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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. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To examine the characteristics of incidents reported after introduction of a voluntary, non-punitive incident reporting system for neonatal intensive care units (NICUs) in the Netherlands; and to investigate which types of reported incident pose the highest risk to patients in the NICU. DESIGN: Prospective multicentre survey. METHODS: Voluntary, non-punitive incident reporting was introduced in eight level III NICUs and one paediatric surgical ICU. An incident was defined as any unintended event which (could have) reduced the safety margin for the patient. Multidisciplinary, unit-based patient safety committees systematically collected and analysed incident reports, and assigned risk scores to each reported incident. Data were centrally collected for specialty-based analysis. This paper describes the characteristics of incidents reported during the first year. Bivariate logistic regression analysis was conducted to identify high-risk incident categories. RESULTS: There were 5225 incident reports on 3859 admissions, of which 4846 were eligible for analysis. Incidents with medication were most frequently reported (27%), followed by laboratory (10%) and enteral nutrition (8%). Severe harm was described in seven incident reports, and moderate harm in 63 incident reports. Incidents involving mechanical ventilation and blood products were most likely to be assigned high-risk scores, followed by those involving parenteral nutrition, intravascular lines and medication dosing errors. CONCLUSIONS: Incidents occur much more frequently in Dutch NICUs than has been previously observed, and their impact on patient morbidity is considerable. Reported incidents concerning mechanical ventilation, blood products, intravascular lines, parenteral nutrition and medication dosing errors pose the highest risk to patients in the NICU. [ABSTRACT FROM AUTHOR]

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.~Background~Background~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.~Methods/design~Methods~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.~Discussion~Conclusions~Current Controlled Trials ISRCTN16211826.~Trial Registration~Background [ABSTRACT FROM AUTHOR]

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.

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., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

We aimed to determine the effects of enteral supplementation of a prebiotic mixture of neutral and acidic oligosaccharides (scGOS/lcFOS/pAOS) on the faecal microbiota and microenvironment in preterm infants. Furthermore, we determined the influence of perinatal factors on the development of the faecal microbiota. In a randomised controlled trial, preterm infants with gestational age <32 weeks and/or birth weight <1,500 g received enteral supplementation of scGOS/lcFOS/pAOS or placebo (maltodextrin) between days 3 and 30 of life. Faecal microbiota, as measured with fluorescent in situ hybridisation (FISH), and microenvironment [short-chain fatty acids (SCFAs), pH, sIgA] were measured at four time points: before the start of the study and at days 7, 14 and 30 of life. In total, 113 preterm infants were included. Enteral supplementation of the prebiotic mixture increased the total bacteria count at day 14 (Exp 3.92; 95 % confidence interval [CI] 1.18-13.04, p = 0.03), but not at day 30 (Exp 1.73; 95 % CI 0.60-5.03, p = 0.31). There was a trend toward increased bifidobacteria counts. There was a delayed intestinal colonisation of all bacteria. Enteral supplementation of the prebiotic mixture decreased the faecal pH (Exp 0.71; 95 % CI 0.54-0.93, p = 0.01) and there was a trend toward increased acetic acid compared to the placebo group (Exp 1.09; 95 % CI 0.99-1.20, p = 0.10). There was no effect on sIgA (Exp 1.94; 95 % CI 0.28-13.27, p = 0.50). Antibiotics decreased the total bacteria count (Exp 0.13; 95 % CI 0.08-0.22, p < 0.001). Enteral supplementation of a prebiotic mixture of neutral and acidic oligosaccharides increases the postnatal intestinal colonisation. However, the extensive use of broad-spectrum antibiotics in preterm infants decreased the growth of all intestinal microbiota, thereby, delaying the normal microbiota development.

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.

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.

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., (© 2010 Blackwell Publishing Ltd.)

Aim: Previously, glutamine-enriched enteral nutrition in very low birth weight infants (VLBW) decreased the incidence of atopic dermatitis at age 1 year. The aim of this study was to determine whether this effect is related to changes in intestinal bacterial species that are associated with allergy, such as bifidobacteria, clostridium histolyticum, clostridium lituseburense (Chis/lit group) and Escherichia coli at age 1 year., Methods:   Eighty-nine infants were eligible for this follow-up study, conducted at a Tertiary care hospital. Bifidobacteria, Chis/lit group and E. coli were measured by fluorescent in situ hybridization in faecal samples collected at age 1 year. Information on allergic and infectious diseases was previously determined by questionnaire., Results:  Seventy-two of 89 (81%) infants were participated. Prevalence of all studied species was not different between glutamine-supplemented and control groups. Allergic infants were less frequently colonized with bifidobacteria than nonallergic infants (p =0.04). Between neonatal period and 1 year, prevalence of bifidobacteria was increased (p < 0.001), of Chis/lit group was unchanged (p=0.84), and of E. coli was decreased (p < 0.001)., Conclusion:  The beneficial effect of glutamine-enriched enteral nutrition on the incidence of atopic dermatitis in the first year of life in VLBW infants is not related to changes in bifidobacteria, Chis/lit group or E. coli. Allergic VLBW infants are less frequently colonized with bifidobacteria compared to nonallergic VLBW infants., (© 2010 The Author(s)/Journal Compilation © 2010 Foundation Acta Paediatrica.)

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.

Aims and Objectives: In this study, the feasibility and reliability of the Prevention Recovery Information System for Monitoring and Analysis (PRISMA)-Medical method for systematic, specialty-based analysis and classification of incidents in the neonatal intensive care unit (NICU) were determined., Methods: After the introduction of a Neonatology System for Analysis and Feedback on Medical Events (NEOSAFE) in eight tertiary care NICUs and one paediatric surgical ICU, PRISMA-Medical was started to be used to identify root causes of voluntary reported incidents by multidisciplinary unit patient safety committees. Committee members were PRISMA-trained and familiar with the department and its processes. In this study, the results of PRISMA-analysis of incidents reported during the first year are described. At t = 3 months and t = 12 months after introduction, test cases were performed to measure agreement at three levels of root cause classification using PRISMA-Medical. Inter-rater reliability was determined by calculating generalised kappa values for each level of classification., Results: During the study period, 981 out of 1786 eligible incidents (55%) were analysed for underlying root causes. In total, 2313 root causes were identified and classified, giving an average of 2.4 root causes for every incident. Although substantial agreement (kappa 0.70-0.81) was reached at the main level of root cause classification of the test cases (discrimination between technical, organisational and human failure) and agreement among the committees at the second level (discrimination between skill-based, rule-based and knowledge-based errors) was acceptable (kappa 0.53-0.59), discrimination between rule-based errors (the third level of classification) was more difficult to assess (kappa 0.40-0.47)., Conclusion: With some restraints, PRISMA-Medical proves to be both feasible and acceptably reliable to identify and classify multiple causes of medical events in the NICU.

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.

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.

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.

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.

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.

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

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.

Objectives: To examine the characteristics of incident reporting systems in neonatal intensive care units (NICUs) in relation to type, aetiology, outcome and preventability of incidents., Methods: Systematic review., Search Strategy: Medline, Embase, Cochrane Library. Included: relevant systematic reviews, randomised controlled trials, observational studies and qualitative research. Excluded: non-systematic reviews, expert opinions, case reports and letters., Participants: hospital units supplying neonatal intensive care., Intervention: none., Outcome: characteristics of incident reporting systems; type, aetiology, outcome and preventability of incidents., Results: No relevant systematic reviews or randomised controlled trials were found. Eight prospective and two retrospective studies were included. Overall, medication incidents were most frequently reported. Available data in the NICU showed that the total error rate was much higher in studies using voluntary reporting than in a study using mandatory reporting. Multi-institutional reporting identified rare but important errors. A substantial number of incidents were potentially harmful. When a system approach was used, many contributing factors were identified. Information about the impact of system changes on patient safety was scarce., Conclusions: Multi-institutional, voluntary, non-punitive, system based incident reporting is likely to generate valuable information on type, aetiology, outcome and preventability of incidents in the NICU. However, the beneficial effects of incident reporting systems and consecutive system changes on patient safety are difficult to assess from the available evidence and therefore remain to be investigated.

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.

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.

Objectives: The purpose of this study was to compare 3D lung volume measurements with 2D biometric parameters in predicting pulmonary hypoplasia in pregnancies complicated by preterm premature rupture of the membranes (PPROM)., Methods: In this prospective study, 18 pregnancies complicated by PPROMs at a mean 21 weeks' gestation (range 14-32 weeks) were examined. The 3D lung volume measurements and the following 2D biometric parameters were measured: thoracic circumference (TC) versus gestational age or femur length (FL), the TC/abdominal circumference (AC) ratio and the thoracic area/heart area (TA/HA) ratio. The sensitivity, specificity, positive and negative predictive value of each measurement to diagnose pulmonary hypoplasia were compared. Pulmonary hypoplasia was diagnosed on the basis of clinical, radiological and/or pathologic criteria., Results: The incidence of pulmonary hypoplasia was 33.3%. The best diagnostic accuracy for predicting pulmonary hypoplasia was achieved using the 3D lung volume measurements versus gestational age (sensitivity 83%, specificity 100%, positive predictive value 100% and negative predictive value 92%)., Conclusions: Three-dimensional lung volume measurements seem to be promising in predicting pulmonary hypoplasia prenatally in pregnancies complicated by PPROM., (Copyright (c) 2007 John Wiley & Sons, Ltd.)

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 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 incidence of nosocomial infection in neonatal intensive care units (NICUs) is high compared with other wards. However, no definitions for hospital-acquired infection are available for NICUs. The aim of this study was to measure the incidence of such infections and to identify risk factors in the NICU of the VU University Medical Center, which serves as a level III regional NICU. For this purpose, a prospective surveillance was performed in 1998-2000. We designed definitions by adjusting the current definitions of the Centers for Disease Control and Prevention (CDC) for children <1 year of age. Birth weight was stratified into four categories and other baseline risk factors were dichotomized. Analysis of risk factors was performed by Cox regression with time-dependent variables. The relationship between the Clinical Risk Index for Babies (CRIB) and nosocomial infection was investigated. Furthermore, for a random sample of cases, we determined whether bloodstream infection and pneumonia would also have been identified with the CDC definitions. Seven hundred and forty-two neonates were included in the study. One hundred and ninety-one neonates developed 264 infections. Bloodstream infection (N=138, 14.9/1000 patient-days) and pneumonia (N=69, 7.5/1000 patient-days) were the most common infections. Of bloodstream infections, 59% were caused by coagulase-negative staphylococci; in 21% of neonates, blood cultures remained negative. In 25% of pneumonias, Enterobacteriaceae were the causative micro-organisms; 26% of cultures remained negative. Compared with the Nosocomial Infections Surveillance System (NNIS) of the CDC, our device utilization ratios and device-associated nosocomial infection rates were high. The main risk factors for bloodstream infection were birth weight [hazard ratio (HR) 1.79, 95% confidence interval (CI) 1.45-2.17] and parenteral feeding with hospital-pharmacy-produced, all-in-one mixture 'Minimix' (HR 3.69, 95%CI 2.03-6.69); administration of intravenous antibiotics (HR 0.39, 95%CI 0.26-0.56) was a protective risk factor. The main risk factors for pneumonia were low birth weight (HR 1.37, 95%CI 1.01-1.85) and mechanical ventilation (HR 9.69, 95%CI 4.60-20.4); intravenous antibiotics were protective (HR 0.37, 95%CI 0.21-0.64). In a subcohort of 232 very-low-birthweight neonates, the CRIB was not predictive for infection. With the CDC criteria, only 75% (21/28) of bloodstream infections and 87.5% of pneumonias (21/24) would have been identified. In conclusion, our local nosocomial infection rates are high compared with those of NICUs participating in the NNIS. This can be partially explained by: (1) the use of our definitions for nosocomial infection, which are more suitable for this patient category; and (2) the high device utilization ratios.

Objectives: Plasma volume expansion may benefit both mother and child in the temporising management of severe and early onset hypertensive disorders of pregnancy., Design: Randomised clinical trial. Setting Two university hospitals in Amsterdam, The Netherlands., Population: Two hundred and sixteen patients with a gestational age between 24 and 34 completed weeks with severe pre-eclampsia, haemolysis, elevated liver enzymes and low platelets (HELLP) syndrome or severe fetal growth restriction (FGR) with pregnancy-induced hypertension, admitted between 1 April 2000 and 31 May 2003., Methods: One hundred and eleven patients were randomly allocated to the treatment group, (plasma volume expansion and a diastolic BP target of 85-95 mmHg) and 105 to the control group (intravenous fluid restriction and BP target of 95-105 mmHg)., Main Outcome Measures: Neonatal neurological development at term age (Prechtl score), perinatal death, neonatal morbidity and maternal morbidity., Results: Baseline characteristics were comparable between groups. The median gestational age was 30 weeks. In the treatment group, patients received higher amounts of intravenous fluids (median 813 mL/day vs 14 mL/day; P < 0.001) with a concomitant decreased haemoglobin count (median -0.6 vs-0.2 mmol/L; P < 0.001). Neither neurological scores nor composite neonatal morbidity differed. A trend towards less prolongation of pregnancy (median 7.4 vs 11.5 days; P= 0.054) and more infants requiring oxygen treatment >21% (66 vs 46; P= 0.09) in the treatment group was observed. There was no difference in major maternal morbidity (total 11%), but there were more caesarean sections in the treatment group (98%vs 90%; P < 0.05)., Conclusion: The addition of plasma volume expansion in temporising treatment does not improve maternal or fetal outcome in women with early preterm hypertensive complications of pregnancy.

In a premature male infant born of consanguineous parents, restrictive dermopathy was diagnosed. This is a rarely described, lethal, congenital skin disease. The diagnosis was based on the clinical and histopathological findings: a fixed facial expression (so-called 'porcelain face') with palpebral fissures inclined laterally downwards, microstomia with the mouth in the 'O'-position, micrognathia and low-set ears inclined toward the rear, prominent blood vessels in the skin and contracture of all the joints; histopathological examination of a skin biopsy revealed a smooth epidermis and a relatively thin dermis with an abnormal structure of the dermal connective tissue in which the collagen fibres were arranged more or less horizontally, parallel to the epidermis, and the number of elastin fibres was sharply decreased. Various adnexal structures were present but the hair follicles had an abortive appearance. Thanks in part to the finding of a homozygous mutation in the so-called ZMPSTE24-gene, it could be concluded that restrictive dermopathy is probably an autosomal recessive laminopathy, related to progeria. Increasing the clinical awareness of this disease may contribute to reducing the presumed under-reporting, so that future research will become possible.

Isolated noncompaction of the ventricular myocardium is a cardiomyopathy influencing almost exclusively the left ventricle in children and adults. We report a case of a neonate presenting with right ventricular failure caused by a noncompaction of the right ventricle. However, later course of the disease demonstrated biventricular involvement. Right ventricular noncompaction can be a cause of early postnatal right ventricular failure.

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.

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.

Birth asphyxia is a major concern in neonatal care. Epileptic seizures are associated with subsequent neurodevelopmental deficits. Eighty-five percent of these seizures remain subclinical and therefore an on-line monitoring device is needed. In an earlier study we showed that the synchronization likelihood was able to distinguish between neonatal EEG epochs with and without epileptic seizures. In this study we investigated whether the synchronization likelihood can be used in complete EEGs, without artifact removal. Twenty complete EEGs from 20 neonatal patients were studied. The synchronization likelihood was calculated and correlated with the visual scoring done by 3 experts. In addition, we determined the influence of seizure length on the likelihood of detection. Using the raw unfiltered EEG data we found a sensitivity of 65.9 % and a specificity of 89.8 % for the detection of seizure activity in each epoch. In addition, the seizure detection rate was 100 % when the seizures lasted for 100 seconds or more. The synchronization likelihood seems to be a useful tool in the automatic monitoring of epileptic seizures in infants on the neonatal ward. Due to the retrospective nature of our study, the consequences for clinical intervention cannot yet be determined and prospective studies are needed. Therefore, we will conduct a prospective study on the neonatal intensive care unit with a recently developed on-line version of the synchronization likelihood analysis.

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.

Objective: To study the effect of minimal enteral feeding (MEF) on intestinal permeability and feeding tolerance in preterm infants with intrauterine growth retardation (gestational age < 37 weeks, birth weight for gestational age p < 10). Furthermore, to determine whether fetal blood flow pulsatility or intestinal permeability predict feeding tolerance in these infants., Design: Randomised controlled trial., Methods: Within 48 hours of birth, infants were randomised to MEF or no enteral feeding (NEF) for five days in addition to parenteral feeding. Intestinal permeability was measured by the sugar absorption test before (SAT1) and after (SAT2) the study. The sugar absorption test measured the urinary lactulose/mannitol (LM) ratio after oral ingestion of a solution (375 mosm) containing mannitol and lactulose. Charts of all infants were assessed for measures of feeding tolerance. Fetal blood flow pulsatility index (U/C ratio) was measured within the seven days before birth., Results: Of the 56 infants enrolled, 42 completed the study: 20 received MEF and 22 NEF. The decrease in LM ratio (LM ratio 1 - LM ratio 2) was not significantly different between the two groups (0.25 v 0.11; p = 0.14). Feeding tolerance, growth, and incidence of necrotising enterocolitis were not significantly different between the two groups. Neither the U/C nor the LM ratio 1 predicted feeding tolerance., Conclusions: The results suggest that MEF of preterm infants with intrauterine growth retardation has no effect on the decrease in intestinal permeability after birth. Neither fetal blood flow pulsatility nor intestinal permeability predicts feeding tolerance.

To determine the value of noninvasive assessment of right ventricular preload in neonates, a prospective unblinded study was performed. Thirty-seven neonates without heart disease (median birth weight 1390 g, range 900 to 4400) were studied at the neonatal intensive care unit, comparing directly measured central venous pressure (CVP) and two-dimensional echocardiographic measurement of the maximum and minimum diameter of the inferior vena cava and calculated vena cava index (VCI). CVP was higher in conventionally ventilated and high-frequency oscillatory ventilated neonates than in those breathing spontaneously ( p < 0.0001). VCI in high-frequency oscillatory ventilated patients was lower (5 +/- 4) than in spontaneously breathing (56 +/- 19) and conventionally ventilated (49 +/- 19) (p = 0.002) neonates. CVP and VCI were inversely correlated in spontaneously breathing (r = -0.631), but not in conventionally and high-frequency oscillatory ventilated patients. VCI does not predict CVP in ventilated premature neonates, the correlation is limited only to spontaneously breathing infants.

Presently, prognosis of infants with perinatal hypoxia-ischaemia is estimated using the Sarnat scale, which combines clinical evaluation and electroencephalography, in combination with magnetic resonance imaging (MRI) and or evoked potentials. While the value of conventional MRI is limited during the first week of life, diffusion-weighted MRI demonstrates effects of acute cerebral ischaemia within hours of onset. However, the exact value of diffusion MRI in the prognosis of infants with hypoxia-ischaemia has to be established in larger follow-up studies. In this report we describe 5 term (post-conceptional age 40 1/7 to 41 2/7 week) neonates with severe hypoxia-ischaemia and a characteristic pattern of diffusion changes. T 1 -weighted images showed a hyperintense cortical signal in only one case and extensive hyperintensity in the basal nuclei in all 5 cases. T 2 -weighted images showed nearly complete loss of cortical delineation in three cases. Increased signal on diffusion-weighted images was seen throughout all cortical and subcortical areas while the cerebellum remained normal. This pattern, which we refer to as the "white cerebrum", is most readily apparent on coronal images. The apparent diffusion coefficient (ADC) was calculated and compared to that of four control infants. In the cortex ADC values were lowered (0.70 +/- 0.17 micro m 2/msec [mean +/- standard deviation (SD)]; controls [n = 4]: 1.18 +/- 0.02 micro m 2/msec) as compared to values of ADC in the cerebellum (1.31 +/- 0.06 micro m 2/msec [mean +/- SD]; controls [n = 4]: 1.25 +/- 0.06 micro m 2/msec). All infants died in the perinatal period. In summary, the "white cerebrum" on diffusion-weighted MRI indicates severe neonatal hypoxia-ischaemia and is the counterpart of the white cerebellum on CT.

Objective: To determine the relation between intestinal permeability and birth weight, gestational age, postnatal age, and perinatal risk factors in neonates., Study Design: Intestinal permeability was measured by the sugar absorption test within two days of birth and three to six days later in preterm and healthy term infants. In the sugar absorption test, the urinary lactulose/mannitol ratio is measured after oral ingestion of a solution (375 mosm) of lactulose and mannitol., Results: A first sugar absorption test was performed in 116 preterm (26-36 weeks gestation) and 16 term infants. A second test was performed in 102 preterm and nine term infants. In the preterm infants, the lactulose/mannitol ratio was not related to gestational age (r = -0.09, p = 0.32) or birth weight (r = 0.07, p = 0.43). The median lactulose/mannitol ratio was higher if measured less than two days after birth than when measured three to six days later (0.427 and 0.182 respectively, p<0.001). The lactulose/mannitol ratio was higher in preterm infants than term infants if measured within the first 2 days of life (0.404 and 0.170 respectively, p < 0.001), but not different three to six days later (0.182 and 0.123 respectively, p = 0.08). In multiple regression analysis of perinatal risk factors, only umbilical arterial pH correlated with the lactulose/mannitol ratio in preterm infants less than 2 days of age (T = -1.98, p = 0.05)., Conclusions: In preterm infants (26-36 weeks gestation), intestinal permeability is not related to gestational age or birth weight but is higher during the first 2 days of life than three to six days later. It is higher in preterm infants than in healthy term infants only if measured within two days of birth. This suggests rapid postnatal adaptation of the small intestine in preterm infants.

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.

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%).

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.

Background: To determine: 1) whether substandard factors were present in cases of perinatal death, and to what extent another course of action might have resulted in a better outcome, and 2) whether there were differences in the frequency of substandard factors by level of care, particularly between midwives and gynecologists/obstetricians and between home and hospital births., Methods: Population-based perinatal audit, with explicit evidence-based audit criteria., Setting: The northern part of the province of South-Holland in The Netherlands. All levels of perinatal care (primary, secondary and tertiary care, and home and hospital births) were included., Cases: Three hundred and forty-two cases of perinatal mortality (24 weeks of pregnancy--28 days after birth)., Main Outcome Measures: Scores by a Dutch and a European audit panel. Score 0: no substandard factors identified; score 1, 2 or 3: one or more substandard factors identified, which were unlikely (1), possibly (2) or probably (3) related to the perinatal death., Results: In 25% of the perinatal deaths (95% Confidence Interval: 20-30%) a substandard factor was identified that according to the Dutch panel was possibly or probably related to the perinatal death. These were mainly maternal/social factors (10% of all perinatal deaths; most frequent substandard factor: smoking during pregnancy), and antenatal care factors (10% of all perinatal deaths; most frequent substandard factor: detection of intra-uterine growth retardation). We did not find statistically significant differences in scores between midwives and gynecologists/obstetricians or between home and hospital births. The European panel identified more substandard factors, but these were again equally distributed by level of care., Conclusions: Perinatal deaths might be partly preventable in The Netherlands. There is no evidence that the frequency of substandard factors is related to specific aspects of the perinatal care system in The Netherlands.

Our goal for this study was to determine whether the maturation of fat absorption in neonatal life is functionally related to an increased ability to hydrolyze dietary fat, to absorb long-chain fatty acids, or to do both. In 16 preterm and in eight term neonates, the intestinal ability to hydrolyze triacylglycerols and the capacity to absorb long-chain fatty acids were determined at several times between birth and 5 mo after the term age. These processes were compared with the percentage of fat absorption (formula-fed infants) or with fecal fat excretion (breast-fed infants). The functional capacity to digest triacylglycerols and to absorb the lipolytic products was evaluated by measuring serum concentrations of the lipolytic product [1-(13)C]palmitate after the enteral administration of tri-1-(13)C palmitoyl-glycerol. Long-chain fatty acids absorption (i.e. independent of lipolysis) was determined by measuring serum concentrations of [1-(13)C]stearate after its enteral administration. The efficacy of fat absorption increased in preterm infants (formula-fed) from 91.2 +/- 1.1% (mean +/- SEM) at 32.3 wk postconceptional age (PCA) to 97.3 +/- 0.6% at 53.6 wk PCA (p < 0.001), and in term infants from 91.7 +/- 1.8% (40.0 wk PCA) to 97.4 +/- 1.3% (58.9 wk PCA, p = 0.07). Both the serum concentration of [1-(13)C]stearate and that of [1-(13)C]palmitate appeared highly correlated with the efficacy of fat absorption (r = 0.82, p = 0.02; and r = 0.91, p = 0.004; respectively) and with PCA (r = 0.99, p < 0.001; and r = 0.85, p < 0.02; respectively). These results indicate that the functional development of fat absorption in preterm and term infants is related to the capacity to absorb long-chain fatty acids from the intestine.

Respiratory morbidity is an important complication of elective caesarean section. The presence of labour preceding caesarean section reduces the risk of neonatal respiratory morbidity. Recently, it has been shown that the incidence of respiratory morbidity is lower in infants with a gestational age of at least 39(+0) weeks at elective caesarean section compared to infants with a gestational age less than 39(+0) weeks.This article describes the results of a 5-year retrospective study on the incidence of respiratory distress in term neonates delivered by elective caesarean section in relation to gestational age and provides a literature review on neonatal respiratory morbidity following elective caesarean section.

From December 1999 to March 2000 a nosocomial outbreak of multiresistant Enterobacter cloacae occurred in the neonatal intensive care unit (NICU) at the VU Medical Center, Amsterdam, the Netherlands. Twenty-six patients were infected or colonized with this strain resistant to third generation cephalosporins and with decreased sensitivity for aminoglycosides. Three neonates experienced sepsis with E. cloacae with serious clinical symptoms and two of them died. Comparison of the Enterobacter isolates by amplified-fragment length polymorphism indicated that this outbreak was caused by the spread of a single strain. Infection control precautions were initiated in order to stop further spread; barrier precautions, enforcement of hand disinfection and cohorting of colonized patients. A multidisciplinary crisis team coordinated these infection control precautions and informed all persons involved. Analysis of antibiotic usage in 1999 showed an increase in the use of third generation cephalosporins from November onwards. Due to the resistance pattern of the epidemic strain the use of third generation cephalosporins was discontinued in February 2000. At the end of February the NICU was temporarily closed. The epidemic strain of E. cloacae was isolated from one digital rectal thermometer. Patient use of thermometers and disposable coverings for rectal thermometers were introduced to eliminate this possible means of spread. No spread of multiresistant E. cloacae was found following the introduction of these interventions. Once all the neonates had been transferred, the NICU was disinfected and reopened in March.

Influenza B infection typically has low mortality. A 1,020-g neonate had a septic clinical picture and pneumonia. Influenza B virus was isolated from nasopharyngeal and tracheal aspirates. The infant died.

Objective: To determine the motor development in infants sleeping in the supine position compared to infants sleeping in the prone position, and to compare the levels of motor development of infants playing only in the supine position and of infants playing in the prone position as well., Design: Prospective blinded comparing study., Setting: Department of Physical Therapy, Maasziekenhuis, Boxmeer, the Netherlands., Methods: Various measuring instruments were used in the home environment to determine the levels of motor development at the age of 5 months of 21 healthy infants born at term selected from a group of 160 infants attending the infant welfare clinic., Results: Infants sleeping in the prone position (n = 8) showed a higher motor development than infants sleeping in the supine position (n = 13). Infants playing in the prone and supine position (n = 5) had a higher motor development than infants who played exclusively in the supine position (n = 15)., Conclusion: Sleeping and playing in the prone position was accompanied by a higher motor development in healthy mature-born infants at the age of 5 months.

The aim of this study was to compare thyroid function in preterm infants born to women with placental insufficiency (n = 15) and those born to women without placental insufficiency (n = 13). Gestational ages ranged between 28 and 33 weeks. Concentrations of free thyroxine (FT4), thyrotropin (TSH), triiodothyronine (T3) and reverse T3 (rT3) were measured by radioimmmunoassays in cord blood and on d 1, 3, 5, 7, 14 and 21. Infants born to the women with placental insufficiency had significantly lower mean FT4 (p = 0.001), TSH (p = 0.002) and rT3 values (p = 0.025) in cord blood, and higher rT3 values on d 5 (p = 0.019) and d 7 (p = 0.025). The following conclusions were reached: (i) preterm infants born to pre-eclamptic women with placental insufficiency have intact hypothalamic-pituitary-thyroid axes; (ii) compared to preterm infants born to healthy women, preterm infants born to pre-eclamptic women with placental insufficiency have lower FT4 and TSH concentrations before birth and (iii) elevated rT3 concentrations after birth, suggesting a temporarily impaired hepatic type 1 deiodination process.

From 1982 to 1989, 705 infants born to HBsAg-positive mothers entered the Dutch neonatal hepatitis B vaccination program and received passive-active hepatitis B immunization in three randomized controlled trials testing variations in time of starting active vaccination, dose and type of vaccine, and number of hepatitis B immunoglobulin (HBIg) injections. A meta-analysis of individual patient data of the three randomized trials was performed to determine which independent host and vaccination related factors influence protective efficacy and long-term immunogenicity, and to assess whether hepatitis B vaccination concomitant with standard DKTP vaccination provides optimal protection. Statistical methodology included multivariate logistic regression analysis. Eight infants (1.1%), all born to HBeAg-positive mothers, became HBsAg carriers within the first year of life. The protective efficacy rate (PER) of passive-active immunization at 12 months follow-up was 92% for the total group of children from 114 HBeAg-positive mothers with no significant differences between children starting active immunization at birth or at 3 months of age, between infants starting at 3 months of age receiving one or two doses of HBIg or between those receiving plasma derived or recombinant vaccine. The only factor that affected the PER significantly was the level of maternal HBV DNA; PER was 100% if maternal HBV DNA was < 150 pg ml-1 and 68% for HBV DNA levels > 150 pg ml-1. After 5 years of follow-up, the group that started active immunization at birth had significantly more infants with loss of seroprotection (anti-HBs levels < 10 IU l-1, 15%) than the corresponding group starting at 3 months of age (anti-HBs < 10 IU l-2, 2%). One of 35 children with loss of seroprotection at 2 years became a HBsAg carrier in the fifth year of follow-up. This meta-analysis shows that the protective efficacy of passive-active hepatitis B vaccination is mainly influenced by material HBV DNA levels, and independent of the time of starting active vaccination at birth or at 3 months of age; long-term immunity was enhanced by starting active vaccination concomitant with DKTP vaccination. These findings allow incorporation of hepatitis B vaccine into the standard infant immunization programs for countries with a passive-active immunization strategy for the control of hepatitis B. Additional measures are needed to protect neonates of highly viremic women.