Mn Exposures at Birth

Concerns Regarding Manganese Exposures from Parenteral (Intravenous) Nutrition – Commonly Given in Cases of Premature & Other Challenges at Birth

 

OCT 2001 – Office of Environmental Health Hazard Assessment, State of California

Children’s Environmental Health Protection Act – Manganese and Compounds

“There is evidence from human studies and animal experiments that manganese exposure can lead to neurodevelopmental and behavioral effects. Neurotoxicity and developmental toxicity are two of the key toxicological endpoints of concern to infants and children.”

“Experiments in farm animals and laboratory animals (rats) indicate that manganese homeostasis is “suspended” during pregnancy and lactation. Suspension of homeostasis allows for higher levels of manganese in blood and in tissues including brain.”

“Children receiving total parenteral nutrition (TPN) are at increased risk for hypermanganesemia, cholestasis, and basal ganglia damage. TPN appears to bypass the normal homeostatic controls on blood manganese levels.”

“The normal “reference range” for manganese in the blood is 72 to 210 nmol/L [nanomoles per liter]. Eleven child patients on TPN who were identified as having hypermanganesemia and cholestasis had blood manganese levels of 615 to 1840 nmol/L.”

Summary statement: “Human studies show that hyperactive children and children with learning disabilities may have higher hair levels of manganese than normal children. This suggests that manganese may act as a neurodevelopmental toxicant on young children. Animal studies show that newborn animals are unable to maintain homeostasis of manganese and that as a result, manganese accumulates in the brains of animals exposed at young ages.”

 

AUG 2005 – Vanderbilt University Medical Center, Nashville, TN

Nutritional Aspects of Manganese Homeostasis

“While naturally occurring deficiency states have not been recognized, Mn-induced neurotoxicity from excess respiratory or dietary exposures has been well described.”

“This review focuses on an area that to date has received little consideration, namely the potential exposure of parenterally [intravenous] fed neonates to exceedingly high Mn concentrations in parenteral nutrition solutions, potentially increasing their risk for Mn-induced adverse health sequellae.”

“It is very common for premature or critically ill infants to be nourished parenterally. Parenteral nutrition solutions contain variable quantities of Mn as a contaminant.”

“Biliary secretion is the main pathway for Mn excretion. More than 90% of Mn is excreted through the bile.”

“Biliary excretion is poorly developed in neonatal animals, and exposure during this period may result in increased delivery of Mn into the brain and other tissues. Urinary excretion of Mn is generally low.”

“Not only is the absorptive control of the intestine bypassed in infants receiving Mn-supplemented parenteral nutrition, but the excretion on Mn is likely to be minimal as parenterally fed infants pass little or no stool and frequently develop overt evidence of hepatic dysfunction and cholestasis.”

Summary statement: “As noted earlier, approximately 8% of Mn in human milk is absorbed. By comparison, retention of intravenous Mn is close to 100%. Thus, the total Mn delivered in trace element-supplemented parenteral nutrition is approximately 6 to 8.5 micrograms/kg/day, about 100 times the Mn burden of infants fed human milk.”

 

MAY 2008 – University of Auckland, Auckland, New Zealand

Is Manganese an Essential Supplement for Parenteral Nutrition?

“Parenteral nutrition usually contains manganese as part of a fixed concentration multiple trace element supplement. Recent literature identifies potential problems in this approach and reports toxic symptoms resulting from hypermanganesaemia in pediatric and long-term home patients.”

“We have identified a need for individual trace element additives to be more widely available and for multi-trace element products to be reformulated. There is now a persuasive argument for not routinely adding manganese to parenteral nutrition admixtures.”

Summary statement: “High intravenous doses of manganese can lead to neurotoxicity. Current dosage guidelines and trace element formulations need revision.”

 

MAR 2011 – Vanderbilt University, Nashville, TN

Brain Manganese Deposition in High Risk Neonates

“Excessive exposure to manganese (Mn) results in Mn deposition in the brain causing adverse neurological effects.”

“Sick infants requiring parenteral nutrition (PN) may be at increased risk of Mn neurotoxicity because neonatal PN solutions contain high concentrations of Mn, PN bypasses the normal intestinal absorptive control and biliary excretory mechanisms for Mn, and infants are at a critical stage of brain development. Furthermore, iron (Fe) deficiency, a common problem among sick neonates, increases Mn brain uptake because Mn and Fe compete for the same carrier transport systems in the central nervous system.”

Summary statement: “The potential for increased brain Mn accumulation in infants and the potential health risks associated with elevated brain Mn burden represent crucial, unexplored issues of exposure and susceptibility. The impact of dietary Mn, and especially parenterally delivered dietary Mn, gestational age, Fe status, and hepatic dysfunction on the ability of the neonatal brain to regulate Mn deposition has not been scientifically addressed.”