Aluminum Neurotoxicity in Preterm Infants Receiving Intravenous-Feeding Solutions

Bishop, Nick; Morley, Ruth; Day, John; Lucas, Alan

doi:10.1056/nejm199705293362203

Cited by 242 publications

(173 citation statements)

References 22 publications

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“…Details of the original trial design are reported elsewhere but summarised briefly here (1) . Two hundred and twenty-seven preterm infants with birthweight <1850 g were recruited from a neonatal unit in Cambridge, UK.…”

Section: Randomised Trial Of Aluminium Exposure From Parenteral Nutrimentioning

confidence: 99%

“…Cognitive outcome at 18 months post-term (1) At 18 months corrected age, all surviving infants were invited for a follow-up examination. A single investigator, blind to the PN allocation, assessed cognitive development using the Mental Scale of the Bayley Scales of Infant development (16) , from which the Mental Development Index (MDI) was derived.…”

Section: Randomised Trial Of Aluminium Exposure From Parenteral Nutrimentioning

confidence: 99%

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Aluminium exposure from parenteral nutrition in preterm infants and later health outcomes during childhood and adolescence

Fewtrell¹,

Edmonds

Isaacs³

et al. 2011

Proc. Nutr. Soc.

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Aluminium is the most common metallic element, but has no known biological role. It accumulates in the body when protective gastrointestinal mechanisms are bypassed, renal function is impaired, or exposure is high – all of which apply frequently to preterm infants. Recognised clinical manifestations of aluminium toxicity include dementia, anaemia and bone disease. Parenteral nutrition (PN) solutions are liable to contamination with aluminium, particularly from acidic solutions in glass vials, notably calcium gluconate. When fed parenterally, infants retain >75% of the aluminium, with high serum, urine and tissue levels. Later health effects of neonatal intravenous aluminium exposure were investigated in a randomised trial comparing standard PN solutions with solutions specially sourced for low aluminium content. Preterm infants exposed for >10 d to standard solutions had impaired neurologic development at 18 months. At 13–15 years, subjects randomised to standard PN had lower lumbar spine bone mass; and, in non-randomised analyses, those with neonatal aluminium intake above the median had lower hip bone mass. Given the sizeable number of infants undergoing intensive care and still exposed to aluminium via PN, these findings have contemporary relevance. Until recently, little progress had been made on reducing aluminium exposure, and meeting Food and Drug Administration recommendations (<5 μg/kg per d) has been impossible in patients <50 kg using available products. Recent advice from the UK Medicines and Healthcare regulatory Authority that calcium gluconate in small volume glass containers should not be used for repeated treatment in children <18 years, including preparation of PN, is an important step towards addressing this problem.

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Section: Randomised Trial Of Aluminium Exposure From Parenteral Nutrimentioning

confidence: 99%

Section: Randomised Trial Of Aluminium Exposure From Parenteral Nutrimentioning

confidence: 99%

Aluminium exposure from parenteral nutrition in preterm infants and later health outcomes during childhood and adolescence

Fewtrell¹,

Edmonds

Isaacs³

et al. 2011

Proc. Nutr. Soc.

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“…Various studies have demonstrated that children affected by chronic renal failure under aluminium hydroxide therapy develop aluminium storage, revealed by serum albumin > 100 μ g/l and increased bone aluminium concentration (29 -32) . Preterm infants submitted to prolonged intravenous feeding have been found at risk of aluminium intoxication, developing neurotoxicity clinically manifested in childhood with a mental development index < 85 and subsequent educational problems (33) . The contamination of parenteral solutions with aluminium has been reported as one of the main factors responsible for the development of metabolic bone disease in parenteral nutrition patients, particularly in preterm newborns, and leading to osteopenic bone disease (34) .…”

Section: Aluminium In Pharmaceutical Productsmentioning

confidence: 99%

The meaning of aluminium exposure on human health and aluminium-related diseases

Crisponi

Fanni²,

Gerosa³

et al. 2013

BioMolecular Concepts

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Abstract:The aim of this review is to attempt to answer extremely important questions related to aluminiumrelated diseases. Starting from an overview on the main sources of aluminium exposure in everyday life, the principal aspects of aluminium metabolism in humans have been taken into consideration in an attempt to enlighten the main metabolic pathways utilised by trivalent metal ions in different organs. The second part of this review is focused on the available evidence concerning the pathogenetic consequences of aluminium overload in human health, with particular attention to its putative role in bone and neurodegenerative human diseases.

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“…Assigning infants to high levels of aluminum exposure would have been unethical However, because standard parenteral nutrition solutions contain significant aluminum, it was ethical for us to conduct a randomised trial comparing these with corresponding solutions specially sourced for low aluminum content. Our trial, conducted in preterm infants, showed those exposed for >10 days to standard solutions had impaired neurologic development at 18 months post-term 6 . Bone health was not assessed at that stage.…”

mentioning

confidence: 99%

Aluminum Exposure From Parenteral Nutrition in Preterm Infants: Bone Health at 15-Year Follow-up

et al. 2009

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OBJECTIVE: Aluminum has known neurotoxicity and may impair short-term bone health. In a randomized trial, we showed reduced neurodevelopmental scores in preterm infants who were previously exposed to aluminum from parenteral nutrition solutions. Here, in the same cohort, we test the hypothesis that neonatal aluminum exposure also adversely affects long-term bone health, as indicated by reduced bone mass. METHODS: Bone area (BA) and bone mineral content (BMC) of lumbar spine, hip, and whole body were measured with dual radiograph absorptiometry in 13- to 15-year-olds who were born preterm and randomly assigned standard or aluminum-depleted parenteral nutrition solutions during the neonatal period. RESULTS: Fifty-nine children (32% of survivors) were followed. Those who were randomly assigned to standard parenteral nutrition solution had lower lumbar spine BMC, apparently explained by a concomitant decrease in bone size. In nonrandomized analyses, children who were exposed to neonatal aluminum intakes above the median (55 μg/kg) had lower hip BMC (by 7.6% [95% confidence interval 0.21–13.8]; P = 0.02), independent of bone (or body) size. CONCLUSIONS: Neonates who are exposed to parenteral aluminum may have reduced lumbar spine and hip bone mass during adolescence, potential risk factors for later osteoporosis and hip fracture. These findings need confirmation in larger, more detailed studies. Nevertheless, given our previous finding of adverse developmental outcome in these individuals and the sizeable number of contemporary infants who undergo intensive neonatal care and are still exposed to aluminum via parenteral feeding solutions, the potential adverse long-term consequences of early aluminum exposure now deserve renewed attention.

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Aluminum Neurotoxicity in Preterm Infants Receiving Intravenous-Feeding Solutions

Abstract: In preterm infants, prolonged intravenous feeding with solutions containing aluminum is associated with impaired neurologic development.

Cited by 242 publications

References 22 publications

Aluminium exposure from parenteral nutrition in preterm infants and later health outcomes during childhood and adolescence

Aluminium exposure from parenteral nutrition in preterm infants and later health outcomes during childhood and adolescence

The meaning of aluminium exposure on human health and aluminium-related diseases

Aluminum Exposure From Parenteral Nutrition in Preterm Infants: Bone Health at 15-Year Follow-up

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