Neurodevelopment and Neuroimaging in Parenterally-fed Infants and Young Children
Condition: Parenteral Nutrition; Necrotizing Enterocolitis; Digestive System Abnormalities; Cholestasis
MeSH terms: Enterocolitis; Cholestasis; Enterocolitis, Necrotizing; Digestive System Abnormalities
Study type: Observational

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.
    

Intervention name(s): Remove Mn from PN if evidence of increased brain Mn on MRI
Intervention type(s): Dietary Supplement
Intervention description(s): Withhold Mn-containing trace element cocktail and add zinc, copper and chromium individually to PN
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
      
Biospecimen description: 
      Blood
    
Keywords: Manganese; Neonatal Intensive Care; MRI; Parenteral Nutrition; Prematurity