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. During normal pregnancy the intrauterine environment attenuates external auditory stimuli while exposing the fetus to filtered maternal voice, intra-abdominal sounds, and external stimuli. In contrast, during the third trimester of development, preterm infants are exposed to a vastly different soundscape including non-attenuated auditory sounds and a lack of womb related stimuli, both of which may affect postnatal brain maturation. Therefore, fostering a nurturing postnatal auditory environment during hospitalization may have a significant impact on related outcomes of preterm infants. Studies using a range of postnatal auditory stimulations have suggested that exposure to sounds or lack thereof can have a significant impact on outcomes. However, studies are inconsistent with sound levels, duration of exposure to auditory stimuli, and the gestational age at which infants are exposed. IMPACT: Auditory stimulation can provide a low cost and low risk intervention to stabilize respiration, improve neuronal maturation and reduce long-term sequelae in preterm infants. The potential benefits of auditory stimulation are dependent on the type of sound, the duration of exposure and age at time of exposure. Future studies should focus on the optimal type and duration of sound exposure and postnatal developmental window to improve outcomes.

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>700extremely preterm infants to identify physiologic features that predict respiratory outcomes.Approach. We calculated a subset of 33 HCTSA features on>7 M 10 min windows of oxygen saturation (SPO2) and heart rate (HR) from the Pre-Vent cohort to quantify predictive performance. This subset included representatives previously identified using unsupervised clustering on>3500HCTSA algorithms. We hypothesized that the best HCTSA algorithms would compare favorably to optimal PreVent physiologic predictor IH90_DPE (duration per event of intermittent hypoxemia events below 90%).Main Results.The top HCTSA features were from a cluster of algorithms associated with the autocorrelation of SPO2 time series and identified low frequency patterns of desaturation as high risk. These features had comparable performance to and were highly correlated with IH90_DPE but perhaps measure the physiologic status of an infant in a more robust way that warrants further investigation. The top HR HCTSA features were symbolic transformation measures that had previously been identified as strong predictors of neonatal mortality. HR metrics were only important predictors at early days of life which was likely due to the larger proportion of infants whose outcome was death by any cause. A simple HCTSA model using 3 top features outperformed IH90_DPE at day of life 7 (.778 versus .729) but was essentially equivalent at day of life 28 (.849 versus .850).Significance. These results validated the utility of a representative HCTSA approach but also provides additional evidence supporting IH90_DPE as an optimal predictor of 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. Clinical data were analyzed for 737 infants (mean gestational age: 26.4 weeks, SD 1.71). Monitoring data were available and analyzed for 719 infants (47 512 patient-days); of whom, 109 had 123 sepsis events. Using continuous monitoring data, we quantified apnea, periodic breathing, bradycardia, and IH. We analyzed the relationships between these daily measures and late-onset sepsis (positive blood culture >72 hours after birth and ≥5-day antibiotics). RESULTS: For infants not on a ventilator, apnea, periodic breathing, and bradycardia increased before sepsis diagnosis. During times on a ventilator, increased sepsis risk was associated with longer events with oxygen saturation <80% (IH80) and more bradycardia events before sepsis. IH events were associated with higher sepsis risk but did not dynamically increase before sepsis, regardless of ventilator status. A multivariable model including postmenstrual age, cardiorespiratory variables (apnea, periodic breathing, IH80, and bradycardia), and ventilator status predicted sepsis with an area under the receiver operator characteristic curve of 0.783. CONCLUSION: We identified cardiorespiratory signatures of late-onset sepsis. Longer IH events were associated with increased sepsis risk but did not change temporally near diagnosis. Increases in bradycardia, apnea, and periodic breathing preceded the clinical diagnosis of sepsis.

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. METHODS: Infants comprised a cohort of preterm neonates <31 weeks gestational age (GA) from the Prematurity-Related Ventilatory Control (Pre-Vent) multicenter study. HA was quantified in urine obtained at 1 week and 1 month of age. Respiratory status at 40 weeks post-menstrual age (PMA) was classified as unfavorable [either (1) deceased at or before 40 weeks PMA, (2) an inpatient on respiratory medication, O2 or other respiratory support at 40 weeks, or (3) discharged prior to 40 weeks on medications/O2/other respiratory support], or favorable (alive and previously discharged, or inpatient and off respiratory medications, off O2, and off other respiratory support at 40 weeks PMA). The association between urine HA and the unfavorable 40 week PMA outcome was examined using a multivariate logistic generalized estimation equation model. RESULTS: Infants with higher HA at 1 week (but not 1 month) showed increased odds of unfavorable respiratory outcome at 40 weeks PMA (OR [95% CI] = 1.87 per 0.01 mg [1.27, 2.73]). DISCUSSION AND CONCLUSION: Neonatal urine screening for HA could identify infants at risk for death or need for respiratory support at term-corrected age (40 weeks PMA). The relationship between elevated HA at 1 week and an unfavorable 40 week outcome was stronger in infants with lower GA.

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. RESULTS: 51/164 (31%) of infants were discharged after 400/7 weeks of corrected gestational age (CGA). A greater average daily number of IH events (OR per 10 events/day 1.33 [95% CI 1.03-1.72]), duration of events (OR per minute 1.14 [1.07-1.21]), and percent time with oxygen saturation <80% (OR per percent 1.88 [1.25-2.85]) on days 7-30 of age were all significantly associated with prolonged hospitalization past 400/7 weeks CGA. In survival analyses, infants with a greater average daily number of IH events (HR per 10 events/day 0.89 [0.81-0.98]), percent time with oxygen saturation <80% (HR per percent 0.79 [0.67-0.94]), and duration of events (HR per minute 0.93 [0.91-0.95]) on days 7-30 of age all had significantly lower probability of earlier discharge. In addition, there was a significant interaction with gestational age; the association between IH and prolonged hospitalization was stronger in more mature infants (p = 0.024). CONCLUSIONS: Physiological instability on days 7-30 of age, as manifested by IH, is significantly associated with prolonged hospitalization. IH likely represents both a marker of initial severity of illness and the beginning of biological cascades, leading to prematurity-associated morbidities.

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 > 7M 10-minute windows of oxygen saturation (SPO2) and heart rate (HR) from the Pre-Vent cohort to quantify predictive performance. This subset included representatives previously identified using unsupervised clustering on > 3500 HCTSA algorithms. Performance of each feature was measured by individual area under the receiver operating curve (AUC) at various days of life and binary respiratory outcomes. These were compared to optimal PreVent physiologic predictor IH90 DPE, the duration per event of intermittent hypoxemia events with threshold of 90%. Main Results: The top HCTSA features were from a cluster of algorithms associated with the autocorrelation of SPO2 time series and identified low frequency patterns of desaturation as high risk. These features had comparable performance to and were highly correlated with IH90_DPE but perhaps measure the physiologic status of an infant in a more robust way that warrants further investigation. The top HR HCTSA features were symbolic transformation measures that had previously been identified as strong predictors of neonatal mortality. HR metrics were only important predictors at early days of life which was likely due to the larger proportion of infants whose outcome was death by any cause. A simple HCTSA model using 3 top features outperformed IH90_DPE at day of life 7 (.778 versus .729) but was essentially equivalent at day of life 28 (.849 versus .850). These results validated the utility of a representative HCTSA approach but also provides additional evidence supporting IH90_DPE as an optimal predictor of respiratory outcomes.

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.gov identifier NCT03174301), an observational study in five level IV neonatal intensive care units. Clinical data were analyzed for 737 infants (mean GA 26.4w, SD 1.71). Monitoring data were available and analyzed for 719 infants (47,512 patient-days), of whom 109 had 123 sepsis events. Using continuous monitoring data, we quantified apnea, periodic breathing, bradycardia, and IH. We analyzed the relationships between these daily measures and late-onset sepsis (positive blood culture >72h after birth and ≥5d antibiotics). Results: For infants not on a ventilator, apnea, periodic breathing, and bradycardia increased before sepsis diagnosis. During times on a ventilator, increased sepsis risk was associated with longer IH80 events and more bradycardia events before sepsis. IH events were associated with higher sepsis risk, but did not dynamically increase before sepsis, regardless of ventilator status. A multivariable model predicted sepsis with an AUC of 0.783. Conclusion: We identified cardiorespiratory signatures of late-onset sepsis. Longer IH events were associated with increased sepsis risk but did not change temporally near diagnosis. Increases in bradycardia, apnea, and periodic breathing preceded the clinical diagnosis of sepsis.

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. Waveforms were downloaded from bedside monitors with a novel sharing analytics strategy utilized to run software locally, with summary data sent to the Data Coordinating Center for compilation. RESULTS: Apnea, periodic breathing, and intermittent hypoxemia events rose from day 3 of life then fell to near-resolution by 8-12 weeks of age. Apnea/intermittent hypoxemia were inversely correlated with gestational age, peaking at 3-4 weeks of age. Periodic breathing was positively correlated with gestational age peaking at 31-33 weeks postmenstrual age. Females had more periodic breathing but less intermittent hypoxemia/bradycardia. White infants had more apnea/periodic breathing/intermittent hypoxemia. Infants never receiving mechanical ventilation followed similar postnatal trajectories but with less apnea and intermittent hypoxemia, and more periodic breathing. CONCLUSIONS: Cardioventilatory events peak during the first month of life but the actual postnatal trajectory is dependent on the type of event, race, sex and use of mechanical ventilation. IMPACT: Physiologic curves of cardiorespiratory events in extremely preterm-born infants offer (1) objective measures to assess individual patient courses and (2) guides for research into control of ventilation, biomarkers and outcomes. Presented are updated maturational trajectories of apnea, periodic breathing, intermittent hypoxemia, and bradycardia in 717 infants born <29 weeks gestation from the multi-site NHLBI-funded Pre-Vent study. Cardioventilatory events peak during the first month of life but the actual postnatal trajectory is dependent on the type of event, race, sex and use of mechanical ventilation. Different time courses for apnea and periodic breathing suggest different maturational mechanisms.

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. METHODS: Time in hypoxemia, frequency of IH, and duration of IH events were assessed from a prospective cohort of 170 neonates (<31 weeks gestation). Urine was collected at 1 week and 1 month. Samples were analyzed for lipid, protein, and DNA oxidation biomarkers. RESULTS: At 1 week, adjusted multiple quantile regression showed positive associations between several hypoxemia parameters with various individual quantiles of isofurans, neurofurans, dihomo-isoprostanes, dihomo-isofurans, and ortho-tyrosine and a negative correlation with dihomo-isoprostanes and meta-tyrosine. At 1 month, positive associations were found between several hypoxemia parameters with quantiles of isoprostanes, dihomo-isoprostanes and dihomo-isofurans and a negative correlation with isoprostanes, isofurans, neuroprostanes, and meta-tyrosine. CONCLUSIONS: Preterm neonates experience oxidative damage to lipids, proteins, and DNA that can be analyzed from urine samples. Our single-center data suggest that specific markers of oxidative stress may be related to IH exposure. Future studies are needed to better understand mechanisms and relationships to morbidities of prematurity. IMPACT: Hypoxemia events are frequent in preterm infants and are associated with poor outcomes. The mechanisms by which hypoxemia events result in adverse neural and respiratory outcomes may include oxidative stress to lipids, proteins, and DNA. This study begins to explore associations between hypoxemia parameters and products of oxidative stress in preterm infants. Oxidative stress biomarkers may assist in identifying high-risk 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). Frequency of intermittent hypoxemia (IH) events and percent time hypoxemic (<80%) were analyzed in a 6 h window after the blood draw. RESULTS: At 1 week, infants with detectable plasma 5-HT had fewer IH events (OR (95% CI) = 0.52 (0.29, 0.31)) and less percent time <80% (OR (95% CI) = 0.54 (0.31, 0.95)) compared to infants with undetectable 5-HT. A similar relationship occurred at 1 month. At 1 week, infants with higher KA showed greater percent time <80% (OR (95% CI) = 1.90 (1.03, 3.50)). TRP, 5-HIAA or KA were not associated with IH frequency at either postnatal age. IH frequency and percent time <80% were positively associated with GA < 29 weeks. CONCLUSIONS: Circulating neuromodulators 5-HT and KA might represent biomarkers of immature respiratory control contributing to hypoxemia in preterm neonates. IMPACT: Hypoxemia events are frequent in preterm infants and are associated with poor outcomes. Mechanisms driving hypoxemia such as immature respiratory control may include central and peripheral imbalances in modulatory neurotransmitters. This study found associations between the plasma neuromodulators serotonin and kynurenic acid and parameters of hypoxemia in preterm neonates. Imbalances in plasma biomarkers affecting respiratory control may help identify neonates at risk of short- and long-term adverse outcomes.

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

Rationale: 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. Objectives: 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. Methods: The Prematurity-related Ventilatory Control (Pre-Vent) study was an observational multicenter prospective cohort study including infants born at <29 weeks of gestation with continuous cardiorespiratory monitoring. The primary outcome was either "favorable" (alive and previously discharged or inpatient and off respiratory medications/O2/support at 40 wk PMA) or "unfavorable" (either deceased or inpatient/previously discharged on respiratory medications/O2/support at 40 wk PMA). Measurements and Main Results: A total of 717 infants were evaluated (median birth weight, 850 g; gestation, 26.4 wk), 53.7% of whom had a favorable outcome and 46.3% of whom had an unfavorable outcome. Physiologic data predicted unfavorable outcome, with accuracy improving with advancing age (area under the curve, 0.79 at Day 7, 0.85 at Day 28 and 32 wk PMA). The physiologic variable that contributed most to prediction was intermittent hypoxemia with oxygen saturation as measured by pulse oximetry <90%. Models with clinical data alone or combining physiologic and clinical data also had good accuracy, with areas under the curve of 0.84-0.85 at Days 7 and 14 and 0.86-0.88 at Day 28 and 32 weeks PMA. Intermittent hypoxemia with oxygen saturation as measured by pulse oximetry <80% was the major physiologic predictor of severe bronchopulmonary dysplasia and death or mechanical ventilation at 40 weeks PMA. Conclusions: Physiologic data are independently associated with unfavorable respiratory outcome in extremely preterm infants.

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. Neonatal rodent models have shown that exposure to short repetitive cycles of hypoxia induce a pathophysiological cascade. However, not all patterns of intermittent hypoxia are deleterious and some may even improve neurodevelopmental outcomes. Therapeutic interventions include supplemental oxygen, pressure support and pharmacologic drugs but prolonged hyperoxia and pressure exposure have been associated with cardiopulmonary morbidity. Therefore, it becomes imperative to distinguish high risk from neutral and/or even beneficial patterns of intermittent hypoxemia during early postnatal life. Identification of such patterns could improve clinical care with targeted interventions for high-risk patterns and minimal or no exposure to treatment modalities for low-risk patterns.

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. Future clinical practice should be directed by an evidence-based approach including automated supplemental oxygen, minimizing the use of medications for gastroesophageal reflux, optimal timing and dosage of caffeine therapy, and standardization of alarm limits and discharge monitoring protocols.

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. In addition, the postnatal decrease in IH duration was comparable in the very and moderately preterm infants. This progression of IH events should assist clinicians and families in managing expectations for resolution of IH events during early postnatal life.

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. OBJECTIVE: To determine the association between oxidative stress and IH in moderate preterm infants. METHOD: Oxygen saturation was continuously monitored in 51 moderate preterm infants (i.e., 31 + 0/7 to 33 + 6/7 weeks' gestation). Urine samples were collected at the end of the first and second weeks of life. Samples were analyzed for total lipid peroxidation products (neurofurans, isofurans, neuroprostanes, isoprostanes, and di-homo-isofurans). RESULT: At week 1, there was a correlation between increased IH frequency and neurofurans (p < 0.04) and di-homo-isofurans (p < 0.003). At week 2, there was no correlation between IH and lipid peroxidation markers. Ele-vations in neurofurans, isofurans, neuroprostanes, and di-homo-isofurans in the first and/or second week of life were associated with a longer stay in hospital. CONCLUSION: Elevations in lipid peroxidation biomarkers in moderate preterm infants during their first weeks of life are associated with a higher frequency of IH and prolonged hospitalization.

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 230/7 and 286/7 weeks of gestation. The primary outcome was number of intermittent hypoxia events. Secondary outcomes included the percent time of Peripheral capillary oxygen saturation (SpO2)of ≤85%, ≤80%, and ≤75%. A mixed ANOVA model was used to examine the relationship between event rate and covariates. RESULTS: The mean number of intermittent hypoxia events per hour decreased from 5.27 ± 5.02 events per hour before pRBC transfusion to 3.61 ± 3.17 per hour after pRBC transfusions (P < .01) and intermittent hypoxia did not change after non-RBC transfusions (before, 4.45 ± 3.19 vs after, 4.47 ± 2.78; P = NS). The percent time with saturations of ≤80% and ≤75% significantly decreased after pRBC transfusions (P = .01). The time with saturations of ≤85% did not significantly change after non-pRBC transfusion. CONCLUSIONS: In very low birth weight infants with a hematocrit of 20%-42%, pRBC transfusions are associated with decreased frequency of intermittent hypoxia. No such diminution of intermittent hypoxia events was observed in infants who had received a non-pRBC transfusion. This finding suggests that the observed beneficial effects of RBC transfusions on apnea and its clinical manifestations of intermittent hypoxia are mediated through an enhanced oxygen carrying capacity.

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. Current treatment modalities used in the clinical setting have been only partially successful in reducing the incidence of apnea and accompanying IH, but the risks and benefits of more aggressive interventions should include knowledge of the relationship between IH and morbidity.

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. This review describes early postnatal patterns of IH in preterm infants, their relationship with morbidity, oxidative stress biomarkers relevant to the newborn infant and the relationship between IH and reactive oxygen species.

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. In this work, a semiquantitative method for the analysis of adrenic acid (AdA, C22:4 n-6) non-enzymatic peroxidation products (i.e. dihomo-isoprostanes and dihomo-isofurans) was developed. The proposed ultra-performance liquid chromatography - tandem mass spectrometry (UPLC-MS/MS) method was applied to the analysis of blood plasma and urine from preterm infants providing information about AdA peroxidation.