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.

Cultural bias in the AAP's 2012 Technical Report and Policy Statement on male circumcision.

The American Academy of Pediatrics recently released its new Technical Report and Policy Statement on male circumcision, concluding that current evidence indicates that the health benefits of newborn male circumcision outweigh the risks. The technical report is based on the scrutiny of a large number of complex scientific articles. Therefore, while striving for objectivity, the conclusions drawn by the 8 task force members reflect what these individual physicians perceived as trustworthy evidence. Seen from the outside, cultural bias reflecting the normality of nontherapeutic male circumcision in the United States seems obvious, and the report's conclusions are different from those reached by physicians in other parts of the Western world, including Europe, Canada, and Australia. In this commentary, a different view is presented by non-US-based physicians and representatives of general medical associations and societies for pediatrics, pediatric surgery, and pediatric urology in Northern Europe. To these authors, only 1 of the arguments put forward by the American Academy of Pediatrics has some theoretical relevance in relation to infant male circumcision; namely, the possible protection against urinary tract infections in infant boys, which can easily be treated with antibiotics without tissue loss. The other claimed health benefits, including protection against HIV/AIDS, genital herpes, genital warts, and penile cancer, are questionable, weak, and likely to have little public health relevance in a Western context, and they do not represent compelling reasons for surgery before boys are old enough to decide for themselves.

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.

Incidents associated with mechanical ventilation and intravascular catheters in neonatal intensive care: exploration of the causes, severity and methods for prevention.

OBJECTIVES: To systematically investigate the causes and severity of incidents with mechanical ventilation and intravascular catheters in neonatal intensive care units (NICUs) in the Netherlands, in order to develop effective strategies to prevent such incidents in the future. DESIGN: Prospective multicentre survey. METHODS: Inclusion criteria were: incidents with mechanical ventilation and intravascular catheters reported to a voluntary, non-punitive, incident-reporting system which had been systematically analysed using the Prevention Recovery Information System for Monitoring and Analysis (PRISMA)-Medical method. The type, severity and causes of incidents reported from 1 July 2005 to 31 March 2007 are described. Local interventions performed as a result of systematic analysis of incidents are also described. RESULTS: 533 of 1306 (41%) reported incidents with mechanical ventilation and intravascular catheters (n=339/856 and n=194/450, respectively) had been PRISMA analysed and were included in the study. Four incidents resulted in severe harm, 18 in moderate harm and 222 in minor harm. Tube-related incidents accounted for the greatest proportion of harm. 1233 root causes were identified, with most being classified as human error (55%). Of the remaining failures, 20% were organisational, 16% technical, 6% patient-related and 4% unclassifiable. The majority of failures were rule-based errors. CONCLUSION: Incidents with mechanical ventilation and intravascular catheters occur regularly in NICUs, and frequently harm patients. Multicentre, systematic analysis increases our knowledge of these events. Continuous training and education of all NICU personnel is required, together with preventive strategies aimed at the whole system--including the technical and organisational environment--rather than at human failure alone.

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.

Neutral and acidic oligosaccharides in preterm infants: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Serious infectious morbidity is high in preterm infants. Enteral supplementation of prebiotics may reduce the incidence of serious infections, especially infections related to the gastrointestinal tract. OBJECTIVE: The objective was to determine the effect of enteral supplementation of a prebiotic mixture consisting of neutral oligosaccharides ((SC)GOS/(LC)FOS) and acidic oligosaccharides (AOS) on serious infectious morbidity in preterm infants. DESIGN: In a randomized controlled trial, preterm infants (gestational age <32 wk and/or birth weight <1500 g) received enteral supplementation of 80% (SC)GOS/(LC)FOS and 20% AOS (1.5 g . kg(-1) . d(-1)) or placebo (maltodextrin) between days 3 and 30 of life. Serious infectious morbidity was defined as a culture positive for sepsis, meningitis, pyelonephritis, or pneumonia. The analysis was performed by intention-to-treat and per-protocol, defined as > or =50% supplementation dose during the study period. RESULTS: In total, 113 preterm infants were included. Baseline and nutritional characteristics were not different between groups. In the intention-to-treat analysis, the incidence of > or =1 serious infection, > or =1 serious endogenous infection, or > or =2 serious infectious episodes was not significantly different in the (SC)GOS/(LC)FOS/AOS-supplemented and placebo groups. In the per-protocol analysis, there was a trend toward a lower incidence of > or =1 serious endogenous infection and > or =2 serious infectious episodes in the (SC)GOS/(LC)FOS/AOS-supplemented group than in the placebo group (P = 0.09 and P = 0.07, respectively). CONCLUSIONS: Enteral supplementation of (SC)GOS/(LC)FOS/AOS does not significantly reduce the risk of serious infectious morbidity in preterm infants. However, there was a trend toward a lower incidence of serious infectious morbidity, especially for infections with endogenous bacteria. This finding suggests a possible beneficial effect that should be evaluated in a larger study. This trial was registered at isrctn.org as ISRCTN16211826.

Hydrops fetalis and early neonatal multiple organ failure in familial hemophagocytic lymphohistiocytosis.

Familial hemophagocytic lymphohistiocytosis (FHLH) is a genetic heterogeneous autosomal recessive disorder. We report two siblings with FHLH caused by a PRF1 mutation. The first child died in utero with hydrops fetalis and the second presented soon after birth with fatal multiple organ failure. Post-mortem DNA analysis showed a homozygous c.666C>A (p.His222Gln) mutation in the PRF1 gene in both cases, with their non-consanguineous parents being heterozygous for the same mutation. Review of the literature shows that perinatal presentation of FHLH is rare. Diagnosis is difficult because in most cases histologic examination reveals no hemophagocytosis and the disease is rapidly fatal. The association between hydrops fetalis and FHLH has been reported in four previous reports. We present the first case of hydrops fetalis caused by FHLH, confirmed by DNA analysis. FHLH should be included in the differential diagnosis of non-immune hydrops fetalis and neonatal multiple organ failure.

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.

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.

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.

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.

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

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.

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.

Low plasma concentrations of arginine and asymmetric dimethylarginine in premature infants with necrotizing enterocolitis.

Several studies have described reduced plasma concentrations of arginine, the substrate for nitric oxide synthase (NOS) in infants with necrotizing enterocolitis (NEC). No information on the plasma concentrations of the endogenous NOS inhibitor asymmetric dimethylarginine (ADMA) in patients with NEC is currently available. We investigated whether plasma concentrations of arginine, ADMA, and their ratio differ between premature infants with and without NEC, and between survivors and non-survivors within the NEC group. In a prospective case-control study, arginine and ADMA concentrations were measured in ten premature infants with NEC (median gestational age 193 d, birth weight 968 g), and ten matched control infants (median gestational age 201 d, birth weight 1102 g), who were admitted to the Neonatal Intensive Care Unit. In the premature infants with NEC, median arginine and ADMA concentrations (micromol/l), and the arginine:ADMA ratio were lower compared to the infants without NEC: 21.4 v. 55.9, P= 0.001; 0.59 v. 0.85, P=0.009 and 36.6 v. 72.3, P=0.023 respectively. In the NEC group, median arginine (micromol/l) and the arginine:ADMA ratio were lower in non-surviving infants than in surviving infants: 14.7 v. 33.8, P=0.01 and 32.0 v. 47.5, P=0.038 respectively. In premature infants with NEC not only the NOS substrate arginine, but also the endogenous NOS inhibitor ADMA and the arginine:ADMA ratio were lower than in infants without NEC. In addition, low arginine and arginine:ADMA were associated with mortality in infants with NEC. Overall, these data suggest that a diminished nitric oxide production may be involved in the pathophysiology of NEC, but this needs further investigation.