Self-reported quantity and quality of sleep in children and adolescents with a chronic condition compared to healthy controls.

To assess self-reported quantity and quality of sleep in Dutch children with a chronic condition compared to healthy controls and to the recommended hours of sleep for youth. Sleep quantity and quality were analyzed in children with a chronic condition (cystic fibrosis, chronic kidney disease, congenital heart disease, (auto-)immune disease, and medically unexplained symptoms (MUS); n = 291; 15 ± 3.1 years, 63% female. A subset of 171 children with a chronic condition were matched to healthy controls using Propensity Score matching, based on age and sex, ratio 1:4. Self-reported sleep quantity and quality were assessed with established questionnaires. Children with MUS were analyzed separately to distinguish between chronic conditions with and without an identified pathophysiological cause. Generally, children with a chronic condition met the recommended amount of sleep, however 22% reported poor sleep quality. No significant differences in sleep quantity and quality were found between the diagnosis groups. Children with a chronic condition and with MUS slept significantly more than healthy controls at ages 13, 15, and 16. Both at primary and secondary school, poor sleep quality was least frequent reported in children with a chronic condition and most often reported in children with MUS.  Conclusion: Overall, children with chronic conditions, including MUS, met the recommended hours of sleep for youth, and slept more than healthy controls. However, it is important to obtain a better understanding of why a substantial subset of children with chronic conditions, mostly children with MUS, still perceived their sleep quality as poor. What is Known: • According to the Consensus statement of the American Academy of Sleep medicine, typically developing children (6 to 12 years) should sleep 9 to 12 h per night, and adolescents (13 to 18 years) should sleep 8 to 10 h per night. • Literature on the optimal quantity and quality of sleep in children with a chronic condition is very limited. What is New: Our findings are important and provide novel insights: • In general, children with a chronic condition sleep according to the recommended hours of sleep. • A substantial subset of children with chronic conditions, perceived their sleep quality as poor. Although this was reported mostly by children with medically unexplained symptoms (MUS), the found poor sleep quality was independent of specific diagnosis.

[Growth failure as a symptom of inflammatory bowel disease]. / Afbuigende lengtegroeicurve bij inflammatoire darmziekte.

BACKGROUND: Growth failure can be a unique manifestation of untreated intestinal inflammation in children with inflammatory bowel disease (IBD). It can, however, be difficult to diagnose IBD in the absence of symptoms or in the presence of aspecific gastrointestinal symptoms. A delay in diagnosis is a risk factor for lower adult height. CASE DESCRIPTION: A 15--year-old boy was referred to a paediatric endocrinologist for growth failure and delayed puberty. Additional investigations were performed and he was diagnosed with Crohn's disease. CONCLUSION: IBD needs to be considered in a child presenting with growth failure and delayed puberty. A detailed medical history of any gastrointestinal symptoms should be taken. One should perform additional investigations according to the guidelines in a patient who fulfils criteria of short stature.

Iron Deficiency in Inflammatory Bowel Disease: The Use of Zincprotoporphyrin and Red Blood Cell Distribution Width.

OBJECTIVES: Iron deficiency (ID) in children with inflammatory bowel disease (IBD) is either an absolute (depleted iron stores) or a functional deficiency (caused by chronic inflammation). Differentiating between these 2 types of ID is important because they require a different therapeutic approach. Zinc protoporphyrin (ZPP) and red blood cell distribution width (RDW) are parameters of functional ID. Studies using these parameters to differentiate are nonexistent. We aimed to evaluate the prevalence of and risk factors for absolute and functional ID in paediatric IBD patients while using ZPP and RDW. METHODS: We evaluated the iron status and medical charts of 59 paediatric IBD patients in a secondary hospital in the Netherlands. Absolute ID was defined as serum ferritin <15 µg/L in the absence of infection and/or acute inflammation (C-reactive protein <10 mg/L). Iron deficiency anaemia (IDA) was defined as absolute ID in combination with anaemia. Functional ID, in patients without absolute ID, was defined as ZPP >70 µmol/mol haem and/or an RDW >14%. Anaemia of chronic disease (ACD) was defined as functional ID in combination with anaemia. RESULTS: Absolute and functional ID were found in 19/59 (32.2%) and 32/40 (80%) patients, respectively. The prevalence of IDA and ACD was 27.1% (16/59) and 20% (8/40), respectively. Multivariate analyses showed that absolute ID and IDA were both associated with a more recent IBD-diagnosis (both P < 0.05). CONCLUSIONS: Absolute and functional ID are common in paediatric IBD patients, and this differentiation is important because of therapeutic consequences. Furthermore, absolute ID and IDA are associated with a more recent IBD-diagnosis.

Glutamine effects on brain growth in very preterm children in the first year of life.

BACKGROUND & AIMS: Glutamine supplementation in the neonatal period has been associated with increased brain structure volumes at school-age in very preterm children. The aim of this study was to clarify the emergence and specificity of differences in brain structure volumes, using growth trajectories of head circumference, weight, and length. METHODS: Sixty-five very preterm (<32 weeks gestation) children, who originally took part in a randomized controlled trial on glutamine supplementation, participated. Head circumference, weight, and length, were measured at the neonatal intensive care unit, and at routine follow-up assessments at the outpatient clinic and well baby clinics. Magnetic Resonance Imaging was used to determine brain structure volumes at school-age. Growth trajectories were investigated using multilevel modeling analyses. RESULTS: Head circumference in the first year of life was positively associated with white matter volume and grey matter volume (range r = 0.55-0.81, all p < 0.002) at school-age. Furthermore, neonatal glutamine supplementation was associated with increased head circumference growth (p = 0.008) in the first year of life, but not with increased growth in weight (p = 0.44) and length (p = 0.73). CONCLUSIONS: This study indicates a specific increase in head circumference growth in very preterm children that received neonatal glutamine supplementation, and suggests that group differences in brain structure volumes at school-age may have emerged during the first year of life.

The effect of enteral supplementation of a prebiotic mixture of non-human milk galacto-, fructo- and acidic oligosaccharides on intestinal permeability in preterm infants.

Preterm infants have an impaired gut barrier function. We aimed to determine the effects of enteral supplementation of a prebiotic mixture consisting of neutral oligosaccharides (short-chain galacto-oligosaccharides (SCGOS)/long-chain fructo-oligosaccharides (LCFOS)) and acidic oligosaccharides (AOS) on intestinal permeability of preterm infants as measured by the sugar absorption test in the first week of life. Furthermore, we determined host- and treatment-related factors associated with intestinal permeability. In a randomised controlled trial, preterm infants with a gestational age < 32 weeks and/or birth weight (BW) < 1500 g received enteral supplementation of SCGOS/LCFOS/AOS or placebo (maltodextrin) between days 3 and 30 of life. Intestinal permeability, reflected by the urinary lactulose/mannitol (L/M) ratio after oral ingestion of lactulose and mannitol, was assessed at three time points: before the start of the study (t = 0), at day 4 (t = 1) and at day 7 (t = 2) of life. Data were analysed by generalised estimating equations. In total, 113 infants were included. Baseline patient and nutritional characteristics were not different between the SCGOS/LCFOS/AOS (n 55) and the placebo groups (n 58). SCGOS/LCFOS/AOS had no effect on the L/M ratio between t = 0 and t = 2. In both the groups, the L/M ratio decreased from t = 0 to t = 2 (P < 0·001). Low BW increased the L/M ratio (P = 0·002). Exclusive breast milk feeding and mixed breast milk/formula feeding during the first week of life decreased the L/M ratio (P < 0·001 and P < 0·05, respectively). In conclusion, enteral supplementation of a prebiotic mixture does not enhance the postnatal decrease in intestinal permeability in preterm infants in the first week of life.

[Less neonatal morbidity with elective caesarean sections at term: local guideline for elective caesarean section is effective]. / Minder neonatale morbiditeit na electieve sectio caesarea vanaf een amenorroeduur van 39 weken.

OBJECTIVE: To assess the effect of a local guideline advising elective caesarean section without maternal comorbidity at a gestational age of >or= 39+0 weeks. DESIGN: Retrospective cohort study. METHODS: Children born by elective caesarean section in the period 2003-2007 at the VUmc with a gestational age >or= 37+0 weeks and without maternal comorbidity were included. Respiratory complications, length of hospital stay, admission to the neonatal intensive care unit (NICU), respiratory support and medication were recorded from charts of admitted children. These data were compared with data collected in 1994-1998 before implementation of the local guideline. RESULTS: In 2003-2007, 501 children were born from 486 elective caesarean sections. In 1994-1998, 333 children were born from 324 elective caesarean sections. In 2003-2007, mean maternal age was younger, local anaesthesia more frequent, elective caesarean section was more often performed at >or= 39+0 weeks (p < 0.001) and the birth weight was higher. In 2003-2007, fewer infants were admitted to an NICU than in 1994-1998 (6/501 versus 17/333, p < 0.001), of whom fewer infants were born with gestational age

Cytokine responses in very low birth weight infants receiving glutamine-enriched enteral nutrition.

OBJECTIVE: Very low birth weight (VLBW) infants receiving glutamine-enriched enteral nutrition may present with a lower infection rate, which may result from enhanced antimicrobial innate or Th1 cytokine responses. We investigated whether glutamine-enriched enteral nutrition in VLBW infants increased these cytokine responses following in vitro stimulation of whole blood cells. METHODS: In a double-blind, placebo-controlled, randomized controlled trial, VLBW infants (gestational age <32 weeks and/or birth weight <1500 g) received enteral glutamine supplementation (0.3 g x kg(-1) x day(-1)) or isonitrogenous placebo supplementation (alanine) between days 3 and 30 of life. Cytokine responses following in vitro whole blood cell stimulation with anti-(alpha)CD3/alphaCD28 or lipopolysaccharide were analyzed by cytometric bead array at 3 time points: before the start of the study, at day 7 of life, and at day 14 of life. RESULTS: Baseline patient and nutritional characteristics were not different between groups. At least 2 blood samples were analyzed in 25 of 52 (48%) and 38 of 50 (76%) infants in the glutamine-supplemented and control groups, respectively. Glutamine-enriched enteral nutrition was not associated with significant alterations in cytokine responses (interferon-gamma, tumor necrosis factor-alpha, interleukin [IL]-2, IL-4, IL-5, and IL-10) of peripheral blood cells upon stimulation with either anti-alphaCD3/alphaCD28 or lipopolysaccharide. CONCLUSIONS: We hypothesize that glutamine-enriched enteral nutrition decreases the infection rate in VLBW infants by influencing the mucosal and not the systemic immune system.

Cytokine profiles in 1-yr-old very low-birth-weight infants after enteral glutamine supplementation in the neonatal period.

In a previous study, we found that glutamine-enriched enteral nutrition in 102 very low-birth-weight (VLBW) infants decreased both the incidence of serious neonatal infections and atopic dermatitis during the first year of life. The aims of this follow-up study were to determine whether these beneficial effects are attended by changes in Th(1) and Th(2) cytokine profiles at age 1 yr. Furthermore, we studied changes in cytokine profiles during the first year of life in these VLBW infants. In total, 89 infants were eligible for the follow-up study (12 died, 1 exclusion due to a chromosomal abnormality). Th(1) (IFN-gamma, TNF- alpha and IL-2) and Th(2) cytokine (IL-10, IL-5, and IL-4) profiles following in vitro whole blood stimulation were measured at 1 yr. Cytokine profiles were measured in 59/89 (66%) infants. Glutamine-enriched enteral nutrition in neonatal period did not influence cytokine profiles at 1 yr. Cytokine profiles were not different in infants with and without allergic or infectious diseases. The beneficial effect of glutamine-enriched enteral nutrition on the incidence of serious neonatal infections and atopic dermatitis during the first year of life is not related to changes in the Th(1) and Th(2) cytokine profiles. Both Th(1) and Th(2) cytokine profiles increased during the first year of life in this cohort of VLBW infants.

Plasma ADMA concentrations at birth and mechanical ventilation in preterm infants: a prospective pilot study.

RATIONALE: Nitric oxide (NO) produced in the lung is an important mediator of normal lung development, vascular smooth muscle relaxation, and ventilation perfusion matching. NO is synthesized from arginine by the action of NO-synthase (NOS). Asymmetric dimethylarginine (ADMA), an endogenous derivate of arginine, inhibits NOS and is thereby a determinant of NO synthesis. We compared ADMA and arginine levels in preterm infants requiring mechanical ventilation with preterm infants who did not require mechanical ventilation and determined the relation between ADMA and the length of mechanical ventilation in these infants. METHODS: Thirty preterm infants, mean (SD) gestational age 29.3 (1.7) weeks and birth weight 1,340 (350) gram, of the Neonatal Intensive Care Unit of the VU University Medical Center were included. ADMA and arginine were measured in umbilical cord blood and the length of mechanical ventilation (days) was registered. RESULTS: Gestational age and birth weight were significantly smaller in infants requiring mechanical ventilation, but were not significantly correlated with plasma ADMA concentration after birth. Plasma ADMA concentrations were significantly higher in infants who required mechanical ventilation than in infants who did not require mechanical ventilation (1.53 +/- 0.23 and 1.37 +/- 0.14 micromol/L, respectively; P = 0.036). ADMA concentration was significantly related to length of mechanical ventilation (B = 3.4; 95% CI: 1.1-5.6; P = 0.006), also after adjustment for gestational age (B = 2.3; 95% CI: 0.4-4.2; P = 0.024). CONCLUSIONS: Preterm infants who require mechanical ventilation have increased ADMA levels compared to non-ventilated preterm infants. ADMA levels at birth are related to the length of mechanical ventilation. An increased ADMA concentration could reduce NO synthesis, which could lead to insufficient gas exchange and, consequently, a longer period of mechanical ventilation.

Design of a randomised controlled trial on immune effects of acidic and neutral oligosaccharides in the nutrition of preterm infants: carrot study.

BACKGROUND: Prevention of serious infections in preterm infants is a challenge, since prematurity and low birth weight often requires many interventions and high utility of devices. Furthermore, the possibility to administer enteral nutrition is limited due to immaturity of the gastrointestinal tract in the presence of a developing immune system. In combination with delayed intestinal bacterial colonisation compared with term infants, this may increase the risk for serious infections. Acidic and neutral oligosaccharides play an important role in the development of the immune system, intestinal bacterial colonisation and functional integrity of the gut. This trial aims to determine the effect of enteral supplementation of acidic and neutral oligosaccharides on infectious morbidity (primary outcome), immune response to immunizations, feeding tolerance and short-term and long-term outcome in preterm infants. In addition, an attempt is made to elucidate the role of acidic and neutral oligosaccharides in postnatal modulation of the immune response and postnatal adaptation of the gut. METHODS/DESIGN: In a double-blind placebo controlled randomised trial, 120 preterm infants (gestational age <32 weeks and/or birth weight <1500 gram) are randomly allocated to receive enteral acidic and neutral oligosaccharides supplementation (20%/80%) or placebo supplementation (maltodextrin) between day 3 and 30 of life. Primary outcome is infectious morbidity (defined as the incidence of serious infections). The role of acidic and neutral oligosaccharides in modulation of the immune response is investigated by determining the immune response to DTaP-IPV-Hib(-HBV)+PCV7 immunizations, plasma cytokine concentrations, faecal Calprotectin and IL-8. The effect of enteral acidic and neutral oligosaccharides supplementation on postnatal adaptation of the gut is investigated by measuring feeding tolerance, intestinal permeability, intestinal viscosity, and determining intestinal microflora. Furthermore, short-term and long-term outcome are evaluated. DISCUSSION: Especially preterm infants, who are at increased risk for serious infections, may benefit from supplementation of prebiotics. Most studies with prebiotics only focus on the colonisation of the intestinal microflora. However, the pathways how prebiotics may influence the immune system are not yet fully understood. Studying the immune modulatory effects is complex because of the multicausal risk of infections in preterm infants. The combination of neutral oligosaccharides with acidic oligosaccharides may have an increased beneficial effect on the immune system. Increased insight in the effects of prebiotics on the developing immune system may help to decrease the (infectious) morbidity and mortality in preterm infants. TRIAL REGISTRATION: Current Controlled Trials ISRCTN16211826.

Nutritional factors influencing infections in preterm infants.

In contrast with clinical studies in term infants or older children, it is very difficult to investigate possible immunoregulatory effects of a novel infant formula composition in preterm infants. This is mainly because of the multicausal origin of infections in this high-risk population that is usually admitted to the neonatal intensive care unit. Possible effects of nutrition composition on onset and incidence of nosocomial infections in these very small infants have to be compared with infections that may have originated in utero. The development of the gastrointestinal tract may be inhibited after severe intrauterine growth retardation, leading to functional impairment of the gut shortly after birth. This may be related to the onset of necrotizing enterocolitis of the newborn. However, this disease in very small preterm infants is possibly also related to the initiation of oral feeding and/or the amount of feeding. Specific infection risks of neonatal intensive care as a result of invasive techniques such as artificial ventilation or total parenteral nutrition using indwelling umbilical and/or Silastic lines and so-called "all-in-one" mixtures may influence the incidence of infections. Widespread use of intravenous antibiotics in the neonatal intensive care unit may create an even larger infection risk. Investigation of possible immunomodulatory effects of factors such as prebiotics and probiotics added to the nutrition of preterm infants should always be considered along with other nutritional factors known to influence the immature immune system.

Neurodevelopmental outcomes of very low-birth-weight infants after enteral glutamine supplementation in the neonatal period.

AIM: To determine the effect of neonatal glutamine-enriched enteral nutrition in very low birth weight (VLBW) infants on neurodevelopmental outcome at 2 years of age. METHODS: Eighty-eight out of one hundred two infants participating in the initial study were eligible for the follow-up study (13 died, one exclusion due to a chromosomal abnormality). Neurodevelopmental outcome (neurologic status, vision, hearing and Mental Developmental Index (MDI) and Psychomotor Developmental Index (PDI) of the Bayley Scales of Infant Development II) was evaluated at the corrected age of 2 years. To adjust for potential confounders, data were analyzed by multiple linear or logistic regression (for continuous and dichotomous variables, respectively) RESULTS: Seventy-two out of eighty-eight (82%) infants participated in the follow-up study: 40 and 32 infants in glutamine-supplemented and control groups, respectively. The incidence of neither an MDI nor a PDI

Glutamine-enriched enteral nutrition in very low-birth-weight infants: effect on the incidence of allergic and infectious diseases in the first year of life.

OBJECTIVE: To determine the effect of glutamine-enriched enteral nutrition in very low-birth-weight infants on the incidence of allergic and infectious diseases during the first year of life. DESIGN: Follow-up study. SETTING: Tertiary care hospital. PARTICIPANTS: All surviving infants who participated in a trial of glutamine-enriched enteral nutrition in very low-birth-weight infants. INTERVENTION: Enteral glutamine supplementation (l-glutamine, 0.3 g/kg per day) from 3 through 30 days of life. MAIN OUTCOME MEASURES: The incidence of allergic and infectious diseases during the first year of life, as assessed by means of validated questionnaires. RESULTS: Seventy-seven of 90 infants (86%) participated in the follow-up study. Baseline patient, maternal, and environmental characteristics did not differ between the glutamine-supplemented (n = 37) and control (n = 40) groups, except for the incidence of serious neonatal infections and child care attendance. After adjustment for confounding factors, the risk for atopic dermatitis was lower in the glutamine-supplemented group (odds ratio [OR], 0.13; 95% confidence interval [CI], 0.02-0.97). However, the incidence of bronchial hyperreactivity (OR, 0.34; 95% CI, 0.10-1.21) and infections of the upper respiratory (OR, 0.99; 95% CI, 0.35-2.79), lower respiratory (OR, 0.39; 95% CI, 0.13-1.24), and gastrointestinal (OR 1.25, 95% CI 0.23-6.86) tracts was not different between the treatment groups. CONCLUSIONS: Glutamine-enriched enteral nutrition in very low-birth-weight infants decreased the incidence of atopic dermatitis during the first year of life but had no effect on the incidence of bronchial hyperreactivity and infectious diseases during the first year of life.

The effect of glutamine-enriched enteral nutrition on intestinal microflora in very low birth weight infants: a randomized controlled trial.

BACKGROUND & AIMS: In a previous study, we have found that glutamine supplementation decreased the infection rate in very low birth weight (VLBW) infants. In this study, we investigated whether this beneficial effect originated from increased number of bifidobacteria and lactobacilli in the intestinal microflora of these infants. METHODS: In a randomized controlled trial, VLBW infants (gestational age <32 weeks and/or birth weight <1500g) received enteral glutamine supplementation (0.3g/kg/day) or isonitrogenous placebo supplementation between d3 and d30 of life. Faecal microflora was determined by fluorescent in situ hybridization <48h, at d7, d14 and d30 of life. RESULTS: In 43/52 (glutamine group) and 43/50 (control group) infants, > or = 2 samples were analyzed. Baseline characteristics were not different between groups. The prevalence of bifidobacteria, lactobacilli, Escheria coIi, streptococci and clostridia was not different between groups (p>0.05). In both groups, colonization with bifidobacteria was delayed, whereas potentially pathogenic bacteria such as E. coli, appeared rapidly after birth. Antibiotic treatment decreased the prevalence of all faecal bacteria (p<0.05). CONCLUSIONS: Decreased infectious morbidity in VLBW infants that received glutamine supplementation was not associated with alterations in the prevalence of bifidobacteria, lactobacilli, E. coIi, streptococci and clostridia. In general, colonization with health-promoting bacteria was delayed, whereas potentially pathogenic bacteria appeared rapidly after birth. Antibiotic treatment delayed the bacterial colonization.

The effect of glutamine-enriched enteral nutrition on intestinal permeability in very-low-birth-weight infants: a randomized controlled trial.

BACKGROUND: Very-low-birth-weight (VLBW) infants are susceptible to glutamine depletion. Glutamine depletion has negative effects on intestinal integrity. The lower infection rate in VLBW infants receiving glutamine-enriched enteral nutrition may originate from improved intestinal integrity, as reflected by decreased intestinal permeability. The aim of our study was to investigate whether glutamine-enriched enteral nutrition in VLBW infants enhances the normal decrease in intestinal permeability, as measured by the sugar absorption test (SAT). METHODS: In a double-blind, randomized, placebo-controlled trial, VLBW infants (gestational age <32 weeks or birth weight <1,500 g) received enteral glutamine supplementation (0.3 g/kg/d) or an isonitrogenous placebo supplementation (alanine) between days 3 and 30 of life. Intestinal permeability, determined from the urinary lactulose/mannitol (L/M) ratio after an oral dose of lactulose and mannitol, was assessed at 4 time points: before the start of the study, and at days 7, 14, and 30 of life. RESULTS: At least 2 SATs were performed in 45/52 (86%) and 45/50 (90%) infants in the glutamine-supplemented and control groups, respectively. Baseline patient and nutrition characteristics were not different between the groups. There was no effect of glutamine-enriched enteral nutrition on the decrease of the L/M ratio between the start and end of the study (p = .78). In both treatment groups, median urinary lactulose concentrations decreased (p < .001), whereas median urinary mannitol concentrations increased (p = .003). CONCLUSIONS: Glutamine-enriched enteral nutrition does not enhance the postnatal decrease in intestinal permeability in VLBW infants. Any beneficial effect of glutamine may involve other aspects of intestinal integrity; for example, modulation of the intestinal inflammatory response.

The intestinal bacterial colonisation in preterm infants: a review of the literature.

The aim of this study is to review the normal development of the intestinal microflora of preterm infants and the factors influencing its development. Preterm infants have an increased intestinal permeability, which may lead to bacterial translocation to systemic organs and tissues. In combination with immaturity of the immune system the risk to systemic infections might be increased. Especially potential pathogenic bacteria are able to translocate. The intestinal microflora of breast-fed term infants, dominated by bifidobacteria and lactobacilli, is thought to suppress the growth of potentially pathogenic bacteria. Many attemps have been made to stimulate the presence of bifidobacteria and lactobacilli with changes in the diet and ingredients-like prebiotics and probiotics. After selection, six studies were included reviewing the intestinal bacterial colonisation of preterm infants. In general, these studies show that the intestinal bacterial colonisation with beneficial bacteria is delayed in preterm infants. The number of potentially pathogenic bacteria is high. Antibiotics influence the intestinal colonisation. Many preterm infants receive prophylactic antibiotics at birth. As antibiotics delay the normal intestinal colonisation, caution should be given to the treatment with broadspectrum antibiotics in preterm infants at birth and every attempt has to be made to restrict the period of treatment.

A randomized controlled trial of enteral glutamine supplementation in very low birth weight infants: plasma amino acid concentrations.

OBJECTIVE: Glutamine depletion has negative effects on the functional integrity of the gut and leads to immunosuppression. Very low birth weight (VLBW) infants are susceptible to glutamine depletion, as enteral nutrition is limited in the first weeks of life. Enteral glutamine supplementation may have a positive effect on feeding tolerance, infectious morbidity and short-term outcome. The aim of the study was to determine the effect of enteral glutamine supplementation on plasma amino acid concentrations, reflecting one aspect of safety of enteral glutamine supplementation in VLBW infants. METHODS: In a double-blind placebo-controlled randomized controlled trial, VLBW infants (gestational age <32 weeks or birth weight <1500 g) received enteral glutamine supplementation (0.3 g/kg per day) or isonitrogenous placebo supplementation (alanine) between day 3 and day 30 of life. Supplementation was added to breast milk or to preterm formula. Plasma amino acid concentrations were measured at four time points: before the start of the study and at days 7, 14 and 30 of life. RESULTS: Baseline patient and nutritional characteristics were not different in glutamine (n = 52) and control (n = 50) groups. Plasma concentrations of most essential and non-essential amino acids increased throughout the study period. There was no effect of enteral glutamine supplementation. In particular, the increase of plasma glutamine and glutamate concentrations was not different between the treatment groups (P = 0.49 and P = 0.34 respectively, day 30). CONCLUSIONS: Enteral glutamine supplementation in VLBW infants does not alter plasma concentrations of glutamine, glutamate or other amino acids. Enteral supplementation in a dose of 0.3 g/kg per day seems safe in VLBW infants.

Glutamine-enriched enteral nutrition in very-low-birth-weight infants and effects on feeding tolerance and infectious morbidity: a randomized controlled trial.

BACKGROUND: Glutamine depletion has negative effects on the functional integrity of the gut and leads to immunosuppression. Very-low-birth-weight (VLBW) infants are susceptible to glutamine depletion because nutrition is limited in the first weeks of life. OBJECTIVE: The objective was to determine the effect of glutamine-enriched enteral nutrition on feeding tolerance, infectious morbidity, and short-term outcome in VLBW infants. DESIGN: In a double-blind randomized controlled trial, VLBW infants (gestational age <32 wk or birth weight <1500 g) were allocated to receive enteral glutamine supplementation (0.3 g . kg(-1) . d(-1)) or isonitrogenous control supplementation (alanine) between days 3 and 30 of life. The supplementations were added to breast milk or to preterm formula. The primary endpoint for the study was time to full enteral feeding. Secondary endpoints were other variables of feeding tolerance, infectious morbidity, and short-term outcome. RESULTS: Baseline patient and nutritional characteristics were not significantly different in the glutamine-supplemented (n = 52) and the control (n = 50) groups. The median time to full enteral feeding was 13 d (range: 7-31 d) in the glutamine-supplemented group and 13 d (range: 6-35 d) in the control group (hazard ratio: 1.19; 95% CI: 0.79, 1.79; P = 0.40). In the glutamine-supplemented group, 26 of 52 infants (50%) had >/=1 serious infection compared with 38 of 50 (76%) in the control group (odds ratio: 0.32; 95% CI: 0.14, 0.74; P = 0.008). Other variables of feeding tolerance and short-term outcome were not significantly different between groups. CONCLUSIONS: Glutamine-enriched enteral nutrition did not improve feeding tolerance or short-term outcome in VLBW infants. However, infectious morbidity was significantly lowered in infants who received glutamine-enriched enteral nutrition.

Glutamine-enriched enteral nutrition in very low birth weight infants. Design of a double-blind randomised controlled trial [ISRCTN73254583].

BACKGROUND: Enteral feeding of very low birth weight (VLBW) infants is a challenge, since metabolic demands are high and administration of enteral nutrition is limited by immaturity of the gastrointestinal tract. The amino acid glutamine plays an important role in maintaining functional integrity of the gut. In addition, glutamine is utilised at a high rate by cells of the immune system. In critically ill patients, glutamine is considered a conditionally essential amino acid. VLBW infants may be especially susceptible to glutamine depletion as nutritional supply of glutamine is limited in the first weeks after birth. Glutamine depletion has negative effects on functional integrity of the gut and leads to immunosuppression. This double-blind randomised controlled trial is designed to investigate the effect of glutamine-enriched enteral nutrition on feeding tolerance, infectious morbidity and short-term outcome in VLBW infants. Furthermore, an attempt is made to elucidate the role of glutamine in postnatal adaptation of the gut and modulation of the immune response. METHODS: VLBW infants (gestational age <32 weeks and/or birth weight <1500 g) are randomly allocated to receive enteral glutamine supplementation (0.3 g/kg/day) or isonitrogenous placebo supplementation between day 3 and 30 of life. Primary outcome is time to full enteral feeding (defined as a feeding volume >/= 120 mL/kg/day). Furthermore, incidence of serious infections and short-term outcome are evaluated. The effect of glutamine on postnatal adaptation of the gut is investigated by measuring intestinal permeability and determining faecal microflora. The role of glutamine in modulation of the immune response is investigated by determining plasma Th1/Th2 cytokine concentrations following in vitro whole blood stimulation.