This ?Pre-Vent Apnea? application brings together established investigators at the University of Alabama at Birmingham (UAB; Clinical Site) with expertise in neonatal clinical and translational research and at the University of Massachusetts Medical School (UMASS; Analytical Core) with complementary expertise in control of breathing and signal processing in physiological systems. The overall objective of the local project is to use a prospective cohort of 200 preterm infants <29 weeks gestation at UAB to prospectively define and validate ventilatory mechanisms associated with resilience against or risk for development of impaired oxygenation at 36 weeks' postmenstrual age (physiologic definition of BPD) and at follow-up (corrected age of 3 months) using multiparametric physiologic monitoring and intensive data collection (96 hours each) at three distinct time frames: 2 weeks postnatal age, 32 weeks post-menstrual age (PMA), 36 weeks PMA, in addition to continuous heart rate, respiratory rate, and pulse oximetry waveform recording from enrollment soon after birth until discharge. We will address the objective by the following Specific Aims:
Specific Aim 1 - Development and validation of mathematical models of personalized ventilatory patterns based on multiparametric vital signs monitoring and signal analysis methods to (a) predict hypoxemic and/or bradycardic episodes in individual infants before they occur, (b) identify patterns of ventilatory abnormalities associated with BPD with and without pulmonary hypertension, as well as with and without respiratory or feeding support at 3 months corrected age.
Specific Aim 2 - Determine if late (at or beyond postnatal day 14) mild permissive hypercapnia is associated with reduction in apnea, bradycardia, and hypoxemic episodes and with improved stability of oxygenation.
Specific Aim 3 ? Determine if servo-controlled oxygen environment is associated with reduction in hypoxemic episodes and improved stability of oxygenation, as compared to oxygen administered by nasal cannula. In addition, for the multicenter collaborative project, we will collaborate with other clinical research centers and a Leadership and Data Coordinating Center (LDCC) on a multicenter protocol that will investigate ventilatory control mechanisms in outcomes of instability of oxygenation and acute and chronic morbidity. The ultimate goal of our participation in this project is to gain greater insight into the pathogenesis of respiratory disorders in extremely preterm infants and discover targets for new prevention and treatment strategies to improve outcomes for very vulnerable children at the beginning of life.

Public Health Relevance

Preterm infants often have abnormal control of breathing, resulting in prolonged pauses in breathing, drops in heart rate, or decreases in blood oxygen levels. In this study, we will use intensive data collection from multiple monitoring methods to develop mathematical models and understand how control of breathing is abnormal in preterm infants, and how it is associated with poor outcomes at follow-up.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01HL133536-04
Application #
9762173
Study Section
Special Emphasis Panel (ZHL1)
Program Officer
Laposky, Aaron D
Project Start
2016-08-22
Project End
2021-06-30
Budget Start
2019-07-01
Budget End
2020-06-30
Support Year
4
Fiscal Year
2019
Total Cost
Indirect Cost
Name
University of Alabama Birmingham
Department
Pediatrics
Type
Schools of Medicine
DUNS #
063690705
City
Birmingham
State
AL
Country
United States
Zip Code
35294
Travers, Colm P; Carlo, Waldemar A; Nakhmani, Arie et al. (2018) Environmental or Nasal Cannula Supplemental Oxygen for Preterm Infants: A Randomized Cross-Over Trial. J Pediatr 200:98-103