Goudoever, J.B. van

Computer screen saver hand hygiene information curbs a negative trend in hand hygiene behavior (Article)

2012-03-13T00:00:00Z

Background: Appropriate hand hygiene among health care workers is the most important infection prevention measure; however, compliance is generally low. Gain-framed messages (ie, messages that emphasize the benefits of hand hygiene rather than the risks of noncompliance) may be most effective, but have not been tested. Methods: The study was conducted in a 27-bed neonatal intensive care unit. We performed an inter- rupted time series analysis of objectively measured hand disinfection events. We used electronic devices in hand alcohol dispensers, which continuously documented the frequency of hand disinfection events. In addition, hand hygiene compliance before and after the intervention period were directly observed. Results: The negative trend in hand hygiene events per patient-day before the intervention (decrease by 2.3 [standard error, 0.5] per week) changed to a significant positive trend (increase of 1.5 [0.5] per week) after the intervention (P < .001). The direct observations confirmed these results, showing a significant improvement in hand hygiene compliance from 193 of 303 (63.6%) observed hand hygiene events at pretest to 201 of 281 (71.5%) at posttest. Conclusions: We conclude that gain-framed messages concerning hand hygiene presented on screen savers may improve hand hygiene compliance.

The profile of executive function in very preterm children at 4 to 12 years (Article)

2012-03-01T00:00:00Z

Aim To examine executive functioning in very preterm (gestational age ≤30wks) children at 4 to 12years of age. Method Two-hundred very preterm (106 males, 94 females; mean gestational age 28.1wks, SD 1.4; mean age 8y 2mo, SD 2y 6mo) and 230 term children (106 males, 124 females; mean gestational age 39.9wks, SD 1.2; mean age 8y 4mo, SD 2y 3mo) without severe disabilities, born between 1996 and 2004, were assessed on an executive function battery comprising response inhibition, interference control, switching, verbal fluency, verbal and spatial working memory, and planning. Multiple regression analyses examined group differences while adjusting for effects of parental education, age, sex, and speed indices. Results Relative to children born at term, very preterm children had significant (ps<0.02; where psrepresents p-values) deficits in verbal fluency (0.5 standardized mean differences [SMD]), response inhibition (0.4 SMD), planning (0.4 SMD), and verbal and spatial working memory (0.3 SMD), independent of slow and highly fluctuating processing speed. A significant group by age interaction indicated that group differences for response inhibition decreased between 4 and 12years. Interpretation Very preterm birth is associated with a profile of affected and non-affected executive functions independent of impaired speed. Deficits are of small to moderate magnitude and persist over time, except for response inhibition for which very preterm children catch up with peers. © The Authors. Developmental Medicine & Child Neurology

Lysine requirement of the enterally fed term infant in the first month of life (Article)

2011-12-01T00:00:00Z

Background: Infant nutrition has a major impact on child growth and functional development. Low and high intakes of protein or amino acids could have a detrimental effect. Objective: The objective of the study was to determine the lysine requirement of enterally fed term neonates by using the indicator amino acid oxidation (IAAO) method. L-[1-13C]phenylalanine was used as an indicator amino acid. Design: Twenty-one neonates were randomly assigned to lysine intakes that ranged from 15 to 240 mg·kg-1·d-1. Breath, urine, and blood samples were collected at baseline and during the plateau. The mean lysine requirement was determined by using biphasic linear regression crossover analysis on the fraction of13CO2recovery from L-[1-13C] phenylalanine oxidation (F13CO2) and phenylalanine oxidation rates calculated from the L-[1-13C]phenylalanine enrichment of urine and plasma. Results: The mean (±SD) phenylalanine flux calculated from urine and plasma L-[1-13C]phenylalanine enrichment data were 88.3 ± 6.9 and 84.5 ± 7.4 μmol·kg-1·h-1, respectively. Graded intakes of lysine had no effect on phenylalanine fluxes. The mean lysine requirement determined by F13CO2was 130 mg·kg-1·d-1(upper and lower CIs: 183.7 and 76.3 mg·kg-1·d-1, respectively). The mean requirement was identical to the requirement determined by using phenylalanine oxidation rates in urine and plasma. Conclusions: The mean lysine requirement of enterally fed term neonates was determined by using F13CO2and phenylalanine oxidation rates calculated from the L-[1-13C] phenylalanine enrichment of urine and plasma. These methods yielded a similar result of 130 mg lysine·kg-1·d-1. This study demonstrates that sampling of13CO2in expired air is sufficient to estimate the lysine requirement by using the IAAO method in infants. This trial was registered at www.trialregister.nl as NTR1610.

Amino acid metabolism in the human fetus at term: Leucine, valine, and methionine kinetics (Article)

2011-12-01T00:00:00Z

Human fetal metabolism is largely unexplored. Understanding how a healthy fetus achieves its fast growth rates could eventually play a pivotal role in improving future nutritional strategies for premature infants. To quantify specific fetal amino acid kinetics, eight healthy pregnant women received before elective cesarean section at term, continuous stable isotope infusions of the essential amino acids [1-13C,15N]leucine, [U-13C5]valine, and [1-13C]methionine. Umbilical blood was collected after birth and analyzed for enrichments and concentrations using mass spectrometry techniques. Fetuses showed considerable leucine, valine, and methionine uptake and high turnover rates. α-Ketoisocaproate, but not α-ketoisovalerate (the leucine and valine ketoacids, respectively), was transported at net rate from the fetus to the placenta. Especially, leucine and valine data suggested high oxidation rates, up to half of net uptake. This was supported by relatively low α-ketoisocaproate reamination rates to leucine. Our data suggest high protein breakdown and synthesis rates, comparable with, or even slightly higher than in premature infants. The relatively large uptakes of total leucine and valine carbon also suggest high fetal oxidation rates of these essential branched chain amino acids.

Reducing glucose infusion safely prevents hyperglycemia in post-surgical children (Article)

2011-12-01T00:00:00Z

Background & aims: To investigate the effects of two different glucose infusions on glucose homeostasis and amino acid metabolism in post-surgical children. Methods: This randomized crossover study evaluated glucose and amino acid metabolism in eight children (age 9.8 ± 1.9 months, weight 9.5 ± 1.1 kg) admitted to a pediatric intensive care unit in a tertiary university hospital after surgical correction for non-syndromal craniosynostosis. Patients were randomized to receive low (LG; 2.5 mg kg-1min-1) and standard (SG; 5.0 mg kg-1min-1) glucose infusion in a crossover setting. After a bolus (4 g kg-1) of deuterium oxide, we conducted a primed, constant, 8 h tracer infusion with [6,6-2H2]Glucose, [1-13C]Leucine, [ring-2H5]Phenylalanine and [3,3-2H2]Tyrosine. Results: SG resulted in hyperglycemia (defined as > 6.1 mmol L-1), while during LG plasma glucose levels were normoglycemic (5.9 ± 0.6 vs. 7.5 ± 1.7 mmol L-1; LG vs. SG respectively, p = 0.02). Hypoglycemia did not occur during LG infusion. Endogenous glucose production was not fully suppressed during the hyperglycemic state under SG and increased with reduced glucose infusion (2.6 ± 1.5 vs. 1.1 ± 1.4 mg kg-1min-1; LG vs. SG; p = 0.05). Whole body protein balance derived from leucine and phenylalanine kinetics was slightly negative but not further affected with a decrease in glucose infusion. Conclusions: The current recommended glucose infusion induces hyperglycemia in post-surgical children. A reduced glucose infusion safely reduced high glucose levels, while children were capable to sustain normoglycemia with increased endogenous glucose production. The reduced glucose infusion did not exacerbate the mild catabolic state in which the patients were.

Current recommended parenteral protein intakes do not support protein synthesis in critically ill septic, insulin-resistant adolescents with tight glucose control (Article)

2011-11-01T00:00:00Z

Objective: To investigate the effects of insulin infusion and increased parenteral amino acid intakes on whole body protein balance, glucose kinetics, and lipolysis in critically ill, insulin-resistant, septic adolescents. Design: A single-center, randomized, crossover study. Setting: A medicosurgical intensive care unit in a tertiary university hospital. Patients: Nine critically ill, septic adolescents (age 15.0 ± 1.2 yrs, body mass index 20 ± 4 kg m-2) receiving total parenteral nutrition. Interventions: Patients received total parenteral nutrition with standard (1.5 g•kg-1•day-1) and high (3.0 g•kg-1•day-1) amino acid intakes in a 2-day crossover setting, randomized to the order in which they received it. On both study days, we conducted a primed, constant, 7-hr stable isotope tracer infusion with [1-13C]leucine, [6,6-2H2]glucose, and [1,1,2,3,3-2H5]glycerol, in combination with a hyperinsulinemic euglycemic clamp during the last 3 hrs. Measurements and Main Results: Insulin decreased protein synthesis at standard amino acid and high amino acid intakes (p < .01), while protein breakdown decreased with insulin at standard amino acid intake (p < .05) but not with the high amino acid intake. High amino acid intake improved protein balance (p < .05), but insulin did not have an additive effect. There was significant insulin resistance with an M value of ∼3 (mg•kg-1•min-1)/(mU•mL-1) which was 30% of reported normal values. At high amino acid intake, endogenous glucose production was not suppressed by insulin and lipolysis rates increased. Conclusion: The current recommended parenteral amino acid intakes are insufficient to maintain protein balance in insulin-resistant patients during tight glucose control. During sepsis, insulin decreases protein synthesis and breakdown, and while high amino acid intake improves protein balance, its beneficial effects may be offset by enhanced endogenous glucose production and lipolysis, raising concerns that insulin resistance may have been exacerbated and that gluconeogenesis may have been favored by high amino acid intakes. Dose-response studies on the effect of the level of amino acid intakes (protein) on energy metabolism are needed.

Colitis development during the suckling-weaning transition in mucin muc2-deficient mice (Article)

2011-10-01T00:00:00Z

The mucin Muc2 is the structural component of the colonic mucus layer. Adult Muc2 knockout (Muc2-/-) mice suffer from severe colitis. We hypothesized that Muc2 deficiency induces inflammation before weaning of mother's milk [postnatal day (P) 14] with aggravation of colitis after weaning (P28). Muc2-/-and wild-type mice were killed at embryonic day 18.5 and P1.5, P7.5, P14, P21, and P28. Colonic morphology, influx of T cells, and goblet cell-specific protein expression was investigated by (immuno)histochemistry. Cytokine and Tolllike receptor (TLR) profiles in the colon were analyzed by quantitative RT-PCR. Muc2-/-mice showed an increased and persistent influx of Cd3ε-positive T cells in the colonic mucosa as of P1.5. This was accompanied by mucosal damage at P28 in the distal colon but not in the proximal colon. At P14, the proinflammatory immune response [i.e., increased interleukin (IL)-12 p35, IL-12 p40, and tumor necrosis factor-α, expression] in the distal colon of Muc2-/-mice presented with an immune suppressive response [i.e., increased Foxp3, transforming growth factor (TGF)-β1, IL-10, and Ebi3 expression]. In contrast, at P28, a proinflammatory response remained in the distal colon, whereas the immune suppressive response (i.e., Foxp3 and TGF-β1 expression) declined. The proximal colon of Muc2-/-mice did not show morphological damage and was dominated by an immune suppressive response at P14 and P28. Interestingly, changes in expression of TLRs and TLR-related molecules were observed in the distal colon at P14 and P28 and in the proximal colon only at P28. Colitis in Muc2-/-mice is limited before weaning by immune suppressive responses and exacerbates in the distal colon after weaning because of the decline in the immune suppressive response.

Colonic gene expression patterns of mucin muc2 knockout mice reveal various phases in colitis development (Article)

2011-10-01T00:00:00Z

Background: Mucin Muc2 knockout (Muc2-/-) mice spontaneously develop colitis. Methods: To identify genes and biological responses which play a pivotal role during colitis development in Muc2-/-mice, gene expression profiles of colonic tissues from 2- and 4-week-old Muc2-/-and wildtype mice were determined using microarrays. Results: The majority of highly upregulated genes in 2-week-old as well as 4-week-old Muc2-/-mice were primarily involved in immune responses related to antigen processing/presentation, B-cell and T-cell receptor signaling, leukocyte transendothelial migration, and Jak-STAT signaling. Specifically, Muc2-/-mice expressed high levels of immunoglobulins, murine histocompatibility-2, proinflammatory cytokines, chemokines, and antimicrobial proteins. Additionally, in 4-week-old Muc2-/-mice, expression of genes involved in cell structure related pathways was significantly altered. Particularly, the tight junction-associated gene claudin-10 was upregulated, whereas claudin-1 and claudin-5 were downregulated. Furthermore, 4-week-old Muc2-/-mice showed increased expression of genes regulating cell growth in conjunction with increased crypt length and increased epithelial proliferation. Conclusions: Muc2-deficiency leads to an active inflammatory response in 2- and 4-week-old Muc2-/-mice as demonstrated by the altered expression in immune response related genes. In addition, 4-week-old Muc2-/-mice also showed a decrease in epithelial barrier function and an increase in epithelial proliferation as indicated by, respectively, the altered expression in tight junction-related genes and upregulation of genes stimulating cell growth. Remarkably, upregulation of genes stimulating cell growth correlated with increased crypt length and increased epithelial proliferation in 4-week-old Muc2-/-mice. Together, these data demonstrate that there are distinct phases in colitis development in 2-4-week-old Muc2-/-mice. (Inflamm Bowel Dis 2011;) Copyright

Measuring body composition and energy expenditure in children with severe neurologic impairment and intellectual disability (Article)

2011-09-01T00:00:00Z

Background: Accurate prediction equations for estimating body composition and total energy expenditure (TEE) in children with severe neurologic impairment and intellectual disability are currently lacking. Objective: The objective was to develop group-specific equations to predict body composition by using skinfold-thickness measurements and bioelectrical impedance analysis (BIA) and to predict TEE by using data on mobility, epilepsy, and muscle tone. Design: Measures of body composition with the use of skinfoldthickness measurements (percentage of body fat) and BIA (total body water) were compared with those from isotope dilution (reference method) by using intraclass correlation coefficients (ICCs) and Bland and Altman limits of agreement analyses. With the use of the same methods, the outcomes of cerebral palsy - specific TEE equations were compared with those of the doubly labeled water method (reference method). Group-specific regression equations were developed by using forward-stepwise-multiple-correlationregression analyses. Results: Sixty-one children with a mean (±SD) age of 10.1 ± 4.3 y (32 boys) were studied. A new equation based on the sum of 4 skinfold-thickness measurements did not improve agreement (n = 49; ICC = 0.61), whereas the newly developed BIA equation - which includes tibia length as an alternative for standing height - did improve agreement (n = 61; ICC = 0.96, SEE = 1.7 kg, R2= 0.92). The newly developed TEE equation, which uses body composition, performed better (n = 52; ICC = 0.87, SEE = 180 kcal, R2= 0.77) than did the equation of Schofield (n = 52; ICC = 0.82, SEE = 207 kcal, R2= 0.69). Conclusions: Current cerebral palsy - specific equations for measuring body composition and energy expenditure are inaccurate. BIA is more accurate at assessing nutritional status in this population than is the measurement of skinfold thickness. The newly developed TEE equation, which uses body composition, provides a reasonable estimate of energy expenditure in these children despite its variability.

Increased protein-energy intake promotes anabolism in critically ill infants with viral bronchiolitis: A double-blind randomised controlled trial (Article)

2011-09-01T00:00:00Z

Objective: The preservation of nutritional status and growth is an important aim in critically ill infants, but difficult to achieve due to the metabolic stress response and inadequate nutritional intake, leading to negative protein balance. This study investigated whether increasing protein and energy intakes can promote anabolism. The primary outcome was whole body protein balance, and the secondary outcome was first pass splanchnic phenylalanine extraction (SPEPhe). Design: This was a double-blind randomised controlled trial. Infants (n=18) admitted to the paediatric intensive care unit with respiratory failure due to viral bronchiolitis were randomised to continuous enteral feeding with protein and energy enriched formula (PE-formula) (n=8; 3.1±0.3 g protein/kg/24 h, 119±25 kcal/kg/24 h) or standard formula (S-formula) (n=10; 1.7±0.2 g protein/kg/24 h, 84±15 kcal/kg/24 h; equivalent to recommended intakes for healthy infants <6 months). A combined intravenous-enteral phenylalanine stable isotope protocol was used on day 5 after admission to determine whole body protein metabolism and SPEPhe. Results: Protein balance was significantly higher with PE-formula than with S-formula (PE-formula: 0.73±0.5 vs S-formula: 0.02±0.6 g/kg/24 h) resulting from significantly increased protein synthesis (PE-formula: 9.6±4.4, S-formula: 5.2±2.3 g/kg/24 h), despite significantly increased protein breakdown (PE-formula: 8.9±4.3, S-formula: 5.2±2.6 g/kg/24 h). SPEPhewas not statistically different between the two groups (PE-formula: 39.8±18.3%, S-formula: 52.4±13.6%). Conclusions: Increasing protein and energy intakes promotes protein anabolism in critically ill infants in the first days after admission. Since this is an important target of nutritional support, increased protein and energy intakes should be preferred above standard intakes in these infants. Dutch Trial Register number: NTR 515.

Albumin synthesis rates in post-surgical infants and septic adolescents; influence of amino acids, energy, and insulin (Article)

2011-08-01T00:00:00Z

Background & aims: To investigate the effects of glucose, parenteral amino acids, and intravenous insulin on albumin synthesis rates in critically ill children. Methods: Two studies were performed in 8 post-surgical infants (age 9.8 ± 1.9 months; weight 9.5 ± 1.1 kg) and 9 septic adolescents (age 15 ± 1 yr; BMI 23 ± 4 kg m-2), respectively. All received a primed, constant, tracer infusion with [1-13C]Leucine. The infants in study 1 were randomized to receive low (2.5 mg kg-1min-1) and standard (5.0 mg kg-1min-1) glucose intake in a cross-over setting of two periods of 4 h each. The adolescents in study 2 were randomized to receive total parenteral nutrition with standard (1.5 g kg-1day-1) and high (3.0 g kg-1day-1) amino acid intake in a two day cross-over setting. On both study days, during the last 3 h of the tracer study, they received insulin infused at 80 mU m-2min-1. Results: The post-surgical infants and the septic adolescents were mildly hypoalbuminemic (∼2.5 g dL-1) with high synthesis rates, which were not affected by different intakes of glucose, amino acids, or insulin infusion. Conclusions: Albumin synthesis rates in hypoalbuminemic critically ill children are high but were not upregulated through nutrient supply, and in septic adolescents are unaffected by insulin.

Intestinal threonine utilization for protein and mucin synthesis is decreased in formula-fed preterm pigs (Article)

2011-07-01T00:00:00Z

Threonine is an essential amino acid necessary for synthesis of intestinal (glyco)proteins such as mucin MUC2 to maintain adequate gut barrier function. In premature infants, reduced barrier function may contribute to the development of necrotizing enterocolitis (NEC). Human milk protects against NEC compared with infant formula. Therefore, we hypothesized that formula feeding decreases the MUC2 synthesis rate concomitant with a decrease in intestinal first-pass threonine utilization, predisposing the preterm neonate to NEC. Preterm pigs were delivered by caesarian section and received enteral feeding with formula (FORM; n = 13) or bovine colostrum (COL; n = 6) for 2 d following 48 h of total parenteral nutrition. Pigs received a dual stable isotope tracer infusion of threonine to determine intestinal threonine kinetics. NEC developed in 38% of the FORM pigs, whereas none of the COL pigs were affected (P = 0.13). Intestinal fractional first-pass threonine utilization was lower in FORM pigs (49 ± 2%) than in COL pigs (60 ± 4%) (P = 0.02). In FORM pigs compared with COL pigs, protein synthesis (369 ± 31 mg·kg-1·d-1vs. 615 ± 54 mg·kg-1·d-1; P = 0.003) and MUC2 synthesis (121 ± 17%/d vs. 184 ± 15%/d; P = 0.02) were lower in the distal small intestine (SI). Our results suggest that formula feeding compared with colostrum feeding in preterm piglets reduces mucosal growth with a concomitant decrease in first-pass splanchnic threonine utilization, protein synthesis, and MUC2 synthesis in the distal SI. Hence, decreased intestinal threonine metabolism and subsequently impaired gut barrier function may predispose the formula-fed infant to developing NEC.

Feeding very-low-birth-weight infants: Our aspirations versus the reality in practice (Article)

2011-06-01T00:00:00Z

Recently, new guidelines for enteral feedings in premature infants were issued by the European Society of Pediatric Gastroenterology, Hepatology, and Nutrition Committee on Nutrition. Nevertheless, practice proves difficult to attain suggested intakes at all times, and occurrence of significant potential cumulative nutritional deficits 'lies in wait' in the neonatal intensive care unit. This review describes several aspects that are mandatory for optimizing nutritional intake in these vulnerable infants. These aspects range from optimal infrastructure to the initiation of parenteral nutrition with proper transition to enteral breast or formula feedings. Proper monitoring of nutritional tolerance includes serum biochemistry although proper specific markers are unknown and safety reference values are lacking. Although a lot of progress has been made through research during the last few decades, numerous questions still remain unanswered as to what would be the optimal quantity and quality of the various macronutrients. The inevitable suboptimal intake may, however, contribute significantly to the incidence of neonatal diseases, including impaired neurodevelopment. Therefore, it is pivotal that all hospital staff acknowledges that preterm birth is a nutritional emergency and that all must be done, both in clinical practice as well as in research, to reduce nutritional deficits. Copyright

Risk factors for auditory neuropathy spectrum disorder in NICU infants compared to normal-hearing NICU controls (Article)

2011-04-01T00:00:00Z

Objectives: To evaluate independent etiologic factors associated with auditory neuropathy spectrum disorder (ANSD) in infants who have been admitted to the neonatal intensive care unit (NICU) compared to normal-hearing controls. Study Design: Case-control study. Methods: We included all infants (n = 9) with the ANSD profile admitted to the NICU of Sophia Children's Hospital between 2004 and 2009. Each patient was matched with four normal-hearing controls of the same gender and postconceptional age. The following possible risk factors were studied: birth weight, dysmorphic features, APGAR scores (at 1, 5, and 10 minutes), respiratory distress (IRDS), cytomegalovirus (CMV) infection, sepsis, meningitis, cerebral bleeding, hyperbilirubinemia requiring phototherapy, peak total bilirubin level, furosemide, dexamethason, vancomycin, gentamycin, and tobramycin administration. Results: Nine infants met the ANSD criteria in one or both ears. IRDS (P =.02), meningitis (P =.04), and vancomycin administration (P =.009) were significantly increased in infants with ANSD compared to controls. Conclusions: In high-risk NICU infants IRDS, meningitis and vancomycin administration are associated with auditory neuropathy spectrum disorder.

Paneth cell hyperplasia and metaplasia in necrotizing enterocolitis (Article)

2011-03-01T00:00:00Z

Paneth cell dysfunction has been suggested in necrotizing enterocolitis (NEC). The aim of this study was to i) study Paneth cell presence, protein expression, and developmental changes in preterm infants with NEC and ii) determine Paneth cell products and antimicrobial capacity in ileostomy outflow fluid. Intestinal tissue from NEC patients (n = 55), preterm control infants (n = 22), and term controls (n = 7) was obtained during surgical resection and at stoma closure after recovery. Paneth cell abundance and protein expression were analyzed by immunohistochemistry. RNA levels of Paneth cell proteins were determined by real-time quantitative RT-PCR. In ileostomy outflow fluid, Paneth cell products were quantified, and antimicrobial activity was measured in vitro. In acute NEC, Paneth cell abundance in small intestinal tissue was not significantly different from preterm controls. After recovery from NEC, Paneth cell hyperplasia was observed in the small intestine concomitant with elevated human alpha-defensin 5 mRNA levels. In the colon, metaplastic Paneth cells were observed. Ileostomy fluid contained Paneth cell proteins and inhibited bacterial growth. In conjunction, these data suggest an important role of Paneth cells and their products in various phases of NEC.

Prolonged mechanical ventilation induces cell cycle arrest in newborn rat lung (Article)

2011-02-28T00:00:00Z

Rationale: The molecular mechanism(s) by which mechanical ventilation disrupts alveolar development, a hallmark of bronchopulmonary dysplasia, is unknown. Objective: To determine the effect of 24 h of mechanical ventilation on lung cell cycle regulators, cell proliferation and alveolar formation in newborn rats. Methods: Seven-day old rats were ventilated with room air for 8, 12 and 24 h using relatively moderate tidal volumes (8.5 mL.kg-1). Measurement and Main Results: Ventilation for 24 h (h) decreased the number of elastin-positive secondary crests and increased the mean linear intercept, indicating arrest of alveolar development. Proliferation (assessed by BrdU incorporation) was halved after 12 h of ventilation and completely arrested after 24 h. Cyclin D1 and E1 mRNA and protein levels were decreased after 8-24 h of ventilation, while that of p27Kip1 was significantly increased. Mechanical ventilation for 24 h also increased levels of p57Kip2, decreased that of p16INK4a, while the levels of p21Waf/Cip1 and p15INK4b were unchanged. Increased p27Kip1 expression coincided with reduced phosphorylation of p27Kip1 at Thr157, Thr187 and Thr198 (p<0.05), thereby promoting its nuclear localization. Similar -but more rapid- changes in cell cycle regulators were noted when 7-day rats were ventilated with high tidal volume (40 mL.kg-1) and when fetal lung epithelial cells were subjected to a continuous (17% elongation) cyclic stretch. Conclusion: This is the first demonstration that prolonged (24 h) of mechanical ventilation causes cell cycle arrest in newborn rat lungs; the arrest occurs in G1 and is caused by increased expression and nuclear localization of Cdk inhibitor proteins (p27Kip1, p57Kip2) from the Kip family.

Supplementation of infant formula with probiotics and/or prebiotics: A systematic review and comment by the ESPGHAN committee on nutrition (Article)

2011-02-01T00:00:00Z

Infant formulae are increasingly supplemented with probiotics, prebiotics, or synbiotics despite uncertainties regarding their efficacy. The present article, developed by the Committee on Nutrition of the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition, systematically reviews published evidence related to the safety and health effects of the administration of formulae supplemented with probiotics and/or prebiotics compared with unsupplemented formulae. Studies in which probiotics/prebiotics were not administered during the manufacturing process, but thereafter, for example in capsules, the contents of which were supplemented to infant formula or feeds, were excluded.On the basis of this review, available scientific data suggest that the administration of currently evaluated probiotic-and/or prebiotic-supplemented formula to healthy infants does not raise safety concerns with regard to growth and adverse effects. The safety and clinical effects of 1 product should not be extrapolated to other products. At present, there is insufficient data to recommend the routine use of probiotic-and/or prebiotic-supplemented formulae. The Committee considers that the supplementation of formula with probiotics and/or prebiotics is an important field of research. There is a need in this field for well-designed and carefully conducted randomised controlled trials, with relevant inclusion/exclusion criteria and adequate sample sizes. These studies should use validated clinical outcome measures to assess the effects of probiotic and/or prebiotic supplementation of formulae. Such trials should also define the optimal doses and intake durations, as well as provide more information about the long-term safety of probiotics and/or prebiotics. Because most of the trials were company funded, independent trials, preferentially financed jointly by national/governmental/European Union bodies and other international organisations, would be desirable.

Differences in the perceptions of parents and healthcare professionals on pediatric intensive care practices (Article)

2011-01-01T00:00:00Z

OBJECTIVE:: To explore similarities and differences in perceptions on pediatric intensive care practices between parents and staff by using data from two studies. DESIGN:: A two-round Delphi method among nurses and physicians followed by an empiric survey among parents. SETTINGS:: Pediatric intensive care units at eight university medical centers. SUBJECTS:: Parents whose child has been admitted to a pediatric intensive care unit, nurses, and physicians. INTERVENTIONS:: None. MEASUREMENTS AND MAIN RESULTS:: Outcome measures were 74 satisfaction-with-care items divided into five domains: 1) information; 2) care and cure; 3) organization; 4) parental participation; and 5) professional attitude. The Delphi study was completed by 218 nurses and 46 physicians and the survey by 559 of 1042 (54%) parents. Parents rated 31 items more important than the professionals based on the standardized mean difference (Cohen's d, 0.21-1.18, p < .003). Ten of these were related to information provision. Information on the effects of medication had the largest effect size (Cohen's d 1.18, p = .001). Correct medication administration by professionals was also rated significantly more important by parents (Cohen's d 0.64, p = .001). The professionals rated 12 items more important than the parents (Cohen's d -0.23 to -0.73, p < .005), including three about multicultural care. Significant differences remained on two of the three multicultural care items when the Dutch (n = 483) and non-Dutch parents (n = 76) were separately compared with professionals. On the domain level, parents rated the domains information and parental participation more important than the professionals (Cohen's d 0.36 and 0.26, p = .001). CONCLUSIONS:: Compared with the parents' perceptions, nurses and physicians undervalued a substantial number of pediatric intensive care unit care items. This finding may reflect a gap in the understanding of parental experiences as well as incongruity in recognizing the needs of parents.

Enteral arginine does not increase superior mesenteric arterial blood flow but induces mucosal growth in neonatal pigs1-3 (Article)

2011-01-01T00:00:00Z

Arginine is an essential amino acid in neonates synthesized by gut epithelial cells and a precursor for NO that regulates vasodilatation and blood flow. Arginine supplementation has been shown to improve intestinal integrity in ischemiareperfusion models and low plasma levels are associated with necrotizing enterocolitis. We hypothesized that enteral arginine is a specific stimulus for neonatal intestinal blood flow and mucosal growth under conditions of total parenteral nutrition (TPN) or partial enteral nutrition (PEN). We first tested the dose dependence and specificity of acute (3 h) enteral arginine infusion on superior mesenteric artery (SMA) blood flow in pigs fed TPN or PEN. We then determined whether chronic (4 d) arginine supplementation of PEN increases mucosal growth and if this was affected by treatment with the NO synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME). Acute enteral arginine infusion increased plasma arginine dose dependently in both TPN and PEN groups, but the plasma response was markedly higher (100-250%) in the PEN group than in the TPN group at the 2 highest arginine doses. Baseline SMA blood flow was 90% higher in the PEN (2.37 ± 0.32 L.kg-1.h-1) pigs than in the TPN pigs (1.23 ± 0.17 L.kg-1.h-1), but was not affected by acute infusion individually of arginine, citrulline, or other major gut fuels. Chronic dietary arginine supplementation in PEN pigs induced mucosal growth in the intestine, but this effect was not prevented by treatment with L-NAME. Intestinal crypt cell proliferation, protein synthesis, and phosphorylation of mammalian target of rapamycin and p70S6 kinase were not affected by dietary arginine. We conclude that partial enteral feeding, but not acute enteral arginine, increases SMA blood flow in the neonatal pig. Furthermore, supplementing arginine in partial enteral feeding modestly increases intestinal mucosal growth and was NO independent.

Early nutrient supply and the preterm infant (Article)

2010-12-01T00:00:00Z

Long term costs and effects of reducing the number of twin pregnancies in IVF by single embryo transfer: The TwinSing study (Article)

2010-10-20T00:00:00Z

Background: Pregnancies induced by in vitro fertilisation (IVF) often result in twin gestations, which are associated with both maternal and perinatal complications. An effective way to reduce the number of IVF twin pregnancies is to decrease the number of embryos transferred from two to one. The interpretation of current studies is limited because they used live birth as outcome measure and because they applied limited time horizons. So far, research on long-term outcomes of IVF twins and singletons is scarce and inconclusive. The objective of this study is to investigate the short (1-year) and long-term (5 and 18-year) costs and health outcomes of IVF singleton and twin children and to consider these in estimating the cost-effectiveness of single embryo transfer compared with double embryo transfer, from a societal and a healthcare perspective.Methods/Design: A multi-centre cohort study will be performed, in which IVF singletons and IVF twin children born between 2003 and 2005 of whom parents received IVF treatment in one of the five participating Dutch IVF centres, will be compared. Data collection will focus on children at risk of health problems and children in whom health problems actually occurred. First year of life data will be collected in approximately 1,278 children (619 singletons and 659 twin children). Data up to the fifth year of life will be collected in approximately 488 children (200 singletons and 288 twin children). Outcome measures are health status, health-related quality of life and costs. Data will be obtained from hospital information systems, a parent questionnaire and existing registries. Furthermore, a prognostic model will be developed that reflects the short and long-term costs and health outcomes of IVF singleton and twin children. This model will be linked to a Markov model of the short-term cost-effectiveness of single embryo transfer strategies versus double embryo transfer strategies to enable the calculation of the long-term cost-effectiveness.Discussion: This is, to our knowledge, the first study that investigates the long-term costs and health outcomes of IVF singleton and twin children and the long-term cost-effectiveness of single embryo transfer strategies versus double embryo transfer strategies.

The impact of an education program on hand hygiene compliance and nosocomial infection incidence in an urban Neonatal Intensive Care Unit: An intervention study with before and after comparison (Article)

2010-10-01T00:00:00Z

Background: Nosocomial bloodstream infections are a major cause of morbidity and mortality in neonatal intensive care units. Appropriate hand hygiene is singled out as the most important measure in preventing these infections. However, hand hygiene compliance among healthcare professionals remains low despite the well-known effect on infection reduction. Objectives: We studied the effectiveness of a hand hygiene education program on the incidence of nosocomial bloodstream infections. Design: Observational study with two pretests and two posttest measurements and interrupted time series analysis. Setting: A 27 bed level IIID neonatal intensive care unit in a teaching hospital in the Netherlands. Participants: Healthcare professionals who had physical contact with very low birth weight (VLBW) infants. Methods: The study was conducted during a period of 4 years. Medical and nursing staff followed a problem-based education program on hand hygiene. Hand hygiene practices before and after the education program were compared by guided observations. The incidence of nosocomial infections in VLBW infants was compared. In addition, numbers of nosocomial bloodstream infections per day-at-risk in very low birth weight infants were analyzed by a segmented loglinear regression analysis. Results: During 1201 observations hand hygiene compliance before patient contact increased from 65% to 88% (p< 0.001). Median (interquartile range) drying time increased from 4. s (4-10) to 10. s (7-14) (p< 0.001).The proportion of very low birth weight infants with one or more bloodstream infections and the infection rate per 1000 patient days (relative risk reduction) before and after the education program on hand hygiene intervention decreased from 44.5% to 36.1% (18.9%, p= 0.03) and from 17.3% to 13.5% (22.0%, p= 0.03), respectively.At the baseline the nosocomial bloodstream infections per day-at-risk decreased by +0.07% (95% CI -1.41 to +1.60) per month and decreased with -1.25% (95% CI -4.67 to +2.44) after the intervention (p= 0.51). The level of instant change was -14.8% (p= 0.48). Conclusions: The results are consistent with relevant improvement of hand hygiene practices among healthcare professionals due to an education program. Improved hand hygiene resulted in a reduction in nosocomial bloodstream infections.

Measuring energy expenditure and body composition in children with neurological impairment and intellectual disability using the doubly labeled water method: Comparing urine and saliva sampling (Article)

2010-10-01T00:00:00Z

Background & Aims: Information is lacking on the comparability of the outcomes of the doubly labeled water method using urine and saliva samples in children with severe neurological impairment and intellectual disability (ID). Our aim is to compare outcomes and feasibility based on both sampling methods. Methods: Total energy expenditure (TEE) and total body water (TBW) were calculated using urine and saliva samples of thirteen children (aged 3-15 y). To correct for age and weight, TEE was expressed as a percentage of recommended daily allowance (%TEE of RDA) and TBW as a percentage of weight (%TBW). Agreement between methods was evaluated using Bland and Altman analyses. Results: 88.5% of urine and 79.5% of saliva samples were successfully analyzed. Limits of agreement between urine and saliva samples were favorable for the outcomes %TEE of RDA (mean difference -1.9% ± 7.5%) and %TBW (mean difference -1.9% ± 3.0%). Conclusions: Both urine and saliva are feasible sample media for the doubly labeled water method in children with severe neurological impairment and ID. Clinical outcomes based on either urine or saliva samples agree well. Thus, choosing either one of the sampling methods is justified if the other fails.

Risk factors for sensorineural hearing loss in NICU infants compared to normal hearing NICU controls (Article)

2010-09-01T00:00:00Z

Objectives: To evaluate independent etiologic factors associated with sensorineural hearing loss in infants who have been admitted to the neonatal intensive care unit compared to normal hearing controls. Method: Between 2004 and 2009, 3366 infants were admitted to the neonatal intensive care unit of Sophia Children's Hospital, of which 3316 were screened with AABR. A total of 103 infants were referred for auditory brainstem response analysis after failure on neonatal hearing screening. We included all infants diagnosed with sensorineural hearing loss. Each patient was matched with two normal hearing controls from the neonatal intensive care unit of the same gender and postconceptional age. The following risk factors were studied: birth weight, dysmorphic features, APGAR scores (at 1, 5 and 10. min), respiratory distress (IRDS), CMV infection, sepsis, meningitis, cerebral bleeding, cerebral infarction, hyperbilirubinemia requiring phototherapy, peak total bilirubin level, furosemide, dexamethason, vancomycin, gentamycin and tobramycin administration. Results: Fifty-eight infants were diagnosed with sensorineural hearing loss: 26 girls and 32 boys. The incidence of dysmorphic features (P= 0.000), low APGAR score (1. min) (P= 0.01), sepsis (P= 0.003), meningitis (P= 0.013), cerebral bleeding (P= 0.016) and cerebral infarction (P= 0.000) were significantly increased in infants with sensorineural hearing loss compared to normal hearing controls (n= 116). Conclusion: Dysmorphic features, low APGAR scores at 1. min, sepsis, meningitis, cerebral bleeding and cerebral infarction are associated with sensorineural hearing loss independent of neonatal intensive care unit admittance.

Diffusion tensor imaging of the cortical plate and subplate in very-low-birth-weight infants (Article)

2010-08-01T00:00:00Z

Background: Many intervention studies in preterm infants aim to improve neurodevelopmental outcome, but short-term proxy outcome measurements are lacking. Cortical plate and subplate development could be such a marker. Objective: Our aim was to provide normal DTI reference values for the cortical plate and subplate of preterm infants. Materials and methods: As part of an ongoing study we analysed diffusion tensor imaging (DTI) images of 19 preterm infants without evidence of injury on conventional MRI, with normal outcome (Bayley-II assessed at age 2), and scanned in the first 4 days of life. Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values in the frontal and temporal subplate and cortical plate were measured in single and multiple voxel regions of interest (ROI) placed on predefined regions. Results: Using single-voxel ROIs, statistically significant inverse correlation was found between gestational age (GA) and FA of the frontal (r = -0.5938, P = 0.0058) and temporal (r = -0.4912, P = 0.0327) cortical plate. ADC values had a significant positive correlation with GA in the frontal (r = 0.5427, P = 0.0164) and temporal (r = 0.5540, P = 0.0138) subplate. Conclusion: Diffusion tensor imaging allows in vivo exploration of the evolving cortical plate and subplate. We provide FA and ADC values of the subplate and cortical plate in very-low-birth-weight (VLBW) infants with normal developmental outcome that can be used as reference values.

Perceptions of parents, nurses, and physicians on neonatal intensive care practices (Article)

2010-08-01T00:00:00Z

OBJECTIVE: To identify satisfaction with neonatal intensive care as viewed by parents and healthcare professionals and to explore similarities and differences between parents and healthcare professionals. STUDY DESIGN: A 3-round Delphi method to identify neonatal care issues (round 1) and to determine the importance of these issues (rounds 2 and 3) was conducted among nurses (n = 84) and physicians (n = 14), followed by an exploratory survey among parents (n = 259). Main outcome measures were 92 neonatal care-related items. RESULTS: Sixty-eight nurses and 13 physicians completed all 3 rounds. The first round yielded 419 neonatal care related statements, which were clustered into 92 items. The survey was completed by 148 (57%) parents. Parents rated 25 of 92 care items significantly higher than did the professionals (effect size of Cohen's d, 0.31 to 1.14, P

Perceptions of parents, nurses, and physicians on neonatal intensive care practices (Article)

2010-08-01T00:00:00Z

Effect of bifidobacterium animalis subsp lactis supplementation in preterm infants: A systematic review of randomized controlled trials (Article)

2010-08-01T00:00:00Z

Objective: To systematically evaluate and update evidence on the efficacy and safety of Bifidobacterium animalis subsp lactis CNCM I-3446 supplementation in preterm infants. Materials and Methods: The Cochrane Library and MEDLINE databases and major pediatric conference proceedings were searched in December 2008 for randomized controlled trials (RCTs). The company that manufactures B lactis was contacted for unpublished data. The review was restricted to RCTs performed in preterm infants <37 weeks of gestation and/or with a birth weight <2500 g. Results: Four RCTs involving 324 infants met the inclusion criteria. Compared with controls, B lactis supplementation has the potential to increase fecal bifidobacteria counts and to reduce Enterobacteriaceae and Clostridium spp counts. It also can reduce stool pH and fecal calprotectin concentrations, increase fecal immunoglobulin A and short-chain fatty acid concentrations, and decrease intestinal permeability. Compared with controls, B lactis supplementation had no effect on the risk of necrotizing enterocolitis stage ≥2 (3 RCTs, n = 293, risk ratio [RR] 0.53, 95% CI 0.16-1.83), risk of sepsis (2 RCTs, 397 cultures, RR 0.6, 95% CI 0.07-5.2), and use of antibiotics (2 RCTs, n = 255, RR 0.67, 95% CI 0.28-1.62). The power of these studies, however, does not allow for a definitive statement regarding a reduced risk of necrotizing enterocolitis. B lactis supplementation did have some effects on anthropometric parameters. No adverse events associated with B lactis supplementation were reported. Conclusions: Evidence regarding the potential beneficial effects of B lactis supplementation in preterm infants is encouraging. Further studies to assess clinically relevant outcomes are needed. Copyright

Practical approach to paediatric enteral nutrition: A comment by the ESPGHAN committee on nutrition (Article)

2010-07-01T00:00:00Z

Enteral nutrition support (ENS) involves both the delivery of nutrients via feeding tubes and the provision of specialised oral nutritional supplements. ENS is indicated in a patient with at least a partially functioning digestive tract when oral intake is inadequate or intake of normal food is inappropriate to meet the patients needs. The aim of this comment by the Committee on Nutrition of the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition is to provide a clinical practice guide to ENS, based on the available evidence and the clinical expertise of the authors. Statements and recommendations are presented, and future research needs highlighted, with a particular emphasis placed on a practical approach to ENS.Among the wide array of enteral formulations, standard polymeric feeds based on cows-milk protein with fibre and age adapted for energy and nutrient content are suitable for most paediatric patients. Whenever possible, intragastric is preferred to postpyloric delivery of nutrients, and intermittent feeding is preferred to continuous feeding because it is more physiological. An anticipated duration of enteral nutrition (EN) exceeding 4 to 6 weeks is an indication for gastrostomy or enterostomy. Among the various gastrostomy techniques available, percutaneous endoscopic gastrostomy is currently the first option. In general, both patients and caregivers express satisfaction with this procedure, although it is associated with a number of well-recognised complications. We strongly recommend the development and application of procedural protocols that include scrupulous attention to hygiene, as well as regular monitoring by a multidisciplinary nutrition support team to minimise the risk of EN-associated complications.

Construction and psychometric testing of the EMPATHIC questionnaire measuring parent satisfaction in the pediatric intensive care unit (Article)

2010-07-01T00:00:00Z

Abstract PURPOSE: To construct and test the reliability and validity of the EMpowerment of PArents in THe Intensive Care (EMPATHIC) questionnaire measuring parent satisfaction in the pediatric intensive care unit (PICU). METHODS: Structured development and psychometric testing of a parent satisfaction-with-care instrument with the results of two cohorts of parents (n = 2,046) from eight PICUs in the Netherlands. RESULTS: In the first cohort, 667/1,055 (63%) parents participated followed by 551/991 (56%) parents in the second cohort. The empirical structure of the instrument was established by confirmatory factor analysis with the first sample of parents confirming 65 statements within five theoretically conceptualized domains: information, care and cure, organization, parental participation, and professional attitude. The standardized factor loadings were greater than 0.40 in 63 statements. Cronbach's α, a measure of reliability, per domain ranged from 0.73 to 0.93 in both cohorts with no significant difference documenting the reliability over time. Beside rigorous content and face validity, the congruent validity of the instrument showed adequate correlation with four gold standard questions measuring overall satisfaction. The non-differential validity was confirmed with no significant differences between the population characteristics and the domains, except that parents with a child for a surgical admission were more satisfied on information issues. CONCLUSIONS: The final EMPATHIC questionnaire incorporates 65 statements. The empirical structure of the satisfaction statements and domains was satisfactory. The reliability and validity proved to be adequate. The EMPATHIC questionnaire is a valid quality performance indicator to measure quality of care as perceived by parents.

Human milk banking-facts and issues to resolve (Article)

2010-07-01T00:00:00Z

The number of human milk banks is increasing worldwide. Although the beneficial effects of feeding premature infants with their mother's milk are well documented, less is known about the effects of feeding these infants with pasteurized donor milk. We propose a randomized trial comparing the effects of a 100% human milk-based diet (human milk supplemented with a human milk-derived fortifier) and a diet (partially) based on bovine milk. In theory, human milk has a beneficial effect on various aspects of human physiology, most of which become apparent after infancy. We therefore propose an extensive follow-up program that takes this aspect into consideration. Other issues concerning the practice of human milk banks need to be addressed as well as optimization of the feeding strategies for preterm infants.

Almost all enteral aspartate is taken up in first-pass metabolism in enterally fed preterm infants (Article)

2010-06-01T00:00:00Z

Background & aims: The intestine is a major site of amino acid metabolism, especially in neonates. Neonatal animals derive energy needed for metabolic processes from dietary glucose and amino acids. Rats were found to oxidize non-essential amino acids such as aspartate, glutamate and glutamine in the intestine at a high rate. We have previously found that glutamate and glucose are important sources of energy for the splanchnic tissues in fully fed preterm infants. However, no data are available on splanchnic aspartate metabolism in human preterm infants. In the present study we studied whole-body and splanchnic aspartate metabolism and determined the metabolic fate of aspartate. Methods: In eight, enterally fed, preterm infants (gestational age 31 weeks (wk)±3 SD, range: 26-34wk) splanchnic and whole-body aspartate kinetics were assessed by dual tracer ([U-13C]aspartate and [D3]aspartate) techniques. Results: Splanchnic first-pass aspartate uptake was almost complete (77±15%). Almost all (80±9%) of the13C administered as [U-13C]aspartate used in first-pass was recovered as CO2in expired breath. Conclusion: The splanchnic tissues extract almost all of the dietary aspartate in preterm infants. The majority of the labeled carbon is recovered in expired breath, making it most likely that the sequestered carbon skeleton of aspartate is utilized for energy generation.

Parenteral amino acid intakes in critically Ill children: A matter of convenience (Article)

2010-05-01T00:00:00Z

Background: Parenteral and enteral amino acid requirements for nutrition balance and function have not been defined in critically ill children or adults. In addition to playing a role in protein synthesis, amino acids trigger signaling cascades that regulate various aspects of fuel and energy metabolism and serve as precursors for important substrates. Amino acids can also be toxic. In this study, parenteral intakes of essential and nonessential amino acids (EAAs and NEAAs) supplied to critically ill children were assessed as an initial step for further studies aimed at establishing parenteral amino acid requirements. Methods: A retrospective review was conducted to assess intakes of parenteral amino acid for 116 critically ill children, and these intakes were compared with EAA intakes recommended by the Institute of Medicine. Because there are no recommended intakes for NEAA, NEAA intakes were compared with mixed muscle protein content in the older children and breast milk amino acid content in the infants. Results: Parenteral EAAs were provided in amounts that exceeded recommended intakes for healthy children, except for phenylalanine and methionine, which although excessive, were given in less generous amounts. NEAAs were supplied in lower or higher amounts than the content of mixed muscle proteins or breast milk. Parenteral amino acid formulas are limited in taurine, glutamine, and asparagine despite the fact that inflammatory/immune proteins are rich in these amino acids. Conclusions: Amino acid composition of parenteral formulas is variable and lacks scientific support. Parenteral amino acid intakes should be based on measured requirements to maintain nutrition and functional balance and on knowledge of toxicity.

Nutritional support for extremely low-birth weight infants: Abandoning catabolism in the neonatal intensive care unit (Article)

2010-05-01T00:00:00Z

Purpose of review: Obviously, the ultimate goal in neonatology is to achieve a functional outcome in premature infants that is comparable to healthy term-born infants. As nutrition is one of the key factors for normal cell growth, providing the right amount and quality of nutrients could prove pivotal for normal development. However, many premature infants are catabolic during the first week of life, which has directly been linked to growth failure, disease, and suboptimal long-term outcome. This review describes the progress in research on parenteral nutrition for premature infants with a focus on amino acids and the influence of nutrition on later outcome. Recent findings: Although randomized clinical trials on early nutrition for premature infants remain relatively sparse, evidence is accumulating on its beneficial effects both on the short-term and long-term. However, some research also warns for adverse effects. Summary: Despite the fact that substantially improved nutritional therapies for preterm neonates have been implemented, still, some reluctance exists when it comes to providing high amounts of nutrition to the most immature infants. Pros and cons are outlined, as well as deficits in knowledge, when it comes to providing the optimal nutrient strategy in the first postnatal phase.

Glutathione synthesis rates in early postnatal life (Article)

2010-04-01T00:00:00Z

Preterm infants have diminished antioxidant defenses. Glutathione (GSH), the main intracellular antioxidant, increases upon amino acid (AA) administration in preterm infants, without an accompanying rise of the fractional synthesis rate of GSH (FSRGSH) This study investigated the mechanism behind this increased GSH concentration by determining GSH synthesis in the first days after birth using stable isotope techniques in very low-birth-weight (VLBW) infants receiving i.v. AAs. Advanced oxidized protein products (AOPPs) were determined to quantify oxidative stress. Eighteen infants (birth weight 989 ± 241 g, gestational age of 27/7 ± 1/7 weeks) were studied either on postnatal day 1 or 2 (7 or 31 h postnatally, respectively). Concentration of GSH increased with postnatal age (1.45 ± 0.48 mM versus 1.99 ± 0.40 mM, p = 0.019). FSRGSH was not significantly different, but the absolute synthesis rate of GSH (ASRGSH) tended to be higher in the infants studied on day 2 [8.1 ± 2.7 mg/(kg • d) versus 10.6 ± 2.4 mg/(kg • d), p = 0.054]. AOPP concentrations were not different between groups. In conclusion, GSH concentration in VLBW infants increases significantly after birth. A concomitant increased synthesis rate was not found, suggesting that GSH consumption decreases upon AA administration.

Interdisciplinary management of infantile short bowel syndrome: resource consumption, growth, and nutrition (Article)

2010-03-01T00:00:00Z

Background/Purpose: To date, there are hardly any data on the treatment costs of infantile short bowel syndrome (SBS), despite growing interest in evidence-based and cost-effective medicine. Therefore, the aim of the study was to evaluate resource consumption and costs, next to studying nutritional and growth outcomes, in children with SBS who were treated by an interdisciplinary short bowel team. Methods: Data were collected for 10 children with infantile SBS (≤1 year of age) born between 2002 and 2007. Data included demographic and medical data of the first admission and data on resource consumption, growth, and type of nutrition for the total follow-up period. Real economic costs were calculated in Euro (€) and US dollar ($). Results: Seven of the 10 patients were discharged with home parenteral nutrition. Total follow-up varied between 9 months and 5.5 years (median, 1.5 years). Six patients could be weaned off parenteral nutrition and 5 patients off enteral tube feeding, resulting in full oral intake. Seven patients had normal growth. Median duration of initial hospital admission was 174 days, and average costs of initial admission amounted to €166,045 ($218,681). Average total costs were €269,700 ($355,195), reaching to a maximum of €455,400 ($599,762). These costs mainly comprised hospital admissions (82%), followed by nutrition (12%), surgical interventions (5%), and outpatient visits (1%). Conclusions: This study is among the first to describe resource consumption and costs in infants with SBS, examining real economic costs and extending beyond the initial hospitalization. Treatment of SBS requires considerable resource consumption, especially when patients depend on parenteral nutrition. Because the costs mainly comprise those of hospital admissions, early home parenteral nutrition could contribute to costs reduction. Interdisciplinary teams have the potential to facilitate early home parenteral nutrition and thus may reduce health care costs.

Majority of dietary glutamine is utilized in first pass in preterm infants (Article)

2010-02-01T00:00:00Z

Glutamine is a conditionally essential amino acid for very low-birth weight infants by virtue of its ability to play an important role in several key metabolic processes of immune cells and enterocytes. Although glutamine is known to be used to a great extend, the exact splanchnic metabolism in enterally fed preterm infants is unknown. We hypothesized that preterm infants show a high splanchnic first-pass glutamine metabolism and the primary metabolic fate of glutamine is oxidation. Five preterm infants (mean ± SD birth weight 1.07 ± 0.22 kg and GA 29 ± 2 wk) were studied by dual tracer ([U-C]glutamine and [N2]glutamine) cross-over techniques on two study days (at postnatal week 3 ± 1 wk). Splanchnic and whole-body glutamine kinetics were assessed by plasma isotopic enrichment of [U-C]glutamine and [N2]glutamine and breath CO2 enrichments. Mean fractional first-pass glutamine uptake was 73 ± 6% and 57 ± 17% on the study days. The splanchnic tissues contributed for a large part (57 ± 6%) to the total amount of labeled carbon from glutamine retrieved in expiratory air. Dietary glutamine is used to a great extent by the splanchnic tissues in preterm infants and its carbon skeleton has an important role as fuel source.

Development of Preschool and Academic Skills in Children Born Very Preterm (Article)

2010-01-01T00:00:00Z

Objective: To examine performance in preschool and academic skills in very preterm (gestational age ≤30 weeks) and term-born comparison children aged 4 to 12 years. Study design: Very preterm children (n = 200; mean age, 8.2 ± 2.5 years) born between 1996 and 2004 were compared with 230 term-born children (mean age, 8.3 ± 2.3). The Dutch National Pupil Monitoring System was used to measure preschool numerical reasoning and early linguistics, and primary school simple and complex word reading, reading comprehension, spelling, and mathematics/arithmetic. With univariate analyses of variance, we assessed the effects of preterm birth on performance across grades and on grade retention. Results: In preschool, very preterm children performed comparably with term-born children in early linguistics, but perform more poorly (0.7 standard deviation [SD]) in numerical reasoning skills. In primary school, very preterm children scored 0.3 SD lower in complex word reading and 0.6 SD lower in mathematics/arithmetic, but performed comparably with peers in reading comprehension and spelling. They had a higher grade repeat rate (25.5%), although grade repeat did not improve their academic skills. Conclusions: Very preterm children do well in early linguistics, reading comprehension, and spelling, but have clinically significant deficits in numerical reasoning skills and mathematics/arithmetic, which persist with time.

Development of Preschool and Academic Skills in Children Born Very Preterm (Article)

2010-01-01T00:00:00Z

A qualitative study exploring the experiences of parents of children admitted to seven Dutch pediatric intensive care units (Article)

2010-01-01T00:00:00Z

Purpose: To explore parents' experiences during the admission of their children to a pediatric intensive care unit (PICU). Method: Qualitative method using in-depth interviews. Thematic analysis was applied to capture parents' experiences. Thirty-nine mothers and 25 fathers of 41 children admitted to seven of the eight PICUs in university medical centers in The Netherlands were interviewed. Results: Parents were interviewed within 1 month after their child's discharge from a PICU. Thematic analysis identified 1,514 quotations that were coded into 63 subthemes. The subthemes were categorized into six major themes: attitude of the professionals; coordination of care; emotional intensity; information management; environmental factors; parent participation. Most themes had an overarching relationship representing the array of experiences encountered by parents when their child was staying in a PICU. The theme of emotional intensity was in particular associated with all the other themes. Conclusions: The findings provided a range of themes and subthemes describing the complexity of the parental experiences of a PICU admission. The subthemes present a systematic and thematic basis for the development of a quantitative instrument to measure parental experiences and satisfaction with care. The findings of this study have important clinical implications related to the deeper understanding of parental experiences and improving family-centered care.

Differences in the perceptions of parents and healthcare professionals on pediatric intensive care practices (Article)

2010-01-01T00:00:00Z

Enteral nutrient supply for preterm infants: Commentary from the european society of paediatric gastroenterology, hepatology and nutrition committee on nutrition (Article)

2010-01-01T00:00:00Z

The number of surviving children born prematurely has increased substantially during the last 2 decades. The major goal of enteral nutrient supply to these infants is to achieve growth similar to foetal growth coupled with satisfactory functional development. The accumulation of knowledge since the previous guideline on nutrition of preterm infants from the Committee on Nutrition of the European Society of Paediatric Gastroenterology and Nutrition in 1987 has made a new guideline necessary. Thus, an ad hoc expert panel was convened by the Committee on Nutrition of the European Society of Paediatric Gastroenterology, Hepatology, and Nutrition in 2007 to make appropriate recommendations. The present guideline, of which the major recommendations are summarised here (for the full report, see http://links.lww.com/A1480), is consistent with, but not identical to, recent guidelines from the Life Sciences Research Office of the American Society for Nutritional Sciences published in 2002 and recommendations from the handbook Nutrition of the Preterm Infant. Scientific Basis and Practical Guidelines, 2nd ed, edited by Tsang et al, and published in 2005. The preferred food for premature infants is fortified human milk from the infant's own mother, or, alternatively, formula designed for premature infants. This guideline aims to provide proposed advisable ranges for nutrient intakes for stable-growing preterm infants up to a weight of approximately 1800 g, because most data are available for these infants. These recommendations are based on a considered review of available scientific reports on the subject, and on expert consensus for which the available scientific data are considered inadequate. Copyright

Recent advances in our understanding of protein and amino acid metabolism in the human fetus (Article)

2010-01-01T00:00:00Z

PURPOSE OF REVIEW: Premature infants often suffer from suboptimal outcome, at least partially due to suboptimal nutrition. Gaining insight into human fetal amino acid metabolism might ultimately lead to an improved nutritional strategy for prematurely born infants. Our aim was, therefore, to discuss recent findings with regard to human fetal amino acid metabolism. RECENT FINDINGS: Human fetal protein and amino acid metabolism can be studied in vivo using stable isotope techniques. To date, however, only a few studies employing these techniques have been performed. For one, it was shown in vivo that essential amino acids are transported at different rates across the human placenta. In addition, tyrosine appears not to be a conditionally essential amino acid in the fetus at term, as phenylalanine is hydroxylated into tyrosine at considerable rates. Furthermore, albumin is synthesized at very high rates at two-thirds of gestation; higher than prematurely born infants do at a neonatal intensive care unit. This could indicate that postnatal nutrition of very immature infants can be improved. SUMMARY: Although technically challenging, more studies regarding human fetal amino acid metabolism should be performed. Premature infants could then benefit from this knowledge from new nutritional strategies.

Analysis of [U-13C6]glucose in human plasma using liquid chromatography/isotope ratio mass spectrometry compared with two other mass spectrometry techniques (Article)

2009-12-15T00:00:00Z

The use of stable isotope labelled glucose provides insight into glucose metabolism. The13C-isotopic enrichment of glucose is usually measured by gas chromatography/mass spectrometry (GC/MS) or gas chromatography/combustion/isotope ratio mass spectrometry (GC/C/IRMS). However, in both techniques the samples must be derivatized prior to analysis, which makes sample preparation more labour-intensive and increases the uncertainty of the measured isotopic composition. A novel method for the determination of isotopic enrichment of glucose in human plasma using liquid chromatography/ isotope ratio mass spectrometry (LC/IRMS) has been developed. Using this technique, for which hardly any sample preparation is needed, we showed that both the enrichment and the concentration could be measured with very high precision using only 20μL of plasma. In addition, a comparison with GC/MS and GC/IRMS showed that the best performance was achieved with the LC/IRMS method making it the method of choice for the measurement of13C-isotopic enrichment in plasma samples. Copyright

Validation of deuterium and oxygen18 in urine and saliva samples from children using on-line continuous-flow isotope ratio mass spectrometry (Article)

2009-11-01T00:00:00Z

The doubly labelled water method is valuable for measuring energy expenditure in humans. It usually involves blood or urine sampling, which might be difficult in neonates and children with cerebral palsy or other disabilities. We therefore aimed to validate a method making use of saliva samples analyzed by automated thermal conversion elemental analyzer in combination with isotope ratio mass spectrometry (TC-EA/IRMS). The subjects received labelled water orally and urine and saliva samples were collected and analyzed. Deuterium as well as oxygen18was measured in one single run using a peak jump method. Excellent linearity was found for measurement of enrichments of deuterium (R2= 0.9999) and oxygen18(R2= 0.9999). The intra-assay precision and the inter-assay precision of the measurement of two standards were good for both deuterium and oxygen18. The variation between urine and saliva samples was small (4.83% for deuterium and 2.33% for oxygen18n = 40). Saliva sampling is to be preferred, therefore, as it can be easily collected and is non-invasive. Moreover, its time of production is almost exactly known. The TC-EA/IRMS method is a good alternative to the more laborious off-line IRMS measurements. Copyright

Initial nutritional management of the preterm infant (Article)

2009-11-01T00:00:00Z

Postnatal nutrition has a large impact on long-term outcome of preterm infants. Evidence is accumulating showing even a relationship between nutrient supply in the first week of life and later cognitive development in extremely low birth weight infants. Since enteral nutrition is often not tolerated following birth, parenteral nutrition is necessary. Yet, optimal parenteral intakes of both energy and amino acids are not well established. Subsequently, many preterm infants fail to grow well, with long-term consequences. Early and high dose amino acid administration has been shown to be effective and safe in very low birth weight infants, but the effect of additional lipid administration needs to be defined.

High-dose cysteine administration does not increase synthesis of the antioxidant glutathione preterm infants (Article)

2009-11-01T00:00:00Z

OBJECTIVE: Our aim was to evaluate whether administration of additional cysteine is safe and stimulates glutathione synthesis in preterm infants in early life. METHODS: We conducted a prospective, randomized, clinical trial with infants with birth weights of <1500 g (N = 20). The infants were assigned randomly to receive either a standard dose (45 mg/kg per day) or a high dose (81 mg/kg per day) of cysteine. Intakes of other amino acids were similar, providing a total protein intake of 2.4 g/kg per day in both groups. We recorded base requirements in the first 6 days of life. On postnatal day 2, we conducted a stable isotope study to determine glutathione concentrations and synthesis rates in erythrocytes. RESULTS: Base requirements were higher in the high-dose cysteine group on days 3, 4, and 5. Despite an 80% increase in cysteine intake, plasma cystine concentrations did not increase. Glutathione concentrations and synthesis rates did not increase with additional cysteine administration. CONCLUSIONS: Administration of a high dose of cysteine (81 mg/kg per day) to preterm infants seems clinically safe but does not stimulate glutathione synthesis, compared with a lower dose (45 mg/kg per day). Further research is required to determine whether there is significant benefit associated with cysteine supplementation. Copyright

Simultaneous analysis of 13C-glutathione as its dimeric form GSSG and its precursor [l-13c]glycine using liquid chromatography/isotope ratio mass spectrometry (Article)

2009-09-30T00:00:00Z

Determination of glutathione kinetics using stable isotopes requires accurate measurement of the tracers and tracees. Previously, the precursor and synthesized product were measured with two separate techniques, liquid chromatography/isotope ratio mass spectrometry (LC/IRMS) and gas chromatography/combustion/isotope ratio mass spectrometry (GC/C/IRMS). In order to reduce sample volume and minimize analytical effort we developed a method to simultaneously determine13C-glutathione as its dimeric form (GSSG) and its precursor [1-13C]glycine in a small volume of erythrocytes in one single analysis. After having transformed13C-glutathione into its dimeric form GSSG, we determined both the intra-erythrocytic concentrations and the13C-isotopic enrichment of GSSG and glycine in 150 μL of whole blood using liquid chromatography coupled to LC/IRMS. The results show that the concentration (range of μmol/mL) was reliably measured using cycloleucine as internal standard, i.e. with a precision better than 0.1 μmol/mL. The13C-isotopic enrichment of GSSG and glycine measured in the same run gave reliable values with excellent precision (standard deviation (sd) <0.3%o) and accuracy (measured between 0 and 5 APE). This novel method opens up a variety of kinetic studies with relatively low dose administration of tracers, reducing the total cost of the study design. In addition, only a minimal sample volume is required, enabling studies even in very small subjects, such as preterm infants. Copyright

Taking up the challenge of measuring prolonged pain in (premature) neonates the COMFORTneo scale seems promising (Article)

2009-09-01T00:00:00Z

Objectives: Pain assessment is essential to tailor intensive care of neonates. The present focus is on acute procedural pain; assessment of pain of longer duration remains a challenge. We therefore tested a modified version of the COMFORT-behavior scale\-named COMFORTneo\-for its psychometric qualities in the Neonatal Intensive Care Unit setting. Methods: In a clinical observational study, nurses assessed patients with COMFORTneo and Numeric Rating Scales (NRS) for pain and distress, respectively. Interrater reliability, concurrent validity, and sensitivity to change were calculated as well as sensitivity and specificity for different cut-off scores for subsets of patients. Results: Interrater reliability was good: median linearly weighted Cohen κ 0.79. Almost 3600 triple ratings were obtained for 286 neonates. Internal consistency was good (Cronbach α 0.84 and 0.88). Concurrent validity was demonstrated by adequate and good correlations, respectively, with NRS-pain and NRS-distress: r=0.52 (95% confidence interval 0.44-0.59) and r=0.70 (95% confidence interval 0.64-0.75). COMFORTneo cut-off scores of 14 or higher (score range is 6 to 30) had good sensitivity and specificity (0.81 and 0.90, respectively) using NRS-pain or NRS-distress scores of 4 or higher as criterion. Discussion: The COMFORTneo showed preliminary reliability. No major differences were found in cut-off values for low birth weight, small for gestational age, neurologic impairment risk levels, or sex. Multicenter studies should focus on establishing concurrent validity with other instruments in a patient group with a high probability of ongoing pain.

Meta-analysis of neurobehavioral outcomes in very preterm and/or very low birth weight children (Article)

2009-08-01T00:00:00Z

OBJECTIVE: Sequelae of academic underachievement, behavioral problems, and poor executive function (EF) have been extensively reported for very preterm (≤33 weeks' gestation) and/or very low birth weight (VLBW) (≤1500 g) children. Great variability in the published results, however, hinders the field in studying underlying dysfunctionsanddeveloping intervention strategies. We conductedaquantitative meta-analysis of studies publishedbetween1998and 2008 on academic achievement, behavioral functioning, and EF with the aim of providing aggregated measures of effect size for these outcome domains. METHODS: Suitable for inclusion were 14 studies on academic achievement, 9 studies on behavioral problems, and 12 studies on EF, which compared a total of 4125 very preterm and/or VLBW children with 3197 term-born controls. Combined effect sizes for the 3 outcome domains were calculated in terms of Cohen's d. Q-test statistics were performed to test homogeneity among the obtained effect sizes. Pearson's correlation coefficients were calculated to examine the impact of mean birth weight and mean gestational age, as well as the influence of mean age at assessment on the effect sizes for academic achievement, behavioral problems, and EF. RESULTS: Combined effect sizes show that very preterm and/or VLBW children score 0.60 SD lower on mathematics tests, 0.48 SD on reading tests, and 0.76 SD on spelling tests than term-born peers. Of all behavioral problems stacked, attention problems were most pronounced in very preterm and/or VLBW children, with teacher and parent ratings being 0.43 to 0.59 SD higher than for controls, respectively. Combined effect sizes for parent and teacher ratings of internalizing behavior problems were small (<0.28) and for externalizing behavior problems negligible (<0.09) and not significant. Combined effect sizes for EF revealed a decrement of 0.57 SD for verbal fluency, 0.36 SD for working memory, and 0.49 SD for cognitive flexibility in comparison to controls. Mean age at assessment was not correlated with the strength of the effect sizes. Mathematics and reading performance, parent ratings of internalizing problems, teacher ratings of externalizing behavior, and attention problems, showed strong and positive correlations with mean birth weight and mean gestational age (all r values > 0.51). CONCLUSIONS: Very preterm and/or VLBW children have moderate-toseveredeficits inacademicachievement,attentionproblems, andinternalizing behavioral problems and poor EF, which are adverse outcomes that were strongly correlated to their immaturity at birth. During transition to young adulthood these children continue to lag behind term-born peers.

Epithelial functions of the residual bowel after surgery for necrotising enterocolitis in human infants (Article)

2009-07-01T00:00:00Z

Objectives: Information on epithelial functions of the residual small or colonic bowel after resection for necrotising enterocolitis (NEC) in human infants is scarce. Our aim is to evaluate epithelial functions in the intestinal resection margins of tissue obtained at bowel resection for acute NEC and consecutive stoma closure. Materials and Methods: Epithelial morphology, proliferation, and protein expression were (immuno) histochemically studied. Results: Acute NEC was associated with severe and mild epithelial damage varying from epithelial loss to fairly unaffected epithelium. Epithelial proliferation was increased both at acute NEC and at stoma closure. In acute NEC, lactase, glucose transporter-2 and -5 expression was downregulated in severely affected epithelium, whereas sucraseisomaltase and intestinal fatty acid binding protein expression was maintained. Goblet cells continued to express mucin 2 and trefoil factor 3, however, their numbers were decreased. Moreover, in acute NEC, Paneth cells were weakly lysozyme positive and were reduced in number. At stoma closure, expression of the above cell type-specific markers had completely been re-established. Conclusions: Residual bowel after resection for acute NEC shows a disturbed epithelial proliferation/differentiation balance. Acute NEC was associated with downregulation of distinct enterocyte-specific proteins. Because of goblet cell and Paneth cell loss in acute NEC, mucosal barrier, and defense functions may be impaired. JPGN 49:31-41, 2009.

Threonine metabolism in the intestine of mice: Loss of mucin 2 induces the threonine catabolic pathway (Article)

2009-07-01T00:00:00Z

Objectives: Previous studies have shown that the intestine uses a major part of the dietary threonine intake for the synthesis of the structural component of the protective intestinal mucus layer, the secretory mucin Muc2. In this context, the high intestinal demand for dietary threonine probably results from its incorporation into secretory mucins rich in threonine residues. Therefore, we compared threonine utilization in the colon of Muc2 knockout (Muc2-/-) and wild-type (Muc2+/+) mice to investigate the intestinal dietary threonine metabolism in the absence of Muc2, which results in inflammation of the colon. Materials and Methods: Concentrations and isotopic enrichment of threonine were measured by gas chromatographyisotope ratio mass spectrometry in the serum, colon, and colonic content of mice given a bolus [U-13C]threonine enterally. Results: We retrieved 37.8% and 40.9% of dietary threonine in Muc2+/+and Muc2-/-mice, respectively, either as free or incorporated threonine. There were no major differences in the availability and concentration of free or incorporated threonine recovered in both serum and colon in both types of mice. However, the Muc2-/-mice did show overall significantly higher threonine oxidation rates compared with Muc2+/+mice. Conclusions: In the absence of Muc2, dietary threonine is mainly used for constitutive protein synthesis or becomes a substrate for metabolic oxidation. This indicates that inflammation also requires high threonine amounts. JPGN 49:99-107, 2009.

Breast-feeding: A commentary by the espghan Committee on Nutrition (Article)

2009-07-01T00:00:00Z

This medical position article by the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition summarises the current status of breast-feeding practice, the present knowledge on the composition of human milk, advisable duration of exclusive and partial breast-feeding, growth of the breast-fed infant, health benefits associated with breastfeeding, nutritional supplementation for breast-fed infants, and contraindications to breast-feeding. This article emphasises the important role of paediatricians in the implementation of health policies devised to promote breast-feeding. The European Society for Paediatric Gastroenterology, Hepatology, and Nutrition Committee on Nutrition recognises breast-feeding as the natural and advisable way of supporting the healthy growth and development of young children. This article delineates the health benefits of breast-feeding, reduced risk of infectious diarrhoea and acute otitis media being the best documented. Exclusive breast-feeding for around 6 months is a desirable goal, but partial breast-feeding as well as breast-feeding for shorter periods of time are also valuable. Continuation of breastfeeding after the introduction of complementary feeding is encouraged as long as mutually desired by mother and child. The role of health care workers, including paediatricians, is to protect, promote, and support breast-feeding. Health care workers should be trained in breast-feeding issues and counselling, and they should encourage practices that do not undermine breast-feeding. Societal standards and legal regulations that facilitate breast-feeding should be promoted, such as providing maternity leave for at least 6 months and protecting working mothers. JPGN 49:112-125, 2009.

Construction of a parent satisfaction instrument: Perceptions of pediatric intensive care nurses and physicians (Article)

2009-06-01T00:00:00Z

Purpose: The aims of the study were (1) to identify parental satisfaction items through the opinions of pediatric intensive care unit (PICU) nurses and physicians, (2) to reach consensus on the identified items, and (3) to apply factor analysis to evaluate the items and domains toward a PICU parental satisfaction instrument. Materials and Methods: Pediatric intensive care unit nurses and physicians working in 8 university hospitals in the Netherlands participated. A 2-round Delphi method was completed. Confirmatory factor analysis was performed on the satisfaction items and domains. Results: Three hundred two nurses and 62 physicians participated in the Delphi study, and 269 (76%) completed 2 questionnaire rounds. In Delphi round 2, 14 of the 78 items had a mean of less than 8.0 (range, 1 [low importance] to 10 [high importance]). The interquartile range of all domains decreased by almost half, and only 10 satisfaction items had a heterogeneity of less than 70%. Structure determination revealed that 4 satisfaction items needed to be excluded. Out of 74 satisfaction items, 72 showed factor loadings greater than 0.50. The reliability estimates, Cronbach α, for the 6 domains varied from 0.74 to 0.92. Conclusions: Priorities in parental satisfaction measures are identified. The findings are fundamental in the development of a PICU parental satisfaction instrument.

Perceptions of parents on satisfaction with care in the pediatric intensive care unit: the EMPATHIC study (Article)

2009-06-01T00:00:00Z

Abstract: PURPOSE: To identify parental perceptions on pediatric intensive care-related satisfaction items within the framework of developing a Dutch pediatric intensive care unit (PICU) satisfaction instrument. METHODS: Prospective cohort study in tertiary PICUs at seven university medical centers in The Netherlands. PARTICIPANTS: Parents of 1,042 children discharged from a PICU. RESULTS: A 78-item questionnaire was sent to 1,042 parents and completed by 559 (54%). Seventeen satisfaction items were rated with mean scores <8.0 (1, completely unimportant, to 10, very important) with standard deviations > or =1.65, and thus considered of limited value. The empirical structure of the items was in agreement with the theoretically formulated domains: Information, Care and Cure, Organization, Parental Participation, and Professional Attitude. The Cronbach's alpha of the domains ranged between 0.87 and 0.94. CONCLUSIONS: Parental perceptions on satisfaction with care measures were identified and prioritized. Reliabilities of the items and domains were of high level.

Critically ill infants benefit from early administration of protein and energy-enriched formula: A randomized controlled trial (Article)

2009-06-01T00:00:00Z

Background & aims: Nutritional support improves outcome in critically ill infants but is impeded by fluid restriction, gastric intolerance and feeding interruptions. Protein and energy-enriched infant formulas may help to achieve nutritional targets earlier during admission and promote anabolism. Methods: Randomized controlled design. Infants with respiratory failure due to RSV-bronchiolitis received a protein and energy-enriched formula (PE-formula, n = 8) or a standard formula (S-formula, n = 10) during 5 days after admission. Primary outcome: nutrient delivery, energy and nitrogen balance and plasma amino acid concentrations. Secondary outcome: tolerance and safety. Results: Nutrient intakes were higher in PE fed infants and met population reference intake (PRI) on day 3-5 whilst in S-fed infants PRI was met on day 5 only. Cumulative nitrogen balance (cNB) and energy balance (cEB) were higher in PE-infants compared to S-infants (cNB: 866 ± 113 vs. 296 ± 71 mg/kg; cEB: 151 ± 31 and 26 ± 17 kcal/kg, both P < 0.01). Essential amino acid levels were higher in PE-infants but within reference limits whereas below these limits in S-infants. Both formulas were well tolerated. Conclusions: Early administration of a protein and energy-enriched formula in critically ill infants is well tolerated, promotes a more adequate nutrient intake and improves energy and nitrogen balance without adverse effects.

The regulation of intestinal mucin MUC2 expression by short-chain fatty acids: Implications for epithelial protection (Article)

2009-06-01T00:00:00Z

SCFAs (short-chain fatty acids), fermentation products of bacteria, influence epithelial-specific gene expression. We hypothesize that SCFAs affect goblet-cell-specific mucin MUC2 expression and thereby alter epithelial protection. In the present study, our aim was to investigate the mechanisms that regulate butyrate-mediated effects on MUC2 synthesis. Human goblet cell-like LS174T cells were treated with SCFAs, after which MUC2 mRNA levels and stability, and MUC2 protein expression were analysed. SCFA-responsive regions and cis-elements within the MUC2 promoter were identified by transfection and gel-shift assays. The effects of butyrate on histone H3/H4 status at the MUC2 promoter were established by chromatin immunoprecipitation. Butyrate (at 1 mM), as well as propionate, induced an increase in MUC2 mRNA levels. MUC2 mRNA levels returned to basal levels after incubation with 5-15 mM butyrate. Interestingly, this decrease was not due to loss of RNA stability. In contrast, at concentrations of 5-15 mM propionate, MUC2 mRNA levels remained increased. Promoter-regulation studies revealed an active butyrate-responsive region at -947/-371 within the MUC2 promoter. In this region we identified an active AP1 (c-Fos/c-Jun) cis-element at -818/-808 that mediates butyrate-induced activation of the promoter. Finally, MUC2 regulation by butyrate at 10-15 mM was associated with increased acetylation of histone H3 and H4 and methylation of H3 at the MUC2 promoter. In conclusion, 1 mM butyrate and 1-15 mM propionate increase MUC2 expression. The effects of butyrate on MUC2 mRNA are mediated via AP-1 and acetylation/methylation of histones at the MUC2 promoter.

Intelligence of very preterm or very low birthweight infants in young adulthood (Article)

2009-05-01T00:00:00Z

Objective: To examine the effect of intrauterine and neonatal growth, prematurity and personal and environmental risk factors on intelligence in adulthood in survivors of the early neonatal intensive care era. Methods: A large geographically based cohort comprised 94% of all babies born alive in the Netherlands in 1983 with a gestational age below 32 weeks and/or a birth weight >1500 g (POPS study). Intelligence was assessed in 596 participants at 19 years of age. Intrauterine and neonatal growth were assessed at birth and 3 months of corrected age. Environmental and personal risk factors were maternal age, education of the parent, sex and origin. Results: The mean (SD) IQ of the cohort was 97.8 (15.6). In multiple regression analysis, participants with highly educated parents had a 14.2-point higher IQ than those with less well-educated parents. A 1 SD increase in birth weight was associated with a 2.6-point higher IQ, and a 1-week increase in gestational age was associated with a 1.3-point higher IQ. Participants born to young mothers (<25 years) had a 2.7-point lower IQ, and men had a 2.1-point higher IQ than women. The effect on intelligence after early (symmetric) intrauterine growth retardation was more pronounced than after later (asymmetric) intrauterine or neonatal growth retardation. These differences in mean IQ remained when participants with overt handicaps were excluded. Conclusions: Prematurity as well as the timing of growth retardation are important for later intelligence. Parental education, however, best predicted later intelligence in very preterm or very low birthweight infants.

Small intestinal MUC2 synthesis in human preterm infants (Article)

2009-05-01T00:00:00Z

Mucin 2 (MUC2) is the structural component of the intestinal protective mucus layer, which contains high amounts of threonine in its peptide backbone. MUC2 synthesis rate might be a potential parameter for intestinal barrier function. In this study, we aimed to determine whether systemic threonine was used for small intestinal MUC2 synthesis and to calculate the MUC2 fractional synthetic rate (FSR) in human preterm infants. Seven preterm infants with an enterostomy following bowel resection for necrotizing enterocolitis received intravenous infusion of [U-13C]threonine to determine incorporation of systemic threonine into secreted MUC2 in intestinal outflow fluid. Small intestinal MUC2 was isolated using cesium chloride gradient ultracentrifugation and gravity gel filtration chromatography. MUC2-containing fractions were identified by SDS-PAGE/ periodic acid-Schiff staining and Western blot analysis and were subsequently pooled. Isotopic enrichment of threonine, measured in MUC2 using gas chromatography isotopic ratio mass spectrometry, was used to calculate the FSR of MUC2. Systemically derived threonine was indeed incorporated into small intestinal MUC2. Median FSR of small intestinal MUC2 was 67.2 (44.3-103.9)% per day. Systemic threonine is rapidly incorporated into MUC2 in the small intestine of preterm infants, and thereby MUC2 has a very high synthesis rate. Copyright

Imaging patterns of brain injury in term-birth asphyxia (Article)

2009-03-01T00:00:00Z

Aim: To develop an extended asphyxia-score based on cerebral ultrasound (US) and MRI in order to gain further insight into the pathophysiology of asphyxia. Patients and Methods: First week cerebral US and MRI of 80 asphyxiated term infants were scored according to a new scoring system based on separate grading of injury to deep grey matter and to (sub)cortical/white matter. Our findings were compared with published scoring systems. Results: Six patterns of brain injury were derived: deep grey matter injury with either limited or extensive cortical involvement, damage to deep grey matter with watershed injury, isolated watershed injury, isolated white matter injury (leukomalacia) and isolated cortical necrosis. The mortality rate was considerable in patterns with extensive cortical injury. Conclusion: Six patterns of brain injury, following term-birth asphyxia were found using a new imaging score.

Construction of a parent satisfaction instrument: Perceptions of pediatric intensive care nurses and physicians (Article)

2009-01-01T00:00:00Z

Human fetal amino acid metabolism at term gestation (Article)

2009-01-01T00:00:00Z

Background: Knowledge on human fetal amino acid (AA) metabolism, largely lacking thus far, is pivotal in improving nutritional strategies for prematurely born infants. Phenylalanine kinetics is of special interest as is debate as to whether neonates will adequately hydroxylate phenylalanine to the semiessential AA tyrosine. Objective: Our aim was to quantify human fetal phenylalanine and tyrosine metabolism. Design: Eight fasted, healthy, pregnant women undergoing elective cesarean delivery at term received primed continuous stable-isotope infusions of [1-13C]phenylalanine and [ring-D4]tyrosine starting before surgery. Umbilical blood flow was measured by ultrasound. Maternal and umbilical cord blood was collected and analyzed by gas chromatography-mass spectrometry for phenylalanine and tyrosine enrichments and concentrations. Data are expressed as medians (25th-75th percentile). Results: Women were in a catabolic state for which net fetal AA uptake was responsible for ≥25%. Maternal and fetal hydroxylation rates were 2.6 (2.2-2.9) and 7.5 (6.2-15.5) μmol phenylalanine/(kg·h), respectively. Fetal protein synthesis rates were higher than breakdown rates: 92 (84-116) and 73 (68-87) μmol phenylalanine/(kg·h), respectively, which indicated an anabolic state. The median metabolized fraction of available phenylalanine and tyrosine in the fetus was <20% for both AAs. Conclusions: At term gestation, fetuses still show considerable net AA uptake and AA accretion [converted to tissue ≈12 g/(kg·d)]. The low metabolic uptake (AA usage) implies a very large nutritional reserve capacity of nutrients delivered through the umbilical cord. Fetuses at term are quite capable of hydroxylating phenylalanine to tyrosine.

Combined defects in epithelial and immunoregulatory factors exacerbate the pathogenesis of inflammation: Mucin 2-interleukin 10-deficient mice (Article)

2008-06-24T00:00:00Z

Expression of the mucin MUC2, the structural component of the colonic mucus layer, is lowered in ulcerative colitis. Furthermore, interleukin (IL)-10 knockout (IL-10-/-) mice develop colitis and have reduced Muc2 levels. Our aim was to obtain insight into the role of Muc2 and IL-10 in epithelial protection. Muc2-IL-10 double-knockout (Muc2/IL-10DKO) mice were characterized and compared to Muc2 knockout (Muc2-/-), IL-10-/-and wild-type (WT) mice. Clinical symptoms, intestinal morphology and differences in epithelial-specific protein levels were analyzed. In addition, levels of the pro-inflammatory cytokines in colonic tissue and serum were determined. IL-10-/-mice were indistinguishable from WT mice throughout this experiment and showed no clinical or histological signs of colitis. Muc2/IL-10DKOand Muc2-/-mice showed significant growth retardation and clinical signs of colitis at 4 and 5 weeks, respectively. Muc2/IL-10DKOmice had a high mortality rate (50% survival/5 weeks) compared to the other types of mice (100% survival). Microscopic analysis of the colon of Muc2/IL-10DKOmice showed mucosal thickening, increased proliferation, superficial erosions and a diminished Muc4 expression. Furthermore, pro-inflammatory cytokines were significantly upregulated, both in tissue (mRNA) and systemically in Muc2/IL-10DKOmice. In conclusion, Muc2/IL-10DKOmice develop colitis, which is more severe in every aspect compared to Muc2-/-and IL-10-/-mice. These data indicate that (i) in case of Muc2 deficiency, the anti-inflammatory cytokine IL-10 can control epithelial damage, though to a limited extent and (ii) the mucus layer is most likely a key factor determining colitis.

Parent Satisfaction in the Pediatric ICU (Article)

2008-06-01T00:00:00Z

Parents are important partners who collaborate with the multidisciplinary team to improve quality of care. This article discusses a framework for action toward quality improvement in pediatric intensive care by parental empowerment through parent satisfaction with care. Incorporating the concepts of family-centered care and parental needs and experiences into a parent satisfaction instrument may provide quality improvement projects based on the empowerment of parents and eventually may facilitate the implementation and evaluation of quality initiatives.

Forkhead box transcription factors Foxa1 and Foxa2 are important regulators of Muc2 mucin expression in intestinal epithelial cells (Article)

2008-05-16T00:00:00Z

The mucin Muc2 is the main component of the intestinal mucus layer and thus plays important roles in intestinal protection. Therefore, it is important to understand its regulation during goblet cell differentiation. Foxa1 and Foxa2 forkhead box transcription factors (TFs) participate in transcriptional programs governing intestinal cell differentiation. Using immunohistochemistry, we showed a spatio-temporal pattern of expression of both TFs in developing and adult mouse intestine and their expression in Muc2-expressing intestinal cells. Down-regulation of Foxa1 and Foxa2 by RNA interference in cultured intestinal cells decreased Muc2 mRNA level by half, and abolished Muc2 protein expression. Chromatin immunoprecipitation and gel shift assays showed that these two TFs directly bind to the Muc2 promoter. Co-transfection experiments indicated that both TFs activate the Muc2 promoter and that mutations of three Foxa cis-elements inhibit Muc2 transactivation. In conclusion, this work identifies Foxa1 and Foxa2 as important regulators of Muc2 expression in the intestine.

Computer-generated versus nurse-determined strategy for incubator humidity and time to regain birthweight (Article)

2008-05-01T00:00:00Z

Objective: To compare effects on premature infants' weight gain of a computer-generated and a nurse-determined incubator humidity strategy. An optimal humidity protocol is thought to reduce time to regain birthweight. Design: Prospective randomized controlled design. Setting: Level IIIC neonatal intensive care unit in the Netherlands. Participants: Infants of 24 to 30 weeks gestational age with a birthweight less than 1,500 g. Intervention: Two incubator humidity strategies were studied: computer-generated and nurse-determined humidity. Main outcome measure:Time needed to regain birthweight. Results: One hundred thirty six infants were enrolled: 65 were exposed to the computer-generated strategy and 71 to the nurse-determined strategy. Demographic characteristics were well balanced between groups, with birthweight 981 ± 245 versus 991 ± 213 g, mean gestational age 27.7 ± 1.7 versus 27.7 ± 1.6 weeks. Main outcome did not significantly differ between strategies: survival analysis showed an equal number of days needed to regain birthweight (median 9 days, with 95% CIs 8-10 and 7-11 for infants exposed to the computer-generated and nurse-determined humidity strategy, respectively). Conclusion: Computer-generated strategy does not reduce the time needed to regain birthweight.

Venous subtypes of preterm periventricular haemorrhagic infarction (Article)

2008-05-01T00:00:00Z

Background: Periventricular haemorrhagic infarction (PVHI) is a complication of preterm birth that may lead to impairment and disability. Early diagnosis is possible by cranial ultrasonography (CUS). Extensive PVHI lesions can be graded using a scoring system that relates to outcome, based on CUS characteristics. Data on more subtle unilateral forms of PVHI are lacking. Objective: To refine the PVHI classification by relating subtypes to affected veins and to evaluate the effects of these anatomical subtypes on neurological outcome. Methods: Retrospective analysis of images and neurological outcome of 20 preterm infants with unilateral PVHI. Based on affected veins, PVHI was classified into six subtypes. Sonographic templates of infarct types are provided in the coronal and parasagittal planes. Standardised neurological examinations were done (according to Amiel-Tison and Touwen examinations) and children were classified as: normal, mildly or definitely abnormal. The outcome was based on the most recent neurological examination, at a corrected age of 1 (n = 7), 2 (n = 5), 3 (n = 5) or 5 (n = 3) years. Results: PVHI classification of the 20 patients was as follows: temporal (n = 3), pure caudate (n = 3), anterior terminal (n = 6), complete terminal (n = 3), extensive (n = 4), other (n = 1). With one exception, only PVHI patients showing the latter three subtypes had developed severe spastic contralesional hemiplegia. Conclusions: The classification was developed for PVHI correlates with neurological outcome. This refined classification can help clinicians in predicting neurological outcome at an early stage, with a subsequent targeted rehabilitation schedule instituted early in life.

Quality of amino acid solutions for preterm infants (Article)

2008-04-01T00:00:00Z

Cyst(e)ine requirements in enterally fed very low birth weight preterm infants (Article)

2008-03-01T00:00:00Z

OBJECTIVE. Optimal nutrition is of utmost importance for the preterm infant's later health and developmental outcome. Amino acid requirements for preterm infants differ from those for term and older Infants, because growth rates differ. Some nonessential amino acids, however, cannot be sufficiently synthesized endog-enously. Cyst(e)ine is supposed to be such a conditionally essential amino acid in preterm infants. The objective of this study was to determine, at 32 and 35 weeks' postmenstrual age, cyst(e)ine requirements in fully enterally fed very low birth weight preterm infants with gestational ages of <29 weeks. METHODS. Infants were randomly assigned to 1 of the 5 graded cystine test diets that contained generous amounts of methionine. Cyst(e)ine requirement was determined with the indicator amino acid oxidation technique ([I-13C]phenylaIanlne) after 24-hour adaptation. RESULTS.Fractional [I13-CJphenylalanine oxidation was established in 47 very low birth weight preterm infants (mean gestational age: 28 weeks ± 1 week SD; birth weight: 1.07 kg ± 0.21 kg SD). Increase in dietary cyst(e)ine intake did not result in a decrease in fractional [l-13,CJphenylalanine oxidation. CONCLUSIONS.These data do not support the hypothesis that endogenous cyst(e)ine synthesis is limited in very low birth weight preterm infants with gestational ages of <29 weeks, both at 32 and 35 weeks postmenstrual age. It is safe to conclude that cyst(e)ine requirement is

Effect of enteral IGF-1 supplementation on feeding tolerance, growth, and gut permeability in enterally fed premature neonates (Article)

2008-02-01T00:00:00Z

OBJECTIVES: The gastrointestinal tract of the premature newborn functions suboptimally with regard to digestion, absorption, and feeding tolerance. Human milk contains trophic factors, such as insulin-like growth factor-1 (IGF-1), that are believed to stimulate gut growth and function. The objective of this double blind, randomized, controlled trial was to assess the effects of enteral IGF-1 supplementation on whole body growth measured by weight gain (in grams per kilogram per day), days to regain birth weight, and anthropometrical characteristics, and gut maturation and permeability (measured by sugar absorption tests). PATIENTS AND METHODS: The study included 60 premature infants (birth weight 750-1250 g) during the first month of life. Patients received either standard infant formula or standard infant formula supplemented with IGF-1 in a concentration twice that of human colostrum (10 μg/100 mL of formula). Primary endpoints were days to full enteral feeding, days to regain birth weight, and growth rate. Sugar absorption tests were performed weekly to assess the secondary endpoints gut permeability and maturation. RESULTS: None of the primary endpoints differed to statistical significance between groups at any point. However, gut permeability was significantly lower in the IGF-1 supplement group on day 14 compared with the control group. At day 21, lactulose/mannitol excretion ratios were (again) comparable between the groups. CONCLUSIONS: Although gut permeability showed a faster decrease in the IGF-1 supplement group, our data do not support IGF-1 supplementation to infant formula.

Vibration therapy reduces CPAP need in a prospective randomised controlled trial (Article)

2008-01-01T00:00:00Z

Background: Increased mucus production is a common phenomena following ventilatory support, which might increase morbidity. In order to reduce airway obstruction we tested the effect of vibration therapy on the duration of ventilatory support. Methodology: We conducted a randomised control study in a level IIIC NICU (28 beds) of a university hospital. Compared were nonactive techniques to vibration therapy in preterm infants with a gestational age of 26 - 33 weeks. All infants were ventilated or receive respiratory support by nasal CPAP. Results: 104 infants were enrolled, 49 in the vibration group and 55 in the control group. Demographic characters were in the vibration group compared to control group mean birth weight 1274 (± 335) gram vs. 1240 (± 351) gram and mean gestational age 29.8 (± 1.3) weeks vs. 29.9 (± 1.4) weeks. Vibration therapy did not reduce ventilation time (100 vs. 80 hours, p = 0.88) however duration of CPAP decreases significant (57 vs 157 hours, p < 0.018). Conclusion: Vibration therapy reduced Mean Airway Pressure, oxygen requirements and CPAP need in preterm infants, but did not reduce the duration of mechanical ventilation.

Complementary feeding: A commentary by the ESPGHAN Committee on Nutrition (Article)

2008-01-01T00:00:00Z

This position paper on complementary feeding summarizes evidence for health effects of complementary foods. It focuses on healthy infants in Europe. After reviewing current knowledge and practices, we have formulated these conclusions: Exclusive or full breast-feeding for about 6 months is a desirable goal. Complementary feeding (ie, solid foods and liquids other than breast milk or infant formula and follow-on formula) should not be introduced before 17 weeks and not later than 26 weeks. There is no convincing scientific evidence that avoidance or delayed introduction of potentially allergenic foods, such as fish and eggs, reduces allergies, either in infants considered at increased risk for the development of allergy or in those not considered to be at increased risk. During the complementary feeding period, >90% of the iron requirements of a breast-fed infant must be met by complementary foods, which should provide sufficient bioavailable iron. Cow's milk is a poor source of iron and should not be used as the main drink before 12 months, although small volumes may be added to complementary foods. It is prudent to avoid both early (<4 months) and late (≥7 months) introduction of gluten, and to introduce gluten gradually while the infant is still breast-fed, inasmuch as this may reduce the risk of celiac disease, type 1 diabetes mellitus, and wheat allergy. Infants and young children receiving a vegetarian diet should receive a sufficient amount (∼500 mL) of breast milk or formula and dairy products. Infants and young children should not be fed a vegan diet.

Insulin therapy in the pediatric intensive care unit (Article)

2007-12-01T00:00:00Z

Background & aims: Hyperglycemia is a major risk factor for increased morbidity and mortality in the intensive care unit. Insulin therapy has emerged in adult intensive care units and several pediatric studies are currently being conducted. This review discusses hyperglycemia and the effects of insulin on metabolic and non-metabolic pathways, with a focus on pediatric critical illness. Methods: A PubMed search was performed by using the following keywords and limits (("hyperglycemia"[MeSH terms] or ("insulin resistance"[MeSH major topic]) and ("critical care"[MeSH terms] or "critical illness"[MeSH terms])) in different combinations with ("metabolism"[MeSH terms] or "metabolic networks and pathways"[MeSH terms]) and ("outcome"[all fields]) and ("infant"[MeSH terms] or "child"[MeSH terms] or "adolescent"[MeSH terms]). Quality assessment of selected studies included clinical pertinence, publication in peer-reviewed journals, objectivity of measurements and techniques used to minimize bias. Reference lists of such studies were included. Results: The magnitude and duration of hyperglycemia are associated with increased morbidity and mortality in the pediatric intensive care unit (PICU), but prospective, randomized controlled studies with insulin therapy have not been published yet. Evidence concerning the mechanism and the effect of insulin on glucose and lipid metabolism in pediatric critical illness is scarce. More is known about the positive effect on protein homeostasis, especially in severely burned children. The effect in septic children is less clear and seems age dependent. Some non-metabolic properties of insulin such as the modulation of inflammation, endothelial dysfunction and coagulopathy have not been fully investigated in children. Conclusion: Future studies on the effect of insulin on morbidity and mortality as well as on the mechanisms through which insulin exerts these effects are necessary in critically ill children. We propose these studies to be conducted under standardized conditions including precise definitions of hyperglycemia and rates of glucose intake.

Fractional anisotropy in white matter tracts of very-low-birth-weight infants (Article)

2007-12-01T00:00:00Z

Background: Advances in neonatal intensive care have not yet reduced the high incidence of neurodevelopmental disability among very-low-birth-weight (VLBW) infants. As neurological deficits are related to white-matter injury, early detection is important. Diffusion tensor imaging (DTI) could be an excellent tool for assessment of white-matter injury. Objective: To provide DTI fractional anisotropy (FA) reference values for white-matter tracts of VLBW infants for clinical use. Materials and methods: We retrospectively analysed DTI images of 28 VLBW infants (26-32 weeks gestational age) without evidence of white-matter abnormalities on conventional MRI sequences, and normal developmental outcome (assessed at age 1-3 years). For DTI an echoplanar sequence with diffusion gradient (b = 1,000 s/mm2) applied in 25 non-collinear directions was used. We measured FA and apparent diffusion coefficient (ADC) of different white-matter tracts in the first 4 days of life. Results: A statistically significant correlation was found between gestational age and FA of the posterior limb of the internal capsule in VLBW infants (r = 0.495, P<0.01). Conclusion: Values of FA and ADC were measured in white-matter tracts of VLBW infants. FA of the pyramidal tracts measured in the first few days after birth is related to gestational age.

Dietary protein absorption of the small intestine in human neonates (Article)

2007-11-01T00:00:00Z

Background: The intestine plays a key role in the absorption of dietary proteins, which determines growth of human neonates. Bowel resection in the neonatal period brings loss of absorptive and protective surface and may consequently lead to malabsorption of dietary nutrients. However, there are no data on net dietary protein absorption of the small intestine in the period after intestinal surgery in human neonates. We therefore evaluated dietary feeding tolerance and quantified net dietary protein absorption capacity of the small intestine in human neonates in whom a temporary jejunostomy or ileostomy was created. Methods: Seventeen patients were included in the study. We collected small intestinal outflow fluid at the level of the enterostomy weekly for 24-48 hours during weeks 3 through 6 postoperatively. Protein levels in the intestinal outflow fluid were determined by bicinchoninic acid (BCA) assay. Results: In 14 patients, an enteral intake of >100 mL/kg/d was reached at a median of 17 days (range, 8-32 days) postoperatively. Three patients did not reach this level within the study period. Overall, the net dietary protein absorption capacity was 70%-90% of the total enteral protein intake. Conclusions: This study demonstrates that the dietary protein absorption capacity of the small intestine is intact in most human neonates after intestinal surgery in a very critical period of their lives. Furthermore, our results do not support the use of hydrolyzed or elemental formula in newborns with an enterostomy to improve amino acid uptake. Copyright

Splanchnic oxidation is the major metabolic fate of dietary glutamate in enterally fed preterm infants (Article)

2007-10-01T00:00:00Z

The intestine is a major site of amino acid metabolism, especially in neonates. The energy needed for the metabolic processes in neonatal animals is derived from dietary glucose and amino acids. No data are available showing that dietary amino acids function as intestinal fuel source in human neonates as well. We hypothesized that preterm infants show a high splanchnic first-pass glutamate metabolism and the primary metabolic fate of glutamate is oxidation. Five preterm infants (birth weight 1.2 ± 0.2 kg, gestational age 29 ± 1 wk) were studied by dual tracer ([U-C]glutamate and [D3]glutamate) techniques on two study days (within postnatal d 14-19). Splanchnic and whole-body glutamate kinetics were assessed by plasma isotopic enrichment of [U-C]glutamate and [D3]glutamate and breath CO2 enrichment. Fractional first-pass glutamate uptake was 77 ± 18% on d 1, and 70 ± 7% on d 2, mean 74 ± 13%. Almost all (86 ± 7%) of the glutamate used in the first pass is directed toward oxidation. There is a high splanchnic fractional first-pass uptake and a high oxidation rate of glutamate in preterm infants. Glutamate is an important source of energy for the splanchnic tissues in preterm infants receiving full enteral feeding.

Functional outcomes and participation in young adulthood for very preterm and very low birth weight infants: The Dutch project on preterm and small for gestational age infants at 19 years of age (Article)

2007-09-01T00:00:00Z

OBJECTIVE. Young adults who were born very preterm or with a very low birth weight remain at risk for physical and neurodevelopmental problems and lower academic achievement scores. Data, however, are scarce, hospital based, mostly done in small populations, and need additional confirmation. METHODS. Infants who were born at <32 weeks of gestation and/or with a birth weight of <1500 g in the Netherlands in 1983 (Project on Preterm and Small for Gestational Age Infants) were reexamined at age 19. Outcomes were adjusted for nonrespondents using multiple imputation and categorized into none, mild, moderate, or severe problems. RESULTS. Of 959 surviving young adults, 74% were assessed and/or completed the questionnaires. Moderate or severe problems were present in 4.3% for cognition, 1.8% for hearing, 1.9% for vision, and 8.1% for neuromotor functioning. Using the Health Utility Index and the London Handicap Scale, we found 2.0% and 4.5%, respectively, of the young adults to have ≥3 affected areas in activities and participation. Special education or lesser level was completed by 24%, and 7.6% neither had a paid job nor followed any education. Overall, 31.7% had ≥1 moderate or severe problems in the assessed areas. CONCLUSIONS. A total of 12.6% of young adults who were born very preterm and/or with a very low birth weight had moderate or severe problems in cognitive or neurosensory functioning. Compared with the general Dutch population, twice as many young adults who were born very preterm and/or with a very low birth weight were poorly educated, and 3 times as many were neither employed nor in school at age 19. Copyright

Novel method for measurement of glutathione kinetics in neonates using liquid chromatography coupled to isotope ratio mass spectrometry (Article)

2007-08-30T00:00:00Z

A novel analytical method using liquid chromatography coupled to isotope ratio mass spectrometry (LC/IRMS) was developed for measuring the fractional synthesis rate (FSR) of glutathione (GSH) in neonates after infusion of [1-13C]-glycine as a tracer. After transformation of GSH into GSSG, its dimeric form, the intra-erythrocytic concentration and13C-isotopic enrichment of GSH were deter-mined using 200 μL of blood. The results showed that, using LC/IRMS, the concentration (range of μmol/mL) was reliably measured using norvaline as internal standard with precision better than 0.1 μmol/mL. In addition, the13C-isotopic enrichment measured in the same run gave reliable values with excellent precision (with standard deviation (sd) lower than 0.3‰) and accuracy (measured between 0 and 2 Atom % Excess (APE)). The inter-assay repeatability of δ13C of norvaline used as internal standard with in vivo samples was assessed at -26.07 ± 0.28‰ with coefficient of variance (CV) at 1.1%. The FSR calculated either with GSH or GSSG showed similar results with slightly higher values for GSSG (41.6 ± 4.7 and 46.5 ± 4.4, respectively). The slightly lower FSR of GSH is probably due to interfering compounds in the biological matrix. Successfully used in a clinical study, this rapid and reliable method opens up a variety of kinetic studies with relatively low administration of tracer infusates, reducing the total cost of the study design. The small volume of blood needed enables studies even in extremely small subjects, such as premature infants, as reported in this study. Copyright

Chemotherapy does not influence intestinal amino acid uptake in children (Article)

2007-08-01T00:00:00Z

Chemotherapy will frequently induce intestinal damage (mucositis). Enteral nutrition is then often withheld for fear of impaired intestinal absorption as shown in animal models. There is no clinical evidence, however, that absorption is indeed compromised during chemotherapy-induced mucositis. The aim of this study was to evaluate systemic availability of dietary amino acids (leucine) during chemotherapy-induced mucositis. We studied eight childhood cancer patients (age 1.5-16 y) on 2 d, i.e. the day before chemotherapy and 3-5 d after. Chemotherapy-induced oral mucositis and diarrhea were scored on a World Health Organization toxicity scale. Stable isotope tracers were used to measure first-pass splanchnic leucine uptake and whole-body leucine kinetics. Patients showed increased mucositis and/or diarrhea toxicity scores (p < 0.0001) after chemotherapy. Systemic availability of enterally administered leucine was not significantly affected by chemotherapy (before 60%, after 90%, p = 0.46). Interestingly, five patients already showed a negative leucine balance before chemotherapy. In conclusion, most children receiving chemotherapy are already catabolic before start of a new cycle of chemotherapy. Amino acid transport as measured by leucine uptake in the intestine is not affected by chemotherapy-induced mucositis.

Albumin synthesis in preterm infants on the first day of life studied with [1-13C]leucine (Article)

2007-04-01T00:00:00Z

Albumin is the major binding protein in the human neonate. Low production of albumin will lower its transport and binding capacity. This is especially important in preterm infants, in whom albumin binds to potentially toxic products such as bilirubin and antibiotics. To study the metabolism of plasma albumin in preterm infants, we administered a 24-h constant infusion of [1-13C]leucine to 24 very low birth weight (VLBW) infants (28.4 ± 0.4 wk, 1,080 ± 75 g) on the first day of life. The caloric intake consisted of glucose only, and therefore amino acids for albumin synthesis were derived from proteolysis. The fractional synthesis rate (FSR) of plasma albumin was 13.9 ± 1.5%/day, and the absolute synthesis rate was 148 ± 17 mg·kg-1·day-1. Synthesis rates were significantly lower (P < 0.03) in infants showing intrauterine growth retardation. Albumin synthesis increased with increasing SD scores for gestation and weight (P < 0.05). The FSR of albumin tended to increase by 37% after administration of antenatal corticosteroids to improve postnatal lung function (P = 0.09). We conclude that liver synthetic capacity is well developed in VLBW infants and that prenatal corticosteroids tend to increase albumin synthesis. Decreased weight gain rates in utero have effects on protein synthesis postnatally. Copyright

Methionine transmethylation and transsulfuration in the piglet gastrointestinal tract (Article)

2007-02-27T00:00:00Z

Methionine is an indispensable sulfur amino acid that functions as a key precursor for the synthesis of homocysteine and cysteine. Studies in adult humans suggest that splanchnic tissues convert dietary methionine to homocysteine and cysteine by means of transmethylation and transsulfuration, respectively. Studies in piglets show that significant metabolism of dietary indispensable amino acids occurs in the gastrointestinal tissues (GIT), yet the metabolic fate of methionine in GIT is unknown. We show here that 20% of the dietary methionine intake is metabolized by the GIT in piglets implanted with portal and arterial catheters and fed milk formula. Based on analyses from intraduodenal and intravenous infusions of [1-13C]methionine and [2H3]methionine, we found that the whole-body methionine transmethylation and remethylation rates were significantly higher during duodenal than intravenous tracer infusion. First-pass splanchnic metabolism accounted for 18% and 43% of the whole-body transmethylation and remethylation, respectively. Significant transmethylation and transsulfuration was demonstrated in the GIT, representing ≈27% and ≈23% of whole-body fluxes, respectively. The methionine used by the GIT was metabolized into homocysteine (31%), CO2(40%), or tissue protein (29%). Cystathionine β-synthase mRNA and activity was present in multiple GITs, including intestinal epithelial cells, but was significantly lower than liver. We conclude that the GIT consumes 20% of the dietary methionine and is a significant site of net homocysteine production. Moreover, the GITs represent a significant site of whole-body transmethylation and transsulfuration, and these two pathways account for a majority of methionine used by the GITs.

Parenteral amino acid and energy administration to premature infants in early life (Article)

2007-02-01T00:00:00Z

After birth, the nutritional supply through the umbilical cord ceases. Premature infants do not immediately tolerate full enteral feedings, yet they retain high nutritional needs for both growth and metabolic maintenance. Parenteral nutrition should therefore be initiated as quickly as possible after premature birth, thereby reducing the dependence on endogenous substrates. Intrauterine studies show very high amino acid uptake, clearly exceeding accretion rates. Studies covering the early neonatal period demonstrate that the initiation of high-dose amino acid administration directly after birth is safe and effective, even at low energy intakes. Future research should reveal whether usage could be improved through better amino acid solutions or by providing more energy via lipids from birth onwards as well.

Splanchnic metabolism of ingested amino acids in neonates (Article)

2007-01-01T00:00:00Z

PURPOSE OF REVIEW: Neonates typically show rapid growth. Nutrient absorption in the neonatal period is higher than during any other time in life so as to meet the requirements for this rapid growth. Generally, nutrients are administered enterally, and in the past the gut was considered to absorb and digest these nutrients without major metabolism. Recent animal and human work has, however, revealed that the intestine and other splanchnic tissues contribute significantly to whole-body metabolism, and have their own specific functions. This review focuses on these observations. RECENT FINDINGS: The splanchnic tissues take up greatly different proportions of each of the amino acids, ranging from 80-100% for threonine and several nonessential amino acids to 15-30% for lysine. The metabolic fates of the utilized substrates differ as well. Some are predominantly used for constitutive protein synthesis, others for energy generation or for formation of (glyco-)proteins that are secreted into the lumen. Glucose appears to be the major contributor to energy generation, but amino acids are important as well. SUMMARY: Both animal and human studies have shown that the intestine uses substantial amounts of dietary amino acids. This has several implications for the nutritional needs of infants to maintain growth, especially during times of inadequate enteral nutrition.

Use of [13C]bicarbonate for metabolic studies in preterm infants: intragastric versus intravenous administration. (Article)

2005-11-01T00:00:00Z

The metabolic fate of substrates in humans can be examined by the use of stable isotopes, one of which, [13C]bicarbonate, may serve to estimate CO2 production rate. In view of minimizing the burden of metabolic studies for preterm infants, the authors determined whether intragastric and intravenous infusions of [13C]bicarbonate would achieve the same 13CO2 enrichment in expired air during steady state. A second aim of this study was to determine the minimum time required to reach steady state during intragastric infusion. Ten preterm infants received a primed continuous [13C]bicarbonate infusion intragastrically, followed by an intravenous infusion the next day. Breath samples were obtained every 30 min by the direct sampling method. 13CO2 isotopic enrichment, expressed as atom percent excess, was measured by isotopic ratio mass spectrometry. Two-tailed t tests were used to detect statistically significant differences between the infusion routes. The isotopic enrichment at plateau did not differ between intragastric and intravenous infusion. A steady state of 13CO2 enrichment was achieved after 60 min of intravenous infusion and after 120 min of intragastric infusion. In conclusion, intragastric infusion of [13C]bicarbonate may serve to estimate the whole-body CO2 production rate in preterm infants. To reach 13CO2 steady state, a minimum of 120 min of bicarbonate administration is required.

Threonine utilization is high in the intestine of piglets (Article)

2005-01-01T00:00:00Z

The whole-body threonine requirement in parenterally fed piglets is substantially lower than that in enterally fed piglets, indicating that enteral nutrition induces intestinal processes in demand of threonine. We hypothesized that the percentage of threonine utilization for oxidation and intestinal protein synthesis by the portal-drained viscera (PDV) increases when dietary protein intake is reduced. Piglets (n = 18) received isocaloric normal or protein-restricted diets. After 7 h of enteral feeding, total threonine utilization, incorporation into intestinal tissue, and oxidation by the PDV, were determined with stable isotope methodology [U-(13)C threonine infusion]. Although the absolute amount of systemic and dietary threonine utilized by the PDV was reduced in protein-restricted piglets, the percentage of dietary threonine intake utilized by the PDV did not differ between groups (normal protein 91% vs. low protein 85%). The incorporation of dietary threonine into the proximal jejunum was significantly different compared with the other intestinal segments. Dietary, rather than systemic threonine was preferentially utilized for protein synthesis in the small intestinal mucosa in piglets that consumed the normal protein diet (P < 0.05). Threonine oxidation by the PDV was limited during normal protein feeding. In protein-restricted pigs, half of the total whole-body oxidation occurred in the PDV. We conclude that, in vivo, the PDV have a high obligatory visceral requirement for threonine. The high rate of intestinal threonine utilization is due mainly to incorporation into mucosal proteins

Te jong om te kiezen (Inaugural Lecture)

2004-09-24T00:00:00Z

Splanchnic bed metabolism of glucose in preterm neonates (Article)

2004-01-01T00:00:00Z

BACKGROUND: Glucose is a major oxidative substrate for intestinal energy generation in neonatal animals; however, few data in preterm infants are available. Early administration of enteral nutrition, including glucose, may be an effective strategy to support intestinal adaptation to extrauterine life in preterm neonates. OBJECTIVE: The purpose of the present study was to quantify the first-pass uptake and oxidation of glucose by the splanchnic tissues (intestine and liver) in human neonates. DESIGN: Eight preterm infants [birth weight ( +/- SD): 1.19 +/- 0.22 kg, gestational age: 29 +/- 1 wk] were studied while they received 2 different enteral intakes (A: 40% enteral, 60% parenteral, total glucose intake = 7.5 +/- 0.5 mg. kg(-1). min(-1), and B: 100% enteral, total glucose intake = 7.8 +/- 0.4 mg. kg(-1). min(-1)). Splanchnic and whole-body glucose kinetics were measured by use of dual-tracer techniques. RESULTS: During both feeding periods, approximately one-third of dietary glucose intake was utilized during the first pass by the splanchnic tissues. More than three-quarters of this utilized glucose was oxidized in both periods (79 +/- 36% with A and 84 +/- 45% with B). Whole-body glucose oxidation was substantial under both circumstances: 72 +/- 5% and 77% +/- 6% of the glucose flux was oxidized during partial (A) and full (B) enteral feeding, respectively. CONCLUSIONS: Approximately one-third of dietary glucose is utilized during the first pass by the splanchnic tissues, irrespective of the dietary intake. Most of the utilized glucose is used for energy generation.

Validation of the direct nasopharyngeal sampling method for collection of expired air in preterm neonates. (Article)

2004-01-01T00:00:00Z

In clinical studies, the oxidation of 13C-labeled substrates to 13CO2 and the measurement of the appearance of excess 13CO2 in expiratory air has progressed to an increasingly common method as it is noninvasive and lacks the radiation exposure associated with the use of 14C. The collection of respiratory CO2 currently used occurs via trapping of CO2 in sodium hydroxide (trapping method), sometimes in conjunction with indirect calorimetry. The aim of the present study was to determine the accuracy of our direct nasopharyngeal sampling method for the collection of breath samples in preterm infants compared with the currently used trapping method. We present a method that simplifies the collection of breath samples in preterm infants. Seven preterm infants with a gestational age of 26-29 wk were studied on different postnatal days (range, 8-52 d) while receiving full enteral feeding. A primed constant 3-h intragastric infusion of [13C]bicarbonate was given, and breath samples were collected by means of direct nasopharyngeal sampling and by a sodium hydroxide trap simultaneously. Breath CO2 isotopic enrichments rose rapidly to reach a plateau by 120 min with <5% variation of plateau in both methods. 13CO2 breath isotopic enrichments obtained by the direct nasopharyngeal sampling method correlated highly (r2 = 0.933; p < 0.0001) with the trapping method. The Bland-Altman analysis showed no significant variability between the two methods and demonstrated that the 95% confidence interval is within +/- 4.68 delta per thousand. These findings validate the simple method of direct nasopharyngeal sampling of expired air in neonates.

Lysine kinetics in preterm infants: the importance of enteral feeding (Article)

2004-01-01T00:00:00Z

INTRODUCTION: Lysine is the first limiting essential amino acid in the diet of newborns. First pass metabolism by the intestine of dietary lysine has a direct effect on systemic availability. We investigated whether first pass lysine metabolism in the intestine is high in preterm infants, particularly at a low enteral intake. PATIENTS AND METHODS: Six preterm infants (birth weight 0.9 (0.1) kg) were studied during two different periods: period A (n = 6): 40% of intake administered enterally, 60% parenterally; lysine intake 92 (6) micromol/(kg x h); and period B (n = 4): 100% enteral feeding; lysine intake 100 (3) micromol/(kg x h). Dual stable isotope tracer techniques were used to assess splanchnic and whole body lysine kinetics. RESULTS: Fractional first pass lysine uptake by the intestine was significantly higher during partial enteral feeding (period A 32 (10)% v period B 18 (7)%; p<0.05). Absolute uptake was not significantly different. Whole body lysine oxidation was significantly decreased during full enteral feeding (period A 44 (9) v period B 17 (3) micromol/(kg x h); p<0.05) so that whole body lysine balance was significantly higher during full enteral feeding (period A 52 (25) v period B 83 (3) micromol/(kg x h); p<0.05). CONCLUSIONS: Fractional first pass lysine uptake was much higher during partial enteral feeding. Preterm infants receiving full enteral feeding have lower whole body lysine oxidation, resulting in a higher net lysine balance, compared with preterm infants receiving partial enteral feeding. Hence parenterally administered lysine is not as effective as dietary lysine in promoting protein deposition in preterm infants.

Growth and body composition in preterm infants with bronchopulmonary dysplasia (Article)

2003-01-01T00:00:00Z

OBJECTIVE: To compare growth and body composition in preterm infants with bronchopulmonary dysplasia (BPD) with normal healthy term infants during the first year of life. DESIGN: Twenty nine preterm infants with BPD (mean (SD) gestational age 27.1 (1.6) weeks; birth weight 852 (173) g) were followed prospectively. Anthropometry and body composition determined by total body electrical conductivity were measured and compared with those of healthy term infants at the same post-term age. RESULTS: In infants with BPD, the mean weight standard deviation scores (SD scores) 6 weeks after term were significantly lower (-1.44 and -2.68, boys and girls respectively) than in healthy term infants of the same age and did not improve during the first year. The mean length SD score was significantly lower in infants with BPD 6 weeks after term than in healthy term infants of the same age, and, although it improved significantly during the first year, the mean length SD score in girls with BPD was significantly below 0 12 months after term. In infants with BPD, the mean free fat mass (FFM) SD score and the mean total body fat (TBF) SD score at 6 weeks post-term age were significantly below 0. The mean FFM SD scores (-1.01 and -2.56, boys and girls respectively) and the mean TBF SD scores (-1.14 and -2.40, boys and girls respectively) 12 months after term were significantly lower than in healthy term infants of the same age. CONCLUSIONS: Preterm infants with BPD have impaired growth, with a deficit in TBF and FFM already 6 weeks after term; FFM and TBF remain low compared with healthy term infants during the first year of life. Nutritional intervention studies in infants with BPD are needed to evaluate if nutrition is the major determinant of growth and body composition or if this pattern of growth in preterm infants with BPD is the result of disturbed endocrine control.

Short-term growth and substrate use in very-low-birth-weight infants fed formulas with different energy contents (Article)

2000-01-01T00:00:00Z

BACKGROUND: Currently available preterm formulas with energy contents of 3350 kJ (800 kcal)/L promote weight and length gain at rates at or above intrauterine growth rates but disproportionately increase total body fat. OBJECTIVE: The objective of this study was to determine whether fat accretion in formula-fed, very-low-birth-weight (VLBW) infants could be decreased and net protein gain maintained by reducing energy intakes from 502 kJ (80 kcal)*kg(-)(1)*d(-)(1) [normal-energy (NE) formula] to 419 kJ (100 kcal)*kg(-)(1)*d(-)(1) [low-energy (LE) formula] while providing similar protein intakes (3.3 g*kg(-)(1)*d(-)(1)). DESIGN: The study was a randomized, controlled trial enrolling 20 appropriate-for-gestational-age (AGA) and 16 small-for-gestational-age (SGA) VLBW infants (mean birth weight: 1.1 kg; mean gestational age: 31 wk); energy expenditure and nutrient balance were measured at 4 wk of age and anthropometric measurements were made when infants weighed 2 kg. RESULTS: The percentage of fat in newly formed tissue was significantly lower in AGA infants fed the LE formula (n = 9) than in those fed the NE formula (n = 10) (9% compared with 23%; analysis of variance, P = 0.001). Energy expenditure was higher in AGA infants fed the NE formula than in those fed the LE formula. Skinfold thickness was markedly lower in AGA infants fed the LE formula than in those fed the NE formula, resulting in a lower estimated percentage body fat (8.0 +/- 1.9% and 10.8 +/- 3.5%, respectively; P < 0.05). Three of 6 SGA infants fed the LE formula were excluded during the study because of poor weight gain. CONCLUSIONS: Body composition can easily be altered by changing the energy intakes of formula-fed VLBW infants. Energy intakes in these infants should be >419 kJ (100 kcal)*kg(-)(1)*d(-)(1).

Nitrogen metabolism in preterm infants (Doctoral Thesis)

1993-09-22T00:00:00Z

The underlying theme of this work has been to try to understand the protein metabolism in the premature human infant, and its response to perturbations including disease and diet. Since the early work of Schoenheimer et al. it has been recognized that growth takes place as a result of protein synthesis and protein breakdown [16]. With the understanding of protein metabolism itself and the response of protein metabolism to diseases and diet, an improved therapy (treatment as well as nutrition) is possible, leading to an improved growth.