Three distinct cases of copper deficiency in hospitalized pediatric patients

Although copper deficiency is a rare occurrence in the developed world, attention should be given to the proper supplementation of minerals to at-risk pediatric patients. This study presents 3 distinct cases of copper deficiency in hospitalized patients aged 14 months, 6 years, and 12 years. Two patients had short bowel syndrome, requiring prolonged parenteral nutrition or complex intravenous fluid supplementation. The third patient was severely malnourished. Copper deficiency manifested in all of our patients as either microcytic anemia or pancytopenia with myelodysplastic syndrome. Copper deficiency is an important diagnosis to be considered in patients with prematurity, parenteral nutrition dependency, malabsorption, and/or those with malnutrition. More studies are needed to establish appropriate amounts of copper supplementation to replenish copper stores in deficient patients.     

Copper deficiency presenting as metabolic bone disease in extremely low birth weight, short-gut infants

Copper deficiency can cause bone lesions in infants, which might be confused with child abuse. Two extremely low birth weight preterm infants had complicated medical courses requiring prolonged parenteral nutrition for short-gut syndrome, which led to the development of cholestasis. Both had spent their entire lives in the hospital. They had been on prolonged ventilator support for chronic lung disease. They developed signs of copper deficiency between 5 and 6 months of age, initially raising child abuse concerns. Musculoskeletal discomfort led to the recognition of radiographic findings of metabolic bone disease. Included were osteoporosis, metaphyseal changes, and physeal disruptions. Copper levels were low; both low copper parenteral nutrition and gut losses from refeeding diarrhea likely contributed to their deficiency. Therapeutic supplementation with copper corrected their deficits and clinical and radiologic findings. The information from these cases, in particular, their radiologic findings, indicate the need to monitor copper status in at-risk premature infants. These findings may aid prevention and earlier recognition of copper deficiency. Their specific radiologic and clinical findings should aid differentiation of such children from abused infants.     

Pancytopenia with myelodysplasia due to copper deficiency

We present a case of pancytopenia in a 9-month-old infant with total parenteral nutrition (TPN) dependence due to short bowel syndrome. Bone marrow examination revealed left-shifted myeloid maturation, erythroid and myeloid dysplasia with normal iron stores. Serum copper level was 2 microm/dl (normal range 90-190 mcg/dl). After supplementation, copper levels normalized at 143 mcg/dl, and the macrocytic anemia, neutropenia, and thrombocytopenia resolved. Copper deficiency should be considered in the differential diagnosis of cytopenias and myelodsyplasia, particularly in the growing number of pediatric patients with TPN dependency or malabsorption.     

Refractory cytopenias secondary to copper deficiency in children receiving exclusive jejunal nutrition

Copper deficiency is a known cause of anemia and neutropenia that is easily remedied with copper supplementation. Copper is primarily absorbed in the stomach and proximal duodenum, so patients receiving enteral nutrition via methods that bypass this critical region may be at increased risk for copper deficiency. In pediatrics, postpyloric enteral feeding is increasingly utilized to overcome problems related to aspiration, severe reflux, poor gastric motility, and gastric outlet obstruction. However, little is known about the prevalence of copper deficiency in this population. We describe three pediatric patients receiving exclusive jejunal feeds who developed cytopenias secondary to copper deficiency.     

Mineral and nutritional requirements of preterm infant

Preterm infants are at risk of growth failure and metabolic bone disease due to insufficient nutrient supply in postnatal life. An ample provision of protein, energy, calcium and phosphates through parenteral or/and enteral nutrition is crucial for bone growth and mineralization. Additional vitamin D supplementation improves bone mineralization and enhance intestinal absorption of minerals.     

Effect of calcitonin replacement therapy in idiopathic juvenile osteoporosis

An 8-year-old boy with idiopathic juvenile osteoporosis and multiple fractures had three abnormalities of bone mineral metabolism: calcitonin deficiency, elevated serum calcitriol concentrations, and hypercalciuria. Calcitonin deficiency was documented by two attempts to stimulate calcitonin secretion with intravenous calcium and pentagastrin. Treatment for 11 months with daily subcutaneous injections of human calcitonin and oral administration of calcitriol failed to reduce the excessive bone resorption observed on bone biopsy, and the fracture rate did not decrease. Treatment was discontinued for two months, then resumed with calcitonin injections and oral calcium supplementation. The fracture rate decreased but bone biopsy continued to show excessive resorption. Therapy was discontinued. After the onset of puberty, endogenous calcitonin was detectable. Exogenous calcitonin therapy may have failed to control bone resorption for several reasons: insufficient dose, reduction of bone receptors from long-term calcitonin exposure, secondary hyperparathyroidism, or lack of association between calcitonin deficiency and the bone disease.     

Aluminum contamination of parenteral nutrition and aluminum loading in children on long-term parenteral nutrition

BACKGROUND: Children who are receiving parenteral nutrition are at risk of aluminum overload, which may contribute to such side effects as osteopenic bone disease. The aim of the present study is to determine the aluminum contamination of parenteral nutrition solutions and their components, and to assess the aluminum status of children on long-term parenteral nutrition. METHODS: Aluminum concentrations were determined by graphite furnace absorption spectroscopy in components and in final parenteral nutrition solutions. The urinary aluminum excretion and plasma aluminum concentration were determined in 10 children on long-term parenteral nutrition. RESULTS: The mean aluminum concentration in the administered parenteral nutrition solutions was 1.6 +/- 0.9 micromol x l(-1)(mean +/- standard deviation (SD)). The resulting mean aluminum daily intake of the 10 patients was 0.08 +/- 0.03 micromol x kg(-1) x day(-1). CONCLUSIONS: Compared to two previous studies performed in 1990 and in 1995 in our hospital, the aluminum contamination of parenteral nutrition solutions and the daily aluminum intake of the children seemed to decrease. However, the plasma aluminum concentration and daily urinary aluminum excretion of the children still remain above normal standards. The children had no clinical symptoms of bone disease but aluminum accumulation in tissue can not be excluded. To prevent this iatrogenic toxicity, the aluminum contamination of parenteral nutrition should be assessed regularly.     

Lebensbedrohliche, durch Thiaminmangel bedingte, Laktatazidose unter total parenteraler Ernährung ohne Vitaminzufuhr

We report on a 13 year old boy after bone marrow transplantation (BMT) who received total parenteral nutrition without vitamins. 15 days after BMT he experienced acute life threatening hyperlactic acidemia refractory to bicarbonate and tris. 100 mg thiamine i.v. resulted in a satisfactory clinical and biochemical response. Conclusion. In any patient under total parenteral nutrition who develops an unexplained hyperlactic acidemia the possibility of thiamine deficiency should be suspected and treated.     

Severe hyperlactacidemia in 2 children treated for malignant tumors. Role of vitamin B1]

Two cases of children treated for malignant tumor and who developed a severe lacticacidosis are reported. A 2 year-old girl and a 8 year-old boy were treated with chemotherapy, irradiation and multiple surgical procedures for nephroblastoma and lymphoma respectively. These two malnourished patients, under exclusive parenteral nutrition for two weeks without vitamin intakes, suddenly developed neurological, cardiovascular and digestive symptoms, associated with cytopenia and lacticacidosis. Injection of vitamin B1 only corrected these abnormalities within a few hours, proving the role of thiamine deficiency as the cause of the symptoms.     

静脉补充谷氨酰胺对外科手术新生儿喂养耐受的影响

目的 评价含丙氨酰谷氨酰胺(Ala-Gin)肠外营养(PN)对接受外科手术新生儿喂养耐受的影响.方法 对两家儿童医疗中心2006年1月至2007年1月收治的40例接受外科手术的新生儿进行研究,采用平行、随机、双盲、对照实验,随机分为常规PN组(对照组)和常规PN+Ala-Gln组(研究组),二组各20例,对照组氨基酸的剂量为2～3g·kg-1·d-1;研究组添加0.3g·kg-1·d-1 Ala-Gln双肽,其中Ala-Gln双肽取代了处方中相应氨基酸的量.首要终点指标为术后开始喂养时间,术后达到全肠内喂养天数(标准配方摄入量≥120 ml·kg-1·d-1)、完全脱离肠外营养时间和病死率.结果 研究组和对照组比较,患儿术后开始喂养时间[研究组(8±4)d,对照组(8±5)d]、术后达到全肠内喂养天数[研究组(14±8)次,对照组(15±7)次]以及完全脱离肠外营养时间[研究组(15±8)d,对照组(16±7)d]差异均无统计学意义.对照组有3例死亡,研究组患儿无死亡,病死率通过非意向性分析,二组比较差异有统计学意义,OR值为0.789,95%CI为0.626～0.996.但是通过意向性分析,OR值为0.706,95%CI为0.136～3.658,病死率比较差异没有统计学意义.结论 本研究显示,静脉补充谷氨酰胺未能使接受外科手术的新生儿减少术后开始喂养时间和术后达到全肠内喂养天数,缩短全肠外营养应用时间;但关于是否能够降低患儿病死率,通过意向性分析和非意向性分析的结果有差异,尚需进一步研究.     

Enterale Ernährung von Frühgeborenen

To a large extent postnatal growth failure is caused by inadequate postnatal nutrition. Postnatal growth failure is associated with poor brain growth, low IQ, coronary heart disease and hypertension. Growth failure is a marker of poor neurocognitive outcome. Owing to safety concerns, parenteral nutrition is started too late and advanced too slowly, and enteral nutrition is started too late, withheld too often and advanced too slowly. The immediate postnatal priority is to reestablish the fetal condition of full parenteral nutrition as fast as possible and gradually introduce enteral nutrition. In the present paper early enteral feeding of preterm infants is reviewed with especial reference to nutritional needs, markers of early feeding tolerance, feeding techniques and supplementation of feeds.     

Fracture of the femur,fish odour,and copper deficiency in a preterm infant.

A preterm baby boy with blood and bone changes of copper deficiency is described. Copper deficiency was suspected after fracture of the left femur during examination of the hip joint. A low serum copper concentration (2.7 mumol/l; 17.2 micrograms/100 ml) and caeruloplasmin (0.04 g/l; 0.004 g/100 ml) confirmed the diagnosis. Despite the introduction of solids at 18 weeks the copper concentration remained low, and treatment with copper sulphate (2.5 mg daily) was started at 6 months. Treatment was stopped at 9 months, when he was both physically and developmentally normal. When given a choline-containing vitamin preparation (Ketovite) he developed a fish odour because of the accumulation of trimethylamine. Withdrawal of this preparation at 6 weeks and substitution with a choline-free preparation (Abidec) was soon followed by disappearance of the odour. It is speculated that prematurity rather than copper deficiency was responsible for the poor activity of liver enzyme, trimethylamine oxidase.     

History,epidemiology and prevalence of neonatal bone mineral metabolic disorders

The evolutionary patterns of human migration and historical pre/post-industrial revolution have changed the face of bone metabolic disease through past centuries. Cultural, religious, and lifestyle practices continue to alter nutritional recommendations for this expanding diagnosis. Likewise, modern advancements in the field of neonatology and, more specifically, aggressive nutritional management of premature infants have shaped the epidemiology of neonatal bone metabolism over the past two decades. Decreased use of long-term parenteral nutrition, early fortification of enteral nutrition, and stringent American Academy of Pediatrics (AAP) practice guidelines instituting early supplementation of vitamin D have attributed to improved bone mineralization outcomes in both term and preterm infants. Nevertheless, neonatal bone mineral metabolic disorders remain prevalent. In this review, we provide an in-depth look at the diagnoses, therapeutics, and subset populations—both genetic and non-genetic—affected by neonatal bone mineral metabolic disorders.     

Oral choline supplementation in children with intestinal failure

Choline deficiency leads to steatohepatitis, elevated transaminases, susceptibility to septic shock, and an increased risk of central catheter thrombosis. Children with intestinal failure (IF) are at risk for choline deficiency. In an unblinded, open-label study, we studied 7 children with IF on parenteral nutrition, measured their plasma free choline level, and, if low, supplemented enterally with adequate intake (AI) doses of choline. Four to 6 weeks later we remeasured their plasma free choline. Unlike adults, infants did not respond to oral choline supplementation at AI doses. Additionally, we have calculated plasma free choline percentiles versus age for normal children.     

Manganese in long term paediatric parenteral nutrition

The current practice of providing manganese supplementation to neonates on long term parenteral nutrition is leading to a high incidence of hypermanganesaemia. Magnetic resonance imaging (MRI) studies in adults on long term manganese parenteral nutrition have shown changes in TI weighted MRI images and similar findings in a neonate receiving trace element supplementation are reported here. Whole blood manganese concentration in the infant was 1740 nmol/l (or 8.3 times upper reference limit). In all neonates on long term parenteral nutrition with evidence of cholestatic liver disease so far investigated, the whole blood manganese concentrations were > 360 nmol/l (reference range 73-210). Manganese supplementation to patients on long term parenteral nutrition requires reappraisal, particularly in those who develop cholestatic liver disease associated with parenteral nutrition.     

Extrauterine growth restriction in very-low-birthweight infants

Postnatal growth failure of very-low-birthweight (VLBW) infants may result from a complex interaction of genetic and environmental factors, including inadequate nutrition, morbidities affecting nutrient requirements, endocrine abnormalities and treatments. Among VLBW infants, those small for gestational age (SGA) at birth and those with postnatal growth restriction at the time of discharge are at higher risk of later growth failure and long-term consequences. Nutritional intervention with an "aggressive nutrition" during the first weeks of life may be able to minimize the interruption of nutrients that occurs at birth, and reduce as much as possible the incidence of growth restriction at the time of discharge and later. Even though aggressive parenteral and enteral nutrition appear to be effective and safe in VLBW infants, further evaluations of their long-term effect on growth and health consequences are needed. Several studies evaluating the effect of enriched nutrient formulas after hospital discharge on growth and neurodevelopment have produced conflicting results, whereas the potential deleterious long-term effects of prolonged use of high protein and/or of later catch-up growth have been questioned. In contrast, recent data seem to indicate that the use of human milk after hospital discharge could be the most beneficial diet for subsequent health and development.

Conclusion: VLBW infants SGA at birth and those with early postnatal growth restriction are at high risk of later growth failure and long-term consequences. Therefore, the first objective of early nutrition should be to reduce the incidence of growth restriction at the time of discharge. Further studies on VLBW infants to evaluate the safety and beneficial effects of prolonged dietary manipulation during the first year of life are needed.     

Manganese in long term paediatric parenteral nutrition.

The current practice of providing manganese supplementation to neonates on long term parenteral nutrition is leading to a high incidence of hypermanganesaemia. Magnetic resonance imaging (MRI) studies in adults on long term manganese parenteral nutrition have shown changes in TI weighted MRI images and similar findings in a neonate receiving trace element supplementation are reported here. Whole blood manganese concentration in the infant was 1740 nmol/l (or 8.3 times upper reference limit). In all neonates on long term parenteral nutrition with evidence of cholestatic liver disease so far investigated, the whole blood manganese concentrations were > 360 nmol/l (reference range 73-210). Manganese supplementation to patients on long term parenteral nutrition requires reappraisal, particularly in those who develop cholestatic liver disease associated with parenteral nutrition.     

Clinical report—bone densitometry in children and adolescents

Concern for bone fragility in children and adolescents has led to increased interest in bone densitometry. Pediatric patients with genetic and acquired chronic diseases, immobility, and inadequate nutrition may fail to achieve the expected gains in bone size, mass, and strength, which leaves them vulnerable to fracture. In older adults, bone densitometry has been shown to predict fracture risk and reflect response to therapy. The role of densitometry in the management of children at risk of bone fragility is less certain. This clinical report summarizes the current knowledge about bone densitometry in the pediatric population, including indications for its use, interpretation of results, and its risks and costs. This report emphasizes consensus statements generated at the 2007 Pediatric Position Development Conference of the International Society of Clinical Densitometry by an international panel of bone experts. Some of these recommendations are evidence-based, and others reflect expert opinion, because the available data are inadequate. The statements from this and other expert panels have provided general guidance to the pediatrician, but decisions about ordering and interpreting bone densitometry still require clinical judgment. Ongoing studies will help to better define the indications and best methods for assessing bone strength in children and the clinical factors that contribute to fracture risk.     

Promoting bone health in children and adolescents following solid organ transplantation

Solid organ transplantation in children and adolescents provides many benefits through improving critical organ function, including better growth, development, cardiovascular status, and quality of life. Unfortunately, bone status may be adversely affected even when overall status is improving, due to issues with pre‐existing bone disease as well as medications and nutritional challenges inherent post‐transplantation. For all children and adolescents, bone status entering adulthood is a critical determinant of bone health through adulthood. The overall health and bone status of transplant recipients benefits from attention to regular physical activity, good nutrition, adequate calcium, phosphorous, magnesium and vitamin D intake and avoidance/minimization of soda, extra sodium, and obesity. Many immunosuppressive agents, especially glucocorticoids, can adversely affect bone function and development. Minimizing exposure to “bone‐toxic” medications is an important part of promoting bone health in children post‐transplantation. Existing guidelines detail how regular monitoring of bone status and biochemical markers can help detect bone abnormalities early and facilitate valuable bone‐directed interventions. Attention to calcium and vitamin D supplementation, as well as tapering and withdrawing glucocorticoids as early as possible after transplant, can provide best bone outcomes for these children. Dual‐energy X‐ray absorptiometry can be useful to detect abnormal bone mass and fracture risk in this population and newer bone assessment methods are being evaluated in children at risk for poor bone outcomes. Newer bone therapies being explored in adults with transplants, particularly bisphosphonates and the RANKL inhibitor denosumab, may offer promise for children with low bone mass post‐transplantation.     

Carnitine deficiency in premature infants receiving total parenteral nutrition: effect of L-carnitine supplementation

To investigate whether L-carnitine supplementation may correct nutritional carnitine deficiency and associated metabolic disturbances in premature infants receiving total parenteral nutrition, an intravenous fat tolerance test (1 gm/kg Intralipid over four hours) was performed in 29 premature infants 6 to 10 days of age (15 receiving carnitine supplement 10 mg/kg . day L-carnitine IV, and 14 receiving no supplement). Total carnitine plasma values were normal or slightly elevated in supplemented but decreased in nonsupplemented infants. In both groups, fat infusion resulted in an increase in plasma concentrations of triglycerides, free fatty acids, D-beta-hydroxybutyrate, and short-chain and long-chain acylcarnitine, but total carnitine values did not change. After fat infusion, the free fatty acids/D-beta-hydroxybutyrate ratios were lower and the increase of acylcarnitine greater in supplemented infants of 29 to 33 weeks' gestation than in nonsupplemented infants of the same gestational age. This study provides evidence that premature infants of less than 34 weeks' gestation requiring total parenteral nutrition develop nutritional carnitine deficiency with impaired fatty acid oxidation and ketogenesis. Carnitine supplementation improves this metabolic disturbance.