Copper Supplementation in Parenteral Nutrition of Cholestatic Infants

Abstract

Background Conventional practice is to reduce or eliminate copper supplementation in the parenteral nutrition of infants with cholestasis due to the increased risk of hepatotoxicity. However, there are reports of copper deficiency in cholestatic infants due to copper reduction in their parenteral nutrition. Objectives 1) To determine the proportion of cholestatic infants who develop elevated serum copper while receiving a non-reduced dose of parenteral copper, 2) To evaluate potential clinical factors that affect serum copper in cholestatic infants, and 3) To evaluate the impact of serum copper on liver disease. Methods This is a retrospective review of 28 cholestatic infants receiving 20 mcg/kg/d of copper via parenteral nutrition. Age-adjusted references were used to determine normality of serum copper levels. Multiple linear regression analyses were performed to determine predictors of serum copper and alanine aminotransferase. Results Serum copper levels were elevated in 2 infants (7%). On average, infants received 80% of their energy intake from parenteral nutrition for 3 months. Intestinal failure was present in 50% of the patients. Birth weight, gestational age and alanine aminotransferase were identified as predictors of serum copper (R2=0.53; p= 0.0001). Serum copper, gestational age and total bilirubin were associated with serum alanine aminotransferase (R2 = 0.43; p = 0.001). Conclusion Supplementation of parenteral copper at 20 mcg/kg/day does not lead to a significant increase in copper toxicity or worsening of liver disease in cholestatic infants.

Role of trace elements in parenteral nutrition support of the surgical neonate

“…All cases resolved after Cu supplementation were reverted to its original dose [41]. Recent studies have demonstrated that supplementation of Cu in its recommended dosage in cholestatic infants may not lead to increased liver Cu deposition or hepatotoxicity, findings previously described in adults [44][45][46].…”

“…Current practice recommendations among some neonatal intensive care units include PN Cu elimination in cholestasis only when toxicity is confirmed. Cu toxicity causes liver cirrhosis in adults, leading to recommendations to omit or reduce parenteral Cu if cholestasis is present because of potential toxicity with impaired biliary excretion; signs of Cu toxicity, however, have not been reported for the infant population [44][45][46].…”

Copper metabolism and pediatric cholestasis

“…There is one retrospective study in cholestatic infants less than 1 year of age who received at least 50% of their nutrition from parenteral nutrition and had a direct bilirubin more than 2 mg/dl [27 ]. The patients all received the standard 20 mg/kg/day copper in their parenteral nutrition and had no metabolic disorders.…”

Nutrición parenteral en situaciones clínicas especiales

“…En situaciones de colestasis se recomienda también suspender los aportes de cobre y manganeso pues se excretan por la bilis (6,57,58). Del mismo modo, es importante asegurar la administración de zinc con la provisión de suplemento específico.…”