA concentrations are associated with several respiratory disorders and is a pathophysiological feature of lung disease. We investigated whether elevated urine HA is a biomarker of an unfavorable 40-week respiratory outcome in preterm infants.

Association between Intermittent Hypoxemia and NICU Length of Stay in Preterm Infants.

Introduction: Length of hospitalization varies widely in preterm infants and can be affected by multiple maternal and neonatal factors including respiratory instability. Therefore, we aimed to determine the association between postnatal intermittent hypoxemia (IH) and prolonged hospitalization.

Methods: This prospective single-center cohort study followed infants born at <31 weeks of gestational age through 2 years corrected age with detailed oxygen saturation data captured from days 7 to 30 of age.

Highly comparative time series analysis of oxygen saturation and heart rate to predict respiratory outcomes in extremely preterm infants.

Objective: Highly comparative time series analysis (HCTSA) is a novel approach involving massive feature extraction using publicly available code from many disciplines. The Prematurity-Related Ventilatory Control (Pre-Vent) observational multicenter prospective study collected bedside monitor data from > 700 extremely preterm infants to identify physiologic features that predict respiratory outcomes. We calculated a subset of 33 HCTSA features on > 7 10-minute windows of oxygen saturation (SPO2) and heart rate (HR) from the Pre-Vent cohort to quantify predictive performance.

Apnea, Intermittent Hypoxemia, and Bradycardia Events Predict Late-Onset Sepsis in Extremely Preterm Infants.

Objectives: Detection of changes in cardiorespiratory events, including apnea, periodic breathing, intermittent hypoxemia (IH), and bradycardia, may facilitate earlier detection of sepsis. Our objective was to examine the association of cardiorespiratory events with late-onset sepsis for extremely preterm infants (<29 weeks' gestational age (GA)) on versus off invasive mechanical ventilation.

Study Design: Retrospective analysis of data from infants enrolled in Pre-Vent (ClinicalTrials.

Maturation of cardioventilatory physiological trajectories in extremely preterm infants.

Background: In extremely preterm infants, persistence of cardioventilatory events is associated with long-term morbidity. Therefore, the objective was to characterize physiologic growth curves of apnea, periodic breathing, intermittent hypoxemia, and bradycardia in extremely preterm infants during the first few months of life.

Methods: The Prematurity-Related Ventilatory Control study included 717 preterm infants <29 weeks gestation.

Cardiorespiratory Monitoring Data to Predict Respiratory Outcomes in Extremely Preterm Infants.

Immature control of breathing is associated with apnea, periodic breathing, intermittent hypoxemia, and bradycardia in extremely preterm infants. However, it is not clear if such events independently predict worse respiratory outcome. To determine if analysis of cardiorespiratory monitoring data can predict unfavorable respiratory outcomes at 40 weeks postmenstrual age (PMA) and other outcomes, such as bronchopulmonary dysplasia at 36 weeks PMA.

Hypoxemia events in preterm neonates are associated with urine oxidative biomarkers.

Background: Intermittent hypoxemia (IH) events are common in preterm neonates and are associated with adverse outcomes. Animal IH models can induce oxidative stress. We hypothesized that an association exists between IH and elevated peroxidation products in preterm neonates.

Plasma serotonergic biomarkers are associated with hypoxemia events in preterm neonates.

Background: Hypoxemia is a physiological manifestation of immature respiratory control in preterm neonates, which is likely impacted by neurotransmitter imbalances. We investigated relationships between plasma levels of the neurotransmitter serotonin (5-HT), metabolites of tryptophan (TRP), and parameters of hypoxemia in preterm neonates.

Methods: TRP, 5-HT, 5-hydroxyindoleacetic acid (5-HIAA), and kynurenic acid (KA) were analyzed in platelet-poor plasma at ~1 week and ~1 month of life from a prospective cohort of 168 preterm neonates <31 weeks gestational age (GA).

The relationship between intermittent hypoxemia events and neural outcomes in neonates.

This brief review examines 1) patterns of intermittent hypoxemia in extremely preterm infants during early postnatal life, 2) the relationship between neonatal intermittent hypoxemia exposure and outcomes in both human and animal models, 3) potential mechanistic pathways, and 4) future alterations in clinical care that may reduce morbidity. Intermittent hypoxemia events are pervasive in extremely preterm infants (<28 weeks gestation at birth) during early postnatal life. An increased frequency of intermittent hypoxemia events has been associated with a range of poor neural outcomes including language and cognitive delays, motor impairment, retinopathy of prematurity, impaired control of breathing, and intraventricular hemorrhage.

Are we over-treating hypoxic spells in preterm infants?

A frequent challenge in Neonatology is the high frequency of spontaneously occurring hypoxemic events, a majority of which are associated with apnea or hypoventilation. These episodes present a challenge for caregivers and families as they frequently delay discharge of preterm infants. Supplemental oxygen, respiratory support, and caffeine therapy are widely used as therapeutic approaches, but challenges remain regarding their precise indications.

Prematurity and postnatal alterations in intermittent hypoxaemia.

Intermittent hypoxaemia (IH) events are well described in extremely preterm infants, but the occurrence of IH patterns in more mature preterm infants remains unclear. The objective of this study was to characterise the effect of gestational age on early postnatal patterns of IH in extremely (<28 weeks), very (28-<32 weeks) and moderately (32-<34 weeks) preterm infants. As expected, extremely preterm infants had a significantly higher frequency of IH events of longer durations and greater time with hypoxaemia versus very and moderately preterm infants.

The Relationship between Oxidative Stress, Intermittent Hypoxemia, and Hospital Duration in Moderate Preterm Infants.

Introduction: Lipid peroxidation products are present following oxidation of polyunsaturated fatty acids in the eye, brain, and various cell membranes. Elevated levels of lipid peroxidation products and increased intermittent hypoxemia (IH) events have been associated with adverse outcomes in extremely preterm infants. The moderate preterm newborn has a still-developing oxidant defense system and immature respiratory control, but little is known about lipid peroxidation levels and IH in this larger and more common preterm population.

Effect of Blood Transfusions on Intermittent Hypoxic Episodes in a Prospective Study of Very Low Birth Weight Infants.

Objectives: To compare the number of intermittent hypoxia events before and after packed red blood cell (pRBC) and non-pRBC transfusions in very low birth weight infants, and to compare the time spent with saturations of ≤85% before and after transfusions in the same population.

Study Design: This prospective observational study was conducted from April 2014 to August 2017. It included 92 transfusions (81 pRBC, 11 non-pRBC) from 41 very low birth weight infants between 23 and 28 weeks of gestation.

Intermittent Hypoxemia in Preterm Infants.

Intermittent hypoxemia (IH) events are common during early postnatal life, particularly in preterm infants. These events have been associated with multiple morbidities, including retinopathy of prematurity, sleep disordered breathing, neurodevelopmental impairment, and mortality. The relationship between IH and poor outcomes may depend on the patterns (frequency, duration, and timing) of the IH events.

Intermittent hypoxemia and oxidative stress in preterm infants.

Intermittent hypoxemia events (IH) are common in extremely preterm infants and are associated with many poor outcomes including retinopathy or prematurity, wheezing, bronchopulmonary dysplasia, cognitive or language delays and motor impairment. More recent data in animal and rodent models have suggested that specific patterns of IH may increase the risk for morbidity. The pathway by which these high risk patterns of IH initiate a pathological cascade is unknown but animal models suggest that oxidative stress may play a role.

Adrenic acid non-enzymatic peroxidation products in biofluids of moderate preterm infants.

Oxidative stress plays an essential role in processes of signaling and damage to biomolecules during early perinatal life. Isoprostanoids and isofuranoids from the free radical-catalyzed peroxidation of polyunsaturated fatty acids (PUFAs) are widely recognized as reliable biomarkers of oxidative stress. However, their quantification is not straightforward due to high structural similarity of the compounds formed.

Pre-Vent: the prematurity-related ventilatory control study.

Background: The increasing incidence of bronchopulmonary dysplasia in premature babies may be due in part to immature ventilatory control, contributing to hypoxemia. The latter responds to ventilation and/or oxygen therapy, treatments associated with adverse sequelae. This is an overview of the Prematurity-Related Ventilatory Control Study which aims to analyze the under-utilized cardiorespiratory continuous waveform monitoring data to delineate mechanisms of immature ventilatory control in preterm infants and identify predictive markers.

Neonatal intermittent hypoxemia events are associated with diagnosis of bronchopulmonary dysplasia at 36 weeks postmenstrual age.

Background: Bronchopulmonary dysplasia (BPD) is a chronic lung disease and major pulmonary complication after premature birth. We have previously shown that increased intermittent hypoxemia (IH) events have been correlated to adverse outcomes and mortality in extremely premature infants. We hypothesize that early IH patterns are associated with the development of BPD.

Early inspired oxygen and intermittent hypoxemic events in extremely premature infants are associated with asthma medication use at 2 years of age.

Objective: Extremely premature infants are at risk for childhood wheezing. Early respiratory support and intermittent hypoxemia (IH) events may be associated with adverse breathing outcomes.

Study Design: A single-center retrospective cohort study of 137 premature infants <28 weeks gestational age characterized the associations of cumulative oxygen, cumulative mean airway pressure, IH, and oxygen saturation (SpO) on the primary outcome of prescription asthma medication use at 2-year follow-up.