Brain Manganese Deposition in High Risk Neonates

December 17, 2013 updated by: Judy Aschner, Vanderbilt University

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Dietary supplement: remove Mn from PN if evidence of increased brain Mn on MRI

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).

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.

Study Type

Observational

Enrollment (Actual)

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

United States
- Tennessee
  - Nashville, Tennessee, United States, 37232-9544
    - Vanderbilt Children's Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 month to 1 year (Child)

Accepts Healthy Volunteers

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Neonates in the NICU on prolonged PN

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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	at hospital discharge and 6 months of age

Secondary Outcome Measures

Outcome Measure	Time Frame
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	at hospital discharge and at 6 months of age

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Vanderbilt University

Collaborators

National Institute of Environmental Health Sciences (NIEHS)

Investigators

Principal Investigator: Judy L Aschner, MD, Vanderbilt University Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 2006

Primary Completion (Actual)

December 1, 2010

Study Completion (Actual)