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Position paper of the Federal Association of German Hospital Pharmacists, the nutrition committees of the German and Austrian Societies of Pediatrics and Adolescent Medicine and the working group on intestinal failure of the Society of Pediatric Gastroenterology and Nutrition. In 2019 the German Federal Institute for Drugs and Medical Devices (Bundesinstitut fur Arzneimittel und Medizinprodukte, BfArM) launched a “doctors letter” (Rote-Hand-Brief) recommending light protection of all parenteral nutrition (PN) solutions during administration for preterm infants, term infants and children less than 2 years of age. The aim of the present paper is to review the available evidence and provide evidence-based recommendations for hospital and home PN light protection in children. The Federal Association of German Hospital Pharmacists, the nutrition committees of the German and Austrian Societies of Pediatrics and Adolescent Medicine and the working group on intestinal failure of the Society of Pediatric Gastroenterology and Nutrition recommend in accordance with the recommendations of the ESPGHAN, ESPEN, ESPR and CESPEN guidelines on pediatric parenteral nutrition: 1. Lipid emulsions and/or vitamins containing PN solutions should be protected from light during administration (bags and tubing) to prevent the generation of oxidants. 2. There is no conclusive evidence for recommending light protection for PN solutions without lipid emulsions and without vitamins during administration (solutions containing, e.g. amino acids, glucose, electrolytes, or trace elements). In addition, in home PN non-light-protected spiral tubing may be used because validated light-protected spiral tubing is currently not available, given that spiral tubing improves the range of motion and safety in infants and young children.

ZusammenfassungEine tägliche Vitamin-D-Supplementierung für Säuglinge bis zum zweiten erlebten Frühsommer zur Prävention der Rachitis und die Gabe von Vitamin K1 bei Neugeborenen zur Prävention von Vitamin-K-Mangel-Blutungen sind empfohlen.Seit einiger Zeit sind in Österreich Kombinationsprodukte der beiden fettlöslichen Vitamine D3 und K2 auf dem Markt erhältlich, die mit gesundheitsfördernden Effekten wie verbesserter Knochenmineralisation und Schutz vor vaskulärer Kalkeinlagerung beworben werden.Die Wirkung einer kombinierten Supplementierung von Vitamin D und Vitamin K2 bei Kindern ist aus physiologischer Sicht gesehen zwar potenziell sinnvoll, um Effekt, Risiken oder unerwünschte Nebenwirkungen zu evaluieren. Zuvor werden aber Dosisfindungs- und Sicherheitsstudien für die kombinierte Verabreichung benötigt. Insbesondere sind randomisierte kontrollierte Studien bei Risikokindern und Frühgeborenen notwendig. Solange diese Daten nicht vorliegen, erscheint die Gabe von Vitamin D in Kombination mit Vitamin K2 im Kindesalter nicht gerechtfertigt und kann daher auch nicht empfohlen werden.

Zusammenfassung Hintergrund Die Leitlinien der „European Society for Paediatric Gastroenterology, Hepatology and Nutrition“ (ESPGHAN) liefern evidenzbasierte Empfehlungen zu parenteraler Ernährung (PE) von Frühgeborenen und kranken Neugeborenen. Im Jahr 2013 wurde gezeigt, dass sie in Westeuropa nur teilweise angewendet werden und ihre klinische Implementierung verbessert werden sollte. Ziel der Arbeit Ziel dieser Arbeit ist, die derzeitige Anwendung der ESPGHAN-Leitlinien in Deutschland sowie Barrieren, die die Umsetzung verhindern, abzubilden. Material und Methoden Zusammen mit einer Expertengruppe und Institutionen aus dem deutschsprachigen Raum hat die „European Foundation for the Care of Newborn Infants“ (EFCNI) eine Befragung durchgeführt. Mit einem Online-Fragebogen wurden Pädiaterinnen/Pädiater (PÄD) und Krankenhausapothekerinnen/Krankenhausapotheker (KHA) aus deutschen Perinatalzentren und Krankenhausapotheken bezüglich der Umsetzung der Leitlinien befragt. Die Ergebnisse wurden qualitativ und quantitativ ausgewertet. Ergebnisse und Diskussion Von 558 angeschriebenen Kontakten wurden 196 gültige Umfragen ausgewertet. Nach Eigenangaben wenden 77 % der PÄD und 48 % der KHA die ESPGHAN-Leitlinien an. Barrieren wurden innerhalb der klinischen Anwendung identifiziert und waren teilweise struktureller und/oder organisatorischer Natur. Verbesserungsbedarf wurde in der Bereitstellung von parenteralen Standardlösungen, insbesondere am Wochenende, und elektronischen Verordnungssystemen, der Verabreichung von Lipiden bereits am 1. Lebenstag und der regelmäßigen Beurteilung aller Laborparameter beobachtet.

Das Zytomegalievirus (CMV) kann wahrend der Laktation reaktiviert und uber Muttermilch ubertragen werden. Diese Ubertragung ist fur reife Neugeborene in der Regel unproblematisch, kann aber bei Fruhgeborenen zu einer CMV-Infektion mit Veranderungen des Blutbildes und der Leberfunktionsparameter, sepsisartigen Symptomen und gastrointestinalen Symptomen wie blutigen Stuhlen bis hin zur nekrotisierenden Enterokolitis fuhren. Je unreifer das Fruhgeborene bei der Geburt ist, umso hoher ist die Wahrscheinlichkeit einer via Muttermilch ubertragenen CMV-Infektion. Um extreme Fruhgeborene vor einer CMV-Infektion zu schutzen, empfiehlt die Ernahrungskommission der Osterreichischen Gesellschaft fur Kinder- und Jugendheilkunde, die Muttermilch von CMV-positiven Muttern (IgM-neg., IgG-pos.) bei Fruhgeborenen mit einem Gestationsalter

Objective To examine whether parenteral nutrition using a mixed lipid emulsion containing fish oil improves the neurodevelopmental outcomes of extremely low birth weight infants. Study design The study is a secondary outcome analysis of a double-blind randomized trial of 230 extremely low birth weight infants performed at a single level IV neonatal care unit (Medical University Vienna; June 2012 to June 2015). Participants received either a mixed lipid emulsion composed of soybean oil, medium chain triglycerides, olive oil, and fish oil, or a soybean oil-based lipid emulsion for parenteral nutrition. Neurodevelopment of study participants was assessed at 12 and 24 months corrected age (August 2013 to October 2017) using the Bayley Scales of Infant-Toddler Development, third edition. Results At discharge, 206 of the 230 study participants were eligible. At 12 and 24 months corrected age, 174 of 206 (85%) and 164 of 206 (80%) infants were evaluated. At 12 months, there was no significant difference in cognitive (mixed lipid: median, 95 [IQR, 85-101]; soybean oil: median, 95 [IQR, 85-100]; P = .71), language (mixed lipid: median, 86 [IQR, 77-94], soybean oil: median, 89 [IQR, 79-94]; P = .48), or motor scores (mixed lipid: median, 88 [IQR, 76-94], soybean oil: median, 88 [IQR, 79-94]; P = .69). At 24 months, there was again no significant difference in cognitive (mixed lipid: median, 95 [IQR, 80-105], soybean oil: median, 95 [IQR, 90-105]; P = .17), language (mixed lipid: median, 89 [IQR, 75-97], soybean oil 89 [IQR, 77-100]; P = .54), and motor scores (mixed lipid: median, 94 [IQR, 82-103], soybean oil: median, 94 [IQR, 85-103]; P = .53). Conclusions Parenteral nutrition using a mixed lipid emulsion containing fish oil did not improve neurodevelopment of extremely low birth weight infants at 12 and 24 months corrected age. Trial registration ClinicalTrials.gov : NCT01585935 .

Introduction Bleeds such as intra-ventricular (IVH) and pulmonary haemorrhage (PH) are life-threatening events in extremely low birth weight (ELBW) infants. Serial coagulation monitoring by measuring the international normalized ratio (INR) with small volume samples might facilitate early diagnosis and possibly prevent major bleeds. Materials and Methods This was a prospective longitudinal study performed in ELBW infants, who received serial INR monitoring by point of care testing during their first 30 days of life. The primary objective was to explore whether INR monitoring could predict major bleeding events (IVH, PH). Secondary objectives were mortality and feasibility in this patient population. Results A total of 127 ELBW infants were stratified into a bleeding and a non-bleeding group. Bleeding events occurred in 31% (39/127) of the infants, whereupon 24% developed IVH and 9% PH. Infants in the bleeding group were 4 days younger at birth (p = 0.05) and had a substantially higher mortality rate of 26% versus 5% in controls (p = 0.005). Median INR during the first 3 days before a bleeding event was 1.55 (95% confidence interval [CI]: 1.39–1.74) compared with the control group with 1.45 (95% CI: 1.44–1.58; p = 0.81). Platelet counts were significantly lower in the bleeding group on the 3rd day and during the 2nd to 4th week of life. Discussion Serial coagulation monitoring by an INR point of care testing is feasible in ELBW infants but could not predict bleeding events. Further studies with daily monitoring of INR and platelet counts during the first days of life might be able to more precisely detect a risk of major haemorrhage in ELBW infants.

BACKGROUND Preterm birth is a medical emergency and it is becoming evident that adequate nutrition starting in the first hours of life is of major importance for short and even more so for long-term health outcomes of the premature newborn. The aim was to analyze postnatal nutrient supply and growth patterns of preterm infants in response to a standardized feeding protocol during stay at neonatal intensive care unit (NICU). METHODS A prospective cohort study was conducted at NICU, Children Hospital Graz. Infants were divided in two groups

Stillen bzw. die Futterung von Muttermilch ist die optimale Ernahrung fur das Neugeborene und beeinflusst Gesundheit, Wachstum, Abwehr und Entwicklung positiv. Mutter sollten im Wochenbett bestmogliche Unterstutzung erfahren, um eine ausreichende Laktation zu etablieren. Fur die meisten Neugeborenen ist ausschliesliches Stillen wahrend der ersten Lebenstage ausreichend. Es gibt aber einige wenige medizinische Indikationen, bei denen ein kurzfristiges Zufuttern notig sein kann. Die Academy of Breastfeeding Medicine (ABM) gibt hierzu eine praktikable Hilfestellung, die unter Berucksichtigung der Kriterien der „Baby-friendly Hospital Initiative“ (BFHI) der WHO notwendige medizinische Indikationen fur Zufuttern klar definiert. Dies konnen sowohl kindliche (z. B. Gewichtsabnahme >10 %) als auch mutterliche (z. B. passagere Medikamenteneinnahme von mit dem Stillen nichtvereinbarer Medikamente) Indikationen sein. Besteht tatsachlich eine Indikation zum Zufuttern, sollte in erster Linie abgepumpte Muttermilch oder pasteurisierte Frauenmilch verwendet werden. Ist diese nicht vorhanden, stehen Formulanahrungen zur Verfugung. Auch fur die „spaten Fruhgeborenen“ (geboren zwischen der 34 + 0 und 36 + 6 Schwangerschaftswoche) ist Muttermilch die optimale Ernahrung. Aufgrund der speziellen Bedurfnisse und des erhohten Nahrstoffbedarfs dieser Patientengruppe muss diese engmaschiger uberwacht werden. Anreicherung der Muttermilch mit Muttermilchsupplementen, Nachpumpen nach dem Stillen zur Laktationsanregung und Trinkwiegungen sind hilfreiche Masnahmen, um das Gedeihen des spaten Fruhgeborenen zu uberwachen und zu optimieren.

Aim This study compared the impact of using either single donor breast milk or formula to start enteral feeding in preterm infants, on the time to full enteral feeding, growth and morbidity. The milk was provided by other preterm mothers. Methods This was an observational prospective study, carried out from June 2012 - March 2013 at the Medical University of Vienna, Austria, on the effects of preterm single donor milk on 133 very low birth weight infants with a birth weight

Several studies have shown a relation between the size of corpus callosum (CC) and outcome in preterm infants. Three-dimensional ultrasound (3D-US) offers new perspectives in cerebral imaging. To establish reference values for biometry of the CC in very low birth weight infants and to correlate these measurements to neurodevelopmental outcome at 5 years of age.Forty-three preterm infants with a gestational age32 weeks were included. Transfontanellar 3D-US measurements were obtained at nine different timepoints.3D-US-based reference values for size, length, circumference and surface area of the CC could be established. Measurements at term-equivalent age showed a correlation to neurodevelopment outcome.Reliable biometric data of the CC can be established in preterm infants by 3D-US and correlate with neurodevelopmental outcome.

Iatrogenic gastrointestinal perforations are rare, but life-threatening events in preterm infants.Aim of the study was to report on incidence, management, morbidity, and mortality.This was a retrospective analysis performed at a tertiary neonatal intensive care unit in Vienna, Austria.Extremely low birth weight infants (ELBW, birth weight 1000 g) with perforations of the upper gastrointestinal tract (GIT) caused by gastric tubes were included.All ELBW infants born within the 6-year study period were identified and their discharge summaries or notes were screened for esophageal and gastric perforations. Data on incidence, management of GIT perforations, morbidity, and mortality were obtained.During a 6-year study period 646 ELBW infants were analyzed. Incidence of perforations was 1.1% (n = 7/646). Median gestational age was 23 + 3 (range: 23 + 0-24 + 5). Perforations occurred on the third day of life (=median, range: day 2-14) and were primarily managed conservatively. Enteral feeding was stopped for 6 days (range: 4-13 days), antibiotic therapy administered for 16 days (range: 8-22 days). In one infant, gastrorrhaphy was performed.Conservative treatment of upper GIT perforations led to spontaneous recovery without major complications in 85.7%.

There is increasing evidence that unconscious bias can affect realworld decision-making processes in publication just as in many other fields.1 In response, the editorial board of Pediatric Research is working to investigate and reduce the bias in the publication acceptance rates in order to preserve the integrity of the peer review process and publication. As news items have suggested that gender bias is a major problem in academia,2 we reviewed papers submitted between 1 November 2017 and 9 August 2018 to Pediatric Research. Encouragingly, we found that the acceptance rates of manuscripts were not significantly different between corresponding authors who were male or female. However, we incidentally uncovered a higher rejection rate in the manuscripts where the corresponding author had a name that could not be identified as either male or female and did not have a picture on their website so that we could identify their gender.3 It is important to point out that we do not know the reason for this, but its identification is the first step to further exploration, including assessing whether unconscious bias may play a role […]

It is well established that nutrition during the first 1,000 days of life can have a long-term effect on growth, metabolic outcome, and long-term health. We review the long-term anthropometric follow-ups of children with risk of later morbidity: (a) very-low-birth-weight (VLBW) infants who have birth weights

Aim This study measured the composition of preterm human breastmilk, particularly the protein content, with the MIRIS Human Milk Analyser, compared our results with published values and determined the relationship between protein content and lactation period. Methods We analysed 83 samples of 24-hour pooled human milk from 76 mothers who delivered preterm infants weighing under 1500 g at less than 32 weeks of gestational age. The milk's protein, fat and energy were measured by the MIRIS Human Milk Analyser and compared to reference values. The relationship between protein content and lactation period was quantified. Results On average, the samples contained 1.1 ± 0.37 g (0.2–2.2 g) of protein, 3.2 ± 0.85 g (range 1.1–6.1 g) of fat, 6.6 ± 0.34 g of lactose (5.5–8.0 g) and 60 ± 11 kcal (39–94 kcal) of energy per 100 mL. The wide variations in macronutrient content were not influenced by the gestational age of the infant and the lactation day results from 70 of the mothers correlated inversely with the protein content (p < 0.0001; r = −0.42). The MIRIS proved useful, but some adjustments are needed. Conclusion Variations in macronutrients were high in the breastmilk of women who delivered preterm babies and the protein content decreased with lactation. With adjustments, the MIRIS might provide a helpful tool for individualised fortification.

A new "ready-to-use" triple-chamber container, Numeta (Baxter, Deerfield, IL), is available for preterm parenteral nutrition (PN) to provide nutrients according to the recommendations of the European Society for Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) and the European Society for Clinical Nutrition and Metabolism (ESPEN) Guidelines for Pediatric Parenteral Nutrition. We investigated the clinical application of Numeta compared with individualized PN in preterm infants (≤1.500 g) and evaluated the effects on nutrient intake, costs, and preparation time.In a clinical observational study, prescriptions for preterm infants were performed with the new prescription software catoPAN (Cato Software Solutions, Becton Dickinson, Vienna, Austria). Individualized PN and Numeta prescriptions were mirrored, and nutrition content of the PNs was compared with each other and with ESPGHAN/ESPEN recommendations. Furthermore, costs and preparation time were assessed.In total, 374 PN solutions (1000 g [n = 333]/≤1000 g [n = 41]) were analyzed. Protein intake with Numeta was significantly lower compared with individualized PN and did not meet the recommendations for infants1500 g during the first day and the period of transition after birth. Energy intake was significantly higher with Numeta. The costs for Numeta preparations were €18 (about US$20) higher than for individualized PN. However, the preparation time/solution was 2 minutes faster with Numeta.Numeta is an alternative to individualized PN for infants1000 g in the period of stable growth when enteral feedings have already started. Protein intake is significantly lower than in individualized PN solutions. Numeta is more expensive in comparison to individualized PN but saves human resources.

Summary Objective Ketogenic parenteral nutrition (kPN) is indicated when enteral intake is temporarily limited or impossible, but evidence‐based prescriptions are lacking. Objective was to evaluate the efficacy and safety of kPN in children with epileptic encephalopathies using a new computer‐based algorithm for accurate component calculating. Methods Children with epilepsy receiving kPN were included. A computer‐based algorithm was established on the basis of guidelines of the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN): fat intake not exceeding 4 g/kg/day, age‐adequate supply of protein, electrolytes, vitamins, and trace elements, but reduced carbohydrates. Primary outcome was successfully reaching relevant ketosis, defined as beta‐hydroxybutyrate plasma level of ≥ 2 mmol/L. Efficacy was defined as seizure reduction ≥50% in de novo kPN and maintenance of response in children already on a ketogenic diet (KD). Safety was assessed by adverse effects, laboratory findings, and the appropriateness of nutritional intake. Results Seventeen children (median 1.84 years) were studied, of which 76% (13/17) were already on an oral ketogenic diet. Indications for kPN were surgery, status epilepticus, vomiting, food refusal, and introduction of enteral feeding in neonates. The parenteral fat/nonfat ratio was mean 0.9 (±0.3; range 0.6–1.5). Relevant ketosis was reached in 10 children (median 2.9 mmol/L), but not in 7 (median = 1.4 mmol/L). In de novo kPN, significant response was observed in 50% (2/4); in patients previously responding to the KD (77%, 10/13), response was maintained. A significant correlation between the degree of ketosis and seizure reduction (correlation coefficient = 0.691; p = .002) was observed. Only mild and transient adverse events occurred during kPN. Significance KPN with fat intake of 3.5–4.0 g/kg/day was safe and effective. KPN was tailored according to guidelines and individual nutritional needs. In nearly half of the patients, ketosis was lower than during oral KD. Despite this, seizures remained controlled.

Objective To evaluate the acceptance, adherence, and feasibility of fortifier administration by finger feeder during breastfeeding and to determine weight, length, and head circumference gains after discharge for preterm infants. Design Observational pilot study. Setting A Level III NICU and its outpatient clinic in Vienna, Austria. Participants Infants born at younger than 34 weeks gestation were included. Methods Mothers were screened in a tertiary NICU and trained by certified lactation consultants to administer fortifier with a finger feeder during breastfeeding. Data on finger feeder use at home were collected by self-reported feeding diaries and questionnaires. Results In total, data from 24 mother–infant dyads were analyzed. The acceptance rate was 67%. In 41.7%, more than 50% of meals were fortified. Mothers did not report problems in preparation, but 33% of the infants stopped latching on or drooled milk during finger feeder use. Conclusion Use of a finger feeder to administer fortifier to preterm infants enabled mothers to exclusively breastfeed their infants and meet their nutritional needs. The development of further methods to augment preterm infant nutrition that do not interfere with breastfeeding is of great interest.

Human milk banks play an essential role by providing human milk to infants who would otherwise not be able to receive human milk. The largest group of recipients are premature infants who derive very substantial benefits from it. Human milk protects premature infants from necrotizing enterocolitis and from sepsis, two devastating medical conditions. Milk banks collect, screen, store, process, and distribute human milk. Donating women usually nurse their own infants and have a milk supply that exceeds their own infants' needs. Donor women are carefully selected and are screened for HIV-1, HIV-2, human T-cell leukemia virus 1 and 2, hepatitis B, hepatitis C, and syphilis. In the milk bank, handling, storing, processing, pooling, and bacterial screening follow standardized algorithms. Heat treatment of human milk diminishes anti-infective properties, cellular components, growth factors, and nutrients. However, the beneficial effects of donor milk remain significant and donor milk is still highly preferable in comparison to formula.

Specific probiotics prevent necrotizing enterocolitis (NEC). A mixture of lactobacilli and bifidobacteria (Infloran) was highly effective in Asian very-low-birth-weight (VLBW) infants. We analyzed the effect of Infloran on NEC, NEC severity, and the influence of enteral feedings (breast milk vs. formula) on NEC prevention in a cohort of European VLBW infants. Infloran was implemented for routine use at our department. VLBW infants receiving probiotics were prospectively followed (2010–2012) and compared with historic controls (2008–2009). Data on NEC, neonatal morbidity, feeding tolerance, and descriptive parameters on NEC cases were analyzed. Infloran had no statistically significant impact on NEC (controls: 24/233 (10.3%); probiotics: 16/230 (7%); P = 0.2). However, NEC was significantly reduced in infants of the probiotics group who were fed any breast milk (20/179 (11.2%) vs. 10/183 (5.5%); P = 0.027), whereas it was ineffective in infants exclusively fed formula (4/54 (7.4%) vs. 6/44 (13.6%); P = 0.345). Occurrence of severe NEC (IIIb), time until full feeds, and gastric residuals were similar. Infloran was of lower efficacy in a European VLBW cohort and showed a reduction of NEC only in infants fed breast milk. Future studies should investigate the influence of feeding formula or breast milk on the effect of probiotics.

Blood transfusions are required by most extremely low birth weight (ELBW) infants, but sometimes an adequate peripheral venous access cannot be achieved. Under these circumstances, we used 27 Gauge (G) peripherally inserted central catheter (PICC) lines that are routinely inserted on the second day of life. Due to their narrow lumen, hemolysis of transfused erythrocytes was a major concern. We therefore performed a retrospective study in ELBW infants to analyze the incidence, safety and feasibility of PRBC transfusions via 27 G PICC lines. ELBW infants admitted from 08/2011–07/2012 were screened for packed red blood cell (PRBC) transfusions. Those applied via 27 G PICC lines were identified. For analysis of transfusion safety (hemolysis), hemoglobin and potassium levels as well as cardiovascular variables (invasive mean arterial blood pressure and heart rate) were evaluated before and after transfusion. For analysis of transfusion feasibility, catheter removal after transfusion and the reason for removal were recorded. A total of 648 transfusions were applied in 110 ELBW infants. 27 infants (24%) received no transfusion. In 12/83 (14.5%) infants who received PRBCs, transfusions were applied using a 27 G PICC line (38/648, 5.9%). Patients who received PRBCs via the PICC line were smaller at birth (582 g [range 380–752 g] vs. 710 g [430–972 g]; 23+6 [23+1-27+6] vs. 26+0 [23+1-31+4]) and required a higher number of PRBC transfusions (n=13 vs. n=5) overall. Transfusion analysis showed an appropriate increase of blood hemoglobin levels and stable potassium levels as well as cardiovascular parameters. 4/38 of PICC lines were removed within 24 h after transfusion, one due to occlusion (15 h after transfusion). We conclude that PRBC transfusions via 27 G PICC lines were feasible and performed without signs of hemolysis in ELBW infants. Our findings may help clinicians in the management of ELBW infants requiring transfusions if a peripheral venous access is not achievable.

Erratum zu: Monatsschr Kinderheilkd 2018 https://doi.org/10.1007/s00112-018-0586-z Im Text wird auf die Stellungnahmen der Ernahrungskommissionen der Deutschen Gesellschaft fur Kinder- und Jugendmedizin e. V. (DGKJ) und der Osterreichischen Gesellschaft fur Kinder- und Jugendheilkunde e. V. (OGKJ) …

Low-birth-weight infants, in particular those with birth weights

Three-dimensional ultrasound (3D-US) offers new perspectives in cerebral imaging.This prospective study aimed to determine whether 3D-US is appropriate to assess cortical development of the premature brain, and compare it to previously established reference values assessed by magnetic resonance imaging (MRI). Preterm infants with a gestational age (GA) of32 weeks were examined by serial 3D-US scans.Data of 30 patients with normal neurological development at the age of 5 years were included in the analysis. Cortical development was graded according to a five-point scoring system, and data were stratified into 6 age groups. Cortical developmental scores were established for various brain regions. In the frontal and frontoparietal regions, 3D-US reference values differed from published MRI reference values, but were consistent with the published data in all other regions.3D-US reference values facilitate routine diagnostics and enable the evaluation of cortical development in preterm infants.

BackgroundParenteral nutrition associated cholestasis (PNAC) is a frequently observed pathology in extremely low birth weight (ELBW) infants. Its pathogenesis is determined by the composition and duration of parenteral nutrition (PN) as well as the tolerance of enteral feeds (EF). “Aggressive” nutrition is increasingly used in ELBW infants to improve postnatal growth. Little is known about the effect of “aggressive” nutrition on the incidence of PNAC. We analyzed the influence of implementing an “aggressive” nutritional regimen on the incidence of PNAC and growth in a cohort of ELBW infants.MethodsELBW infants were nourished using a “conservative” (2005–6;n= 77) or “aggressive” (2007–9;n= 85) nutritional regimen that differed in the composition of PN after birth as well as the composition and timing of advancement of EFs. We analyzed the incidence of PNAC (conjugated bilirubin > 1.5 mg/dl (25 µmol/l)) corrected for confounders of cholestasis (i.e., NEC and/or gastrointestinal surgery, sepsis, birth weight, Z-score of birth weight, time on PN and male sex), growth until discharge (as the most important secondary outcome) and neonatal morbidities.ResultsThe incidence of PNAC was significantly lower during the period of “aggressive” vs. “conservative “nutrition (27% vs. 46%,P< 0.05; adjusted OR 0.275 [0.116–0.651],P< 0.01). Body weight (+411g), head circumference (+1 cm) and length (+1 cm) at discharge were significantly higher. Extra-uterine growth failure (defined as a Z-score difference from birth to discharge lower than −1) was significantly reduced for body weight (85% vs. 35%), head circumference (77% vs. 45%) and length (85% vs. 65%) (P< 0.05). The body mass index (BMI) at discharge was significantly higher (11.1 vs. 12.4) using “aggressive” nutrition and growth became more proportionate with significantly less infants being discharged below the 10th BMI percentile (44% vs. 9%), while the percentage of infants discharged over the 90th BMI percentile (3% vs. 5%) did not significantly increase.Discussion“Aggressive” nutrition of ELBW infants was associated with a significant decrease of PNAC and marked improvement of postnatal growth.

High protein requirements of premature infants during the first weeks of postnatal life are a well-established fact. Those infants gain fat-free mass and protein rapidly during the first weeks of postnatal growth and require a much higher protein/energy ratio than term infants. Recommended protein intakes are 3.5-4.0 g/kg per day. For term infants, on the other hand, FAO and WHO have recently lowered recommended protein intakes to better reflect our current knowledge about the protein concentration in breast milk during the first 12 months of lactation. Longitudinal randomized clinical trials now confirm that term infants who are fed infant and follow-up formulas with protein concentrations >2.25 g/100 kcal (high protein formulas) during the first year of life grow faster than indicated by the WHO growth standards. Rapid weight gain during infancy is a predictor of childhood and adult obesity. Infants fed high protein quality formulas with protein concentrations of 1.6-2.2 g/100 kcal from 3 to 4 months onwards experience weight gain that is very close to that of breastfed infants. Biomarkers (insulin or IGF-1) of infants receiving low protein formulas differ from those of infants receiving high protein formulas. Six-year-old children who received low protein formulas in the first year of life had a lower risk of childhood obesity (BMI >95th percentile of WHO standards) compared with children who received high protein formulas as infants. BMI at 5 years of age is similar in children who were breastfed or received low protein formulas as infants. It is most important that the new low protein formulas are safe and adequate for all healthy term infants. Based on new protein technologies, the levels of essential and branched-chain amino acids in low protein formulas are now close to those in breast milk. Safety has been confirmed by following anthropometric parameters to 5-6 years of age and comparing these parameters with the WHO growth standards. Body composition measurements indicate similar protein accretion between 3 and 6 months of age in infants fed high or low protein formulas. Longitudinal data on body composition indicate that children who received a low protein formula until age 12 months gain less fat between 6 and 60 months than children who received a high protein formula. Breastfeeding and the use of low/high protein quality formulas in term infants who cannot be breastfed can help support appropriate metabolic programming during this critical period and reduce the risk of later obesity.

Stillen bzw. die Futterung von Muttermilch ist die optimale Ernahrung fur das Neugeborene und beeinflusst Gesundheit, Wachstum, Abwehr und Entwicklung positiv. Mutter sollten im Wochenbett bestmogliche Unterstutzung erfahren, um eine ausreichende Laktation zu etablieren. Fur die meisten Neugeborenen reicht ausschliesliches Stillen wahrend der ersten Lebenstage aus. Bei einigen wenigen medizinischen Indikationen kann ein kurzfristiges Zufuttern notig sein. Die American Academy of Breastfeeding Medicine (ABM) gibt eine praktikable Hilfestellung, die unter Berucksichtigung der Kriterien der „baby-friendly hospital initiative“ (BFHI) der Weltgesundheitsorganisation (WHO) notwendige medizinische Indikationen fur Zufuttern klar definiert. Hierfur sollten dann in erster Linie abgepumpte Muttermilch oder pasteurisierte Frauenmilch verwendet werden. Sind diese nicht vorhanden, stehen industriell gefertigte Produkte zur Verfugung. Auch fur die sog. spaten Fruhgeborenen ist Muttermilch die optimale Ernahrung. Sie mussen aber aufgrund ihrer speziellen Bedurfnisse und ihres erhohten Nahrstoffbedarfs engmaschiger uberwacht werden.

Hintergrund Evidenzbasierte Empfehlungen fur die Verwendung von Kuhmilch im Sauglingsalter konnen derzeit mangels valider Studien nicht gegeben werden. Dennoch mochte die Ernahrungskommission der OGKJ einen praktikablen Handlungsleitfaden vorgeben, der den wissenschaftlichen Kenntnisstand in einer praktisch durchfuhrbaren Form beinhaltet.

Background: In the early weeks of life, very low birth weight (VLBW) infants experience intense laboratory blood sampling leading to clinically significant anemia and the need for red blood cell transfusion. Although controversial, treatment with recombinant human erythropoietin (EPO) and iron has been recommended to stimulate erythropoiesis; optimal dosing of EPO and iron is still uncertain. Objectives: To assess the validity of a four-quadrant diagnostic plot of iron availability (ferritin index) versus iron demand for erythropoiesis (reticulocyte hemoglobin content, CHr) for differentiating iron status in anemic VLBW infants. Methods: Study subjects were enrolled in a previously reported randomized controlled trial of clinically stable VLBW infants Results: At the end of treatment the ferritin index was significantly higher in both EPO groups compared to the control group. By day 18, CHr of the control group declined into the quadrant of the diagnostic plot characteristic of functional iron deficiency and anemia of chronic disease. Both EPO groups ended in the quadrants that are characteristic for latent iron deficiency and iron deficiency anemia, respectively. Conclusions: The diagnostic plot for differentiating anemia in VLBW infants may be an informative, clinically useful tool for iron status assessment under different physiologic and therapeutic erythropoietic states. Larger additional studies in difficult patient populations are needed before the clinical utility of this diagnostic procedure can be unequivocally confirmed.

We hypothesized that small volume enemas accelerate meconium evacuation in very low birth weight (VLBW) infants. In a randomized controlled trial, VLBW infants (n = 81) received either repeated daily small volume enemas if complete spontaneous meconium passage failed within 24 h or no intervention. Small volume enemas did not accelerate complete meconium evacuation, which occurred after 6.0 to 9.6 (95% CI) d in the intervention group and after 7.7 to 11.0 (95% CI) d in the control group. No adverse events were observed. Daily administration of small volume enemas had no effect on total meconium evacuation defined by the time of last meconium passage.

Bacterial counts in 1466 expressed breast milk (EBM) samples from women following one of two infection control regimens (standard vs strict) were investigated. Overall, 12% of samples yielded Gram-negative bacteria, with no significant differences between the standard [11.9% (94/788)] and strict [12.1% (82/678)] regimens (P = 0.92). Significantly more samples were contaminated when expressed at home (standard regimen home/hospital: 17.9% vs 6.1%; strict regimen home/hospital: 19.6% vs 3.4%; P < 0.001). Bacterial contamination of EBM was not associated with the regimen, but was associated with the location of breast milk expression. Attempts to improve personal hygiene during milk collection seem to be of limited value. Good hygiene of collection and storage equipment is likely to be the most important way to ensure the microbiological quality of EBM.

Central line-associated blood stream infections (CLABSIs) are common problems in neonatal intensive care units (NICUs). Implementation of catheter care bundles has been shown to reduce CLABSI rates. We developed a care bundle aiming at establishing a uniform central line insertion technique and improving teaching practices focusing on simulation-based techniques. The purpose of this study was to assess the impact of this care bundle on CLABSI rates in very low birth weight infants (VLBWI).In September 2010, a CLABSI prevention bundle was introduced in our NICU, consisting of simulation-based standardization and education of a peripherally inserted central catheter insertion technique. Data of all VLBWI admitted to our NICU during 2010-2012 were analyzed. Diagnosis of CLABSI required a positive blood culture in the presence of a central venous catheter and clinical signs of infection.Five hundred twenty-six VLBWI admitted during the study period were included into the analysis. CLABSI rates decreased significantly from 13.9 in 2010 to 9.5 in 2011 and 4.7 in 2012 (P0.0001). This significant reduction was true for the overall population and for subgroups separated by birth weight. Distribution of blood culture pathogens revealed a constant absolute and relative decline of infections with coagulase-negative staphylococci from 2010 (n = 43/50, 86%) to 2012 (n = 12/18, 67%), as opposed by a slight increase of Staphylococcus aureus infections (n = 1/50, 2% in 2010 versus n = 2/18, 11% in 2012).Our data provide evidence of a potential effect of simulation-based training of central line placement in decreasing CLABSI rates in VLBWI and encourage its implementation into care bundles.

Background To determine whether the complementary approach of visceral manipulative osteopathic treatment accelerates complete meconium excretion and improves feeding tolerance in very low birth weight infants. Methods This study was a prospective, randomized, controlled trial in premature infants with a birth weight

Several long-term effects of alcohol abuse in children and adolescents are well described. Alcohol abuse has severe effects on neurodevelopmental outcome, such as learning disabilities, memory deficits, and decreased cognitive performance. Additionally, chronic alcohol intake is associated with chronic liver disease. However, the effects of acute alcohol intoxication on liver function in children and adolescents are not well characterized. The aim of this study was to determine if a single event of acute alcohol intoxication has short-term effects on liver function and metabolism. All children and adolescents admitted to the Department of Pediatrics and Adolescent Medicine between 2004 and 2011 with the diagnosis "acute alcohol intoxication" were included in this retrospective analysis. Clinical records were evaluated for age, gender, alcohol consumption, blood alcohol concentration, symptoms, and therapy. Blood values of the liver parameters, CK, creatinine, LDH, AP, and the values of the blood gas analysis were analyzed. During the 8-year study period, 249 children and adolescents with the diagnosis "acute alcohol intoxication" were admitted, 132 (53%) girls and 117 (47%) boys. The mean age was 15.3 ± 1.2 years and the mean blood alcohol concentration was 0.201 ± 0.049%. Girls consumed significantly less alcohol than boys (64 g vs. 90 g), but reached the same blood alcohol concentration (girls: 0.199 ± 0.049%; boys: 0.204 ± 0.049%). The mean values of liver parameters were in normal ranges, but AST was increased in 9.1%, ALT in 3.9%, and γGT in 1.4%. In contrast, the mean value of AST/ALT ratio was increased and the ratio was elevated in 92.6% of all patients. Data of the present study showed significant differences in the AST/ALT ratio (p < 0.01) in comparison to a control group. Data of the present study indicate that there might be an effect of acute alcohol intoxication on transaminase levels. The AST/ALT ratio seems to reflect the damage in hepatocytes after intensive alcohol consumption. The present study indicates a sex-specific difference in alcohol metabolism and effects between girls and boys: girls need less alcohol than boys to achieve the same blood alcohol levels than boys, and are more prone to loss of consciousness.

OBJECTIVES. Erythropoietin is frequently administered to premature infants to stimulate erythropoiesis. The primary goal of erythropoietin therapy is to reduce transfusions, but the efficacy of erythropoietin has not been convincingly demonstrated in this regard. The aim of this trial was to investigate whether combined administration of vitamin B12, folic acid, iron, and erythropoietin could decrease transfusion requirements in extremely low birth weight infants.PATIENTS AND METHODS. In a randomized, controlled trial, extremely low birth weight infants with a birth weight ≤800g and a gestational age ≤32 weeks were randomly assigned to a group receiving combination treatment or a control arm.RESULTS. The treatment increased levels of folate in red blood cells, vitamin B12, ferritin, transferrin receptor levels in plasma, and reticulocyte counts. The proportion of infants requiring no transfusions was lower in the treatment group (38%) as compared with controls (5%). The treatment group and the need for mechanical ventilation were independent predictors of the number of transfusions in multiple regression analysis. Cox regression analysis indicated that combined therapy resulted in a 79% risk reduction for any transfusion.CONCLUSION. Combined treatment with erythropoietin, intravenous iron, folate, and vitamin B12 during the first weeks reduces the need for transfusion in extremely low birth weight infants.

Because critically ill premature infants experience significant iron loss due to phlebotomy and have high iron needs for growth, Fe absorption and incorporation studies are clinically important. A prospective, controlled, randomized, open 21-d study was conducted in infants with birth weight

The purpose of the study was to assess reference ranges for lateral ventricular volume of very low birth weight (VLBW) infants using 3-D ultrasound (US). A total of 108 patients with birth weightsor =1500 g or mother's postmenstrual ageor =32 weeks were examined prospectively in a longitudinal study. Infants in conditions considered being potential confounders such as intraventricular haemorrhage (IVH) and periventricular leukomalacia (PVL) were not included in the calculations. Hence, 77 subjects remained for final statistical analysis. Mean postmenstrual age at birth was 194.5 (27 weeks and 5.5 days) +/- 14 SD days, mean birth weight was 972.5 +/- 236.3 SD g. Reference ranges for lateral ventricle volume were established from serial images. The exponential regression analyses revealed a weekly increase in volume of 6.3% (95% CI 4.4%-8.3%) and 6.6% (95% CI 4.7%-8.6%) in respect to the left and the right ventricle (p0.001). Postmenstrual age correlated significantly (por = 0.015) with ventricle volume. No significant association to head circumference could be determined. Establishment of reference values for the lateral ventricle volume of VLBW infants should facilitate application of 3-D US in routine diagnostics in neonatal intensive care units and detection of ventricular enlargement as a prediction of risk for poor neurodevelopmental outcome in high-risk cohorts.

Neonates are sensitive to pain and vulnerable to both its short-term and long-term effects. Management of analgesia is thought to be hampered by lack of awareness that newborns are capable of experiencing pain and by fears about adverse effects associated with analgesics. The purpose of this study was to assess current medical practice in preventive analgesia and sedation in the neonate throughout Austria. This report details the results of a survey in 28 neonatal intensive care units (NICUs) in Austria. Data collection took place from October to December 2001. All NICUs reported the capability of newborns to experience and express pain and nearly all stated the possibility of pain affecting morbidity. Validated scores for pain assessment were used by 11% of NICUs, standardized protocols for analgesia existed in 75%, and 100% practiced non-pharmacological treatment strategies. The use of preventive measures in routinely performed painful procedures ranged from 8% to 96%. For example, only 8% of NICUs prevent distress and pain prior to umbilical vessel catheterization, 29% prior to subcutaneous injections and 46% prior to heel lancing. Nearly all NICUs apply analgesia before lumbar puncture and thoracic-drain placement, and all use analgesic and/or sedative medication in elective intubation.There is widespread awareness among neonatologists of the importance and effects of distress caused by pain in newborns. However, the necessity of providing sufficient analgesia is underestimated. Further information on the safety of analgesic drugs in neonatology is imperative.

Objective One of the most common brain abnormalities in preterm infants is thinning of the corpus calloisum (CC). Such injury may be partly explained by the vulnerability of the developing CC to hypoxic-ischemic damage and hemorrhage due to intrinsic vulnerability of immature oligodendrocytes. The CC is among the last structures to be completed during postnatal maturation. Several studies have shown a relation between the size of CC and motor outcome in preterm infants. Three-dimensional ultrasound (3D-US) offers new perspectives in cerebral imaging. Methods 43 preterm infants with a gestational age Results By 3D US reference values for size, length, circumference and surface area of the CC at all different timepoints could be established. The data examined at corrected term age showed a significant correlation of corpus size of CC and visual motor integration (p=0.04) and of circumference and surface area of CC and simultanous processing scale (p=0.01) and mental processing composite (p=0.04) of K-ABC. A trend was seen for the correlation of surface area oft the CC and achievement scale of the K-ABC (p=0.08) and visual perception assessed by VMI (p=0.08). Conclusion Biometry of the CC in preterm infants can sufficiently be done by 3D US. Especially surface area of the CC at corrected term age correlates with later neurodevelopmental outcome.

OBJECTIVE:To determine whether enteral application of the osmotic contrast agent Gastrografin accelerates complete meconium excretion and improves feeding tolerance in very low birth weight infants.METHODS:This study was a stratified, randomized, placebo-controlled trial in premature infants with a birth weight RESULTS:Passage of last meconium occurred after a median of 7 days (95% confidence interval: 6–9 days, n = 39) in the intervention group and after 8 days (95% confidence interval: 7–10 days, n = 39) in the control group (P = .61); however, Gastrografin application was associated with a 7.5-day shorter time to full enteral feedings, a 24-day shorter stay in the NICU, and a 17-day reduction in the overall hospital stay in the intervention group compared with the control group. A numerically higher incidence of necrotizing enterocolitis (21%) was observed in the intervention group, however.CONCLUSIONS:Gastrografin application did not accelerate meconium evacuation, but the higher stool frequency during the first week of life had a beneficial effect on the time to full enteral feedings and later hospital stay; however, it may increase the necrotizing enterocolitis risk. Further investigations are needed with modified protocols, and the prophylactic use of Gastrografin cannot currently be recommended without further clinical trials.

AIMS To evaluate the association between the presence of bacterial pathogens in the amniotic cavity at the time of preterm delivery and neuromotor outcome at two years adjusted age in preterm infants born at < or =33 weeks' gestation. METHODS The cohort included 114 preterm infants, born at 23-33 weeks' gestation to mothers with amniotic cavity cultures taken during cesarean delivery who were subsequently evaluated at 24.0+/-1.1 months corrected age with the Bayley Scales of Infant Development II and a standardized neurologic examination. RESULTS A group of 67 infants with negative amniotic cavity cultures was compared to 47 infants with positive amniotic cavity cultures (Ureaplasma urealyticum (Uu) in 32 cases and other bacteria in 15 cases). Patients with positive amniotic cavity cultures had a significantly higher risk for an adverse psychomotor development index (PDI) score (OR 3.1, CI 1.3-7.1), an abnormal neurologic outcome (OR 4.8, CI 1.7-13.8), and a higher probability for diagnosis of cerebral palsy (OR 4.8, CI 1.4-16.4) at two years compared to patients with negative culture results. Isolation of Uu at birth was associated with a particular adverse outcome of preterm infants. CONCLUSIONS Isolation of pathogens from the amniotic cavity at birth is significantly associated with abnormal PDI and adverse neuromotor outcome in preterm infants, irrespective of gestational age and birthweight.

SummaryErythropoietin (Epo) is frequently administered to premature infants to stimulate erythropoiesis. There is evidence from studies in animals and healthy adults that Epo also interacts with thrombopoiesis and platelet function.This study investigates the effect of Epo therapy on platelet reactivity, peripheral platelet counts and thiazole orange-positive (TO+) platelets in extremely low birth weight (ELBW) infants. In a randomised-controlled trial, ELBW infants with a birth weight ≤ 800g and a gestational age ≤ 32 weeks were either randomised to a group receiving Epo during the first weeks of life or to a control group. Our results show that thrombin receptor-activating peptide (TRAP-6) -induced expression of P-selectin increased significantly during the first two weeks of Epo treatment.With the exception of week five, the number of TO+ platelets was significantly higher during the first eight weeks in Epo-treated infants compared to controls. The increase of TO+ platelets was not paralleled by an increase in total platelet count.We can conclude that Epo therapy has a short-lasting effect on platelet reactivity toTRAP-6 in ELBW infants during the first two weeks of life.Furthermore, Epo therapy is associated with an increase in the number of TO+ platelets compared to controls.

Aims: To evaluate the potential benefit of amniotic fluid and amniotic/placental membrane cultures for the management of early-onset sepsis in preterm infants. Methods: The results of amniotic cavity cultures obtained during cesarean section and of peripheral blood cultures and surface swabs obtained from the preterm infant at the time of admission were analyzed with respect to the diagnosis of clinical sepsis in 221 preterm infants

AIM To develop a simplified amikacin dosage regimen for nosocomial infections in preterm infants including a loading dose in order to achieve therapeutic Maximum Serum Concentrations early in the course of therapy. METHODS Open, non-comparative study during November 2000 to April 2001. The modified amikacin dosing and monitoring protocol included a loading dose of 10 mg/kg in the first week of life, followed by a maintenance regimen of 7.5 mg/kg every 24 h. After the first week of life the corresponding doses were 17 mg/kg (loading) and 15 mg/kg (maintenance). A peak level was measured 30 min after the second dose, a trough level immediately before the third dose. RESULTS Twenty-five very low birthweight infants (median birthweight 739 g, median gestational age 25 wk) who had 34 episodes of amikacin treatment were included in the analysis. Median amikacin peak and trough values were 37.1 micromol/l and 6.3 micromol/l, respectively. Twenty-nine of all peak levels (85%) and 30 of all trough levels (88%) were within the targeted range of >35 micromol/l and