Article Text

Are patients fed directly into the jejunum at risk of copper deficiency?
1. Harriet Barraclough,
2. Katarzyna Cooke
1. Department of Paediatrics, Leeds General Infirmary, Leeds, UK
1. Correspondence to Dr Harriet Barraclough, Leeds General Infirmary, Leeds LS1 3EX, UK; harriet.barraclough{at}nhs.net

## Scenario

A 7-year-old patient established on total parenteral nutrition inclusive of 0.11 mg/kg/day (0.17µmol/kg) of copper daily was transitioned to exclusive nasojejunal (NJ) feeding following a small bowel transplant. Prior to this, his serum copper level was stable at 18.6 µmol/L (reference range 11.0–22.0 µmol/L). Five months into NJ Peptamen Junior Advance feeds inclusive of 0.13 mg/kg/day copper, he was noted to have poor growth and had developed pancytopaenia. This prompted investigations, including a full serum nutritional screen, which led to detection of a low serum copper level of 1.7 μmol/L. He had no neurological abnormalities on examination. Questions were raised regarding whether jejunal feeding was causative in this trace element deficiency.

## Structured clinical question

In individuals younger than 18 years (patient), are those fed exclusively into the jejunum (intervention), compared with those fed via the mouth or the stomach (comparison), more likely to develop copper deficiency (outcome)?

## Search

An Ovid MEDLINE (1946–February 2019, week 5) and EMBASE (1947–2019, week 10) search was conducted on 9 March 2019 using the search terms ‘copper deficiency’ OR ‘low copper’ AND ‘jejunal feeding’ OR ‘jejunal nutrition’ OR ‘tube feeding’ OR ‘exclusive jejunal feeding’ OR ‘ feeding’ OR ‘jej$’ AND ‘paediat$’ OR ‘pediat\$’. Results were limited to humans. Six results were identified and screened to ensure relevance. The Cochrane database was also searched, and all references were reviewed to find other papers. Three relevant papers were identified once irrelevant results were excluded. These papers were inclusive of two case series and two case reports. All relevant papers were critically appraised and are found in table 1.

Table 1

A critical appraisal of paediatric papers relevant to the clinical question

## Commentary

Copper is an important trace element which is predominantly absorbed by humans in the stomach and the proximal small intestine.1 It is recommended that infants and children up to 5 years receive 20 µg/kg/day of copper and children older than 5 years receive 0.3–0.5 mg/day.2 The rate of copper absorption is dependent on a number of factors, including the concentration of copper in consumed foods, the form of copper and the composition of an individual’s diet. It is reported that some trace elements, for example, zinc and iron, have an inhibitory effect on copper absorption, while other elements, for example, phosphate, aids copper absorption.2 In the absence of an underlying medical disorder such as Menkes disease, copper is absorbed readily if dietary intake is sufficient. This absorption is essential for the function of multiple enzymes, principally in the neurological and haematological systems.3 4 Deficiency of copper can, therefore, have significant consquences neurologically and haematologically, which carries a high level of morbidity. It has been reported that copper deficiency causes anaemia and neutropaenia with eventual progressive myelopathy which, if unrecognised by the time cytopaenias develop, is irreversible.5

There are numerous causes for copper deficiency, including malnutrition, zinc toxicity and inadequate supplementation in at-risk patients, for example, those on parenteral nutrition.6 Case reports of copper deficiency associated with gastric bypass surgery have also been reported,7 8 as copper is predominantly absorbed within the stomach and the proximal duodenum.9 These reports have prompted the recommendation for routine copper supplementation in such patients.

It is becoming increasingly common for paediatric patients to be fed directly into the jejunum due to gastro-oesophageal reflux disease, gastrointestinal dysmotility, pulmonary aspiration and postoperative complications. Since this feeding route bypasses the site of copper absorption, these patients are at increased risk of copper deficiency and its associated complications. It is essential to monitor such patients as it may be difficult to detect and assess clinical changes in a proportion of those requiring jejunal feeding, for example, those with neurological impairment or inborn errors of metabolism.

Numerous authors5 6 10–14 have presented cases of copper deficiency in patients fed exclusively by jejunum. Paediatric papers have been appraised in table 1. In the majority of these reports, the deficiency was detected while investigations were undertaken for anaemia and leucopenia alongside neurological symptoms. Despite the varied clinical indications for jejunal feeding and patient age, these papers consistently report copper deficiency in jejunally fed patients, manifesting with haematological disturbances, predominantly leucopenias. They also endorse the need for supplementation to be given gastrically or parenterally. Varied therapeutic options, including cocoa powder or pharmacological preparations, are presented.

Considering the available evidence, it is reasonable to conclude that patients fed exclusively into the jejunum are at risk of copper deficiency. Given the significant haematological and neurological consequences that develop with delayed detection, it is important to monitor serum copper levels in this patient population. There is limited evidence to support a single monitoring schedule; however, we propose checking a full nutritional screen (see figure 1) at initiation of jejunal feeds (baseline), at 6 months and then annually. If concerns arise, clinicians should not hesitate to check a nutritional screen sooner than these proposed intervals. If supplementation is required, it is important to consider an appropriate route of delivery, especially since oral/gastric supplementation may be risky in those with severe reflux or an unsafe swallow.

Figure 1

Components of a full nutritional screen. GGT, gamma-glutamyltransferase.

### Clinical bottom line

• Jejunally fed patients are at risk of copper deficiency, though the absolute risk is unclear (grade of recommendation D).

• Monitoring serum copper levels as part of a nutritional screen at 6 months and annually in even asymptomatic patients could prevent the development of complications, most importantly, leucopenia, anaemia and progressive myelopathy (grade of recommendation D).

View Abstract

## Footnotes

• Contributors HB completed the literature review. HB and KC equally contributed to the writing of this report.

• Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

• Competing interests None.

• Provenance and peer review Not commissioned; internally peer reviewed.

• Patient consent for publication Not required.

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