Neonatology/Paediatrics - Guidelines on Parenteral Nutrition, Chapter 13.

There are special challenges in implementing parenteral nutrition (PN) in paediatric patients, which arises from the wide range of patients, ranging from extremely premature infants up to teenagers weighing up to and over 100 kg, and their varying substrate requirements. Age and maturity-related changes of the metabolism and fluid and nutrient requirements must be taken into consideration along with the clinical situation during which PN is applied. The indication, the procedure as well as the intake of fluid and substrates are very different to that known in PN-practice in adult patients, e.g. the fluid, nutrient and energy needs of premature infants and newborns per kg body weight are markedly higher than of older paediatric and adult patients. Premature infants <35 weeks of pregnancy and most sick term infants usually require full or partial PN. In neonates the actual amount of PN administered must be calculated (not estimated). Enteral nutrition should be gradually introduced and should replace PN as quickly as possible in order to minimise any side-effects from exposure to PN. Inadequate substrate intake in early infancy can cause long-term detrimental effects in terms of metabolic programming of the risk of illness in later life. If energy and nutrient demands in children and adolescents cannot be met through enteral nutrition, partial or total PN should be considered within 7 days or less depending on the nutritional state and clinical conditions.

Effect of n-3 polyunsaturated fatty acids in asthma after low-dose allergen challenge.

BACKGROUND: We investigated the anti-inflammatory potential of n-3 polyunsaturated fatty acids (PUFA) on specific bronchial inflammation. Allergic asthmatics were challenged using a low-dose allergen provocation model. METHODS: Our parallel double-blinded study randomly assigned 23 house dust mite-allergic asthmatics (aged 22-29 years; 13 females, 10 males) to dietary supplementation with either an n-3 PUFA-enriched fat blend (0.69 g/day) or placebo for 5 weeks. After 3 weeks, the patients were challenged daily with low doses of mite allergen for 2 weeks. Primary outcome parameters were effects on lung function (forced expiratory volume in 1 s, FEV(1)) and exhaled nitric oxide (eNO) as a marker of bronchial inflammation. RESULTS: Even before the bronchial challenge, eNO was significantly lower in the n-3 PUFA group (p=0.014). Levels of eNO increased during allergen exposure in both groups, but differences in means were significantly lower in the n-3 PUFA group (p=0.022). During the low-dose allergen challenge, there were no differences between the groups with regard to symptoms, FEV(1) or the allergen dose required to induce deterioration of lung function (PD(20)). Numbers of sputum eosinophils did not differ significantly, while serum eosinophils (10.1+/-0.1.84 vs. 5.79+/-0.69%) as well as changes in eosinophilic cationic protein (20.5+/-9.93 vs. -1.68+/-4.36 ng/ml) and in vitro cysteinyl leukotriene release (2,889+/-872 vs. 1,120+/-173 ng/ml) were significantly lower in the n-3 PUFA group (p<0.05 each). CONCLUSION: Our results provide evidence that dietary supplementation with n-3 PUFA is able to reduce bronchial inflammation even after low-dose allergen challenge.

Antioxidative capacity in patients with common variable immunodeficiency.

Highly reactive oxygen species (ROS) are involved in T-cell activation and in the defense against environmental pathogens. An imbalance of ROS generation, detoxifying scavenger enzymes, and molecules with antioxidant capacity could contribute to the increased susceptibility to cancer and infections in severe humoral immunodeficiency. We studied antioxidant status, i.e., plasma antioxidant capacity (TEAC), retinol, alpha-to-copherol, ubiquinol, and the number of activated T cells in 16 patients with common variable immunodeficiency (CVID) compared to age-matched healthy controls. As expected, patients showed significantly increased levels of activated HLA-DR and CD45RO-expressing T cells. Plasma levels of the endogenous ROS scavenger ubiquinol (Q 10) were significantly lower in patients as compared to controls. However, patients showed only slightly reduced levels of TEAC as well as the exogenous antioxidants retinol and alpha-tocopherol. Although no correlation of the number of activated T cells and antioxidant capacity could be demonstrated, an increase in ROS and a diminished reactive oxygen scavenger capacity may be involved in the disease process in patients with common variable immunodeficiency.

Peripubertal perturbations in elite gymnasts caused by sport specific training regimes and inadequate nutritional intake.

Low body fat masses of elite female gymnasts are favoured for the current aesthetic appeal required for complex movements performed by the gymnasts. Optimal nutritional intake relative to physical training regimes is essential for pubertal development. Here we evaluate how high intensity training in combination with nutritional intake affects pubertal development. Twenty-two female (13.6 +/- 1.0 years) and 18 male (12.4 +/- 1.6 years) elite gymnasts from national cadres were enlisted in this study. Skeletal maturation and hormonal levels of the hypophyseal, gonadal, and adrenal axes were estimated. Prepubertal and pubertal stages were determined, and body composition was measured using two indirect methods. Whereas female gymnasts showed bone retardation (1.7 years), reduced height potential, minimal fat mass (4.3 +/- 1.3 kg), no significant increase in pubertal oestradiol levels (17.6 +/- 4.2 pg/ml vs. 23.9 +/- 13.4 pg/ml), and delayed menarche (2.3 years), male gymnasts displayed virtually unaltered pubertal development due to different training regimes. Nutritional intake was insufficient in all gymnasts although to a lesser extent for male gymnasts. Intensive physical training of elite female gymnasts combined with inadequate nutritional intake can alter the normal pattern of pubertal development. In female gymnasts the onset of menarche can be influenced by keeping the amount of fat mass low. There is a peripubertal change favouring fat mass over muscle mass in females while there is a net gain of muscle mass during pubertal development in males.

Hypoleptinemia in female and male elite gymnasts.

BACKGROUND: Elite gymnasts favour low body fat mass as the current aesthetic ideal required for complex movements in this sports discipline. Pubertal development and growth are retarded in juvenile gymnasts. Leptin, the protein product of the ob-gene, is secreted by fat cells. Besides its role in regulation of body weight, leptin also stimulates the reproductive axis. We investigated various serum hormones including leptin, body composition and nutrition in cohorts of female and male elite gymnasts to elucidate if there is a relationship between leptin levels and delayed puberty in elite gymnasts. MATERIALS AND METHODS: Twenty-two female and 18 male elite gymnasts were enrolled in this study. Pubertal stage, various hormonal levels and body composition were determined and nutritional intake was assessed. Leptin was analysed using a specific RIA. RESULTS: Pubertal development and growth were delayed in the study group, especially in girls. The percentage of body fat was reduced as compared to a normal age-matched population: 14.4% versus 21.9% in girls and 10.4% versus 15.1% in boys. Serum leptin levels were decreased, especially in pubertal girls, and did not show the normal developmental pattern with a steady increase in girls and a peak in boys of pubertal stage 2. In all gymnasts leptin levels correlated with the amount of fat mass (r = 0.6, P = 0.005 in girls; r = 0.44, P = 0.038 in boys). When leptin levels were transformed into standard deviation scores (SDS) it became obvious that the gymnasts, especially pubertal females, had significantly lower values than normal controls of the same sex, pubertal stage and body mass index (BMI): leptin SDS (BMI) = -1.21 and -3.99 in prepubertal and pubertal girls, - 0.94 and -0.91 in prepubertal and pubertal boys, respectively. When leptin SDS were based on % body fat instead of BMI, mean values were still significantly decreased compared to normal controls: -1.05 in girls (P < 0.001) and -0.60 in boys (P = 0. 025). CONCLUSIONS: Adjustment of serum leptin levels in elite gymnasts for gender, pubertal stage and BMI or % body fat reveals inappropriately low values. The reason for this hypoleptinemia is most probably insufficient caloric intake. The data suggest that hypoleptinemia in turn causes delayed puberty and growth in this particular group of athletes.

[Acute acne fulminans et conglobata after the end of high-dose testosterone therapy for hereditary tall stature]. / Akute Akne fulminans et conglobata nach Beendigung einer hochdosierten Testosterontherapie bei konstitutionellem Hochwuchs.

We report on a 13.2 years old boy who was treated for tall stature (expected target height of 204.8 +/- 5.4 cm) with high dose of testosterone. Therapy for height reduction was started with testosterone injections (250 mg Testoviron Depot i.m.) once a week. There occurred no side effects during 6 months of treatment. Maximal blood testosterone concentration was 1209 ng/dl (norm: 300-1000 ng/dl). After six months height reduction was successful with a final height of 192.7 cm. Four weeks after cessation of therapy a severe acne conglobata et fulminans appeared in the face, the back and the breast lacking any familial predisposition for acne or other skin diseases. The exacerbation was accompanied by decreased endurance, nausea and indisposition. Leucocytosis with left shift, elevation of blood sedimentation rate and C-reactive protein in addition with an increase of immunglobulin G (IgG) were detectable. At that time testosterone concentration was 192 ng/dl. Systemic treatment was started with isoretretinoin therapy (retinoid 13-cis retinacid (Roaccutan) 0.3 mg/kg), 8 mg methylprednisolon (Urbason) and cefaclor (Panoral). Local therapy included external disinfectants. After 4 months of treatment infection parameters disappeared and the acne healed with visible skin defects and severe scars. This is the first case report on acne conglobata et fulminans that appeared after cessation of testosterone therapy. High testosterone treatment seems to trigger the outbreak of sex hormone related skin disorders such as acne fulminans. It can be presumed that testosterone leads to longer lasting induction of androgen receptors resulting in acne fulminans even four weeks after treatment. Patients asking for hormonal height reduction should be aware of this rare but serious side effect.

Anti-oxidative capacity in patients with ataxia telangiectasia.

Highly reactive oxygen species (ROS) are involved in T-cell activation and in the defense against environmental pathogens. An imbalance of ROS generation and detoxifying scavenger enzymes could contribute to the increased susceptibility to cancer and infections in ataxia telangiectasia. We studied oxidative status, i.e. plasma total antioxidant capacity (TEAC), retinol, alpha-tocopherol, ubiquinol, and the number of activated T cells in 10 patients with ataxia telangiectasia (AT) compared to age-matched healthy controls. As expected, patients showed significantly increased levels of activated human leukocyte antigen-DR and CD45RO expressing T cells. TEAC levels as well as the exogenous antioxidants retinol and alpha-tocopherol were significantly reduced in patients. In addition, patients showed slightly reduced plasma levels of the endogenous ROS scavenger enzyme ubiquinol (Q10). Although no correlation between number of activated T-cells and antioxidant capacity could be demonstrated, an increase in ROS and a diminished reactive oxygen scavenger capacity may be involved in the disease process of patients with AT.

alpha-Lipoic acid treatment decreases serum lactate and pyruvate concentrations and improves glucose effectiveness in lean and obese patients with type 2 diabetes.

OBJECTIVE: We examined the effect of lipoic acid (LA), a cofactor of the pyruvate dehydrogenase complex (PDH), on insulin sensitivity (SI) and glucose effectiveness (SG) and on serum lactate and pyruvate levels after oral glucose tolerance tests (OGTTs) and modified frequently sampled intravenous glucose tolerance tests (FSIGTTs) in lean (n = 10) and obese (n = 10) patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: FSIGTT data were analyzed by minimal modeling technique to determine SI and SG before and after oral treatment (600 mg, twice a day, for 4 weeks). Serum lactate and pyruvate levels of diabetic patients after glucose loading were compared with those of lean (n = 10) and obese (n = 10) healthy control subjects in which SI and SG were also determined from FSIGTT data. RESULTS: Fasting lactate and pyruvate levels were significantly increased in patients with type 2 diabetes. These metabolites did not exceed elevated fasting concentrations after glucose loading in lean patients with type 2 diabetes. However, a twofold increase of lactate and pyruvate levels was measured in obese diabetic patients. LA treatment was associated with increased SG in both diabetic groups (lean 1.28 +/- 0.14 to 1.93 +/- 0.13; obese 1.07 +/- 0.11 to 1.53 +/- 0.08 x 10(-2) min-1, P < 0.05). Higher SI and lower fasting glucose were measured in lean diabetic patients only (P < 0.05). Lactate and pyruvate before and after glucose loading were approximately 45% lower in lean and obese diabetic patients after LA treatment. CONCLUSIONS: Treatment of lean and obese diabetic patients with LA prevents hyperglycemia-induced increments of serum lactate and pyruvate levels and increases SG.

Lipid and lipoprotein profiles in children with familial hypercholesterolaemia: effects of therapy.

UNLABELLED: In 71 children with familial hypercholesterolaemia the effect of dietary and/or medical treatment was evaluated. Initial total cholesterol and low density lipoprotein (LDL)-cholesterol levels were significantly lower in children who were consecutively treated by diet (Step-One-Diet) than in those who received additional medication. By dietary treatment, the median total cholesterol level (236.5 mg/dl; range 210-510 mg/dl) was reduced by 7.4% and the median LDL-cholesterol level (162 mg/dl; range 126-423 mg/dl) by 9.9%. By dietary and medical therapy, the median total cholesterol level (330 mg/dl; range 270-424 mg/dl) was reduced by 29.7% and the median LDL-cholesterol level (263 mg/dl; 192-333 mg/dl) by 25.9%. High density lipoprotein (HDL)-cholesterol and HDL 3 remained unchanged. HDL 2 showed a significant decrease of 15.6% up to 27 mg/dl (13-42 mg/dl) on medical treatment. Apolipoprotein A I levels did not change during therapy. Initial apolipoprotein B levels were significantly higher in children who were treated by diet and medication and were reduced by 28.9% by combined therapy. In 28 patients (39.4%) an excess of lipoprotein (a) was detected. Regarding the apolipoprotein E phenotype, 32.2% of the patients carried the risk gene epsilon4 in a hetero- or homozygous form. CONCLUSION: Early dietary and/or medical treatment in hypercholesterolaemic children significantly ameliorates the lipoprotein status. The pretherapy lipoprotein status seems to prognosticate the effectiveness of therapy.

[Effect of high performance sports on puberty development of female and male gymnasts]. / Auswirkungen des Hochleistungssports auf die Pubertätsentwicklung von Kunstturnerinnen und Kunstturnern.

High impact training may influence the pubertal development of athletes. The effects of high intensity training on pubertal development of female and male elite gymnasts are presented. 22 female and 18 male elite gymnasts were enlisted in this study. Prepubertal and pubertal stages were determined and hormonal levels regarding the hypophyseal, gonadal and adrenal axes were measured. The LH/FSH ratio necessary for the advancement of full pubertal maturation was assessed at 13.9 amd 13.0 years in female and male gymnasts, respectively. Female gymnasts demonstrated, on average, a delayed bone age of 1.7 years compared to their chronological age, whereas both bone and chronological age were identical in male gymnasts. There were no significant pubertal increase of estrogen levels in female gymnasts during their peripubertal development indicating a low amount of fat mass in female elite gymnasts. Intensive physical training of elite female gymnasts combined with inadequate nutritional intake markedly affect pubertal development. These peripubertal effects are not observable in male gymnasts due to different training regimes in male and female elite gymnast. Regular monitoring of female gymnast during their vulnerable growth phase is necessary to minimize life-long physiological and psychological side effects of high impact training.

Oestrogen treatment of constitutional tall stature: a risk-benefit ratio.

Oestrogens are given in high doses for the treatment of tall stature in girls. The aim of this study was to obtain data considering efficiency, side effects, and acceptance of the treatment of 50 constitutionally tall girls treated with conjugated oestrogens (7.5-11.25 mg/day). The mean (SD) adult height predictions were 188.3 (4.4) cm and the achieved height was 5.2 (3.3) cm less than the predicted height. A greater reduction from final predicted height occurred when treatment was started at an early bone age (< 13.0 years) and with a remaining growth potential of greater than 10 cm. Even postmenarcheal girls, however, had a mean reduction of 4.8 (3.2) cm. The main side effects were considerable weight gain (> 10 kg), an increase in triglyceride concentrations (37.5% of the patients), and increased platelet aggregation (60% of the patients). Altogether 84.6% of the patients were satisfied with the treatment and 15.4% regretted having had it.

Ineffectiveness of oral coenzyme Q10 supplementation in 3-methylglutaconic aciduria, type 3.

Coenzyme Q10 was administered under placebo controlled blinded crossover conditions to six subjects suffering from type 3 3-methylglutaconic aciduria ('optic atrophy plus'), following a report of benefit. Despite attainment of high plasma levels of coenzyme Q10, no clinical benefit was observed and there was no diminution of urinary excretion of 3-methylglutaconic acid.

Diabetes insipidus due to hypophysitis.

Central diabetes insipidus is a chronic disorder which in most patients occurs secondary to tumor, infection, trauma or other lesions. In about 20-30% of patients etiology is unclear, however a destructive autoimmune process in the hypophysis may play a role. We report the case of an 18-year-old girl with central diabetes insipidus. Vasopressin levels were typically decreased. Examinations performed 1.5 years after manifestation showed no pathologic changes on MRI and no additional endocrine disorder. MRI was repeated 1.5 years later whereon a thickening of the pituitary stalk as a typical sign of hypophysitis was apparent. No other reasons could be found for the vasopressin deficiency. The finding of hypophysitis in our patient 3 years after disease manifestation suggests that the characteristic MRI changes may take as long as 3 years to become apparent.

Congenital microgastria, growth hormone deficiency and diabetes insipidus.

UNLABELLED: Microgastria is a rare malformation of the stomach always associated with variable patterns of malformations of the lung, heart, aortic arch, skeleton, and central nervous system. Many cases present with asplenia and hepatic symmetry as well as intestinal malrotation. We report a first case of a 4.5-year-old girl with congenital microgastria in association with growth hormone deficiency, diabetes insipidus, brachyoesophagus, hernia of the diaphragm, gastro-oesophageal reflux, intestinal malrotation, enlarged symmetrical liver, asplenia, as well as mental and statomotor retardation. CONCLUSION: Congenital microgastria is always associated with malformations of other organs. Patients at any age presenting one of the symptoms: failure to thrive, vomiting, asplenia, midline defects and parts of the VACTERL association should be carefully examined to exclude microgastria.

Docosahexaenoic and arachidonic acid absorption in preterm infants fed LCP-free or LCP-supplemented formula in comparison to infants fed fortified breast milk.

The absorption of long-chain polyunsaturated fatty acids (LCP) with particular respect to docosahexaenoic (DHA) and arachidonic acid (AA) has been studied in 39 very-low-birth-weight infants appropriate for gestational age after a 10-day feeding period. The infants were fed either a LCP-supplemented formula (n = 11), or a LCP-free formula (n = 11) or breast milk fortified with protein and carbohydrates to have similar protein and energy intakes as in the formula-fed infants (n = 17). Total fat content and fatty acid profile were measured in the human milk, the two formulas, and in the stool samples. After a 10-day feeding period, the fecal excretions of total fat, DHA and AA were measured during a 3-day balance period. The total fat apparent absorption rates were similar in all groups (84.1, 82.1 and 80.6% of intake, respectively). The DHA and AA intakes were significantly (p < 0.01) higher in the group fed the fortified breast milk than in the group fed the LCP-supplemented formula (DHA: 75.5 +/- 12.4 vs. 50.2 +/- 4.2 mg/72 h; AA: 45.5 +/- 5.8 vs. 30.2 +/- 2.7 mg/72 h). There was a tendency for lower apparent absorption rates for both LCPs studied in the group fed fortified breast milk when compared to the group fed LCP-supplemented formula (AA: 70.6 +/- 10.9 vs. 73.0 +/- 8.7% of intake, DHA: 69.0 +/- 10.6 vs. 74.2 +/- 9.5% of intakes, but the differences were not significant. As consequence of the different intakes, the net absorption of the two studied LCP fatty acids were significantly (p < 0.01) higher in the breast milk group than in the group fed the LCP-supplemented formula (DHA: 52.6 +/- 6.1 vs. 36.8 +/- 4.5 mg/72 h; AA: 31.4 +/- 3.1 vs. 22.4 +/- 2.3 mg/72 h). The data demonstrate that DHA and AA are absorbed from the studied LCP-supplemented formula at least as effectively as from human milk. The net absorption of these LCP depend on the amount of dietary intake, and seems to be influenced by the dietary LCP source.

Docosahexaenoic and arachidonic acid content of serum and red blood cell membrane phospholipids of preterm infants fed breast milk, standard formula or formula supplemented with n-3 and n-6 long-chain polyunsaturated fatty acids.

UNLABELLED: The contents of docosahexaenoic (DHA) and arachidonic acid (AA) of plasma and red blood cell membrane phospholipids were studied in 41 very low birth weight infants fed either breast milk (n = 18), a standard formula without long-chain polyunsaturated fatty acids with 20 or 22 carbon atoms (LCP) but with alpha-linolenic acid and linoleic acid (n = 11) or a formula additionally supplemented with n-3 and n-6 LCP in relations typical for human milk (n = 12) after 2, 6, and 10 weeks of feeding. The content of DHA and AA in plasma phospholipids declined in the infants fed the LCP-free formula but remained more or less constant during the whole feeding period in those infants fed breast milk as well as in those fed the LCP-supplemented formula. The differences between the group fed the LCP-free standard formula and the two groups fed LCP-containing diets became significant during the first 2 weeks of feeding. In contrast, there were no differences between the group fed breast milk and the group fed the supplemented formula during the study period. Similar effects could be observed regarding the composition of red blood cell membrane phospholipids, but the differences between the infants fed the LCP-free standard formula and the two other groups with LCP-containing diets were significant only for AA. The data indicate that very low birth weight infants are unable to synthesize LCP from alpha-linolenic acid and linoleic acid in sufficient amounts to prevent a decline of LCP in plasma and red blood cell phospholipids. Additionally, the data show, that supplementation of formulas with n-3 and n-6 LCP in amounts typical for human milk fat results in similar fatty acid profiles of plasma and red blood cell membrane phospholipids as found during breast milk feeding. CONCLUSION: Supplementation of formula with long-chain polyunsaturated fatty acids improves the LCP status of very low birth weight infants.

Acylcarnitines in intermediary metabolism.

From the time of its discovery in 1905 until the first description of its deficiency in 1973, the role of carnitine in intermediary metabolism was decidedly vague. Identification of carnitine acyl transferases and their products, acylcarnitines, have paved the way to the confirmation of the importance of carnitine in the transfer of fatty acid CoAs into the mitochondrion for beta-oxidation and energy production. The elucidation of defects in fatty acid oxidation together with the concept of carnitine therapy in certain organoacidaemias have given a new meaning to the term acylcarnitine. Not only are these compounds of diagnostic importance, their formation may be part of a secondary carnitine depletion which may be brought about as a result of various medications. Recent evidence suggests that long-chain acylcarnitines are responsible for cardiac arrhythmias and other effects, both good and bad, will certainly be found. This review will attempt to highlight the importance of acylcarnitines, from their production, the difficulties in analysis, the diagnostic possibilities and their positive and negative effects on intermediary metabolism.