Clinical trial NCT00392730: Neurodevelopment and Neuroimaging in Parenterally-fed Infants and Young Children
Official title: Neurodevelopment and Neuroimaging in Parenterally-fed Infants and Young Children
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Parenteral Nutrition
Necrotizing Enterocolitis
Digestive System Abnormalities
Cholestasis
Keywords: Manganese
Neonatal Intensive Care
MRI
Parenteral Nutrition
Prematurity
Lead sponsor: Vanderbilt University
Sponsor class: OTHER
Collaborators: name: The Gerber Foundation
First posted: 2006-10-26
Enrollment: 122
Sex: ALL
Minimum age (years): 30
Maximum age (years): 6
Standard ages: CHILD
Accepts healthy volunteers: yes
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Term and preterm infants on prolonged PN in the NICU and post-discharge and young children on home PN and age-matched controls

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Brain Mn deposition measured by MR relaxometry
timeFrame: baseline (at study enrolment)
Secondary outcomes:
measure: Neurodevelopmental outcomes
timeFrame: 2 years
Other outcomes:
Locations:
city: Nashville
country: United States
facility: Vanderbilt Children's Hospital
state: Tennessee
Study officials:
affiliation: Vanderbilt University Medical Center
name: Judy L Aschner, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Aschner JL, Aschner M. Nutritional aspects of manganese homeostasis. Mol Aspects Med. 2005 Aug-Oct;26(4-5):353-62. doi: 10.1016/j.mam.2005.07.003.
citation: Fitsanakis VA, Zhang N, Avison MJ, Gore JC, Aschner JL, Aschner M. The use of magnetic resonance imaging (MRI) in the study of manganese neurotoxicity. Neurotoxicology. 2006 Sep;27(5):798-806. doi: 10.1016/j.neuro.2006.03.001. Epub 2006 Apr 18.
citation: Fitsanakis VA, Piccola G, Marreilha dos Santos AP, Aschner JL, Aschner M. Putative proteins involved in manganese transport across the blood-brain barrier. Hum Exp Toxicol. 2007 Apr;26(4):295-302. doi: 10.1177/0960327107070496.
citation: Yin Z, Aschner JL, dos Santos AP, Aschner M. Mitochondrial-dependent manganese neurotoxicity in rat primary astrocyte cultures. Brain Res. 2008 Apr 8;1203:1-11. doi: 10.1016/j.brainres.2008.01.079. Epub 2008 Feb 11.
citation: Aschner JL, Anderson A, Slaughter JC, Aschner M, Steele S, Beller A, Mouvery A, Furlong HM, Maitre NL. Neuroimaging identifies increased manganese deposition in infants receiving parenteral nutrition. Am J Clin Nutr. 2015 Dec;102(6):1482-9. doi: 10.3945/ajcn.115.116285. Epub 2015 Nov 11.