Neurodevelopment and Neuroimaging in Parenterally-fed Infants and Young Children

Completed

• Conditions: Necrotizing Enterocolitis; Cholestasis; Parenteral Nutrition; Digestive System Abnormalities
• Interventions: Dietary Supplement: Remove Mn from PN if evidence of increased brain Mn on MRI

• Registration Number: NCT00392730
• Lead Sponsor: Vanderbilt University

Brief Summary

Manganese (Mn) is an essential metal required for normal growth and development. However, exposure to high Mn levels can be toxic to the brain. The objectives of this project are to identify neonatal and young pediatric populations that are at increased risk of excessive brain Mn deposition and altered cognitive and motor development based on their dietary parenteral Mn exposure, and to make sound and evidence-based recommendations for appropriate Mn supplementation and monitoring of infants and young children receiving parenteral nutrition (PN). Our studies are designed to test the hypotheses that, compared with unexposed age-matched controls, infants and young children receiving prolonged Mn-supplemented PN will have increased deposition of Mn in their brains and lower scores on neurodevelopmental, cognitive and psychophysiological assessments.

Detailed Description

Specific Aims have been designed to test these hypotheses in three developmentally distinct populations:

1. preterm infants and

2. full term infants in the Neonatal Intensive Care Unit (NICU) requiring prolonged PN and

3. older infants and young children on home PN.

Mn neurotoxicity will be investigated by longitudinal assessments of cognitive (executive functioning battery), neurodevelopmental (Bayley III Scales of Infant Development), and psychophysiological (event-related potential) measures and will be correlated with brain deposition of Mn using the technique of magnetic resonance (MR) relaxometry in a vulnerable population of infants receiving Mn-supplemented PN and age-matched controls. This proposal addresses a clinically relevant and unexplored link between nutritional practices, brain Mn deposition and neurodevelopmental sequelae in an at-risk population of infants and young children utilizing state-of-the-art magnetic resonance imaging (MRI) technology and neurodevelopmental assessment techniques. The potential for increased brain Mn accumulation in infants, and by inference, the potential health risks associated with elevated brain Mn burden, represents crucial, unexplored issues of exposure and susceptibility. The potential contribution of Mn toxicity to the poor outcomes of infants dependent for an extended time on PN has not been fully acknowledged or studied. Improved understanding of the relationships between Mn exposure and developmental outcomes will undoubtedly lead to altered clinical practices and more careful monitoring of Mn intake and blood and/or brain Mn levels in high risk infants. Our studies will also contribute to an improved understanding of the value of non-invasive MR imaging in the monitoring of pediatric patients on PN.

Study Timeline

• Study Start: 2006-08
• Study First Submitted: 2006-10-25
• Study First Submitted QC: 2006-10-25
• Study First Posted: 2006-10-26
• Primary Completion: 2010-12
• Study Completion: 2010-12
• Status Verified: 2013-12
• Last Update Submitted: 2013-12-18
• Last Update Posted: 2013-12-19

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 122

Inclusion Criteria

1. Greater than 30 days postnatal age
2. In the preceding four weeks, have received >75% of their nutrition as Mn-supplemented PN
3. Clinically stable for transport to the MR facility
4. Signed parental consent.

Or healthy age-matched controls

Exclusion Criteria

1. Any infant not expected to survive to the age of 3 months or
2. Not expected to achieve sufficient clinical stability to tolerate the MRI procedure.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
3	Remove Mn from PN if evidence of increased brain Mn on MRI	Children on home PN (to age 6) and age-matched controls
2	Remove Mn from PN if evidence of increased brain Mn on MRI	Term infants in NICU and age-matched controls
1	Remove Mn from PN if evidence of increased brain Mn on MRI	Preterm infants in NICU and age-matched controls

Primary Outcome Measures

Name	Time	Method
Brain Mn deposition measured by MR relaxometry	baseline (at study enrolment)	Mn neurotoxicity will be investigated by magnetic resonance (MR) relaxometry in a population of infants receiving Mn-supplemented parenteral nutrition and age-matched controls.

Secondary Outcome Measures

Name	Time	Method
Neurodevelopmental outcomes	2 years	Neurodevelopment will be investigated by longitudinal assessments of cognitive (executive functioning battery), neurodevelopmental (Bayley III Scales of Infant Development), and psychophysiological (event-related potential) measures

Trial Locations

Locations (1)

Vanderbilt Children's Hospital; 🇺🇸 Nashville, Tennessee, United States