Introduction: Copper is necessary for normal function of hematopoietic, cardiovascular, connective/skeletal and the central nervous systems. A >50% prevalence of copper deficiency has been reported in retrospective case series of children with intestinal failure (IF) during transition from parenteral to enteral nutrition (Yang CJ et al, 2011; Namjoshi SS et al, 2017). We sought to determine the frequency and factors associated with copper deficiency in children with IF who had their copper plasma levels monitored according to a standard protocol.

Methods: Prospective cohort study in children with IF followed-up at an intestinal rehabilitation center between July 2015 and November 2018 and who were receiving home parenteral nutrition (PN). Patient’s micronutrient status was routinely monitored at 3-month intervals or once a month when deficiency was detected. Copper was given at a standard dose of 20 mcg/kg as part of a trace-element solution, and was omitted in the PN if the patient developed intestinal failure liver associated disease. The outcome variable was copper plasma level during the follow-up period. The effect of the exposure variables (length of time on PN, prematurity, serum direct bilirubin levels, C-reactive protein, length of remnant small bowel and ostomy) on the outcome was analyzed by generalized estimating equations.

Results: Thirteen patients aged 34.2 months (IQR: 25.3; 41.1) were included; median time on PN was 26.4 months (IQR: 15.2 to 32.9). An average of 7 (range 2 to 15) copper measurements/patient were performed; 53.8% of patients had at least 1 copper measurement below normal during the follow-up. Eight patients who had cholestasis had trace elements of PN discontinued for 4 months (IQR: 1.6 to 12.2); from June 2017 these patients began to receive copper solution separately in doses to achieve basal requirements or to correct deficiency. Direct bilirubin levels (β coeff. -5.9, 95% CI: -9.0;-2.7, p=0.04), time on PN without copper (β coeff. -1.7, 95% CI: -3.2;-0.2, p<0.001) and ostomy (β coeff. -20.3, 95% CI: -37.6;-2.9, p=0.02) were associated with decreased copper levels in multivariable analysis. The figure shows adjusted predictions and marginal effects of the length of time without copper on copper serum levels.

Conclusion: Direct bilirubin levels, length of time on PN without copper and ostomy are independently associated with the high frequency of decreased copper plasma levels in patients with IF receiving long term PN.