Vitamin D and calcium intakes in general pediatric populations: A French expert consensus paper.

OBJECTIVES: Nutritional vitamin D supplements are often used in general pediatrics. Here, the aim is to address vitamin D supplementation and calcium nutritional intakes in newborns, infants, children, and adolescents to prevent vitamin D deficiency and rickets in general populations. STUDY DESIGN: We formulated clinical questions relating to the following categories: the Patient (or Population) to whom the recommendation will apply; the Intervention being considered; the Comparison (which may be "no action," placebo, or an alternative intervention); and the Outcomes affected by the intervention (PICO). These PICO elements were arranged into the questions to be addressed in the literature searches. Each PICO question then formed the basis for a statement. The population covered consisted of children aged between 0 and 18 years and premature babies hospitalized in neonatology. Two groups were assembled: a core working group and a voting panel from different scientific pediatric committees from the French Society of Pediatrics and national scientific societies. RESULTS: We present here 35 clinical practice points (CPPs) for the use of native vitamin D therapy (ergocalciferol, vitamin D2 and cholecalciferol, vitamin D3) and calcium nutritional intakes in general pediatric populations. CONCLUSION: This consensus document was developed to provide guidance to health care professionals on the use of nutritional vitamin D and dietary modalities to achieve the recommended calcium intakes in general pediatric populations. These CPPs will be revised periodically. Research recommendations to study key vitamin D outcome measures in children are also suggested.

[Neonatal intoxication to vitamin D in premature babies: A series of 16 cases]. / Intoxication néonatale à la vitamine D chez des anciens prématurés : une série de 16 cas.

INTRODUCTION: Preterm neonates are particularly at risk of vitamin D (25-D) deficiency. To prevent rickets and osteopenia in this population, international guidelines vary between 800 and 1000IU per day of vitamin D in Europe and recommend 400IU per day in the USA. Target levels of circulating 25-D are not well identified, with the lower target level 50-75nmol/L and the upper target level probably 120nmol/L. METHODS: Between 2013 and 2015, 16 premature infants (born<35WG) were referred to pediatric nephrology clinics because of symptoms secondary to 25-D overdose during the neonatal period. Clinical and biological data were retrospectively reviewed to better define this population. The results are presented as the median (range). RESULTS: Gestational age was 27 (24-35)WG with a birth weight of 810 (560-2120)g. Nephrocalcinosis was the initial symptom in 37% of cases, hypercalcemia in 44%, and hypercalciuria in 19%. Daily vitamin D doses were 333 (35-676)IU. Age and body weight at initial symptom were 36.6 (27.6-47.6)WG and 2300 (640-3760)g, respectively. The 25-D level at the time of the first dosage was 210 (119-350)nmol/L and the 1-25 vitamin D level was 370 (245-718)pmol/L (local normal values for age<240). During follow-up, 12 patients displayed nephrocalcinosis, ten hypercalciuria, and three hypercalcemia. The 25-D level normalized in ten patients within 10 (3-32)months after vitamin D withdrawal. Nephrocalcinosis improved in ten of 12 patients, within 12 (3-30)months. Vitamin D could be readministered in ten patients. When searched (n=3), no CYP24A1 mutation was identified in two patients, but was identified in the heterozygous state in one. CONCLUSION: A 25-D overdose should be systematically ruled out in the presence of nephrocalcinosis, hypercalcemia, and/or hypercalciuria during infancy in children born preterm. Studies are required to assess the exact frequency of 25-D deficiency and overdose in this population, as well as to evaluate the potential deleterious effects of this imbalance on bone, kidney, and brain development.

A new method for permeability measurement of hydrophobic membranes in Vacuum Membrane Distillation process.

In this paper, a new method for permeability measurement of hydrophobic membranes used in Vacuum Membrane Distillation, instead of common measurement methods, was proposed. As VMD is a pressure and temperature driven process, the idea of this work is to propose a new water vapour permeability measurement method based on variation of feed temperature at a fixed vacuum pressure. This new method showed a greater stability and simplicity than the existing pressure variation method by not only allowing a wide range of feed temperature (25 °C ÷ 60 °C) to be scanned continuously, but also avoiding fluctuations of the system as observed in the pressure variation test. Permeabilities of two different kinds of hydrophobic membranes were measured by this new method and also by the existing pressure variation test. A comparison between these two methods was also presented to assess the feasibility and applicability of this new method.

Study on performance of ultrafiltration membrane-based pretreatment for application to seawater reverse osmosis desalination.

The objective of the work was to study at lab-scale the efficiency of hybrid process- coupling powdered activated carbon (PAC) adsorption or FeCl(3) coagulation and UF- for marine organic matter removal. Regenerated cellulose membrane with 30 kDa and actual seawater from Mediterranean Sea were used. The coagulant was FeCl(3) and adsorbents were two PAC types, with different surface area and pore size distribution. The results showed that PAC adsorption/UF performed higher efficiency in terms of organic removal than FeCl(3) coagulation/UF. Organic matter removal up to 50% was obtained for a PAC dose of 200 mg/L. According to high performance size exclusion chromatography (HP-SEC) analysis, the organics removed by PAC/UF are approximately 10 kDa. Therefore, the effect of PAC adsorption was deeply evaluated in terms of UF membrane fouling rate. The fouling rate was reduced when increasing PAC dose for both PAC types, in particular when PAC with a higher BET surface area and larger fraction of micropores was used. On the other hand, the results showed that UF unit could highly reduce SDI(3) from 26 to 9. The addition of PAC and FeCl(3) to UF allowed a further reduction of SDI(3) from 9 to 4-6.

Lipid peroxidation assessment by malondialdehyde measurement in parenteral nutrition solutions for newborn infants: a pilot study.

AIM: To determine malondialdehyde (MDA) concentrations in parenteral nutrition admixtures exposed to ambient room light, and in the serum of neonates. METHODS: Using a new method to measure MDA specifically, this study analysed MDA of lipid-containing all-in-one admixtures provided by the pharmacy, with a composition identical to that used in routine clinical conditions. First, 12 admixtures were exposed to ambient light for 24 h, in the neonatal intensive care unit. Secondly, 18 solutions were either exposed to (n = 9) or protected from ambient light (n = 9) during the same period. Samples of admixtures were collected at baseline and 24 h later, for MDA measurement. Serum MDA was also randomly measured in orally fed healthy neonates. RESULTS: After 24 h exposure to ambient room light, MDA concentrations in parenteral nutrition admixtures increased from 179 (129, 348) nmol l(-1) to 5800 (1632, 14679) nmol l(-1) (p = 0.0002) [50th (10th, 90th) centiles]. When admixtures were protected from light, the increase in MDA was significantly lower than without protection: 187 (60, 429)nmol l(-1) versus 13 696 (3472, 26 049)nmol l(-1) (p = 0.0003). In 54 infants with a gestational age of 33 (28, 39) wk and a birthweight of 1750 (960, 3388) g, plasma MDA concentrations were 173 (98, 315) nmol l(-1). CONCLUSION: In solutions protected from light, MDA concentrations were low and were close to the serum MDA concentrations observed in orally fed neonates. Administration of all-in-one admixtures containing lipids in ambient lighting results in intravenous infusion of high levels of MDA which may present an additional source of morbidity in immature infants. This study confirms the need to protect parenteral admixtures from light.

Vitamin D deficiency in Iranian mothers and their neonates: a pilot study.

UNLABELLED: We conducted a pilot study to assess the prevalence of hypovitaminosis D among Iranian women and their newborns. Blood samples were taken from 50 mothers (age 16-40 yr) and their neonates at term delivery in the largest Tehran hospital. The results showed that 80% of the women had 25-hydroxyvitamin D (25-OHD) concentrations of less than 25 nmol/l. Mean maternal plasma calcium and phosphatase alkaline concentrations were in the normal range. The mean maternal serum immunoreactive parathyroid hormone concentration of women with hypovitaminosis D (i.e., 25-OHD levels <25 nmol/l) was above normal range and significantly different from that of women without hypovitaminosis D. CONCLUSION: The mean cord serum 25-OHD concentration was very low (4.94+/-9.4 nmol/l) and that of infants of mother with hypovitaminosis D were almost undetectable (1.2+/-1.2 nmol/l).

Photoprotection of solutions of parenteral nutrition decreases the infused load as well as the urinary excretion of peroxides in premature infants.

Light exposure and multivitamins are contributing factors to the generation of peroxides in solutions of parenteral nutrition. This article verifies if peroxides infused with parenteral nutrition are of biological significance in neonates. The mechanisms responsible for the generation of peroxides in total parenteral nutrition solutions are reviewed. The consequences of infused peroxides on an index of oxidant stress and on levels of a central antioxidant are evaluated in an animal model. The effect of photoprotection of parenteral nutrition on a biological marker of redox imbalance is evaluated in the urine of premature infants. Parenteral multivitamins produce a drop in glutathione and an oxidant stress similar to peroxides in the lungs of newborn guinea pigs. Infused peroxides elicited an increased urinary peroxide excretion in infants receiving parenteral nutrition exposed to light. Photoprotection reduced levels of infused and excreted peroxides. The results suggest that peroxides infused with total parenteral nutrition are not fully quenched by premature infants.

Parenteral multivitamin supplementation induces both oxidant and antioxidant responses in the liver of newborn guinea pigs.

BACKGROUND: The multivitamin solution is a major component of photo-induced generation of peroxides in parenteral nutrition. The aim of this study was to determine whether the parenteral multivitamin preparation induces in the liver a peroxide-induced oxidant challenge or an antioxidant protection associated with the antiradical components of the solution. METHODS: Newborn guinea pigs were infused with dextrose supplemented with peroxides (250 micromol/L H2O2 or 350 micromol/L tert-butylhydroperoxide) or with a multivitamin preparation (MVP, 1% vol/vol). After 4 days, total glutathione and a free radical-sensitive eicosanoid marker (prostaglandin I2 [PGI2]/total prostaglandins) were measured in livers. RESULTS: There was a significant decrease in the PGI2/total prostaglandin ratio (mean +/- SEM) [dextrose: 0.068 +/- 0.007 vs. (dextrose + H2O2: 0.048 +/- 0.001, dextrose + TBH: 0.043 +/- 0.001)] and glutathione concentrations decreased [dextrose: 55 +/- 7 vs. (dextrose + H2O2: 37 +/- 7, dextrose + TBH: 18 +/- 7 nmol/mg protein)] after infusion of peroxides. Despite the peroxide load in the multivitamin solution, it did not alter the measured variables as prostanoid ratio remained at control concentrations (dextrose: 0.066 +/- 0.008 vs. dextrose + MVP: 0.065 +/- 0.006), as did glutathione levels (dextrose: 52 +/- 6 vs. dextrose + MVP: 45 +/- 7 nmol/mg prot). CONCLUSION: In the liver of guinea pig pups, infused peroxides cause oxidation of membrane-derived prostanoids. The decrease in glutathione in response to administration of peroxides suggests consumption rather than a response to a free radical attack. Despite the oxidant load associated with peroxides generated in MVP, the multivitamin preparation protected membranes as the prostanoid ratio, and glutathione levels remained at control levels.

Peroxide-like oxidant response in lungs of newborn guinea pigs following the parenteral infusion of a multivitamin preparation.

The multivitamin solution is a major component responsible for the photo-induced generation of peroxides in parenteral nutrition. The lung is a target of oxidant injury; however, the specific role of infused peroxides is unknown. The aim of this study was to determine if parenteral multivitamins induce in the lung an oxidant challenge similar to that of peroxides. Newborn guinea pigs were infused with dextrose plus relevant concentrations of H(2)O(2) (0,250,500 microM) or multivitamins (0,1%), as well as parenteral nutrition supplemented with multivitamins (0,1%). After 4 days, total glutathione, glutathione-related enzymes, and oxidant-sensitive eicosanoids were measured in the lungs. Peroxides as well as multivitamins led to a significant decrease in glutathione and the activity of glutathione synthase, indicating that infused peroxides were not entirely transformed into free radicals, which would have stimulated glutathione synthesis. The multivitamin solution induced a response in oxidant-sensitive eicosanoids similar to the response to peroxides, suggesting an oxidant stress that was not alleviated by the antiradical properties of its components. The effects on prostaglandins occurred independently from the stimulation in glutathione levels induced by parenteral nutrition. The multivitamin solution carries an oxidant load and causes effects similar to those of peroxides in the lungs of newborn guinea pigs.

Increased urinary peroxides in newborn infants receiving parenteral nutrition exposed to light.

OBJECTIVES: To determine whether peroxide loads infused with total parenteral nutrition (TPN) are fully quenched by premature infants. STUDY DESIGN: After baseline urine peroxide levels were established, the effect of various parenteral regimens was correlated with urinary peroxide levels in 64 newborn infants

Contribution of multivitamins, air, and light in the generation of peroxides in adult and neonatal parenteral nutrition solutions.

OBJECTIVE: To compare the concentrations of peroxides between adult and neonatal total parenteral nutrition (TPN) solutions in response to protection against inducers of peroxidation such as multivitamins and exposure to light or air. METHODS: Peroxide concentrations were measured in freshly prepared adult and neonatal solutions of fat-free TPN in four settings: with or without an air inlet, and protected or unprotected from ambient light. An oxygen washout was performed by exposing a fat-free neonatal TPN solution to a continuous flow of nitrogen. RESULTS: Globally, light was the main inducer of peroxides in adult and neonatal solutions. However, in adult solutions the concentration of peroxides remained <15 micromol/L, while in neonatal solutions the peroxide concentration was as high as 300 micromol/L in ambient light. Although the oxygen washout did prevent the generation of peroxides, avoiding air inlet was not as effective as was photoprotection in decreasing the important peroxide load in the neonatal TPN solution. CONCLUSIONS: The higher concentration of peroxides found in neonatal solutions compared with adult solutions is explained by the differences in nutrient composition between the two solutions. Contamination of parenteral solutions by air during compounding accounts for the photoinduced generation of peroxides in TPN solutions. It is more convenient to protect TPN solutions from light exposure after the admixture of the multivitamin solution than to avoid contact with oxygen.

Survival of guinea pig pups in hyperoxia is improved by enhanced nutritional substrate availability for glutathione production.

The imbalance between high oxidant loads and immature antioxidant defenses is associated with long-term complications of prematurity. Glutathione is a central element among the antioxidants. Depletion of pulmonary glutathione accelerates the development of oxygen-induced lung injury in neonatal animal models. After the observation that newborn infants exposed to oxygen have low glutathione levels, a study was designed to test the hypothesis that in neonates from a species susceptible to oxygen toxicity, the lethal effect of hyperoxia is related to a low availability of substrates for glutathione production rather than an impairment in synthetic activity. One-day-old guinea pigs, randomly assigned to room air or oxygen (>95%), were fed by their mothers (n = 16) or i.v. by dextrose (n = 14) or by total parenteral nutrition (TPN, n = 20). After 3 d, glutathione and activities of enzymes involved in maintaining intracellular glutathione levels were determined in lungs and liver. The lethal effect of oxygen (p < 0.05) observed in animals without TPN was not related to glutathione depletion, as oxygen induced a 33% increase in lung glutathione, positively correlated (r2 = 0.35) with enhanced synthesis. With TPN, the animals were protected against the lethal effects of hyperoxia and lung glutathione increased by 67% in oxygen. The results suggest that the glutathione demand by the lungs in the presence of an oxidant stimulus was met by the increased (p < 0.001) hepatic production supported by TPN. Under hyperoxic conditions, early nutritional support is of vital importance.

Protecting solutions of parenteral nutrition from peroxidation.

BACKGROUND: Light exposure induces the generation of peroxides in solutions of total parenteral nutrition (TPN). Peroxide toxicity has been documented in cell, in tissue, and in isolated organs. To decrease the infused peroxide load and to protect the quality of the parenteral nutrients, we tested the photoprotective properties of different infusion sets. METHODS: Solutions of fat-free TPN and all-in-one total nutrient admixture (TNA) were run through sets of bags (clear and covered) and tubings (clear and colored: black, orange, and yellow) offering different levels of protection against light. Peroxide levels were determined by ferrous oxidation of xylenol orange, thiol functions by the 5,5,-dithiobis(2-nitrobenzoic acid) technique, and absorbance of tubings by spectroscopy. RESULTS: Protection of only the bag had little effect on peroxide generation. In fat-free TPN solutions kept in covered bags, peroxide concentrations were 1.5 to 2 times higher when run through clear compared with colored tubings. When exposed to phototherapy or in the presence of lipids, peroxides were two to three times higher with the clear compared with the black tubing; meanwhile, orange and yellow tubings offered varying levels of protection related to their light-absorbing properties. Colored tubings offered a greater protection against the disappearance of thiol functions. CONCLUSIONS: Covering bags and using orange and yellow tubings may be a practical solution to reduce infused peroxide loads from about 400 to 100 microM. This is especially relevant in patients with an immature or a compromised antioxidant capacity or when phototherapy or preparations of TNA are used.

Growth hormone, insulin-like growth factor-I and insulin-like growth factor binding protein-3 are regulated differently in small-for-gestational-age and appropriate-for-gestational-age neonates.

Growth hormone (GH), insulin-like growth factor-I (IGF-I) and IGF-binding protein-3 (IGFBP-3) were measured in 90 neonates during the first 5 days of life. Twenty-six small-for-gestational-age (SGA) neonates were compared with 64 appropriate-for-gestational-age (AGA) neonates. There were no differences in nutritional status between the 2 groups. Mean GH levels were significantly higher in the SGA group (53.4 +/- 30.8 vs. 39.9 +/- 23.3 microg/l; p < 0.05). In both groups GH levels correlated with birth weight (expressed as SDS) but not with gestational age. IGF-I levels were significantly lower in SGA neonates (6.6 +/- 4.0 vs. 11.7 +/- 8.2 ng/ml; p < 0.01). In SGA neonates with short stature, IGF-I levels were lower and GH levels were higher than in normal stature SGA neonates. IGFBP-3 levels were significantly lower in SGA neonates than in AGA neonates (0.72 +/- 0.40 vs. 0.98 +/- 0.43 microg/l; p < 0.01). IGF-I and IGFBP-3 correlated with gestational age in AGA but not in SGA neonates and there was no correlation with birth weight in either group. Our data provide evidence for a graduation in the severity of impact of fetal 'malnutrition' on the somatotropic axis and on intrauterine growth. The most severe state (SGA with short stature) was associated with a GH-resistance syndrome, characterized by very low IGF-I levels and high GH levels.

Paradoxical role of ascorbic acid and riboflavin in solutions of total parenteral nutrition: implication in photoinduced peroxide generation.

In the presence of light, a multivitamin preparation is the main source of peroxides in solutions of total parenteral nutrition (TPN). This preparation contains two photosensitive products, 5'-phosphate flavin mononucleotide (FMN) and polysorbates (PS), as well as electron donors such as ascorbate (AH). We hypothesized that the admixture of FMN or PS with electron donors generates peroxides in TPN and alters the quality of nutrients. Using xylenol orange, peroxide concentrations were measured in solutions containing AH, FMN, and/or PS in water, a dextrose solution, an amino acid preparation, and a lipid emulsion. Thiol functions were evaluated by reduction of 5,5-dithiobis(2-nitrobenzoic acid) in the amino acid preparation. After 24-h light exposure, dextrose solutions with admixtures of AH + FMN or AH + FMN + PS generated peroxides at concentrations similar to those observed in a 1% multivitamin solution, and over three times higher than those observed with FMN, PS, or AH alone. However, in the presence of amino acids, FMN alone induced a generation of peroxides comparable to that observed with FMN + AH. In the lipid emulsion, peroxides increased over 3-fold in the presence of FMN or FMN + AH. The addition of catalase suggested that lipid peroxides and H2O2 were produced, and the loss of thiol function suggested that an oxidation of amino acids occurred. When exposed to light, FMN induces reactions with amino acids, polyunsaturated fatty acids, and even AH, altering the quality of nutrients. Paradoxically, AH without FMN has a protective effect on peroxide generation in TPN.

[Cardiac tamponade secondary to umbilical venous catheterization accident in a premature infant]. / Tamponnade cardique secondaire à un accident de cathétérisme veineux ombilical chez un prématuré.

BACKGROUND: Cardiac tamponade is a rare and sometimes severe complication of umbilical venous catheterization. CASE REPORT: A premature newborn (gestational age: 30 weeks, birth weight: 1,215 g) required assisted ventilation and umbilical venous catheterization for respiratory distress. Subsequent chest X-ray showed the ascending tip of the catheter lying in the left atrium, inside the auricle. At the age of 16 hours, the infant presented with episodes of bradycardia. Despite a second endotracheal intubation, a sudden vascular collapse necessitated cardiac massage plus sodium bicarbonate and epinephrine. An ultrasound examination was performed because of the persistence of the vascular collapse; it showed a clear echo-free space between the epicardium and pericardium, suggesting pericardial effusion. The patient responded dramatically to pericardial aspiration, providing hemorrhagic fluid containing 20 g per liter glucose. DISCUSSION: Cardiac tamponade probably occurred in this patient as a result of perforation of the atrial wall. Ultrasonography showed no local thrombus, but confirmed the cardiac compression by pericardial fluid and the localization of the tip of catheter in contact with the atrial wall. This case led us to review the mechanical complications of umbilical venous and/or percutaneous catheterization and the rules for their use. CONCLUSION: This complication must be suspected in all patients having a central venous catheter that present with vascular collapse.