Effect of neutral and acidic oligosaccharides on fecal IL-8 and fecal calprotectin in preterm infants.

The gastrointestinal inflammatory response may play a role in the susceptibility of preterm infants for infections. We previously reported a trend toward lower endogenous infection morbidity after enteral supplementation of neutral and acidic oligosaccharides (SC GOS/LC FOS/AOS). We hypothesize that enteral supplementation of prebiotics may decrease infectious morbidity by reducing intestinal inflammation. Therefore, we aimed to determine the effect of enteral supplementation of prebiotics on intestinal inflammation, as measured by fecal IL-8 (f-IL-8) and calprotectin (f-calprotectin), in preterm infants. In a randomized controlled trial, infants with a GA <32 wk and/or birth weight <1,500 g received enteral supplementation of prebiotics or placebo (maltodextrin) between d 3 and 30 of life. F-IL-8 and f-calprotectin was assessed at baseline, d 7, 14, and 30 of life. In total, 113 infants were included. Baseline patient and nutritional characteristics were not different in the SC GOS/LC FOS/AOS (n = 55) and the placebo group (n = 58). Enteral supplementation of prebiotics had no effect on f-IL-8 and f-calprotectin. F-IL-8 and f-calprotectin were strongly correlated at all time points (p < 0.001). In conclusion, enteral supplementation of prebiotics (SC GOS/LC FOS/AOS) does not affect f-IL-8 and f-calprotectin levels in preterm infants.

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.

Glutamine-enriched enteral nutrition in very low birthweight infants and allergic and infectious diseases at 6 years of age.

In a previous randomised controlled trial, we found that glutamine-enriched enteral nutrition in 102 very low birthweight (VLBW) infants decreased both the incidence of serious infections in the neonatal period and the risk of atopic dermatitis during the first year of life. We hypothesised that glutamine-enriched enteral nutrition in VLBW infants in the neonatal period influences the risk of allergic and infectious disease at 6 years of age. Eighty-eight of the 102 infants were eligible for the follow-up study (13 died, 1 chromosomal abnormality). Doctor-diagnosed allergic and infectious diseases were assessed by means of validated questionnaires. The association between glutamine-enriched enteral nutrition in the neonatal period and allergic and infectious diseases at 6 years of age was based on univariable and multivariable logistic regression analyses. Seventy-six of the 89 (85%) infants participated, 38 in the original glutamine-supplemented group and 38 in the control group. After adjustment, we found a decreased risk of atopic dermatitis in the glutamine-supplemented group: adjusted odds ratio (aOR) 0.23 [95% CI 0.06, 0.95]. No association between glutamine supplementation and hay fever, recurrent wheeze and asthma was found. A decreased risk of gastrointestinal tract infections was found in the glutamine-supplemented group (aOR) 0.10 [95% CI 0.01, 0.93], but there was no association with upper respiratory, lower respiratory or urinary tract infections. We concluded that glutamine-enriched enteral nutrition in the neonatal period in VLBW infants decreased the risk of atopic dermatitis and gastrointestinal tract infections at 6 years of age.

Which aspects of safety culture predict incident reporting behavior in neonatal intensive care units? A multilevel analysis.

OBJECTIVES: Safety culture assessments are increasingly used to evaluate patient-safety programs. However, it is not clear which aspects of safety culture are most relevant in understanding incident reporting behavior, and ultimately improving patient safety. The objective of this study was to examine which aspects of safety culture predict incident reporting behavior in the neonatal intensive care unit (NICU), before and after implementation of a voluntary, nonpunitive incident reporting system. DESIGN: Survey study based on a translated, validated version of the Agency for Healthcare Research and Quality Hospital Survey on Patient Safety Culture. This survey incorporates two outcome measures, 11 dimensions of patient-safety culture as well as demographic data. SETTING: Eight tertiary care NICUs and one surgical pediatric ICU. SUBJECTS: All unit personnel. INTERVENTION: Implementation of a specialty-based, voluntary, nonpunitive incident reporting system. MEASUREMENTS AND MAIN RESULTS: The survey was conducted before (t = 0) and after (t = 1 yr) the intervention. PRIMARY OUTCOME: number of self-reported incidents in the past 12 months. Overall response rate was 80% (n = 700) at t = 0 and 76% (n = 670) at t = 1 yr. Based on a multivariate multilevel regression prediction model, the number of self-reported incidents increased after the intervention and was positively associated with a nonpunitive response to error and negatively associated with overall perceptions of safety and hospital management support for patient safety. CONCLUSIONS: A nonpunitive approach to error, hospital management support for patient safety, and overall perceptions of safety predict incident reporting behavior in the NICU. The relation between these aspects of safety culture and patient outcome requires further scrutiny and therefore remains an important issue to address in future research.

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.

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.

Mannose-binding lectin in term newborns and their mothers: genotypic and phenotypic relationship.

Functional mannose-binding lectin (f-MBL) plays an important role in the innate neonatal immune system. We studied the origin of f-MBL in umbilical cord blood (UCB) by measuring maternal MBL (n=47), collected before elective cesarean section, and neonatal MBL (n=43) in arterial umbilical cord blood. In a subgroup, arterial and venous UCB MBL levels were measured. In addition, MBL expression was correlated with genetic mutations. The f-MBL levels in term infants were lower than in their mothers (0.70 microg/ml vs 1.11 microg/ml, p<0.01) and maternal and neonatal MBL levels were only weakly correlated (R=0.32, p<0.001), which suggests a fetal origin of f-MBL. Arterial and venous UCB median MBL levels did not differ (0.98 microg/ml vs. 1.40 microg/ml, p=0.20). No homozygous mutations were found. MBL was lower in mothers and infants with a (compound) heterozygous mutation than in those with a wild type. One new (HYPB) and two rare haplotypes (HXPA, LYPD) were reported in our population. Levels of MBL differed depending on the genotype of the mother or the infant. Because the role of MBL in host defense is still unclear, both f-MBL and haplotype should be measured to determine the clinical implications of MBL deficiency in infants.

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.

Predicting pulmonary hypoplasia with 2- or 3-dimensional ultrasonography in complicated pregnancies.

OBJECTIVE: The aim of this study was to compare 3-dimensional (3D) lung volume measurements with 2-dimensional (2D) biometric parameters in predicting pulmonary hypoplasia in complicated pregnancies. STUDY DESIGN: In this prospective study, 1-4 scans of the fetal lungs were obtained in 33 pregnancies complicated by various disorders or complications with regard to pulmonary hypoplasia. The 3D lung volumes vs gestational age or estimated fetal weight, the thoracic circumference vs gestational age or femur length, the thoracic/abdominal circumference ratio, and the thoracic/heart area ratio were measured. RESULTS: Of the 33 infants, 16 (48.5%) were diagnosed with pulmonary hypoplasia on postmortem examination or the clinical and radiological presentation. Three dimensional lung volume measurements had a better diagnostic accuracy for predicting pulmonary hypoplasia (sensitivity, 94%; specificity, 82%; positive predictive value [PPV], 83%; negative predictive value [NPV], 93%), compared with the best 2D biometric measurement thoracic/heart area ratio (sensitivity, 94%; specificity, 47%; PPV, 63%; NPV, 89%). CONCLUSION: 3D lung volume measurements seem to be useful in predicting pulmonary hypoplasia prenatally.

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.

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 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.

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.

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.

Seizure detection in the neonatal EEG with synchronization likelihood.

OBJECTIVE: To investigate whether epileptic seizure activity can be distinguished from non-epileptic background activity in the neonatal electroenceplalogram (EEG), using synchronization likelihood as a measure of synchronization between EEG channels. METHODS: Forty-two 21s EEG epochs and two complete EEGs from 21 different neonatal patients in a 12-channel bipolar recording were studied (AD-conversion 16bit; sample frequency 200Hz; filter setting 0.5-30Hz). For EEG of each patient, we selected one epoch with epileptic discharges and one without. Synchronization was calculated in all epochs. In two complete EEGs, synchronization was calculated and correlated with a visual scoring of the EEG. RESULTS: Synchronization likelihood was higher in all the epochs with epileptic seizures as compared to the epochs without epileptic activity (P<0.01). When synchronization likelihood exceeded 0.11, the sensitivity for the presence of epileptic activity was 0.85 (95% confidence limits [CL(95)]=0.69-1) and the specificity was 0.75 (CL(95)=0.56-0.94).Analysis of EEG score and synchronization likelihood of two complete EEGs revealed a high correlation between the occurrence of epileptic seizures and elevated synchronization likelihood (Spearman r=0.707, P<0.001). CONCLUSIONS: The results of this study demonstrate that synchronization likelihood is a potential tool in the automatic monitoring of high-risk infants for epileptic activity on neonatal wards.

Neuromotor function and school performance in 7-year-old children born as high-risk preterm infants.

Neuromotor behavior was studied in 63 children at a mean age of 7 years. They were born at a gestational age less than 32 weeks and/or birthweight under 1500 g and were categorized according to their medical history in conformance with the Neonatal Medical Index (from category I to V, from few to serious complications). We included only children considered at high risk as categorized in III to V. The neuromotor behavior study focuses on different subcategories, such as hand function, quality of walking, posture, passive muscle tone, coordination, and diadochokinesia. Hand preference and/or lateralization, the presence of associated movements, and/or asymmetry were noted, as was school performance. Then gender, gestational age, birthweight, and dysmaturity were investigated as confounding factors. The outcome at 7 years was correlated with the Neonatal Medical Index and the neonatal brain ultrasonography classification. None of the children scored 100% on the combined subcategories. Nineteen children (30%) had an overall score between 75 and 99%. Significant relationships between all different subcategories were found. Lack of hand preference, poor lateralization, and male gender were related to poor overall outcome. Poor motor control was correlated to special schooling and education below age level. The Neonatal Medical Index proved to have a significant influence on total outcome and the subcategories at the age of 7 years, with the worst outcome in children formerly classified in category V. Neuromotor behavior at 7 years of age was not related to birthweight, gestational age, dysmaturity, and neonatal brain ultrasonography classification only.

Muscle power development during the first year of life predicts neuromotor behaviour at 7 years in preterm born high-risk infants.

The aim of the study was to find if neurological function during the first year of life could predict neuromotor behaviour at 7 years of age in children born preterm with a high risk. A follow-up study of neuromotor behaviour in 52 children at a mean age of 3, 6, 12 months (corrected age) and 7 years was performed. All children were born with a gestational age less than 32 weeks and/or a birthweight under 1500 g and the infants were categorised according to their medical history in the three highest categories of the 'Neonatal Medical Index' (NMI, from category I to V, from few to serious complications). In addition, neonatal cerebral ultrasound abnormalities were used to divide the infants further into the different NMI categories. At 3 and 6 months, the relationship between active and passive muscle power was measured in shoulders, trunk and legs and (a)symmetry between right and left was noted. The results at 3 and 6 months were ranged from 1 for optimal to 5 for poor muscle power regulation. At 12 months of age, a neurological examination was done with special emphasis on the assessment of postural control, spontaneous motility, hand function and elicited infantile reactions with special attention to (a)symmetry. Outcome at 12 months was expressed as percentage of the optimal score on each subcategory. At 7 years, the motor behaviour study based on Touwen's examination for minor neurological dysfunction was performed. This investigation focuses on different functions, such as hand function, quality of walking, posture, passive muscle tone, coordination and diadochokinesis. The outcome was expressed as percentage of the optimal score on the combined subcategories. The best prediction of neuromotor behaviour at 7 years was assessed with stepwise linear multiple regression, using as potential predictors perinatal factors and outcome of motor behaviour at the corrected age of 3, 6 and 12 months. At 7 years none of the children scored 100% on the combined subcategories, 15 children (29%) scored between 75% and 99%, whereas 15 children scored less than 50%. Neuromotor behaviour at 7 years could be predicted by the NMI categorisation and gender with a sensitivity of 92% (specificity 47%; positive and negative predictive value 81% and 70%). No direct relation was found between neuromotor behaviour and cerebral ultrasound classification only, days on the ventilator and/or continuous positive airway pressure, birthweight, gestational age and dysmaturity. The best predictor of neuromotor behaviour at 7 years was the combination of outcome of muscle power in shoulders and legs at 3 months and postural control at 12 months, taking into account the gender of the child (sensitivity 95%; specificity 40%; positive predictive value 80%; negative predictive value 75%).

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.

The bilirubin albumin ratio in the management of hyperbilirubinemia in preterm infants to improve neurodevelopmental outcome: a randomized controlled trial--BARTrial.

BACKGROUND AND OBJECTIVE: High bilirubin/albumin (B/A) ratios increase the risk of bilirubin neurotoxicity. The B/A ratio may be a valuable measure, in addition to the total serum bilirubin (TSB), in the management of hyperbilirubinemia. We aimed to assess whether the additional use of B/A ratios in the management of hyperbilirubinemia in preterm infants improved neurodevelopmental outcome. METHODS: In a prospective, randomized controlled trial, 615 preterm infants of 32 weeks' gestation or less were randomly assigned to treatment based on either B/A ratio and TSB thresholds (consensus-based), whichever threshold was crossed first, or on the TSB thresholds only. The primary outcome was neurodevelopment at 18 to 24 months' corrected age as assessed with the Bayley Scales of Infant Development III by investigators unaware of treatment allocation. Secondary outcomes included complications of preterm birth and death. RESULTS: Composite motor (100 ± 13 vs. 101 ± 12) and cognitive (101 ± 12 vs. 101 ± 11) scores did not differ between the B/A ratio and TSB groups. Demographic characteristics, maximal TSB levels, B/A ratios, and other secondary outcomes were similar. The rates of death and/or severe neurodevelopmental impairment for the B/A ratio versus TSB groups were 15.4% versus 15.5% (P = 1.0) and 2.8% versus 1.4% (P = 0.62) for birth weights ≤ 1000 g and 1.8% versus 5.8% (P = 0.03) and 4.1% versus 2.0% (P = 0.26) for birth weights of >1000 g. CONCLUSIONS: The additional use of B/A ratio in the management of hyperbilirubinemia in preterm infants did not improve their neurodevelopmental outcome. TRIAL REGISTRATION: Controlled-Trials.com ISRCTN74465643.

Diagnostic procedures and treatment of childhood obesity by pediatricians: 'The Dutch approach'.

Child Public Health professionals in the Netherlands refer obese children to a pediatrician to check for underlying causes and comorbidity. What happens to these children in terms of diagnostics and treatment when they visit a pediatrician? To get an overview of the diagnostic procedures and treatment methods a questionnaire was developed and sent to all 583 pediatricians in the Netherlands. Data was obtained of 290 pediatricians from 85% of the general hospitals and all (8) academic hospitals. To define childhood obesity Dutch pediatricians most often use the adult Body Mass Index, only 34% use the sex and age specific IOTF-BMI-criteria. 11% of the (non-obese) overweight children visiting a pediatrician have already comorbidities. All pediatricians perform at least weight and height measurements. Waist circumference is measured by only 42%, ninety-five percent measure blood pressure. To treat obese children without comorbidity thirty different intervention programs were reported. A large variation in diagnostics and interventions of childhood obesity exist. Guidelines in pediatric obesity for diagnostics and treatment are urgently needed.