LAUSR

Introduction: Hematological cytopenias have been reported in copper-deficient children with intestinal failure (IF) and receiving parenteral nutrition (PN). However, no cohort study has investigated a possible association between copper deficiency and low blood cell count in patients who had their copper plasma levels monitored according to a standard protocol. We investigated how much copper plasma levels influence anemia, neutropenia and thrombocytopenia in children receiving long-term home PN. Methods: Children with IF admitted to a pediatric intestinal rehabilitation program and who were receiving home PN were followed-up prospectively from July 2015 to November 2018. Outcome variables were hemoglobin (Hb, g/ dL), neutrophils and platelet counts (mm3); plasma copper levels during the follow-up were considered as the main explanatory variable. Patient’s micronutrient status was routinely monitored at 3-month intervals or once a month when deficiency was detected. All patients were receiving a fixed dose of vitamins, and multi-trace element solution including copper (at a standard dose of 20mcg/kg). Complete blood counts were performed bi-weekly. Generalized estimating equations models were adjusted for vitamin B12, iron and folate plasma levels. Results: Thirteen patients aged 34.2 months (IQR: 25.3; 41.1) were included; median time on PN was months 26.4 (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. Eight patients who had cholestasis had trace elements of PN discontinued. All but one patient had anemia; neutropenia was seen in 11 patients (among them 8 had < 1000 neutrophils/mm3), and 8 patients had thrombocytopenia. Copper deficiency (plasma level <72μg/dL) was associated with lower Hb and lower neutrophils and platelet counts. The decrease of 10 μg/dL in plasma copper resulted in decreases in Hb level (β coeff.: -0.08 (95% CI: -0.02;-0.14, p=0.009), in neutrophil (β coeff. -201.6, 95% CI:-134.8;-268, p<0.001) and in platelet counts (β coeff. -6278, 95% CI: -2026;-10529, p=0.004). The figure shows predictions and marginal effects of copper serum levels on neutrophils count. Conclusion: Copper deficiency is associated with lower blood cell counts and higher risk of anemia, neutropenia and thrombocytopenia. This effect was more pronounced for neutropenia. Copper status should be routinely monitored in children with IF receiving long term PN.