This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Almost 5,000 extremely low birth weight (ELBW, birth weight d1000 g; d2 lbs, 3 ounces) infants per year in the US develop severe intraventricular hemorrhage (IVH) that is associated with mental retardation, cerebral palsy, and learning disabilities. As lifetime care costs in these infants exceed $3 billion, IVH in ELBW infants is a major public health problem. Unfortunately, the incidence of severe IVH in ELBW infants has remained constant over the last decade, and accurately identifying the ELBW infants at highest risk of developing IVH has been difficult. Therefore, the long-term goal of our patient-oriented clinical research is to determine the effects of disturbed physiological phenomena associated with IVH in order to predict those infants most at risk and to develop best care clinical practices that may limit severe brain injury. We hypothesize that reducing alterations and extremes of carbon dioxide, blood pressure, and heart rate, factors that influence cerebral blood flow and cerebral autoregulation in ELBW infants, may mitigate the development of IVH and serve as important predictors of ELBW infants most at risk of developing IVH. This will be investigated through a series of clinical studies that will address: 1) whether normocapnic ventilation vs. traditional hypercapnic ventilation will reduce the develop of severe IVH by shifting the incidence to lower grade or no IVH (randomized controlled trial), 2) whether hypotensive ELBW infants have restored intact cerebral autoregulation or continued pressure-passive cerebral blood flow when blood pressure is normalized, and how the postnatal pattern of development of cerebral autoregulation is altered in hypotensive infants, using our novel continuous physiological monitoring system, and 3) whether altered fractal heart rhythm dynamics will serve as an accurate predictor of impending IVH. We will use our continuous physiological monitoring system developed during our K23 studies to determine cerebral autoregulatory capacity during treatment of hypotension and the developmental pattern of cerebral autoregulation during the first week of life. Heart rhythm dynamics on the first day of life will be determined and its value at a predictor of impending IVH will be evaluated. If successful, our proposed clinical studies will reduce the burden of neurological disease in newborn ELBW infants by developing better care clinical practices and by providing a new accurate predictor of impending IVH, so that high risk infants may be identified and interventions applied to limit the development of IVH.
| Odle, Angela; Allensworth-James, Melody; Childs, Gwen V (2018) The War on the Placenta: The Differing Battles of High-Fat Diet and Obesity. Endocrinology 159:1642-1643 |
| MacNicol, Melanie C; Cragle, Chad E; McDaniel, F Kennedy et al. (2017) Evasion of regulatory phosphorylation by an alternatively spliced isoform of Musashi2. Sci Rep 7:11503 |
| Rhee, Christopher J; Kaiser, Jeffrey R; Rios, Danielle R et al. (2016) Elevated Diastolic Closing Margin Is Associated with Intraventricular Hemorrhage in Premature Infants. J Pediatr 174:52-6 |
| Odle, Angela Katherine; Allensworth-James, Melody; Haney, Anessa et al. (2016) Adipocyte Versus Somatotrope Leptin: Regulation of Metabolic Functions in the Mouse. Endocrinology 157:1443-56 |
| Gannon, Brenda M; Williamson, Adrian; Suzuki, Masaki et al. (2016) Stereoselective Effects of Abused ""Bath Salt"" Constituent 3,4-Methylenedioxypyrovalerone in Mice: Drug Discrimination, Locomotor Activity, and Thermoregulation. J Pharmacol Exp Ther 356:615-23 |
| Rhee, Christopher J; Kibler, Kathleen K; Easley, R Blaine et al. (2016) The Diastolic Closing Margin Is Associated with Intraventricular Hemorrhage in Premature Infants. Acta Neurochir Suppl 122:147-50 |
| Odle, Angela K; Allensworth-James, Melody L; Akhter, Noor et al. (2016) A Sex-Dependent, Tropic Role for Leptin in the Somatotrope as a Regulator of POU1F1 and POU1F1-Dependent Hormones. Endocrinology 157:3958-3971 |
| MacNicol, Melanie C; Cragle, Chad E; Arumugam, Karthik et al. (2015) Functional Integration of mRNA Translational Control Programs. Biomolecules 5:1580-99 |
| Rhee, Christopher J; Fraser 3rd, Charles D; Kibler, Kathleen et al. (2015) Ontogeny of cerebrovascular critical closing pressure. Pediatr Res 78:71-5 |
| Odle, Angela K; Drew, Paul D; Childs, Gwen V (2015) Giant mice reveal new roles for GH in regulating the adipose immune microenvironment. Endocrinology 156:1613-5 |
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