Brain Manganese Deposition in High Risk Neonates
| Status: | Archived |
|---|---|
| Conditions: | Colitis, Women's Studies, Gastrointestinal |
| Therapuetic Areas: | Gastroenterology, Reproductive |
| Healthy: | No |
| Age Range: | Any |
| Updated: | 7/1/2011 |
Excessive exposure to manganese (Mn) results in Mn deposition in the brain causing adverse
neurological effects. Sick infants requiring parenteral nutrition (PN) may be at increased
risk of Mn neurotoxicity because neonatal PN solutions contain high concentrations of Mn.
This proposal will investigate brain deposition of Mn, a paramagnetic element, by magnetic
resonance (MR) imaging in preterm and term neonates receiving Mn-supplemented PN and
gestational age-matched control infants. The goals of this project are to identify neonatal
populations that are at increased risk of excessive brain Mn deposition based on their
gestational age, iron status, hepatic function and dietary Mn intake, and to make
evidence-based recommendations for appropriate Mn supplementation and monitoring of infants
receiving PN.
Manganese (Mn) is an essential metal needed for normal growth and development. Excessive
environmental or dietary exposure results in Mn deposition in Mn-sensitive brain regions
causing adverse psychological and neurological effects. Sick infants requiring parenteral
nutrition (PN) may be at increased risk of Mn neurotoxicity because neonatal PN solutions
contain high concentrations of Mn, PN bypasses the normal intestinal absorptive control and
biliary excretory mechanisms for Mn, and infants are at a critical stage of brain
development. Furthermore, iron (Fe) deficiency, a common problem among sick neonates,
increases Mn brain uptake because Mn and Fe compete for the same carrier transport systems
in the central nervous system. This proposal will investigate brain deposition of Mn, a
paramagnetic element, by magnetic resonance (MR) imaging in 40 neonates receiving
Mn-supplemented PN and 10 control infants.
Two specific aims will test the following hypotheses:
1. Shortening of MR T1 and T2 relaxation times (a marker for Mn) in Mn-sensitive brain
regions in neonates receiving PN will correlate directly with
- dietary Mn intake,
- days on PN,
- blood Mn levels (measured by Inductively Coupled Plasma-Mass Spectrometry)
- hepatic dysfunction/cholestasis (assessed by conjugated bilirubin levels).
2. shortening of T1 and T2 relaxation times will correlate inversely with
- gestational age
- Fe status (assessed by serum Fe, ferritin, transferrin, soluble transferrin
receptor and hemoglobin).
The potential for increased brain Mn accumulation in infants and the potential health risks
associated with elevated brain Mn burden represent crucial, unexplored issues of exposure
and susceptibility. The impact of dietary Mn, and especially parenterally delivered dietary
Mn, gestational age, Fe status, and hepatic dysfunction on the ability of the neonatal brain
to regulate Mn deposition has not been scientifically addressed. The proposed clinical
investigation has enormous health significance and may shed light on the development and
progression of neurological dysfunction in infants and children on prolonged parenteral
nutrition.
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