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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.
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Frecuencia Cardíaca , Recien Nacido Extremadamente Prematuro , Saturación de Oxígeno , Humanos , Frecuencia Cardíaca/fisiología , Recién Nacido , Saturación de Oxígeno/fisiología , Recien Nacido Extremadamente Prematuro/fisiología , Factores de Tiempo , Algoritmos , Respiración , Femenino , Estudios ProspectivosRESUMEN
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.
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Apnea , Bradicardia , Hipoxia , Recien Nacido Extremadamente Prematuro , Sepsis , Humanos , Bradicardia/epidemiología , Bradicardia/etiología , Apnea/epidemiología , Estudios Retrospectivos , Recién Nacido , Hipoxia/complicaciones , Femenino , Masculino , Sepsis/complicaciones , Sepsis/epidemiología , Enfermedades del Prematuro/epidemiología , Enfermedades del Prematuro/diagnóstico , Respiración Artificial , Unidades de Cuidado Intensivo Neonatal , Edad GestacionalRESUMEN
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.
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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.
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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.
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Enfermedades del Prematuro , Trastornos Respiratorios , Lactante , Femenino , Recién Nacido , Humanos , Recien Nacido Extremadamente Prematuro , Apnea , Bradicardia/terapia , Respiración , HipoxiaRESUMEN
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.
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Displasia Broncopulmonar , Recien Nacido Extremadamente Prematuro , Lactante , Recién Nacido , Humanos , Estudios Prospectivos , Respiración Artificial , HipoxiaRESUMEN
Rationale: Preterm infants are at risk for ventilatory control instability that may be due to aberrant peripheral chemoreceptor activity. Although term infants have increasing peripheral chemoreceptor contribution to overall ventilatory drive with increasing postnatal age, how peripheral chemoreceptor contribution changes in preterm infants with increasing postmenstrual age is not known. Objectives: To evaluate peripheral chemoreceptor activity between 32 and 52 weeks postmenstrual age in preterm infants, using both quantitative and qualitative measures. Methods: Fifty-five infants born between 24 weeks, 0 days gestation and 28 weeks, 6 days gestation underwent hyperoxic testing at one to four time points between 32 and 52 weeks postmenstrual age. Quantitative [Formula: see text] decreases were calculated, and qualitative responses were categorized as apnea, continued breathing with a clear reduction in [Formula: see text], sigh breaths, and no response. Measurements and Main Results: A total of 280 hyperoxic tests were analyzed (2.2 ± 0.3 tests per infant at each time point). Mean peripheral chemoreceptor contribution to ventilatory drive was 85.2 ± 20.0% at 32 weeks and 64.1 ± 22.0% at 52 weeks. Apneic responses were more frequent at earlier postmenstrual ages. Conclusions: Among preterm infants, the peripheral chemoreceptor contribution to ventilatory drive was greater at earlier postmenstrual ages. Apnea was a frequent response to hyperoxic testing at earlier postmenstrual ages, suggesting high peripheral chemoreceptor activity. A clearer description of how peripheral chemoreceptor activity changes over time in preterm infants may help explain how ventilatory control instability contributes to apnea and sleep-disordered breathing later in childhood. Clinical trial registered with www.clinicaltrials.gov (NCT03464396).
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Hiperoxia , Síndromes de la Apnea del Sueño , Humanos , Lactante , Recién Nacido , Células Quimiorreceptoras/fisiología , Recien Nacido Prematuro/fisiología , RespiraciónRESUMEN
Type I collagen alterations cause osteogenesis imperfecta (OI), a connective tissue disorder characterized by severe bone fragility. Patients with OI can suffer from significant pulmonary manifestations including severe respiratory distress in the neonatal period and a progressive decline in respiratory function in adulthood. We and others have shown intrinsic lung defects in some mouse models of OI. In this large study, we performed histological, histomorphometric, microcomputed tomography and invasive studies on oim/+, Col1a2+/G610C , CrtapKO and oim/oim mice, mimicking mild to moderate to severe OI, with the overall goal of determining the extent of their pulmonary and respiratory mechanics defects and whether these defects correlate with the skeletal disease severity and affect each sex equally. Although with variable severity, OI lung histology consistently showed alveolar simplification with enlarged acinar airspace and reduced alveolar surface. Numerous respiratory mechanics parameters, including respiratory system resistance and elastance, tissue damping, inspiratory capacity, total lung capacity, and others, were significantly and similarly impacted in CrtapKO and oim/oim but not in oim/+ or Col1a2+/G610C compared to control mice. Our data indicate that the impact of type I collagen alterations and OI on lung morphology and function positively correlate with the severity of the extracellular matrix deficiency. Moreover, the respiratory defects were more pronounced in male compared to female mice. It will be important to determine whether our observations in mice translate to OI patients and to dissect the respective contribution of intrinsic lung defects vs. extrinsic skeletal defects to impaired lung function in OI. KEY POINTS: Different type I collagen alterations in mouse models of osteogenesis imperfecta (OI) cause similar abnormal lung histology, with alveolar simplification and reduced alveolar surface, reminiscent of emphysema. Several respiratory mechanics parameters are altered in mouse models of OI. The impact of type I collagen alterations and OI on lung morphology and function positively correlate with the severity of the extracellular matrix deficiency. Respiratory defects were more pronounced in male compared to female mice. It will be important to determine whether our observations in mice translate to OI patients and to dissect the respective contribution of intrinsic lung defects vs. extrinsic skeletal defects to impaired lung function in OI.
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Colágeno Tipo I , Osteogénesis Imperfecta , Animales , Femenino , Masculino , Ratones , Colágeno Tipo I/genética , Modelos Animales de Enfermedad , Pulmón/patología , Osteogénesis Imperfecta/complicaciones , Osteogénesis Imperfecta/genética , Osteogénesis Imperfecta/patología , Microtomografía por Rayos XRESUMEN
The Ehlers-Danlos syndromes (EDS) are inherited connective tissue diseases with primary manifestations that affect the skin and the musculoskeletal system. However, the effects of EDS on the respiratory system are not well understood and are described in the literature as sporadic case reports. We performed histological, histomorphometric, and the first in-depth characterization of respiratory system function in a mouse model of classical EDS (cEDS) with haploinsufficiency of type V collagen (Col5a1+/-). In young adult male and female mice, lung histology showed reduced alveolar density, reminiscent of emphysematous-like changes. Respiratory mechanics showed a consistent increase in respiratory system compliance accompanied by increased lung volumes in Col5a1+/- compared to control mice. Flow-volume curves, generated to mimic human spirometry measurements, demonstrated larger volumes throughout the expiratory limb of the flow volume curves in Col5a1+/- compared to controls. Some parameters showed a sexual dimorphism with significant changes in male but not female mice. Our study identified a clear respiratory phenotype in the Col5a1+/- mouse model of EDS and indicated that intrinsic respiratory and lung changes may exist in cEDS patients. Their potential impact on the respiratory function during lung infections, other respiratory disease processes, or insults may be significant and justify further clinical evaluation.
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Síndrome de Ehlers-Danlos , Animales , Colágeno/genética , Colágeno Tipo V/genética , Modelos Animales de Enfermedad , Síndrome de Ehlers-Danlos/genética , Síndrome de Ehlers-Danlos/patología , Femenino , Haploinsuficiencia , Humanos , Pulmón/patología , Masculino , Ratones , MutaciónRESUMEN
Over 450 adverse incidents have been reported in infant inclined sleep products over the past 17â¯years, with many infants found dead in both the supine and prone positions. The unique design of inclined sleep products may present unexplored suffocation risks related to how these products impact an infant's ability to move. The purpose of this study was to assess body movement and muscle activity of healthy infants when they lie supine and prone on different inclined sleep products. Fifteen healthy full-term infants (age: 17.7⯱â¯4.9â¯weeks) were recruited for this IRB-approved study. Three inclined sleep products with unique features, representative of different sleeper designs, were included. Surface electromyography (EMG) was recorded from infants' cervical paraspinal, abdominal, and lumbar erector spinae muscles for 60â¯s during supine and prone positioning. Neck and trunk sagittal plane movements were evaluated for each testing condition. Paired t-tests and Wilcoxon signed-rank tests were performed to compare each inclined sleeper to a flat crib mattress (0° baseline condition). During prone positioning, abdominal muscle activity significantly nearly doubled for all inclined sleep products compared to the flat crib mattress, while erector spinae muscle activity decreased by up to 48%. Trunk movement significantly increased compared to the flat crib mattress during prone lying. During prone lying, inclined sleep products resulted in significantly higher muscle activity of the trunk core muscles (abdominals) and trunk movement, which has the potential to exacerbate fatigue and contribute to suffocation if an infant cannot self-correct to the supine position.
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Músculos Paraespinales , Sueño , Fenómenos Biomecánicos , Electromiografía , Humanos , Lactante , Movimiento , Posición Prona , Posición SupinaRESUMEN
The design of inclined sleep products may be associated with an increased risk of suffocation when an infant finds themselves prone in the product. It is important to understand how different inclined sleep surface angles impact infants' muscle activity when considering a safe sleep environment. The purpose of this study was to assess muscle activity of healthy infants when they lie supine and prone on different inclined crib mattress surfaces (0° vs. 10° vs. 20°). Fifteen healthy infants were recruited for this study. Surface EMG was recorded from cervical paraspinal, abdominal, lumbar erector spinae, and triceps muscles for 60 s during supine and prone positioning. Repeated measures ANOVAs and Bonferroni post-hoc adjustments were performed to test the effect of incline angles. Paired t-tests were performed to test the effect of position (supine vs. prone). During prone lying, abdominal muscle activity increased by 33% and 71% for 10° and 20° compared to 0°, while erector spinae and triceps muscle activity decreased for 20° compared to 0°. Lumbar erector spinae and cervical paraspinal muscle activity increased by 185% and 283% for prone compared to supine lying. During prone positioning, the 20° inclined surface resulted in significantly higher muscle activity of the trunk core muscles (abdominals), which may exacerbate fatigue and contribute to suffocation if an infant cannot self-correct to the supine position. Compared to supine positioning, prone lying requires higher musculoskeletal effort to maintain a safe posture to prevent suffocation, and babies likely fatigue faster when lying prone.
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Movimiento , Postura , Electromiografía , Humanos , Lactante , Músculos Paraespinales , Posición Prona , Sueño , Posición SupinaRESUMEN
BACKGROUND: The transition from an ICU ventilator to a portable home ventilator (PHV) for children requiring long-term mechanical ventilation is a crucial step in preparing for discharge home and may not be successful on the first attempt. A review of this process at our institution revealed that some children required multiple trials before they were able to tolerate a PHV. A protocol was developed to standardize the transition process and reduce the number of failed attempts. Key features of the protocol included a transition readiness assessment and criteria for changing to the PHV. METHODS: A retrospective chart review was completed to evaluate the process of changing to a PHV before and after the protocol was in place during the time period of 2011-2018. Primary outcome measures included the number of transition attempts and the length of time to achieve successful transition. A successful transition attempt was defined as the ability to tolerate a PHV for 14 d. RESULTS: The study included 56 children ≤ 3 y old with a tracheostomy who required long-term ventilator support. The majority of subjects were from the neonatal ICU and had a diagnosis of bronchopulmonary dysplasia. There was a significant decrease in the number of attempts (P = .005) and in the length of time (P = .01) to successfully transition to a PHV for those who underwent the protocol. CONCLUSIONS: The process of changing from an ICU ventilator to a PHV in children requiring long-term mechanical ventilation was improved through the use of a standardized protocol. Both the number of failed attempts and the length of time to achieve successful transition were reduced when the protocol was applied. Further study is needed to evaluate other medical and nonmedical factors that may affect successful transition to a PHV.
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Servicios de Atención de Salud a Domicilio , Ventiladores Mecánicos , Niño , Humanos , Unidades de Cuidados Intensivos , Respiración Artificial , Estudios Retrospectivos , Desconexión del VentiladorRESUMEN
Respiratory disease is a leading cause of mortality in patients with osteogenesis imperfecta (OI), a connective tissue disease that causes severely reduced bone mass and is most commonly caused by dominant mutations in type I collagen genes. Previous studies proposed that impaired respiratory function in OI patients was secondary to skeletal deformities; however, recent evidence suggests the existence of a primary lung defect. Here, we analyzed the lung phenotype of Crtap knockout (KO) mice, a mouse model of recessive OI. While we confirm changes in the lung parenchyma that are reminiscent of emphysema, we show that CrtapKO lung fibroblasts synthesize type I collagen with altered posttranslation modifications consistent with those observed in bone and skin. Unrestrained whole body plethysmography showed a significant decrease in expiratory time, resulting in an increased ratio of inspiratory time over expiratory time and a concomitant increase of the inspiratory duty cycle in CrtapKO compared with WT mice. Closed-chest measurements using the forced oscillation technique showed increased respiratory system elastance, decreased respiratory system compliance, and increased tissue damping and elasticity in CrtapKO mice compared with WT. Pressure-volume curves showed significant differences in lung volumes and in the shape of the curves between CrtapKO mice and WT mice, with and without adjustment for body weight. This is the first evidence that collagen defects in OI cause primary changes in lung parenchyma and several respiratory parameters and thus negatively impact lung function.
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Colágeno Tipo I/genética , Proteínas de la Matriz Extracelular/genética , Chaperonas Moleculares/genética , Osteogénesis Imperfecta/genética , Animales , Células Cultivadas , Modelos Animales de Enfermedad , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Mutación/genética , Procesamiento Proteico-Postraduccional/genéticaRESUMEN
RATIONALE: To determine if ventilatory pattern instability, manifested as periodic breathing (PB) during physiologic challenge testing, affects postmenstrual age (PMA) at discharge. METHODS: Eighty infants underwent challenge testing at 36 weeks PMA. Infants breathing supplemental O2 received a room air challenge (RAC, N = 51); those breathing ambient air underwent a hypoxic challenge test (HCT, N = 29). Infants were assigned one of four ventilatory control phenotypes based on the presence or absence of PB during their test, and if they passed or failed because of hypoxemia during the challenge test. RESULTS: There were no clinical or demographic differences between groups. Infants who passed their challenge testing were, on average, discharged 1.6 weeks sooner than those who failed. The groups of ventilatory control phenotypes differed in PMA at discharge (p = 0.0020), but those with PB were younger by PMA at discharge. CONCLUSIONS: Ventilatory pattern instability did not prolong time to discharge. Passing either challenge was associated with earlier discharge, suggesting these tests might identify infants who can have nasal cannula support removed and be safely discharged sooner. Most of the infants who failed their challenge tests with PB were receiving nasal cannula support. Nasal cannula support may be not only treating hypoxemia due to bronchopulmonary dysplasia (BPD), but also mitigating their ventilatory pattern instability.
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Recien Nacido Prematuro , Tiempo de Internación , Enfermedades Pulmonares/diagnóstico , Alta del Paciente , Respiración Artificial , Factores de Edad , Displasia Broncopulmonar/fisiopatología , Enfermedad Crónica , Femenino , Humanos , Hipoxia , Recién Nacido , Enfermedades del Prematuro/diagnóstico , Enfermedades del Prematuro/fisiopatología , Enfermedades del Prematuro/terapia , Enfermedades Pulmonares/fisiopatología , Enfermedades Pulmonares/terapia , MasculinoRESUMEN
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. METHODS: Continuous ECG, heart rate, respiratory, and oxygen saturation data will be collected throughout the NICU stay in 500 infants < 29 wks gestation across 5 centers. Mild permissive hypercapnia, and hyperoxia and/or hypoxia assessments will be conducted in a subcohort of infants along with inpatient questionnaires, urine, serum, and DNA samples. RESULTS: Primary outcomes will be respiratory status at 40 wks and quantitative measures of immature breathing plotted on a standard curve for infants matched at 36-37 wks. Physiologic and/or biologic determinants will be collected to enhance the predictive model linking ventilatory control to outcomes. CONCLUSIONS: By incorporating bedside monitoring variables along with biomarkers that predict respiratory outcomes we aim to elucidate individualized cardiopulmonary phenotypes and mechanisms of ventilatory control contributing to adverse respiratory outcomes in premature infants.
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Displasia Broncopulmonar/fisiopatología , Protocolos Clínicos , Femenino , Humanos , Recién Nacido , Recien Nacido Prematuro , Masculino , Monitoreo Fisiológico , Estudios Prospectivos , Proyectos de Investigación , Fenómenos Fisiológicos RespiratoriosRESUMEN
Study Objectives: Periodic breathing (PB) is common in newborns and is an obvious manifestation of ventilatory control instability. However, many infants without PB may still have important underlying ventilatory control instabilities that go unnoticed using standard clinical monitoring. Methods to detect infants with "subclinical" ventilatory control instability are therefore required. The current study aimed to assess the degree of ventilatory control instability using simple bedside recordings in preterm infants. Methods: Respiratory inductance plethysmography (RIP) recordings were analyzed from ~20 minutes of quiet sleep in 20 preterm infants at 36 weeks post-menstrual age (median [range]: 36 [34-40]). The percentage time spent in PB was also calculated for each infant (%PB). Spontaneous sighs were identified and breath-by-breath measurements of (uncalibrated) ventilation were derived from RIP traces. Loop gain (LG, a measure of ventilatory control instability) was calculated by fitting a simple ventilatory control model (gain, time-constant, delay) to the post-sigh ventilatory pattern. For comparison, periodic inter-breath variability was also quantified using power spectral analysis (ventilatory oscillation magnitude index [VOMI]). Results: %PB was strongly associated with LG (r2 = 0.77, p < 0.001) and moderately with the VOMI (r2 = 0.21, p = 0.047). LG (0.52 ± 0.05 vs. 0.30 ± 0.03; p = 0.0025) and the VOMI (-8.2 ± 1.1 dB vs. -11.8 ± 0.9 dB; p = 0.026) were both significantly higher in infants that displayed PB vs. those without. Conclusions: LG and VOMI determined from the ventilatory responses to spontaneous sighs can provide a practical approach to assessing ventilatory control instability in preterm infants. Such simple techniques may help identify infants at particular risk for ventilatory instabilities with concomitant hypoxemia and its associated consequences.
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Recien Nacido Prematuro/fisiología , Pletismografía/métodos , Mecánica Respiratoria/fisiología , Sueño/fisiología , Femenino , Humanos , Hipoxia/diagnóstico , Hipoxia/fisiopatología , Lactante , Recién Nacido , Proyectos Piloto , Estudios RetrospectivosAsunto(s)
Atención a la Salud/tendencias , Población Rural , Espirometría/estadística & datos numéricos , Telemedicina/métodos , Adolescente , Niño , Servicios de Salud Comunitaria , Femenino , Humanos , Masculino , Modelos Estadísticos , Garantía de la Calidad de Atención de Salud , Mejoramiento de la Calidad , Centros de Atención Terciaria , Estados Unidos/epidemiologíaRESUMEN
RATIONALE: The contribution of ventilatory control to the pathogenesis of obstructive sleep apnea (OSA) in preterm-born children is unknown. OBJECTIVES: To characterize phenotypes of ventilatory control that are associated with the presence of OSA in preterm-born children during early childhood. METHODS: Preterm- and term-born children without comorbid conditions were enrolled. They were categorized into an OSA group and a non-OSA group on the basis of polysomnography. MEASUREMENTS AND MAIN RESULTS: Loop gain, controller gain, and plant gain, reflecting ventilatory instability, chemoreceptor sensitivity, and blood gas response to a change in ventilation, respectively, were estimated from spontaneous sighs identified during polysomnography. Cardiorespiratory coupling, a measure of brainstem maturation, was estimated by measuring the interval between inspiration and the preceding electrocardiogram R-wave. Cluster analysis was performed to develop phenotypes based on controller gain, plant gain, cardiorespiratory coupling, and gestational age. The study included 92 children, 63 of whom were born preterm (41% OSA) and 29 of whom were born at term (48% OSA). Three phenotypes of ventilatory control were derived with risks for OSA being 8%, 47%, and 77% in clusters 1, 2, and 3, respectively. There was a stepwise decrease in controller gain and an increase in plant gain from clusters 1 to 3. Children in cluster 1 had significantly higher cardiorespiratory coupling and gestational age than clusters 2 and 3. No difference in loop gain was found between clusters. CONCLUSIONS: The risk for OSA could be stratified according to controller gain, plant gain, cardiorespiratory coupling, and gestational age. These findings could guide personalized care for children at risk for OSA.