This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Manganese (Mn) is an essential metal needed for normal growth and development. Exposure to high Mn concentrations can cause neurologic symptoms and brain injury. Sick infants requiring intravenous nutrition (total parenteral nutrition or TPN) may be at increased risk of Mn toxicity because current neonatal TPN formulations contain high concentrations of Mn ( ~100 times the daily Mn absorption of infants fed human milk). Iron deficiency, common among sick newborns, increases uptake of Mn into the brain. Liver problems also increase the risk of Mn uptake in the brain. Mn specifically accumulates in the brain and as a paramagnetic trace element, can be detected by Magnetic Resonance Imaging (MRI). The hypothesis is that MR intensities in selective Mn-sensitive brain regions of neonates receiving TPN will correlate directly with (1) dietary Mn intake, (2) total days on TPN, (3) blood Mn levels,(4) degree of liver dysfunction, and correlate inversely with gestational age and iron status. Forty eligible infants receiving intravenous nurtrition for more than 4 weeks will be enrolled over a 2-3 year period. Mn supplementation will be removed from the TPN of any infant with evidence of increased Mn deposits in the brain on the initial MRI study. This study will increase scientific knowledge by identifying neonatal populations at increased risk of excessive brain Mn uptake based on their degree of prematurity, iron status, liver dysfunction and dietary Mn intake. This study will provide the basis for evidence-based recommendations for appropriate Mn supplementation and monitoring of infants receiving intravenous nutrition.
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