Brain Manganese Deposition in High Risk Neonates
Trial Snapshot
- Phase
- Not Applicable
- Status
- Completed
- Sponsor
- Vanderbilt University
- Enrollment
- 43
- Locations
- 1
- Primary Endpoint
- Correlation between changes in MR signals and dietary Mn intake, number of days on PN and blood Mn levels
Study Overview
Brief Summary
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.
Detailed Description
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).
Study Design
- Study Type
- Observational
- Time Perspective
- Prospective
Eligibility Criteria
- Ages
- 30 Days to 12 Months (Child)
- Sex
- All
- Accepts Healthy Volunteers
- No
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.
Outcomes
Primary Outcomes
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
Secondary Outcomes
- Comparison of pallidal-white matter T1 ratios and absolute T1 and T2 values in control infants and neonates receiving Mn-supplemented PN.(at hospital discharge and at 6 months of age)
Investigators
Judy Aschner
Adjunct Professor of Pediatrics
Vanderbilt University