Neuroimaging identifies increased manganese deposition in infants receiving parenteral nutrition

Judy L. Aschner, Adam Anderson, James Christopher Slaughter, Michael Aschner, Steven Steele, Amy Beller, Amanda Mouvery, Heather M. Furlong, Nathalie L. Maitre

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Background: Manganese, an essential metal for normal growth and development, is neurotoxic on excessive exposure. Standard trace element-supplemented neonatal parenteral nutrition (PN) has a high manganese content and bypasses normal gastrointestinal absorptive control mechanisms, which places infants at risk of manganese neurotoxicity. Magnetic resonance (MR) relaxometry demonstrating short T1 relaxation time (T1R) in the basal ganglia reflects excessive brain manganese accumulation. Objective: This study tested the hypothesis that infants with greater parenteral manganese exposure have higher brain manganese accumulation, as measured by MR imaging, than do infants with lower parenteral manganese exposure. Design: Infants exposed to parenteral manganese were enrolled in a prospective cohort study. Infants classified as having high manganese exposure received .75% of their nutrition in the preceding 4 wk as PN. All others were classified as having low exposure. Daily parenteral and enteral manganese intakes were calculated. Wholeblood manganese was measured by high-resolution inductively coupled plasma mass spectrometry. Brain MR relaxometry was interpreted by a masked reviewer. Linear regression models, adjusted for gestational age (GA) at birth, estimated the association of relaxometry indexes with total and parenteral manganese exposures. Results: Seventy-three infants were enrolled. High-quality MR images were available for 58 infants, 39 with high and 19 with low manganese exposure. Four infants with a high exposure had blood manganese concentrations .30 mg/L. After controlling for GA, higher parenteral and total manganese intakes were associated with a lower T1R (P = 0.01) in the globus pallidus and putamen but were not associated with whole-blood manganese (range: 3.6-56.6 mg/L). Elevated conjugated bilirubin magnified the association between parenteral manganese and decreasing T1R. Conclusion: A short T1R for GA identifies infants at risk of increased brain manganese deposition associated with PN solutions commonly used to nourish critically ill infants. These trials were registered at clinicaltrials.gov as NCT00392977 and NCT00392730.

Original languageEnglish (US)
Pages (from-to)1482-1489
Number of pages8
JournalAmerican Journal of Clinical Nutrition
Volume102
Issue number6
DOIs
StatePublished - Dec 1 2015

Fingerprint

Parenteral Nutrition
Manganese
Neuroimaging
Gestational Age
Magnetic Resonance Spectroscopy
Brain
Linear Models
Parenteral Nutrition Solutions
Globus Pallidus
Putamen
Trace Elements
Basal Ganglia

Keywords

  • Infants
  • Manganese
  • Neuroimaging
  • Parenteral nutrition
  • Trace metals

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Nutrition and Dietetics

Cite this

Neuroimaging identifies increased manganese deposition in infants receiving parenteral nutrition. / Aschner, Judy L.; Anderson, Adam; Slaughter, James Christopher; Aschner, Michael; Steele, Steven; Beller, Amy; Mouvery, Amanda; Furlong, Heather M.; Maitre, Nathalie L.

In: American Journal of Clinical Nutrition, Vol. 102, No. 6, 01.12.2015, p. 1482-1489.

Research output: Contribution to journalArticle

Aschner, JL, Anderson, A, Slaughter, JC, Aschner, M, Steele, S, Beller, A, Mouvery, A, Furlong, HM & Maitre, NL 2015, 'Neuroimaging identifies increased manganese deposition in infants receiving parenteral nutrition', American Journal of Clinical Nutrition, vol. 102, no. 6, pp. 1482-1489. https://doi.org/10.3945/ajcn.115.116285
Aschner, Judy L. ; Anderson, Adam ; Slaughter, James Christopher ; Aschner, Michael ; Steele, Steven ; Beller, Amy ; Mouvery, Amanda ; Furlong, Heather M. ; Maitre, Nathalie L. / Neuroimaging identifies increased manganese deposition in infants receiving parenteral nutrition. In: American Journal of Clinical Nutrition. 2015 ; Vol. 102, No. 6. pp. 1482-1489.
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abstract = "Background: Manganese, an essential metal for normal growth and development, is neurotoxic on excessive exposure. Standard trace element-supplemented neonatal parenteral nutrition (PN) has a high manganese content and bypasses normal gastrointestinal absorptive control mechanisms, which places infants at risk of manganese neurotoxicity. Magnetic resonance (MR) relaxometry demonstrating short T1 relaxation time (T1R) in the basal ganglia reflects excessive brain manganese accumulation. Objective: This study tested the hypothesis that infants with greater parenteral manganese exposure have higher brain manganese accumulation, as measured by MR imaging, than do infants with lower parenteral manganese exposure. Design: Infants exposed to parenteral manganese were enrolled in a prospective cohort study. Infants classified as having high manganese exposure received .75{\%} of their nutrition in the preceding 4 wk as PN. All others were classified as having low exposure. Daily parenteral and enteral manganese intakes were calculated. Wholeblood manganese was measured by high-resolution inductively coupled plasma mass spectrometry. Brain MR relaxometry was interpreted by a masked reviewer. Linear regression models, adjusted for gestational age (GA) at birth, estimated the association of relaxometry indexes with total and parenteral manganese exposures. Results: Seventy-three infants were enrolled. High-quality MR images were available for 58 infants, 39 with high and 19 with low manganese exposure. Four infants with a high exposure had blood manganese concentrations .30 mg/L. After controlling for GA, higher parenteral and total manganese intakes were associated with a lower T1R (P = 0.01) in the globus pallidus and putamen but were not associated with whole-blood manganese (range: 3.6-56.6 mg/L). Elevated conjugated bilirubin magnified the association between parenteral manganese and decreasing T1R. Conclusion: A short T1R for GA identifies infants at risk of increased brain manganese deposition associated with PN solutions commonly used to nourish critically ill infants. These trials were registered at clinicaltrials.gov as NCT00392977 and NCT00392730.",
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AU - Aschner, Judy L.

AU - Anderson, Adam

AU - Slaughter, James Christopher

AU - Aschner, Michael

AU - Steele, Steven

AU - Beller, Amy

AU - Mouvery, Amanda

AU - Furlong, Heather M.

AU - Maitre, Nathalie L.

PY - 2015/12/1

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N2 - Background: Manganese, an essential metal for normal growth and development, is neurotoxic on excessive exposure. Standard trace element-supplemented neonatal parenteral nutrition (PN) has a high manganese content and bypasses normal gastrointestinal absorptive control mechanisms, which places infants at risk of manganese neurotoxicity. Magnetic resonance (MR) relaxometry demonstrating short T1 relaxation time (T1R) in the basal ganglia reflects excessive brain manganese accumulation. Objective: This study tested the hypothesis that infants with greater parenteral manganese exposure have higher brain manganese accumulation, as measured by MR imaging, than do infants with lower parenteral manganese exposure. Design: Infants exposed to parenteral manganese were enrolled in a prospective cohort study. Infants classified as having high manganese exposure received .75% of their nutrition in the preceding 4 wk as PN. All others were classified as having low exposure. Daily parenteral and enteral manganese intakes were calculated. Wholeblood manganese was measured by high-resolution inductively coupled plasma mass spectrometry. Brain MR relaxometry was interpreted by a masked reviewer. Linear regression models, adjusted for gestational age (GA) at birth, estimated the association of relaxometry indexes with total and parenteral manganese exposures. Results: Seventy-three infants were enrolled. High-quality MR images were available for 58 infants, 39 with high and 19 with low manganese exposure. Four infants with a high exposure had blood manganese concentrations .30 mg/L. After controlling for GA, higher parenteral and total manganese intakes were associated with a lower T1R (P = 0.01) in the globus pallidus and putamen but were not associated with whole-blood manganese (range: 3.6-56.6 mg/L). Elevated conjugated bilirubin magnified the association between parenteral manganese and decreasing T1R. Conclusion: A short T1R for GA identifies infants at risk of increased brain manganese deposition associated with PN solutions commonly used to nourish critically ill infants. These trials were registered at clinicaltrials.gov as NCT00392977 and NCT00392730.

AB - Background: Manganese, an essential metal for normal growth and development, is neurotoxic on excessive exposure. Standard trace element-supplemented neonatal parenteral nutrition (PN) has a high manganese content and bypasses normal gastrointestinal absorptive control mechanisms, which places infants at risk of manganese neurotoxicity. Magnetic resonance (MR) relaxometry demonstrating short T1 relaxation time (T1R) in the basal ganglia reflects excessive brain manganese accumulation. Objective: This study tested the hypothesis that infants with greater parenteral manganese exposure have higher brain manganese accumulation, as measured by MR imaging, than do infants with lower parenteral manganese exposure. Design: Infants exposed to parenteral manganese were enrolled in a prospective cohort study. Infants classified as having high manganese exposure received .75% of their nutrition in the preceding 4 wk as PN. All others were classified as having low exposure. Daily parenteral and enteral manganese intakes were calculated. Wholeblood manganese was measured by high-resolution inductively coupled plasma mass spectrometry. Brain MR relaxometry was interpreted by a masked reviewer. Linear regression models, adjusted for gestational age (GA) at birth, estimated the association of relaxometry indexes with total and parenteral manganese exposures. Results: Seventy-three infants were enrolled. High-quality MR images were available for 58 infants, 39 with high and 19 with low manganese exposure. Four infants with a high exposure had blood manganese concentrations .30 mg/L. After controlling for GA, higher parenteral and total manganese intakes were associated with a lower T1R (P = 0.01) in the globus pallidus and putamen but were not associated with whole-blood manganese (range: 3.6-56.6 mg/L). Elevated conjugated bilirubin magnified the association between parenteral manganese and decreasing T1R. Conclusion: A short T1R for GA identifies infants at risk of increased brain manganese deposition associated with PN solutions commonly used to nourish critically ill infants. These trials were registered at clinicaltrials.gov as NCT00392977 and NCT00392730.

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