Tag Archives: copper

Micronutrient Monitoring in Intestinal Failure

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J Pediatr 2013; 163: 1692-6.  This retrospective study of prospectively collected data from 178 children provides data with regard to micronutrient deficiency among intestinal failure patients transitioning to enteral feeds. Figures 1 and 2 along with Table 2 provide the prevalence of micronutrient deficiency while receiving supplemental parenteral nutrition (PN) and while on full enteral nutrition (FEN).  Iron deficiency was most common in both situations with prevalence of 84% and 61% respectively. With the exception of folate (0%), all of the vitamins and micronutrients had fairly high rates of deficiency.  While on FEN,  deficiencies were  the following:

  • Vitamin A        19%
  • Vitamin B12    6.5%
  • Vitamin D        30%
  • Vitamin E          6%
  • Copper            8%
  • Iron                61%
  • Selenium         4%
  • Zinc               23%

The study does not indicate that the deficiency values were adjusted based on CRP values.  Instead, “low serum levels were used to define deficiencies.”  This is likely to lead to numerous errors.  Nevertheless, it is clear that these deficiencies are common.  Another finding of the study was that normal anthropometrics did not reduce the frequency of these deficiencies.  In their patient population, 57 of 136 (42%) with sufficient height and weight data had a height-for-age z-scores of <-2 by the time of FEN; where as 52 of 139 patients (37%) had weight-for-age z-scores of <-2.

A recent post on The Pediatric Nutritionist blog provides a suggested approach to the monitoring of vitamins and micronutrients based on the need for parenteral nutrition and on the need to consider inflammatory markers in the interpretation of these lab values: The Importance of Nutrition Lab Monitoring Protocols Featuring …

Bottomline: Vitamin and micronutrient deficiencies are common among intestinal failure patients.  In addition, a large percentage of these kids are not large at all.

Related blog post:

What happens to micronutrient levels in the hospital setting …

What happens to micronutrient levels in the hospital setting?

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When atypical labs need to be obtained, many times this is easier in the hospital setting for logistical reasons including insurance and accessibility to specialty labs.  One group of labs that may be less suited for checking in the hospital, despite convenience, would be micronutrients.  Many of the micronutrients can be affected by systemic inflammatory response (Am J Clin Nutr 2012; 95: 64-71).  Thanks to Kipp Ellsworth for this reference (from his @PedNutritionGuy twitter feed).

Previous studies on systemic inflammatory response (SIR), as assessed by elevated C-reactive protein (CRP) concentrations, has shown that with elective surgery there are transient decreases in plasma concentrations of zinc, selenium, iron, vitamin A, vitamin E, carotenoids, riboflavin, vitamin B-6, vitamin C, and vitamin D.

This current study adds to this body of information.  Between 2001-2011, 2217 whole-blood samples were taken from 1303 patients. Specific micronutrients that were studied: plasma zinc, copper, selenium, vitamins A, B-6, C, and E.  For vitamin D, the authors examined 4327 samples from 3677 patients. The authors did not include manganese, thiamine or riboflavin because these are measured in erythrocytes.

For each analyte, the concentrations were separated according to 6 categories of CRP values: <5, 6-10, 11-20, 21-40, 41-80, and >80 mg/L.

Key finding: Except for copper and vitamin E, all plasma micronutrient concentrations decreased with increasing severity of acute inflammatory response.  For selenium, vitamin B-6, and vitamin C, this occurred with only slight increases in CRP (5 to 10 mg/L).

The magnitude of the SIR effect on micronutrients was quite variable among patients and analytes.  When CRP was >80 mg/L, analyte deficiency rate was noted to be the following:

  • 60 % for selenium (vs. 33% with NL CRP)
  • 48% for vitamin A (vs. 7% with NL CRP)
  • 35% for vitamin B-6 (vs. 14% with NL CRP)
  • 80% for vitamin C (vs. 33% with NL CRP)
  • 88% for vitamin D (vs. 69% with NL CRP)
  • 81% for zinc (vs. 33% with NL CRP)
  • 9% for copper (vs. 4% with NL CRP)
  • 16% for vitamin E (vs. 9% with NL CRP)

**The specific normal value cutoffs and more data at all CRP values are noted in Table 9 of the manuscript.

The implications from this study are clear.  When micronutrient values are derived from plasma during a SIR, a false-positive diagnosis of a micronutrient deficiency is more likely. The study has several limitations and the findings may not be applicable to all types of medical conditions.

Authors conclusion: When CRP concentration is >20 mg/L (>2 mg/dL), “plasma concentrations of selenium, zinc, and vitamins A, B-6, C, and D are clinically uninterpretable.”

Related blog entries:

Copper in Cholestasis

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More data indicate that copper levels in infants receiving parenteral nutrition are usually not affected by cholestasis (JPEN 2013; 37: 92-96).

A retrospective study reviewed all patients younger than 1 year who had copper levels measured between 1999-2009 at Riley Hospital for Children.  Inclusion criteria: parenteral nutrition for at least 50% of caloric needs and cholestasis (direct bilirubin >2 mg/dL).

Key findings:

  • 26 of 28 patients had gastrointestinal disorders.  82% were receiving standard parenteral nutrition (PN) dose of copper (20 mcg/kg/day).
  • Only one elevated copper level was found in a child with congenital heart disease.
  • 46% (n=13) of cholestatic infants had low copper levels.  Three of theses infants had no copper in their PN.
  • There was no correlation between bilirubin level and measured copper values.

Bottomline:

Measure copper values periodically in patients requiring parenteral nutrition.  Most patients, even cholestatic patients, will require standard dosing but some will need less and some more.

Additional References:

  • -JPGN 2010; 50: 650-54.  n=28.  (only 2 had elevated Cu). Typical Cu supplementation in HAL did not lead to significant increase in Cu toxicity or worsening of liver disease in cholestatic infants.  Study prompted by single infant who developed Cu deficiency/anemia.
  • -Clin Gastro & Hepatol 2004; 2: 1074. Two patients with Cu deficiency after bariatric surgery
  • -JPGN 2000; 31: 102-111. (review)