Copper Supplementation in Premature Infants With Parenteral Nutrition–Associated Cholestasis

Abstract

The aim of this study was to evaluate the effect of intermittent parenteral copper supplementation (IPC) on serum copper status and biochemical and hematological measures of copper toxicity and deficiency in premature infants with parenteral nutrition (PN)-associated cholestasis (PNAC). We performed a prospective nested observational study in premature infants with PNAC who received IPC after the development of PNAC. Infants with chromosomal disorders, TORCH (toxoplasmosis, parvovirus, syphilis, rubella, cytomegalovirus, herpes, human immunodeficiency virus) infection, metabolic disorder, and/or surgical abnormality of the hepatobiliary system were excluded. Serum copper concentrations were measured once every 2-4 weeks while receiving PN; 24 premature infants were studied. The mean gestational age (GA) of infants was 28.6 ± 4.7 weeks. On regression analysis, there was no significant association between IPC and serum copper concentration (coefficient 2.72, 95% CI: -27 to 32; P = .84) after controlling for GA, gender, and baseline copper intake before PNAC. There was no significant association of IPC with alanine and aspartate transaminases levels (hepatotoxicity) and platelet count, hematocrit, white blood cell count, and neutrophil count (measures of copper deficiency) after controlling for confounders. GA and postmenstrual age were independently and positively associated with serum copper concentration after controlling for confounders on regression analyses. Thus, IPC in premature infants with PNAC does not influence copper status and is not associated with biochemical and hematological measures of copper deficiency and/or toxicity. Serum copper concentration in premature infants with PNAC receiving IPC is determined by the degree of prematurity and postmenstrual age.

Trace Element Provision in Parenteral Nutrition in Children: One Size Does Not Fit All

“…Preterm infants have high copper requirements but are also at risk of biliary stasis [ 9 , 23 ]. The European Society of Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) and the European Society of Parenteral and Enteral Nutrition (ESPEN) 2018 guidelines recommend to double the provision of copper in PN to preterm infants (from 20 to 40 μg/kg/day) [ 3 ].…”

“…While the previous dose is sufficient to prevent acute copper deficiency, it is thought to be lower than the preterm infant’s actual needs to achieve in utero accretion rates (63 μg/kg/day) [ 9 ]. However, studies of copper deficiency in premature cholestatic infants primarily report either a copper-free PN use or a dose of 10 μg/kg/day [ 22 , 23 , 24 , 25 , 26 ]. Reducing parenteral copper supplementation in cholestatic preterm infants may increase the risk of copper deficiency [ 9 , 27 , 28 ].…”

“…The increased requirements, limited stores and potential increased gastrointestinal losses of copper must be balanced against the reduced biliary excretion in preterm babies. Furthermore, low concentrations of serum ceruleoplasmin commonly seen in premature infants may be associated with accumulation of copper in hepatocytes without a concurrent increase in serum copper [ 23 ]. Therefore, the provision of 20 μg/kg/day for preterm infants with careful monitoring of copper and ceruleoplasmin levels to adjust the dose, particularly in presence of cholestasis, appears a safe approach.…”

Prematüre Bebeklerde Parenteral Beslenme Komplikasyonları

“…TPN ile ilişkili kolestazlı (PNAC) bebeklerde, parenteral bakır takviyesi, bakır atılımı sonucu biliyer atılımın azalmasından dolayı hepatik bakır birikimi nedeniyle hepatoselüler hasar görülebilmektedir. Bu nedenle, PNAC'lı bebeklerde günlük parenteral bakır desteği rutin olarak kullanılmamaktadır (Gupta, K., Wang, H., & Amin, S. B., 2018). Kolestaz tedavisinde ursodeoksikolik asit kullanımı sonucunda ursodeoksikolik asitin kolestaz süresini kısalttığı gözlemlenmiştir (Çetin ve diğer., 2006).…”

Effect of Nutritional Intervention by the Nutrition Support Team on Postnatal Growth in Preterm Infants

“…25 The zinc deficiency in long-term PN-provided patients and an impact on the excretion of copper and manganese in cholestasis patients were reported. [26][27][28] Therefore, we reduced the supply of trace elements to PN-induced cholestasis patients by regularly monitoring serum Cu, Mn, and Zn levels.…”