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Gastrointestinal viral infections are a major global cause of disease and mortality in infants. Cytotoxic CD8+ T cells are critical to achieve viral control. However, studies investigating the development of CD8+ T cell immunity in human tissues early in life are lacking. Here, we investigated the maturation of the CD8+ T cell compartment in human fetal, infant and adult intestinal tissues. CD8+ T cells exhibiting a memory phenotype were already detected in fetal intestines and increased after birth. Infant intestines preferentially harbored effector CCR7−CD45RA−CD127−KLRG1+/− CD8+ T cells compared to tissue-resident memory CD69+CD103+CD8+ T cells detected in adults. Functional cytotoxic capacity, including cytokine and granzyme B production of infant intestinal effector CD8+ T cells was, however, markedly reduced compared to adult intestinal CD8+ T cells. This was in line with the high expression of the inhibitory molecule PD-1 by infant intestinal effector CD8+ T cells. Taken together, we demonstrate that intestinal CD8+ T cell responses are induced early in human development, however exhibit a reduced functionality. The impaired CD8+ T cell functionality early in life contributes to tolerance during foreign antigen exposure after birth, however functions as an immune correlate for the increased susceptibility to gastrointestinal viral infections in infancy.

Objective: The objective of this research is to study effects of a 4-week high-protein (HP) diet on energy intake, resting energy expenditure (REE), protein turnover and body composition in children with obesity. Methods: In this randomized placebo-controlled single-blind crossover study, children with obesity (n = 14; mean age: 10.1 years ± 1.2 standard deviation; body mass index–standard deviation score [BMI-SDS]: 2.8 ± 0.5) received an ad libitum HP (+50 g protein per day) or normal-protein (NP) diet for 4 weeks with a washout period of ≥2 weeks. Energy intake, REE, protein turnover, weight, BMI-SDS and body composition were measured. Results: No differences were found in energy intake or REE between HP and NP. There was an increased urea production and phenylalanine hydroxylation after HP compared with NP (p

Background: Preterm infants are at risk for impaired bone mineralization and growth in length later in life due to inadequate nutritional intake in the early postnatal period. Objective: To investigate whether increased nutritional supplementation of calcium, phosphate and protein in Very Low Birth Weight (VLBW) infants during the first 14 days after birth was associated with improvement in length and bone development until 9-10 years of age. Design: Observational follow-up study of VLBW infants (birth weight< 1500 g or gestational age < 32 weeks) born in two consecutive years (eligible infants: 2004 n: 63 and 2005: n: 66). Cohort 2005 received higher intake of calcium, phosphate and protein with parenteral nutrition compared to Cohort 2004. Anthropometric data were collected during standard follow-up visits until five years, and additionally at 9-10 years of age including measurements of bone mineral content, bone mineral density of the whole body and lumbar spine determined by dual-energy X-ray absorptiometry. Long-term growth trajectories of both cohorts were evaluated separately for participants born appropriate (AGA) and small for gestational age (SGA), stratified by gender. Multivariate linear regression was used to examine the effect of nutritional intalce and clinical covariates on length and bone mineralization. Results: Both cohorts achieved a catch-up in length to SDS within the normal range by 6 months (length SDS: estimated mean (95% confidence interval (CI): 6 months: Cohort 2004: -0.7 ( -1.1, -0.3) Cohort 2005: -0.5 (-0.8, -0.2)). Bone mineral content and density were within the normal range and not different between the cohorts. SGA children achieved a catch-up in length at 5 years with bone mineralization comparable to AGA children. Only for girls birth weight was significantly associated with length SDS (per gram: beta 0.001; 95% CI (0.000, 0.003); p = 0.03) There was no evidence of an association between early nutritional intake and bone mineralization. Conclusion: Children born as appropriate or small for gestational age preterm infants are able to catch up in length after the postnatal period, and achieve a normal length and bone mineralization at age nine-ten years. An improvement of calcium and phosphate intake during the first 14 days after birth was not associated with improvement in length and bone development. (C) 2017 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license

Background: In children with profound intellectual and multiple disabilities (PIMD), discussions about end-of-life decisions (EoLDs) are comparatively common. Nurses play a crucial role in the care for these children, yet their involvement in EoLD discussions is largely unknown. The objective of this research was to investigate the involvement in the hospital of nurses in discussions with parents and physicians about EoLDs for children with PIMD. Method: In a retrospective, qualitative study, we conducted semi-structured interviews with the nurses of 12 children with PIMD for whom an EoLD was made within the past 2 years. Results: Parents primarily discuss EoLDs with nurses before and after the meeting with the physician. Nurses who were involved in EoL discussions with parents and physicians assisted them by giving factual information about the child and by providing emotional support. Some nurses, especially nurses from ID-care services, were not involved in EoL discussions, even if they had cared for the child for a long period of time. Some of the nurses had moral or religious objections to carrying out the decisions. Conclusion: Most nurses were not involved in EoL discussions with parents and physicians in the hospital. Excluding nurses from EoL discussions can cause them moral distress. The involvement of nurses in EoL discussions for children with PIMD should be improved, especially by involving nurses from ID-care services. Because these nurses are usually familiar with the child, they can be valuable sources of information about the child's quality of life.

Background End-of-life decisions (EoLDs) are very difficult to make. How parents and physicians incorporate quality of life (QoL) considerations into their end-of-life decision making (EoLDM) for children with profound intellectual and multiple disabilities (PIMD) remains unknown. Aims To determine which elements contribute to QoL according to parents and physicians, how QoL is incorporated into EoLDM and how parents and physicians discuss QoL considerations in the Netherlands. Methods Semi-structured interviews were conducted with the physicians and parents of 14 children with PIMD for whom an EoLD had been made within the past two years. Results Parents and physicians agreed on the main elements that contribute to QoL in children with PIMD. The way in which QoL was incorporated differed slightly for different types of decisions. Parents and physicians rarely discussed elements contributing to the child’s QoL when making EoLDS. Conclusions and Implications Although QoL was highly important during EoLDM for children with PIMD, parents and physicians did not fully explore the elements that contribute to the child’s QoL when they made EoLDs. We recommend the development of a communication tool that will help parents and physicians discuss elements that contribute to QoL and the consequences these elements have for upcoming decisions.

Background: End-of-life decisions (EoLD) often concern children with profound intellectual and multiple disabilities (PIMD). Yet, little is known about how parents and physicians discuss and make these decisions. Aims: The objective of this research was to investigate the experiences of the parents and the involved physician during the end-of-life decision-making (EoLDM) process for children with PIMD. Methods: In a retrospective, qualitative study, we conducted semi-structured interviews with the physicians and parents of 14 children with PIMD for whom an EoLD was made within the past two years. Results: A long-lasting relationship appeared to facilitate the EoLDM process, although previous negative healthcare encounters could also lead to distrust. Parents and physicians encountered disagreements during the EoLDM process, but these disagreements could also improve the decision-making process. Most parents, as well as most physicians, considered the parents to be the experts on their child. In making an EoLD, both parents and physicians preferred a shared decision-making approach, although they differed in what they actually meant by this concept. Conclusion: The EoLDM process for children with PIMD can be improved if physicians are more aware of the specific situation and of the roles and expectations of the parents of children with PIMD. (C) Elsevier Ltd. All rights reserved.

This study, performed as part of the international EarlyNutrition research project (http://www.project-earlynutrition.eu), provides a systematic review of systematic reviews on the effects of nutritional interventions or exposures in children (up to 3 years of age) on the subsequent risk of obesity, overweight and adiposity. Electronic databases (including MEDLINE, Embase and Cochrane Library) were searched up until September 2015. Forty systematic reviews were included. A consistent association of breastfeeding with a modest reduction in the risk of later overweight and obesity in childhood and adulthood was found (the odds decreased by 13% based on high-quality studies), but residual confounding cannot be excluded. Lowering the protein content of infant formula is a promising intervention to reduce the risk of later overweight and obesity in children. There is no consistent evidence of an association of the age of introducing complementary foods, sugar-sweetened beverage or energy intake in early childhood with later overweight/obesity, but there are some indications of an association of protein intake during the complementary feeding period with later overweight/obesity. There was inadequate evidence to determine the effects of other nutritional interventions or exposures, including modifications of infant formula composition, fat intake or consumption of different food groups.

Summary Background & aims Maternal obesity at conception is considered a major predictor of offspring obesity. This could by driven at least in part by an altered placental fat transfer. However, the pathophysiological mechanisms involved are not fully understood. We investigated the in vivo materno-fetal transfer of fatty acids (FAs) in obese pregnant women using stable isotopes. Methods Ten obese and ten normo-weight pregnant women (control) received orally a bolus of 13C-labeled FAs 12 h before elective caesarean section: oleic acid (13C-OA), linoleic acid (13C-LA) and docosahexaenoic acid (13C-DHA). Maternal blood samples were collected at −12 (basal), −8, −4, −2, 0 h relative to the time of cesarean section. At the time of birth, arterial and venous cord bloods as well as placental tissue were collected. FAs composition was determined by gas-liquid chromatography and isotopic enrichment by gas chromatography-combustion-isotope ratio mass spectrometry. Results Maternal plasma insulin and placental weight tended to higher values in obese pregnant women although they did not present serum hyperlipidemia. Higher concentrations of 13C-LA and 13C-DHA were found in non-esterified FAs fraction in maternal plasma of obese mothers. The ratio of placental uptake for 13C-LA and 13C-DHA was lower in obese women compared to normal weight pointing toward a limited capacity of FA placental transfer, especially of essential FAs. Maternal insulin was associated to this lower placenta/maternal plasma ratio for both 13C-LA (R = −0.563, P = 0.012) and 13C-DHA (R = −0.478, P = 0.033). In addition, the ratio cord/maternal plasma of 13C-LA was significantly lower in obese women compared to controls. Conclusions In conclusion, obese mothers without hyperlipidemia showed a reduced materno-fetal transfer of polyunsaturated FAs which could affect fetal development. This affect dietary recommendation for obese pregnant women. Trial registry number ISRCTN69794527.

Late preterm infants (born ⩾32 weeks of gestation) are at risk for developing iron deficiency and iron deficiency anaemia, and this may lead to impaired neurodevelopment. In the Netherlands, there is no guideline for standardised iron supplementation in these infants. Individualised iron supplementation has been suggested (that is, treating those infants with the highest risk), but risk factors for deprived iron stores in this specific group of infants are not well documented. In this prospective multi-centre study, we analysed the iron status at the postnatal age of 6 weeks of 68 infants born between 32 and 35 weeks of gestation in the Netherlands. Serum ferritin (SF)

We aimed to evaluate the isolation of strains contained in the Infloran™ probiotic preparation in blood cultures and its efficacy in reducing necrotizing enterocolitis (NEC) and late-onset sepsis (LOS) in extremely preterm infants. Routine use of probiotics was implemented in 2008. Infants born at

Background: Previous guidelines on Paediatric Parenteral Nutrition (PN) were published in 2010, by the European Society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) and the European Society for Clinical Nutrition and Metabolism (ESPEN), supported by the European Society of Paediatric Research (ESPR) were published. The aim of the present paper was to provide up-to-date evidence for health professionals working with infants, children and adolescents receiving PN. Methods: The current document is a revision of the 2005 guidelines produced by the same 3 organizations (ESPEN, ESPGHAN, ESPR) together with the Chinese Society of Parenteral and Enteral Nutrition (CSPEN). Experts participating in the guideline updating process were all professionals with extensive experience in managing PN from a wide range of European countries, Israel and China. The guideline development process was coordinated by a guideline steering committee. Each chapter of the guideline was prepared by a separate author group. These author groups were responsible for screening titles and abstracts identified by a systematic literature search for inclusion, for conducting additional expert searches (including secondary sources such as other published valid guidelines), for evaluating the quality of studies included in the given chapter and assigning evidence levels to the literature. Based on the evidence level of included studies experts formulated and graded recommendations. A consensus conference was held in February 2015. All chapter manuscripts were revised following the recommendations of the consensus conference and then reviewed and edited by the project steering committee. Final consensus on each individual guideline and its individual recommendations was achieved and assessed by online voting. This process lasted until January 2018. Funding for the consensus conference (including travel expenses for participants) was provided by all participating societies. No other funding was received for the guideline updating process and participants received no payment. Support was provided by the Hungarian Cochrane organization. Results/conclusions: The present document provides guideline for the use of PN across the wide range of pediatric patients, ranging from extremely premature infants up to teenagers weighing up to and over 100 kg [1]. It covers their individual macro- and micronutrient needs [2], [3], [4], [5], [6], [7], [8], fluid requirements [9], venous access [10], organizational aspects [11], home parenteral nutrition [12], standardized vs. individualized PN [13], and last but not least a wide range of safety considerations for prevention and management of complications such central line associated bloodstream infections (CLABSI)

To study the variability in human milk oligosaccharide (HMO) composition of Chinese human milk over a 20-wk lactation period, HMO profiles of 30 mothers were analyzed using CE-LIF. This study showed that total HMO concentrations in Chinese human milk decreased significantly over a 20-wk lactation period, independent of the mother's SeLe status, although with individual variations. In addition, total acidic and neutral HMO concentrations in Chinese human milk decreased over lactation, and levels are driven by their mother's SeLe status. Analysis showed that total neutral fucosylated HMO concentrations in Chinese human milk were higher in the two secretor groups as compared to the nonsecretor group. On the basis of the total neutral fucosylated HMO concentrations in Chinese human milk, HMO profiles within the Se+Le+ group can be divided into two subgroups. HMOs that differed in level between Se+Le+ subgroups were 2′FL, DF-L, LNFP I, and F-LNO. HMO profiles in Dutch human milk also showed Se+Le+ subgroup division, with 2′FL, LNT, and F-LNO as the driving force.

Item does not contain fulltext STUDY QUESTION: Do in vitro fertilization (IVF) multiples generate higher hospital costs than IVF singletons, from birth up to age 5? SUMMARY ANSWER: Hospital costs from birth up to age 5 were significantly higher among IVF/ICSI multiple children compared with IVF/ICSI singletons; however, when excluding the costs incurred during the birth admission period, hospital costs of multiples and singletons were comparable. WHAT IS KNOWN ALREADY: Concern has risen over the long-term outcome of children born after IVF. The increased incidence of multiple births in IVF as a result of double-embryo transfer predisposes children to a poorer neonatal outcome such as preterm birth and low birthweight. As a consequence, IVF multiples require more medical care. Costs and consequences of poorer neonatal outcomes in multiples may also exist later in life. STUDY DESIGN, SIZE, DURATION: All 5497 children born from IVF in 2003-2005, whose parents received IVF or ICSI treatment in one of five participating Dutch IVF centers, served as a basis for a retrospective cohort study. Based on gestational age, birthweight, Apgar and congenital malformation, children were assigned to one of three risk strata (low-, moderate- or high-risk). PARTICIPANTS/MATERIALS, SETTING, METHODS: To enhance the efficiency of the data collection, 816 multiples and 584 singletons were selected for 5-year follow-up based on stratified (risk) sampling. Parental informed consent was received of 322 multiples and 293 singletons. Individual-level hospital resource use data (hospitalization, outpatient visits and medical procedures) were retrieved from hospital information systems and patient charts for 302 multiples and 278 singletons. MAIN RESULTS AND THE ROLE OF CHANCE: The risk of hospitalization (OR 4.9, 95% CI 3.3-7.0), outpatient visits (OR 2.6, 95% CI 1.8-3.6) and medical procedures (OR 1.7, 95% CI 1.2-2.2) was higher for multiples compared with singletons. The average hospital costs amounted to euro10 018 and euro2093 during the birth admission period (P < 0.001), euro1131 and euro696 after the birth admission period to the first birthday (not significant (n.s.)) and euro1084 and euro938 from the second to the fifth life year (n.s.) for multiples and singletons, respectively. Hospital costs from birth up to age 5 were 3.3-fold higher for multiples compared with singletons (P < 0.001). Among multiples and singletons, respectively, 90.8 and 76.2% of the total hospital costs were caused by hospital admission days and 8.9 and 25.2% of the total hospital costs during the first 5 years of life occurred after the first year of life. LIMITATIONS, REASONS FOR CAUTION: Resource use and costs outside the hospital were not included in the analysis. WIDER IMPLICATIONS OF THE FINDINGS: This study confirms the increased use of healthcare resources by IVF/ICSI multiples compared with IVF/ICSI singletons. Single-embryo transfer may result in substantial savings, particularly in the birth admission period. These savings need to be compared with the extra costs of additional embryo transfers needed to achieve a successful pregnancy. Besides costs, health outcomes of children born after single-embryo transfer should be compared with those born after double-embryo transfer. STUDY FUNDING/COMPETING INTERESTS: This study was supported by a research grant (grant number 80-82310-98-09094) from the Netherlands Organization for Health Research and Development (ZonMw). There are no conflicts of interest in connection with this article. TRIAL REGISTRATION NUMBER: Not applicable.

Pediatricians in the Netherlands have been confronted with high numbers of refugee children in their daily practice. Refugee children have been recognized as an at-risk population because they may have an increased burden of physical and mental health conditions, and their caretakers may experience barriers in gaining access to the Dutch health care system. The aim of the study was to gain insight into the barriers in the health care for refugee children perceived by pediatricians by analyzing logistical problems reported through the Dutch Pediatric Surveillance Unit, an online system where pediatricians can report predefined conditions. Pediatricians reported 68 cases of barriers in health care ranging from mild to severe impact on the health outcome of refugee children, reported from November 2015 till January 2017. Frequent relocation of children between asylum seeker centers was mentioned in 28 of the reports on lack of continuity of care. Unknown medical history (21/68) and poor handoffs of medical records resulting in poor communication between health professionals (17/68) contributed to barriers to provide good medical care for refugee children, as did poor health literacy (17/68) and cultural differences (5/68). Conclusion: Frequent relocations and the unknown medical history were reported most frequently as barriers impacting the delivery of health care to refugee children. To overcome these barriers, the Committee of International Child Health of the Dutch Society of Pediatrics recommends stopping the frequent relocations, improving medical assessment upon entry in the Netherlands, improving handoff of medical records, and improving the health literacy of refugee children and their families. What is Known: • Pediatricians in the Netherlands are confronted with high numbers of refugee children• Refugee children represent a population that is especially at risk due to their increased burden of physical and mental health conditions What is New: • Refugee children experience barriers in accessing medical care• To start overcoming these barriers, we recommend that frequent relocations be stopped, health assessment upon entry in the Netherlands be improved, medical handoffs be improved, and that the refugees be empowered by increasing their health literacy

Objective:To determine the natural course of zinc protoporphyrin/heme ratio (ZnPP/H) and its role in the detection of iron deficiency (ID) and iron-deficiency anemia (IDA) in the first 4 months of life in moderately preterm infants.Study Design:ZnPP/H was measured at 1 week, 6 weeks and 4 months postnatal age in a prospective cohort of 161 Dutch infants born at a gestational age of 32+0 to 36+6 weeks who did not receive an erythrocyte transfusion or iron supplementation.Results:ZnPP/H levels decreased in the first 6 weeks and increased thereafter. At 4 months postnatal age, ZnPP/H was higher in the 11 (8.5%) infants with IDA (mean (s.d.): 260.8 (16.1)) but not in the 27 (21.3%) infants with ID (mean (s.d.): 177.0 (15.1)) compared with normal infants (mean (s.d.): 157.3 (12.5)).Conclusion:In moderately preterm infants, ZnPP/H can be of additional value to detect infants at risk for IDA due to iron-deficient erythropoiesis at 4 months of age.

OBJECTIVES: Reticulocyte hemoglobin (Ret-Hb) content and soluble transferrin receptor (sTfR) are described as promising biomarkers in the analysis of iron status. However, the value of Ret-Hb and sTfR in the early detection of iron depletion, as frequently observed in children in high-income countries, is unclear. We hypothesized that young children to iron depletion, using the WHO cutoff of ferritin < 12 mu g/l, would have lower Ret-Hb and higher sTfR concentrations compared to children with a ferritin >= level 12 mu g/l. SUBJECTS/METHODS: In this cross-sectional study, we analyzed mean concentrations of Ret-Hb and sTfR in 351 healthy children aged 0.5-3 years in a high-income country. The Student's t-test was used to compare Ret-Hb and sTfR concentrations between groups. RESULTS: We showed that concentrations of Ret-Hb and sTfR are similar in children with and without iron depletion. A decrease in Ret-Hb concentration was present only when ferritin concentrations were < 8 mu g/l. sTfR concentrations were similar in children with ferritin concentrations < 6 mu g/l and >= 12 mu g/l. CONCLUSIONS: Our results showed that the discriminative value of Ret-Hb and sTfR for the detection of iron depletion is limited. Our findings suggest that ferritin is the most useful biomarker in the screening of iron depletion in healthy children in high-income countries. However, ideally, reference ranges of iron status biomarkers should be based on studies showing that children with concentrations outside reference ranges have poor neurodevelopmental outcomes.

Low iron stores in children, absolute iron deficiency (AID), can lead to impaired neurodevelopment and requires iron therapy. In the presence of infection/inflammation, like in cystic fibrosis (CF), serum ferritin (SF) is not a reliable biomarker for AID. Red blood cell distribution width (RDW) is a promising alternative reported not to be influenced by infection in healthy children. Currently, there are no data on the diagnostic capacity of RDW to detect AID in pediatric CF patients. This was a prospective observational study that investigated iron status biomarkers in 53 Dutch pediatric CF patients. AID was defined using World Health Organization criteria for SF in stable patients (no recent pulmonary exacerbation) and C-reactive protein (CRP) ≤10 mg/l. Patients with AID had higher RDW levels than patients without AID (p = 0.019). An RDW ≥13.2% showed the following test statistics: sensitivity 100%; specificity 39.4%; positive predictive value 20%; and negative predictive value 100%. Furthermore, we found a correlation between RDW and CRP in the total group that originated from the stable patients (r = 0.308; p = 0.042). In conclusion, the diagnostic capacity of RDW for detecting AID in pediatric CF patients seems limited because RDW levels might also be influenced by chronic infection/inflammation in these patients.

Poor nutrition and impaired growth of premature infants is associated with adverse consequences in the long term. The overall goal of feeding preterm infants is to mimic intrauterine growth pattern and, as importantly, to obtain a body composition and achieve a functional outcome comparable to term born infants. Over the last decades knowledge on nutrition of preterm infants has accumulated and clinical guidelines on nutritional requirements have been regularly revised. Nevertheless, extrauterine growth restriction is still the rule rather than the exception in preterm infants and is associated with impaired neurocognitive development later in life. Postnatal growth restriction has multifactorial causes, but it has been estimated that about 50% of the variance in early postnatal growth restriction can be attributed to nutrition. In a large proportion of the premature infants the actual dietary intake does not meet the recommended intake during the first weeks of life, while this takes time to establish. Additionally, adequate growth is best achieved with optimal enteral nutrition, but bringing the intestine of a prematurely born infant in a condition that allows administration of sufficient amounts of nutrients takes a while. Once the recommended dietary intake is established it rarely can be maintained during the entire hospital stay due to the possible appearance of complications related to prematurity, such as sepsis, necrotizing enterocolitis or chronic lung disease, which increases the nutrient deficit.

Amino acids play crucial roles as precursors for proteins and neurotransmitters, as transport molecules, and in cell signaling. In this review, we describe the unique functions of the individual amino acids and conclude that the amino acid requirements of parenterally fed neonates are inadequately defined. Parenterally fed neonates are at risk of amino acid deficiency or toxicity because the intestines serve as an important site of metabolism, regulating systemic availability of individual amino acids.

Objective The preservation of nutritional status and growth is an important aim in critically ill infants, but difficult to achieve due to the metabolic stress response and inadequate nutritional intake, leading to negative protein balance. This study investigated whether increasing protein and energy intakes can promote anabolism. The primary outcome was whole body protein balance, and the secondary outcome was first pass splanchnic phenylalanine extraction (SPE(Phe)). Design This was a double-blind randomised controlled trial. Infants (n=18) admitted to the paediatric intensive care unit with respiratory failure due to viral bronchiolitis were randomised to continuous enteral feeding with protein and energy enriched formula (PE-formula) (n=8; 3.1+/-0.3 g protein/kg/24 h, 119+/-25 kcal/kg/24 h) or standard formula (S-formula) (n=10; 1.7+/-0.2 g protein/kg/24 h, 84+/-15 kcal/kg/24 h; equivalent to recommended intakes for healthy infants

Pulse contour methods determine cardiac output semi-invasively using standard arterial access. This study assessed whether cardiac output can be determined non-invasively by replacing the intra-arterial pressure input with a non-invasive finger arterial pressure input in two methods, Nexfin CO-trek and Modelflow , in 25 awake patients after coronary artery bypass surgery. Pulmonary artery thermodilution cardiac output served as a reference. In the supine position, the mean (SD) differences between thermodilution cardiac output and Nexfin CO-trek were 0.22 (0.77) and 0.44 (0.81) l.min(-1) , for intra-arterial and non-invasive pressures, respectively. For Modelflow, these differences were 0.70 (1.08) and 1.80 (1.59) l.min(-1) , respectively. Similarly, in the sitting position, differences between thermodilution cardiac output and Nexfin CO-trek were 0.16 (0.78) and 0.34 (0.83), for intra-arterial and non-invasive arterial pressure, respectively. For Modelflow, these differences were 0.58 (1.11) and 1.52 (1.54) l.min(-1) , respectively. Thus, Nexfin CO-trek readings were not different from thermodilution cardiac output, for both invasive and non-invasive inputs. However, Modelflow readings differed greatly from thermodilution when using non-invasive arterial pressure input.

A multidisciplinary human-centred design approach is presented to tackle complex interacting problems with ICT in healthcare. Especially when Human Factors problems are related to multiple levels, i.e., physical, psychological, team, organizational and political, a systems approach is required. By the case of neonatal equipment alarms it is explained how a framework of ‘Human Factors and Design Thinking’ can be used to identify research questions, methods, research domains and research activities. Cognitive systems engineering could play a major role in solving many problems with ICT in healthcare, a domain where cognitive ergonomics and systems ergonomics has been neglected.

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

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

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

The survival rate for infants born preterm has improved over the last two decades. However, the incidence of moderate and severe neurodevelopmental disability amongst the surviving infants is high, and these infants require prolonged intensive care. Many countries have developed guidelines how and when to treat these infants. Usually, these guidelines are based upon the outcome data of large studies, but social, cultural and economical factors have a major impact on these guidelines as well. Some European countries have set guidelines at when to start treatment based upon gestational age alone. However, recent data show that ethnicity, gender and birth weight are important determinants for survival and morbidity as well. Thus, policies for initiating and withdrawing intensive care for those born extremely preterm should not be based upon gestational age, but infants should have a chance of proving themselves.

Introduction: Lysine is the first limiting essential amino acid in the diet of newborns. First pass metabolism by the intestine of dietary lysine has a direct effect on systemic availability. We investigated whether first pass lysine metabolism in the intestine is high in preterm infants, particularly at a low enteral intake. Patients and methods: Six preterm infants ( birth weight 0.9 ( 0.1) kg) were studied during two different periods: period A ( n = 6): 40% of intake administered enterally, 60% parenterally; lysine intake 92 ( 6) mumol/( kgxh); and period B ( n = 4): 100% enteral feeding; lysine intake 100 ( 3) mumol/( kgxh). Dual stable isotope tracer techniques were used to assess splanchnic and whole body lysine kinetics. Results: Fractional first pass lysine uptake by the intestine was significantly higher during partial enteral feeding ( period A 32 ( 10)% v period B 18 ( 7)%; p

Early detection of iron deficiency (ID) and iron deficiency anemia (IDA) in young children is important to prevent impaired neurodevelopment. Unfortunately, many biomarkers of ID are influenced by infection, thus limiting their usefulness. The aim of this study was to investigate the value of red blood cell distribution width (RDW) and the platelet count for detecting ID(A) among otherwise healthy children. A multicenter prospective observational study was conducted in the Netherlands to investigate the prevalence of ID(A) in 400 healthy children aged 0.5-3years. ID was defined as serum ferritin (SF) 14.3% had a 2.7 higher odds (95% confidence interval [CI]: 1.2-6.3) to be iron deficient, compared with anemic children with a RDW

Background and aims: The objectives of this integrative review were to understand how parents of children with severe developmental disorders experience their involvement in end-of-life decision-making, how they prefer to be involved and what factors influence their decisions. Methods and procedures: We searched MEDLINE, EMBASE, CINAHL and PsycINFO. The search was limited to articles in English or Dutch published between January 2004 and August 2014. We included qualitative and quantitative original studies that directly investigated the experiences of parents of children aged 0-18 years with severe developmental disorders for whom an end-of-life decision had been considered or made. Outcomes and results: We identified nine studies that met all inclusion criteria. Reportedly, parental involvement in end-of-life decision-making varied widely, ranging from having no involvement to being the sole decision-maker. Most parents preferred to actively share in the decision-making process regardless of their child's specific diagnosis or comorbidity. The main factors that influenced parents in their decision-making were: their strong urge to advocate for their child's best interests and to make the best (possible) decision. In addition, parents felt influenced by their child's visible suffering, remaining quality of life and the will they perceived in their child to survive. Conclusions and implications: Most parents of children with severe developmental disorders wish to actively share in the end-of-life decision-making process. An important emerging factor in this process is the parents' feeling that they have to stand up for their child's interests in conversations with the medical team. (C) 2015 Elsevier Ltd. All rights reserved.

De door de vena portae gedraineerde viscera (darm, maag, milt en pancreas) zijn bekend om hun hoge eiwitmetabolisme en energieverbruik. Deze organen dragen dan ook meer bij aan de behoefte van verschillende voedingsstoffen dan op basis van hun gewicht mag worden verondersteld. Doordat de darm als eerste in contact komt met de voeding, kan een hoog verbruik van voedingsstoffen door de darm, een lage systemische beschikbaarheid veroorzaken. In dit artikel bespreken we het energieverbruik van de door de vena portae gedraineerde viscera, welke voedingsbestanddelen daarvoor verbruikt worden, het aminozuurverbruik van de darm onder normale condities, de aanpassing daarop ingeval van een eiwitbeperkt dieet en het hergebruik van aminozuren door de darm. Onze conclusies uit onderzoeken bij continu gevoede biggen zijn de volgende

The objective of this study was to determine whether insulin administration would prevent the well-documented catabolic effect of dexamethasone given to preterm infants with chronic lung disease. We studied leucine metabolism in 11 very-low-birth-weight infants before dexamethasone treatment and on d 2, 4, and 7 thereafter. During the first 4 d of dexamethasone, insulin was administered i.v. at a dose of 0.5 (n = 7) or 1.0 (n = 5) IU/kg/d. Leucine turnover was not significantly different between d 0 (337 +/- 41.3 micromol leucine/kg/h), d 2 (288 +/- 27.2 micromol leucine/kg/h), d 4 (302 +/- 22.1 micromol leucine/kg/h), and d 7 (321 +/- 21.2 micromol leucine/kg/h), and neither was leucine breakdown (272 +/- 21.9 micromol leucine/kg/h on d 0, 225 +/- 21.5 micromol leucine/kg/h on d 2, 231 +/- 21 micromol leucine/kg/h on d 4, and 242 +/- 17.6 micromol leucine/kg/h on d 7). Weight gain rates were significantly lower during the first week of dexamethasone treatment compared with the week before treatment or the second and third week. We conclude that during insulin and corticosteroid administration in very-low-birth-weight infants, no changes were observed in leucine kinetics in contrast to previous studies. The decrease in weight gain was not reversed.

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

The relationship between aortic flow and pressure is described by a three-element model of the arterial input impedance, including continuous correction for variations in the diameter and the compliance of the aorta (Modelflow). We computed the aortic flow from arterial pressure by this model, and evaluated whether, under orthostatic stress, flow may be derived from both an invasive and a non-invasive determination of arterial pressure. In 10 young adults, Modelflow stroke volume (MFSV) was computed from both intra-brachial arterial pressure (IAP) and non-invasive finger pressure (FINAP) measurements. For comparison, a computer-controlled series of four thermodilution estimates (thermodilution-determined stroke volume; TDSV) were averaged for the following positions: supine, standing, head-down tilt at 20 degrees (HDT20) and head-up tilt at 30 degrees and 70 degrees (HUT30 and HUT70 respectively). Data from one subject were discarded due to malfunctioning thermodilution injections. A total of 155 recordings from 160 series were available for comparison. The supine TDSV of 113+/-13 ml (mean+/-S.D.) dropped by 40% to 68+/-14 ml during standing, by 24% to 86+/-12 ml during HUT30, and by 51% to 55+/-15 ml during HUT70. During HDT20, TDSV was 114+/-13 ml. MFSV for IAP underestimated TDSV during HDT20 (-6+/-6 ml; P

Item does not contain fulltext AIM: To evaluate whether increasing the amount of amino acids and energy in parenteral nutrition combined with rapid increment of enteral feeding improves postnatal growth in preterm infants. METHODS: Observational study; two consecutive year-cohorts of preterm infants; Cohort 2 received higher supplementation of parenteral amino acids and energy with more rapid enhancement of enteral feeding than Cohort 1. Nutritional intake, weight and head circumference (HC) were compared. RESULTS: Cohort 2 [N: 79, gestational age (GA): 29.8 +/- 2.2 weeks, birth weight (BW): 1248 +/- 371 g] achieved full enteral feeds earlier (p < 0.001) and had a higher protein/energy intake during the first week (p < 0.001) than Cohort 1 (N: 68, GA: 29.5 +/- 2.3 weeks, BW: 1261 +/- 339 g). Both cohorts developed cumulative protein/energy deficits, but less in Cohort 2 (p < 0.01). Appropriate for gestational age infants (AGA) of Cohort 2 improved weight gain until week 5 (p < 0.01) compared to AGA of Cohort 1, nevertheless all infants demonstrated a decline in mean standard deviation score (>1) for weight at term. Small for GA infants failed to improve HC. CONCLUSION: Improved parenteral intake may lead to improved short-term postnatal weight gain. Faster increase of enteral nutrition was well tolerated but failed to prevent nutritional deficits. Practising early enteral feeding with higher supplementation of nutrients may be needed and requires further study. 01 mei 2013

Functional outcome of preterm infants is highly related to the quality and quantity of nutrients provided during the first few weeks of life. New guidelines, as published by the ESPGHAN in 2010, have provided means to prevent undernutrition in the NICU. Especially proteins and amino acids seem to play a pivotal role, and the optimal regimen has not yet been determined. New data on the intrauterine nutrient supply suggest a high amino acid intake during the fetal period. How these results might translate into improvement of especially neurocognitive outcome needs to be investigated.

STUDY QUESTION: What is the cost-effectiveness of elective single embryo transfer (eSET) versus double embryo transfer (DET) strategies from a societal perspective, when applying a time horizon of 1, 5 and 18 years?SUMMARY ANSWER: From a short-term perspective (1 year) it is cost-effective to replace DET with single embryo transfer; however when intermediate- (5 years) and long-term (18 years) costs and consequences are incorporated, DET becomes the most cost-effective strategy, given a ceiling ratio of €20 000 per quality-adjusted life years (QALY) gained.WHAT IS ALREADY KNOWN: According to previous cost-effectiveness research into embryo transfer strategies, DET is considered cost-effective if society is willing to pay around €20 000 for an extra live birth. However, interpretation of those studies is complicated, as those studies fail to incorporate long-term costs and outcomes and used live birth as a measure of effectiveness instead of QALYs. With this outcome, both multiple and singletons were valued as one live birth, whereas costs of all children of a multiple were incorporated.STUDY DESIGN, SIZE, DURATION: A Markov model (cycle length: 1 year; time horizon: 1, 5 and 18 years) was developed comparing a maximum of: (i) three cycles of eSET in all patients; (ii) four cycles of eSET in all patients; (iii) five cycles of eSET in all patients; (iv) three cycles of standard treatment policy (STP), i.e. eSET in women PARTICIPANTS/MATERIALS, SETTING, METHODS: Expected life years (LYs), child QALYs and costs were estimated for all comparators. Input parameters were derived from a retrospective cohort study, in which hospital resource data were collected (n=580) and a parental questionnaire was sent out (431 respondents). Probabilistic sensitivity analysis (5000 iterations) was performed.MAIN RESULTS AND THE ROLE OF CHANCE: With a time horizon of 18 years, DETx3 is most effective (0.54 live births, 10.2 LYs and 9.8 QALYs) and expensive (€37 871) per couple starting IVF. Three cycles of eSET are least effective (0.43 live births, 7.1 LYs and 6.8 QALYs) and expensive (€25 563). We assumed that society is willing to pay €20 000 per QALY gained. With a time horizon of 1 year, eSETx3 was the most cost-effective embryo transfer strategy with a probability of being cost-effective of 99.9%. With a time horizon of 5 or 18 years, DETx3 was most cost-effective, with probabilities of being cost-effective of 77.3 and 93.2%, respectively.LIMITATIONS, REASONS FOR CAUTION: This is the first study to use QALYs generated by the children in the economic evaluation of embryo transfer strategies. There remains some disagreement on whether QALYs generated by new life should be used in economic evaluations of fertility treatment. A further limitation is that treatment ends when it results in live birth and that only child QALYs were considered as measure of effectiveness. The results for the time horizon of 18 years might be less solid, as the data beyond the age of 8 years are based on extrapolation.WIDER IMPLICATIONS OF THE FINDINGS: The current Markov model indicates that when child QALYs are used as measure of outcome it is not cost-effective on the long term to replace DET with single embryo transfer strategies. However, for a balanced approach, a family-planning perspective would be preferable, including additional treatment cycles for couples who wish to have another child. Furthermore, the analysis should be extended to include QALYs of family members.STUDY FUNDING/COMPETING INTERESTS: This study was supported by a research grant (grant number 80-82310-98-09094) from the Netherlands Organization for Health Research and Development (ZonMw). There are no conflicts of interest in connection with this article.TRIAL REGISTRATION NUMBER: Not applicable.

A large number of very-low-birth weight infants are fed formulas containing medium-chain triglycerides (MCT) to enhance fat and calcium absorption. Studies are available on the intestinal absorption of MCT, which is nearly complete, but uncertainties exist on the metabolic fate of octanoic acid, the major component of MCT. Oxidation accounts for approximately 50% of the dietary intake, and losses as dicarboxylic acids in the urine are negligible. Since storage in adipose tissue is limited, conversion into long-chain fatty acids (LCFA) is likely to be an important route. To study the nonoxidative metabolism of MCT, six preterm infants fed a standard premature formula containing 38 weight% (wt%) MCT (54 mol% medium-chain fatty acids (MCFA), of which 35 mol% is octanoic acid) were studied at 4 weeks of age, when on full oral intake and receiving on average 130 kcal/kg/d. The study consisted of an oral primed constant-rate infusion of [13C]-octanoate and the measurement of the 13C enrichment of individual fatty acids in plasma triglycerides (TG) by a highly sensitive on-line combustion method using gas chromatography-isotope ratio mass spectrometry (GC-IRMS). We observed a significant incorporation of the dietary [13C]-octanoic acid in plasma TG (10.0% +/- 4.5% of the enrichment of the diet). A noticeable incorporation of the label was detected in myristic and palmitic acids (4.6% +/- 2.5% and 7.8% +/- 4.1% of the octanoic enrichment of the diet). The absolute amount of the fatty acids was studied with conventional GC, and the plasma TG fatty acid profile differed markedly from the diet.(ABSTRACT TRUNCATED AT 250 WORDS)

Glucose production and oxidation were measured in ventilated preterm appropriate-for-gestational-age and small-for-gestational-age infants on the first day of life. Using a new technique of NaH13CO3 infusion followed by a [U-13C]glucose infusion, we measured glucose oxidation rates without measuring the CO2 production rate. Infants were studied at 18 +/- 4 h (mean +/- 1 SD) of life and received parenterally administered glucose only (4.2 +/- 0.5 mg.kg-1 x min-1). In 13 of 16 patients, the glucose production rate exceeded 1.0 mg.kg-1 x min-1. Infants born from mothers who had been receiving steroids antenatally had higher glucose production rates (2.3 +/- 1.1 mg.kg-1 x min-1) compared with infants from mothers who had not (1.1 +/- 0.8 mg.kg-1 x min-1, p = 0.036). The glucose oxidized (2.9 +/- 1.0 mg.kg-1 x min-1) was lower than the amount of glucose infused (p = 0.005) and was not different for appropriate-for-gestational-age and small-for-gestational-age infants. Plasma levels of glucose, insulin, glucagon, and total IGF-I were not correlated with glucose metabolism on the first day of life. Total IGF-II levels were negatively correlated with the rate of glucose appearance. We conclude that preterm infants on the first day of life receiving a glucose infusion of 4.2 mg.kg-1 x min-1 continue to produce glucose. The glucose oxidation rate is lower than the glucose infusion rate and the contribution of glucose oxidation to the total energy expenditure is limited.

Transient hyperinsulinaemia is a well-known cause of hypoglycaemia in newborn infants. The hypoglycaemia may be caused by a decreased glucose production and/or an increased glucose uptake. Whether the increased uptake is caused by increased glucose oxidation or increased non-oxidative disposal is not known. The aim of this study was to investigate the fate of the large amount of glucose infused in a term infant who developed hypoglycaemia due to transient hyperinsulinaemia shortly after birth and was treated with high glucose infusions. On day 6 an indirect calorimetry study was performed, together with a glucose turnover study. Carbohydrate intake was 13.6 mg/kg per minute (19.6 g/kg per day). Both studies were repeated on day 11, when carbohydrate intake was normalised to 7.8 mg/kg per minute (11.2 g/kg per day). Glucose oxidation was 28% higher and non-oxidative glucose disposal was 257% higher on day 6 as compared to day 11. Our results indicate that hypoglycaemia during hyperinsulinism is the result of increased non-oxidative disposal of glucose and not increased glucose oxidation. The results indicate a remarkable capacity of the newborn for lipogenesis during high carbohydrate intake.

Several formulas for preterm infants contain medium-chain triglycerides (MCT) to enhance fat absorption. Although fat absorption with MCT was slightly higher in several studies in preterm infants, a beneficial effect on growth has only been reported in one publication. We hypothesized that when part of the fat blend of preterm formula is substituted by MCT oil, this might lead to a different metabolic pattern in which, due to the preferential oxidation of MCT, an increase in lipogenesis from glucose could lead to an increase in metabolic rate. To study the impact of MCT on glucose metabolism, 18 preterm infants were randomized to receive either an MCT or an LCT formula containing 38- and 6%-by-weight medium-chain fatty acids, respectively, in their fat blend. At 4 wk of age, the metabolic rate, substrate utilization, glucose kinetics, and oxidation were measured by indirect respiratory calorimetry in combination with a constant-rate oral infusion of [U-13C]glucose. The "true" rate of appearance of glucose (Ra "true") was measured from the dilution of the uniformly labeled (m + 6) species of infused tracer, whereas "apparent" rate of appearance of glucose (Ra "apparent") was measured from the dilution of infused tracer C (carbon). The latter was measured by an on-line combustion method using a gas chromatograph-isotope ratio mass spectrometer. At a carbohydrate intake of 8.4 mg.kg-1.min-1, total utilization of carbohydrate was equal in both groups at 7.6 mg.kg-1.min-1.(ABSTRACT TRUNCATED AT 250 WORDS)

International audience; The number of surviving children born prematurely has increased substantially during the last 2 decades. The major goal of enteral nutrient supply to these infants is to achieve growth similar to foetal growth coupled with satisfactory functional development. The accumulation of knowledge since the previous guideline oil nutrition of preterm infants from the Committee oil Nutrition of the European Society of Paediatric Gastroenterology aid Nutrition in 1987 has made a new guideline necessary. Thus, all ad hoc expert panel was convened by the Committee oil Nutrition of the European Society of Paediatric Gastroenterology, Hepatology, and Nutrition in 2007 to make appropriate recommendations. The present guideline, of which the major recommendations are summarised here (for the full report, see http://links.lww.com/A1480). is consistent with, but not identical to, recent guidelines from the Life Sciences Research Office of the American Society for Nutritional Sciences published in 2002 and recommendations from the handbook Nutrition of the Preterm Infant. Scientific Basis (aid Practical Guidelines, 2nd ed, edited by Tsang et al, and published in 2005. The preferred food for premature infants is fortified human milk from the infant's own mother, or, alternatively, formula designed for premature infants. This guideline aims to provide proposed advisable ranges for nutrient intakes for stable-growing preterm infants up to a weight of approximately 1900 g because most data are available for these infants. These recommendations are based on a considered review of available scientific reports oil the Subject, and on expert consensus for which the available scientific data are considered inadequate.

1. We investigated the effects of starting amino acid administration on post-natal day 2 on protein turnover and nitrogen balance in appropriate-for-gestational-age, very-low-birth-weight infants. Eighteen infants were divided into two groups. Group A received from day 2 onwards an amino acid solution, whereas group B started on this solution after day 4. Both groups were exclusively parenterally fed, 200 kJ day−1 kg−1 on post-natal days 3 and 4. Group A (birth weight 1.5 ± 0.3 kg) received 4.6 g of glucose, 1.9 g of fat and 2.3 g of amino acids day−1 kg−1 body weight. Group B (birth weight 1.4 ± 0.2 kg) received 7.0 g of glucose and 1.9 g of fat day−1 kg−1 body weight. 2. At post-natal day 3, a primed constant infusion of 3 mg of [15N]glycine day−1 kg−1 was given. Protein flux, protein synthesis and protein breakdown were calculated from the 15N enrichment in urinary ammonia. In five out of nine infants in group B no plateau of 15N enrichment in urinary urea could be detected, whereas in group A two out of nine infants did not reach a plateau. For this reason we did not use the end product urea for our calculations. 3. The administration of the amino acids resulted in a higher protein flux (6.9 ± 1.5 g day−1 kg−1 versus 5.2 ± 0.9 g day−1 kg−1) and a higher protein synthesis rate (6.0 ± 1.4 g day−1 kg−1 versus 4.6 ± 0.8 g day−1 kg−1) in group A. There was no statistically significant difference in protein breakdown. The administration of amino acids reversed a negative protein balance (−0.6 ± 0.2 g day−1 kg−1) into a positive one (1.4 ± 0.2 g day−1 kg−1. No adverse effects of the amino acid infusion were seen. 4. We conclude that the early introduction of amino acids has, even at this relatively low energy intake of 200 kJ day−1 kg−1, a positive effect on protein balance by increasing protein synthesis.

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

To the Editor. — With great interest, we read the article by Clark et al1 published in the December 2007 issue of Pediatrics. The authors concluded that higher doses of amino acid supplementation did not improve neonatal growth, and might even be unfavorable in terms of metabolic tolerance (increased blood amino acid and urea nitrogen levels). However, we have some comments. Blood chemistry results, including amino acid concentrations, are reported for postnatal days 1, 7, and 28. Regrettably, no such information is provided for day 4, which shows a peak amino acid intake in the “high-dose group” and the largest difference in amino acid intake between groups. We also learn that, for most infants, the parenteral nutrition had been gradually replaced by enteral nutrition. Except for a single value on day 7, however, no …

OBJECTIVE. Young adults who were born very preterm or with a very low birth weight remain at risk for physical and neurodevelopmental problems and lower academic achievement scores. Data, however, are scarce, hospital based, mostly done in small populations, and need additional confirmation. METHODS. Infants who were born at RESULTS. Of 959 surviving young adults, 74% were assessed and/or completed the questionnaires. Moderate or severe problems were present in 4.3% for cognition, 1.8% for hearing, 1.9% for vision, and 8.1% for neuromotor functioning. Using the Health Utility Index and the London Handicap Scale, we found 2.0% and 4.5%, respectively, of the young adults to have ≥3 affected areas in activities and participation. Special education or lesser level was completed by 24%, and 7.6% neither had a paid job nor followed any education. Overall, 31.7% had ≥1 moderate or severe problems in the assessed areas. CONCLUSIONS. A total of 12.6% of young adults who were born very preterm and/or with a very low birth weight had moderate or severe problems in cognitive or neurosensory functioning. Compared with the general Dutch population, twice as many young adults who were born very preterm and/or with a very low birth weight were poorly educated, and 3 times as many were neither employed nor in school at age 19.

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

Introduction Albumin is one of the most important proteins in plasma and plays a key role in physiological processes like preservation of colloid osmotic pressure and binding of bilirubin and drugs. However, albumin concentrations are often low during the first days of life in preterm infants. We hypothesized that early parenteral lipid and high dose amino acid (AA) administration from birth onwards to very low birth weight (VLBW) infants increases hepatic albumin synthesis rates and albumin concentration. Methods Inborn VLBW infants were randomized to one of three different parenteral nutritional regimens within 6hrs after birth (Figure 1). Lipids were started at 2 g/(kg.d) and increased to 3 g/(kg.d) the following day. At postnatal day 2, infants received a primed continuous infusion of [ 13 C 6 , 15 N]leucine. Mass spectrometry was used to determine the fractional and absolute albumin synthesis rates (FSR and ASR, respectively). Results Albumin FSR, concentration, and ASR were not significantly different between groups (Figure 2; median, IQR). Conclusion Albumin concentration was in normal range in all groups. Albumin synthesis rates and concentration are not increased upon introduction of 2g lipids/(kg.d) and 3.6g AA/(kg.d) from birth onwards.

Preterm infants are at risk of iron deficiency (ID). In the Netherlands, preterm infants born after 32 weeks of gestational age (GA) do not receive iron supplementation on a routine basis. We hypothesized that dietary iron intake in these infants might not be sufficient to meet the high iron requirements during the first 6 months of life.Subjects/methods:In a prospective cohort study, we analyzed the prevalence and risk factors of ID in 143 infants born between 32+0 and 36+6 weeks GA who did not receive iron supplementation.Results:ID at the age of 4 and 6 months was present in 27 (18.9%) and 7 (4.9%) infants. Results of a multivariable logistic regression analysis showed that ID was associated with lower birth weight, a shorter duration of formula feeding, more weight gain in the first 6 months of life and lower ferritin concentrations at the age of 1 week.Conclusions:Preterm infants born after 32 weeks GA have an increased risk of ID compared with those born at term, supporting the need of iron supplementation. Our results suggests that measurement of ferritin at the age of 1 week might be useful to identify those infants at particular risk and could be used in populations without general supplementation programs. However, the efficacy and safety of individualized iron supplementation, based on ferritin concentrations at the age of 1 week, together with other predictors of ID, needs to be further investigated, preferably in a randomized controlled trial.