Brain Manganese Deposition in High Risk Neonates
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Purpose
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.
| Condition | Intervention |
|---|---|
|
Necrotizing Enterocolitis Digestive System Abnormalities Cholestasis |
Dietary Supplement: remove Mn from PN if evidence of increased brain Mn on MRI |
| Study Type: | Observational |
| Study Design: | Time Perspective: Prospective |
| Official Title: | Brain Manganese Deposition in High Risk Neonates |
- Correlation between changes in MR signals and dietary Mn intake, number of days on PN and blood Mn levels [ Time Frame: at hospital discharge and 6 months of age ] [ Designated as safety issue: No ]
- Comparison of pallidal-white matter T1 ratios and absolute T1 and T2 values in control infants and neonates receiving Mn-supplemented PN. [ Time Frame: at hospital discharge and at 6 months of age ] [ Designated as safety issue: No ]
Biospecimen Retention: Samples Without DNA
Blood
| Enrollment: | 43 |
| Study Start Date: | August 2006 |
| Study Completion Date: | December 2010 |
| Primary Completion Date: | December 2010 (Final data collection date for primary outcome measure) |
-
Dietary Supplement: remove Mn from PN if evidence of increased brain Mn on MRI
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:
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).
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.
Eligibility| Ages Eligible for Study: | up to 12 Months |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
| Sampling Method: | Non-Probability Sample |
Neonates in the NICU on prolonged PN
Inclusion Criteria:
- Greater than 30 days postnatal age
- In the preceding four weeks have received >75% of their nutrition as Mn-supplemented PN
- Clinically stable for transport to the MR facility
- Signed parental consent.
Exclusion Criteria:
- Any infant not expected to survive to the age of 3 months or
- Not expected to achieve sufficient clinical stability to tolerate the MRI procedure.
Contacts and Locations| United States, Tennessee | |
| Vanderbilt Children's Hospital | |
| Nashville, Tennessee, United States, 37232-9544 | |
| Principal Investigator: | Judy L Aschner, MD | Vanderbilt University |
More Information
Publications:
| Responsible Party: | Judy L. Aschner, MD, Vanderbilt University Medical Center |
| ClinicalTrials.gov Identifier: | NCT00392977 History of Changes |
| Other Study ID Numbers: | ES013730, ES013730 |
| Study First Received: | October 25, 2006 |
| Last Updated: | March 29, 2011 |
| Health Authority: | United States: Institutional Review Board |
Keywords provided by Vanderbilt University:
|
Manganese Neonatal Intensive Care MRI Parenteral Nutrition Prematurity |
Additional relevant MeSH terms:
|
Enterocolitis Enterocolitis, Necrotizing Congenital Abnormalities Cholestasis Digestive System Abnormalities Bile Duct Diseases Biliary Tract Diseases Digestive System Diseases Gastroenteritis |
Gastrointestinal Diseases Intestinal Diseases Manganese Trace Elements Micronutrients Growth Substances Physiological Effects of Drugs Pharmacologic Actions |
ClinicalTrials.gov processed this record on June 17, 2013