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Hibbs -Association Between Intermittent Hypoxia and Later Respiratory Morbidity

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Project Summary Longer term respiratory morbidity remains a major consequence of preterm birth. We seek to characterize the association between immature respiratory control manifest as intermittent hypoxia [IH] and later respiratory morbidity in a cohort of preterm infants less than or equal to 30 weeks' gestation. Our hypotheses in Aims 1 and 2 are that IH episodes at one week and one month of life are significantly associated with prolonged duration of hospitalization and respiratory support, as well as a high incidence of wheezing disorders by six months adjusted age. In Aim 3 we hypothesize that low serotonin levels are associated with a high incidence of IH and a prolonged recovery of respiratory effort after onset of desaturation. Finally, in Aim 4 we hypothesize a temporal relationship between IH episodes and markers of oxidative stress determined by urine and blood samples. In prior studies we have demonstrated that apnea almost always precedes desaturation in preterm infants and have documented a novel association between retinopathy of prematurity, and both the duration of IH events and the time interval between IH events. From these data we speculate that it is both longer IH events and a distinct time interval of at least one minute between IH events that will be associated with respiratory morbidity and accompanying oxidative stress. This proposal provides a unique opportunity to quantify, for the first time, a relationship between IH and biomarkers of oxidation. We provide additional retrospective data that IH is associated with both increased length of stay and postnatal wheezing disorders, as well as a remarkable track record for both meeting enrollment goals and effective follow-up in prior clinical trials. Additionally, we have a strong track record for collection of continuous cardiorespiratory waveforms with bioengineering expertise in signal acquisition and processing that is ideally suited for multicenter data collection. In conclusion, our investigators' expertise in the measurement and analysis of respiratory and saturation waveforms, characterization of IH events, the basic science of respiratory control, and the measurement of clinical respiratory outcomes, makes us ideally poised to execute this single center, as well as multisite, proposal.
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