Neurodevelopment and Neuroimaging in Parenterally-fed Infants and Young Children

Study Overview
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Brief Summary
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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
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Specific Aims have been designed to test these hypotheses in three developmentally distinct populations: preterm infants and full term infants in the Neonatal Intensive Care Unit (NICU) requiring prolonged PN and 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.

Official Title
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Neurodevelopment and Neuroimaging in Parenterally-fed Infants and Young Children

Conditions
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Parenteral Nutrition, Necrotizing Enterocolitis, Digestive System Abnormalities, Cholestasis

Intervention / Treatment
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* Dietary Supplement: Remove Mn from PN if evidence of increased brain Mn on MRI


Participation Criteria
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Eligibility Criteria
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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. Or healthy age-matched controls 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.

Ages Eligible for Study
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Minimum Age: 30 Days
Maximum Age: 6 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| 1<br>Preterm infants in NICU and age-matched controls | Dietary Supplement: Remove Mn from PN if evidence of increased brain Mn on MRI<br>* Withhold Mn-containing trace element cocktail and add zinc, copper and chromium individually to PN<br>|
| 2<br>Term infants in NICU and age-matched controls | Dietary Supplement: Remove Mn from PN if evidence of increased brain Mn on MRI<br>* Withhold Mn-containing trace element cocktail and add zinc, copper and chromium individually to PN<br>|
| 3<br>Children on home PN (to age 6) and age-matched controls | Dietary Supplement: Remove Mn from PN if evidence of increased brain Mn on MRI<br>* Withhold Mn-containing trace element cocktail and add zinc, copper and chromium individually to PN<br>|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neurodevelopmental outcomes | 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 | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MRI, Manganese, Neonatal Intensive Care, Parenteral Nutrition, Prematurity