Safe and efficient practice of parenteral nutrition in neonates and children aged 0-18 years - The role of licensed multi-chamber bags.

Parenteral nutrition (PN) is recognized as a complex high-risk therapy. Its practice is highly variable and frequently suboptimal in pediatric patients. Optimizing care requires evidence, consensus-based guidelines, audits of practice, and standardized strategies. Several pediatric scientific organizations, expert panels, and authorities have recently recommended that standardized PN should generally be used over individualized PN in the majority of pediatric patients including very low birth weight premature infants. In addition, PN admixtures produced and validated by a suitably qualified institution are recommended over locally produced PN. Licensed multi chamber bags are standardized PN bags that comply with Good Manufacturing Practice and high-quality standards for the finished product in the frame of their full manufacturing license. The purpose of this article is to review the practical aspects of PN and the evidence for using such multi-chamber bags in pediatric patients. It highlights the safety characteristics and the limitations of the different PN practices and provides some guidance for ensuring safe and efficient therapy in pediatric patients.

Arachidonic acid and docosahexaenoic acid levels correlate with the inflammation proteome in extremely preterm infants.

BACKGROUND & AIM: Clinical trials supplementing the long-chain polyunsaturated fatty acids (LCPUFAs) docosahexaenoic acid (DHA) and arachidonic acid (AA) to preterm infants have shown positive effects on inflammation-related morbidities, but the molecular mechanisms underlying these effects are not fully elucidated. This study aimed to determine associations between DHA, AA, and inflammation-related proteins during the neonatal period in extremely preterm infants. METHODS: A retrospective exploratory study of infants (n = 183) born below 28 weeks gestation from the Mega Donna Mega trial, a randomized multicenter trial designed to study the effect of DHA and AA on retinopathy of prematurity. Serial serum samples were collected after birth until postnatal day 100 (median 7 samples per infant) and analyzed for phospholipid fatty acids and proteins using targeted proteomics covering 538 proteins. Associations over time between LCPUFAs and proteins were explored using mixed effect modeling with splines, including an interaction term for time, and adjusted for gestational age, sex, and center. RESULTS: On postnatal day one, 55 proteins correlated with DHA levels and 10 proteins with AA levels. Five proteins were related to both fatty acids, all with a positive correlation. Over the first 100 days after birth, we identified 57 proteins to be associated with DHA and/or AA. Of these proteins, 41 (72%) related to inflammation. Thirty-eight proteins were associated with both fatty acids and the overall direction of association did not differ between DHA and AA, indicating that both LCPUFAs similarly contribute to up- and down-regulation of the preterm neonate inflammatory proteome. Primary examples of this were the inflammation-modulating cytokines IL-6 and CCL7, both being negatively related to levels of DHA and AA in the postnatal period. CONCLUSIONS: This study supports postnatal non-antagonistic and potentially synergistic effects of DHA and AA on the inflammation proteome in preterm infants, indicating that supplementation with both fatty acids may contribute to limiting the disease burden in this vulnerable population. CLINICAL REGISTRATION NUMBER: ClinicalTrials.gov (NCT03201588).

Enteral supplementation with arachidonic and docosahexaenoic acid and pulmonary outcome in extremely preterm infants.

Enteral supplementation with arachidonic acid (AA) and docosahexaenoic acid (DHA) in extremely preterm infants has shown beneficial effects on retinopathy of prematurity and pulmonary outcome whereas exclusive DHA supplementation has been associated with increased pulmonary morbidity. This secondary analysis evaluates pulmonary outcome in 204 extremely preterm infants, randomized to receive AA (100 mg/kg/day) and DHA (50 mg/kg/day) enterally from birth until term age or standard care. Pulmonary morbidity was primarily assessed based on severity of bronchopulmonary dysplasia (BPD). Serum levels of AA and DHA during the first 28 days were analysed in relation to BPD. Supplementation with AA:DHA was not associated with increased BPD severity, adjusted OR 1.48 (95 % CI 0.85-2.61), nor with increased need for respiratory support at post menstrual age 36 weeks or duration of oxygen supplementation. Every 1 % increase in AA was associated with a reduction of BPD severity, adjusted OR 0.73 (95 % CI 0.58-0.92). In conclusion, in this study, with limited statistical power, enteral supplementation with AA:DHA was not associated with an increased risk of pulmonary morbidity, but higher levels of AA were associated with less severe BPD. Whether AA or the combination of AA and DHA have beneficial roles in the immature lung needs further research.

The development of blood protein profiles in extremely preterm infants follows a stereotypic evolution pattern.

BACKGROUND: Preterm birth is the leading cause of neonatal mortality and morbidity. Early diagnosis and interventions are critical to improving the clinical outcomes of extremely premature infants. Blood protein profiling during the first months of life in preterm infants can shed light on the role of early extrauterine development and provide an increased understanding of maturation after extremely preterm birth and the underlying mechanisms of prematurity-related disorders. METHODS: We have investigated the blood protein profiles during the first months of life in preterm infants on the role of early extrauterine development. The blood protein levels were analyzed using next generation blood profiling on 1335 serum samples, collected longitudinally at nine time points from birth to full-term from 182 extremely preterm infants. RESULTS: The protein analysis reveals evident predestined serum evolution patterns common for all included infants. The majority of the variations in blood protein expression are associated with the postnatal age of the preterm infants rather than any other factors. There is a uniform protein pattern on postnatal day 1 and after 30 weeks postmenstrual age (PMA), independent of gestational age (GA). However, during the first month of life, GA had a significant impact on protein variability. CONCLUSIONS: The unified pattern of protein development for all included infants suggests an age-dependent stereotypic development of blood proteins after birth. This knowledge should be considered in neonatal settings and might alter the clinical approach within neonatology, where PMA is today the most dominant age variable.

Being born too early can affect a baby's health. We looked at how babies born extremely preterm, meaning more than 12 weeks earlier than a full-term baby, develop. We looked at the proteins present in their blood from the day they were born until their original due date. Our study of 182 extremely preterm babies born at different points in the pregnancy (gestational ages) found that the proteins present in their blood changed in a similar way over time. This means that the age of a baby after birth, and not how early they were born, mostly affects the proteins in their blood. These findings help us understand how extremely preterm babies develop after birth, which could lead to improvements to their healthcare during the first few weeks of their life.

[Changes in neonatal care : Implications for ophthalmological care]. / Wandel der neonatologischen Versorgung : Implikationen für die augenärztliche Versorgung.

BACKGROUND: Preterm infants are at risk of characteristic, sometimes life-threatening diseases and development of deficits related to immaturity. In the field of ophthalmology, retinopathy of prematurity (ROP) and vision impairment reflect structural and functional disturbances in this large group of patients. In high income countries, more and more very immature preterm infants survive into adolescence and adulthood. OBJECTIVE: To characterize the impact of an increasing number of surviving individuals born preterm on the provision of ophthalmological care in Germany. MATERIAL AND METHODS: A literature search and analysis of key figures and quality indicators published in national health registers were carried out. RESULTS: Currently, about 60,000 preterm infants are born in Germany every year. Of these, approximately 3600 extremely immature preterm infants with a gestational age < 28 weeks are treated with a curative approach on neonatal units. The survival rate is around 80%. A rise in the proportion of infants suffering from severe ROP has not been observed in recent years in Germany. The incidences of other structural and functional visual impairments vary between 3% and 25% in high income countries. CONCLUSION: The incidence of ROP apparently has not increased in Germany. However, specific peculiarities of the structure and function of the visual system of individuals born preterm have to be taken into account. Approximately 70,000 outpatient check-ups of infants and toddlers, who require both, ophthalmological and developmental neurological expertise, are estimated for Germany each year.

Identifying neonatal adverse events in preterm and term infants using a paediatric trigger tool.

AIM: To explore the incidence and characteristics of inpatient neonatal adverse events in a Swedish setting. METHODS: A retrospective record review, using a trigger tool, performed by registered nurses and a neonatologist, at a University Hospital. The identified adverse events were categorised by, for example, preventability, severity and time of occurrence. RESULTS: A random selection of 150 admissions representing 3531 patient days were reviewed (mean [SD] birthweight 2620 [1120]g). Three hundred and sixty adverse events were identified in 78 (52.0%) infants, and 305 (84.7%) of these were assessed as being preventable. The overall adverse event rate was 240 per 100 admissions and 102.0 per 1000 patient days. Preterm infants had a higher rate than term infants (353 versus 79 per 100 admissions, p = 0.001); however, with regard to the length of stay, the rates were similar. Most adverse events were temporary and less severe (n = 338/360, 93.9%) and the most common type involved harm to skin, tissue or blood vessels (n = 163/360, 45.3%). Forty percent (n = 145) of adverse events occurred within the first week of admission. CONCLUSION: Adverse events were common in neonatal care, and many occurred during the first days of treatment. Characterisation of adverse events may provide focus areas for improvements in patient safety.

Equally Good Neurological, Growth, and Health Outcomes up to 6 Years of Age in Moderately Preterm Infants Who Received Exclusive vs. Fortified Breast Milk-A Longitudinal Cohort Study.

Moderately preterm infants (32-36 weeks of gestational age) have an increased risk of worse health and developmental outcomes compared to infants born at term. Optimal nutrition may alter this risk. The aim of this study was to investigate the neurological, growth, and health outcomes up to six years of age in children born moderately preterm who receive either exclusive or fortified breast milk and/or formula in the neonatal unit. In this longitudinal cohort study, data were collected for 142 children. Data were collected up to six years of age via several questionnaires containing questions about demographics, growth, child health status, health care visits, and the Five to Fifteen Questionnaire. Data on the intake of breast milk, human milk fortification, formula, and growth during hospitalization were collected from the children's medical records. No statistically significant differences in neurological outcomes, growth, or health at six years of age were found between the two groups (exclusive breast milk, n = 43 vs. fortified breast milk and/or formula, n = 99). There is a need for research in larger populations to further assess potential effects on health and developmental outcomes when comparing the use of exclusive versus fortified breast milk for moderately preterm infants during neonatal hospitalization.

Hyper high haemoglobin content in red blood cells and erythropoietic transitions postnatally in infants of 22 to 26 weeks' gestation: a prospective cohort study.

OBJECTIVE: Blood cell populations, including red blood cells (RBC) unique to the extremely preterm (EPT) infant, are potentially lost due to frequent clinical blood sampling during neonatal intensive care. Currently, neonatal RBC population heterogeneity is not described by measurement of total haemoglobin or haematocrit. We therefore aimed to describe a subpopulation of large RBCs with hyper high haemoglobin content, >49 pg (Hyper-He) following EPT birth. DESIGN: Prospective observational cohort study. SETTING: Two Swedish study centres. PARTICIPANTS: Infants (n=62) born between gestational weeks 22+0 to 26+6. METHODS: Prospective data (n=280) were collected from March 2020 to September 2022 as part of an ongoing randomised controlled trial. Blood was sampled from the umbilical cord, at postnatal day 1-14, 1 month, 40 weeks' postmenstrual age and at 3 months' corrected age. RESULTS: At birth, there was a considerable inter-individual variation; Hyper-He ranging from 1.5% to 24.9% (median 7.0%). An inverse association with birth weight and gestational age was observed; Spearman's rho (CI) -0.38 (-0.63 to -0.07) and -0.39 (-0.65 to -0.05), respectively. Overall, Hyper-He rapidly decreased, only 0.6%-5.0% (median 2.2%) remaining 2 weeks postnatally. Adult levels (<1%) were reached at corresponding term age. CONCLUSION: Our results point to gestational age and birth weight-dependent properties of the RBC population. Future work needs to verify results by different measurement techniques and elucidate the potential role of differing properties between endogenous and transfused RBCs in relation to neonatal morbidities during this important time frame of child development. TRIAL REGISTRATION NUMBER: NCT04239690.

Modification of serum fatty acids in preterm infants by parenteral lipids and enteral docosahexaenoic acid/arachidonic acid: A secondary analysis of the Mega Donna Mega trial.

BACKGROUND & AIM: Preterm infants risk deficits of long-chain polyunsaturated fatty acids (LCPUFAs) that may contribute to morbidities and hamper neurodevelopment. We aimed to determine longitudinal serum fatty acid profiles in preterm infants and how the profiles are affected by enteral and parenteral lipid sources. METHODS: Cohort study analyzing fatty acid data from the Mega Donna Mega study, a randomized control trial with infants born <28 weeks of gestation (n = 204) receiving standard nutrition or daily enteral lipid supplementation with arachidonic acid (AA):docosahexaenoic acid (DHA) (100:50 mg/kg/day). Infants received an intravenous lipid emulsion containing olive oil:soybean oil (4:1). Infants were followed from birth to postmenstrual age 40 weeks. Levels of 31 different fatty acids from serum phospholipids were determined by GC-MS and reported in relative (mol%) and absolute concentration (µmol l-1) units. RESULTS: Higher parenteral lipid administration resulted in lower serum proportion of AA and DHA relative to other fatty acids during the first 13 weeks of life (p < 0.001 for the 25th vs the 75th percentile). The enteral AA:DHA supplement increased the target fatty acids with little impact on other fatty acids. The absolute concentration of total phospholipid fatty acids changed rapidly in the first weeks of life, peaking at day 3, median (Q1-Q3) 4452 (3645-5466) µmol l-1, and was positively correlated to the intake of parenteral lipids. Overall, infants displayed common fatty acid trajectories over the study period. However, remarkable differences in fatty acid patterns were observed depending on whether levels were expressed in relative or absolute units. For example, the relative levels of many LCPUFAs, including DHA and AA, declined rapidly after birth while their absolute concentrations increased in the first week of life. For DHA, absolute levels were significantly higher compared to cord blood from day 1 until postnatal week 16 (p < 0.001). For AA, absolute postnatal levels were lower compared to cord blood from week 4 throughout the study period (p < 0.05). CONCLUSIONS: Our data show that parenteral lipids aggravate the postnatal loss of LCPUFAs seen in preterm infants and that serum AA available for accretion is below that in utero. Further research is needed to establish optimal postnatal fatty acid supplementation and profiles in extremely preterm infants to promote development and long-term health. CLINICAL TRIAL REGISTRY: ClinicalTrials.gov, identifier: NCT03201588.

Preterm infant circulating sex steroid levels are not altered by transfusion with adult male plasma: a retrospective multicentre cohort study.

OBJECTIVE: To determine if plasma transfusions with male donor plasma to very preterm infants affect circulatory levels of sex steroids. DESIGN AND PATIENTS: Retrospective multicentre cohort study in 19 infants born at gestational age <29 weeks requiring plasma transfusion during their first week of life. SETTING: Three neonatal intensive care units in Sweden. MAIN OUTCOME MEASURES: Concentrations of sex steroids and sex hormone-binding globulin (SHBG) in donor plasma and infant plasma measured before and after a plasma transfusion and at 6, 12, 24 and 72 hours. RESULTS: The concentrations of progesterone, dehydroepiandrosterone and androstenedione were significantly lower in donor plasma than in infant plasma before the transfusion (median (Q1-Q3) 37.0 (37.0-37.0), 1918 (1325-2408) and 424 (303-534) vs 901 (599-1774), 4119 (2801-14 645) and 842 (443-1684) pg/mL), while oestrone and oestradiol were higher in donor plasma (17.4 (10.4-20.1) and 16.0 (11.7-17.2) vs 3.1 (1.1-10.2) and 0.25 (0.25-0.25) pg/mL). Median testosterone and dihydrotestosterone (DHT) levels were 116-fold and 21-fold higher in donor plasma than pre-transfusion levels in female infants, whereas the corresponding difference was not present in male infants. Plasma sex steroid levels were unchanged after completed transfusion compared with pre-transfusion levels, irrespective of the gender of the receiving infant. The SHBG concentration was significantly higher in donor than in recipient plasma (22.8 (17.1-33.5) vs 10.2 (9.1-12.3) nmol/L) before transfusion but did not change in the infants after the transfusion. CONCLUSIONS: A single transfusion of adult male plasma to preterm infants had no impact on circulating sex steroid levels.

Effect of Enteral Lipid Supplement on Severe Retinopathy of Prematurity: A Randomized Clinical Trial.

Importance: Lack of arachidonic acid (AA) and docosahexaenoic acid (DHA) after extremely preterm birth may contribute to preterm morbidity, including retinopathy of prematurity (ROP). Objective: To determine whether enteral supplementation with fatty acids from birth to 40 weeks' postmenstrual age reduces ROP in extremely preterm infants. Design, Setting, and Participants: The Mega Donna Mega trial, a randomized clinical trial, was a multicenter study performed at 3 university hospitals in Sweden from December 15, 2016, to December 15, 2019. The screening pediatric ophthalmologists were masked to patient groupings. A total of 209 infants born at less than 28 weeks' gestation were tested for eligibility, and 206 infants were included. Efficacy analyses were performed on as-randomized groups on the intention-to-treat population and on the per-protocol population using as-treated groups. Statistical analyses were performed from February to April 2020. Interventions: Infants received either supplementation with an enteral oil providing AA (100 mg/kg/d) and DHA (50 mg/kg/d) (AA:DHA group) or no supplementation within 3 days after birth until 40 weeks' postmenstrual age. Main Outcomes and Measures: The primary outcome was severe ROP (stage 3 and/or type 1). The secondary outcomes were AA and DHA serum levels and rates of other complications of preterm birth. Results: A total of 101 infants (58 boys [57.4%]; mean [SD] gestational age, 25.5 [1.5] weeks) were included in the AA:DHA group, and 105 infants (59 boys [56.2%]; mean [SD] gestational age, 25.5 [1.4] weeks) were included in the control group. Treatment with AA and DHA reduced severe ROP compared with the standard of care (16 of 101 [15.8%] in the AA:DHA group vs 35 of 105 [33.3%] in the control group; adjusted relative risk, 0.50 [95% CI, 0.28-0.91]; P = .02). The AA:DHA group had significantly higher fractions of AA and DHA in serum phospholipids compared with controls (overall mean difference in AA:DHA group, 0.82 mol% [95% CI, 0.46-1.18 mol%]; P < .001; overall mean difference in control group, 0.13 mol% [95% CI, 0.01-0.24 mol%]; P = .03). There were no significant differences between the AA:DHA group and the control group in the rates of bronchopulmonary dysplasia (48 of 101 [47.5%] vs 48 of 105 [45.7%]) and of any grade of intraventricular hemorrhage (43 of 101 [42.6%] vs 42 of 105 [40.0%]). In the AA:DHA group and control group, respectively, sepsis occurred in 42 of 101 infants (41.6%) and 53 of 105 infants (50.5%), serious adverse events occurred in 26 of 101 infants (25.7%) and 26 of 105 infants (24.8%), and 16 of 101 infants (15.8%) and 13 of 106 infants (12.3%) died. Conclusions and Relevance: This study found that, compared with standard of care, enteral AA:DHA supplementation lowered the risk of severe ROP by 50% and showed overall higher serum levels of both AA and DHA. Enteral lipid supplementation with AA:DHA is a novel preventive strategy to decrease severe ROP in extremely preterm infants. Trial Registration: ClinicalTrials.gov Identifier: NCT03201588.

Low Splanchnic Oxygenation and Risk for Necrotizing Enterocolitis in Extremely Preterm Newborns.

OBJECTIVE: The aim of the study was to investigate whether splanchnic oxygenation (SrSO2), measured with near-infrared spectroscopy (NIRS), during the first week of life is associated with the risk of developing necrotizing enterocolitis (NEC) in extremely preterm infants. METHODS: This was a prospective observational cohort study including extremely preterm infants (<28 weeks of gestation) born at Karolinska University Hospital from September 2014 to December 2016. Using 1-hour NIRS monitoring during enteral feeding, mainly continuous enteral feeding, in the first week of life we measured both cerebral and splanchnic oxygenation. Primary outcome was risk of developing NEC (Bell stage ≥ II). Secondary outcome was the association between low mean SrSO2 during the first week of life and postnatal age at full enteral nutrition. RESULTS: We enrolled 52 extremely preterm newborns, but only 45 infants had complete NIRS data. One infant developed NEC within 1 day of NIRS monitoring and was excluded from the study. Median gestational age was 25.6 weeks (range 23.0-27.9) and median birth weight 698 g (range 485-1353). Eight infants developed NEC at the median postnatal age of 15 days (range 6-35). Median postnatal age at full enteral nutrition was 10 days (range 6-23). Infants with mean SrSO2 <30% had a higher risk for developing NEC compared with those with SrSO2 >30% (crude risk ratio 5.25; 95% CI [1.19-23.01]). Small for gestational age, gestational age, birth weight, postnatal age did not affect the results. We found no association between SrSO2 and age at full enteral nutrition. CONCLUSIONS: Low mean SrSO2 (<30%) during the first week of life is associated with an increased risk for developing NEC in extremely preterm infants on mainly continuous enteral nutrition.

Accuracy of pulse oximetry in preterm and term infants is insufficient to determine arterial oxygen saturation and tension.

AIM: Oxygen saturation is frequently monitored with pulse oximetry to assess vital signs in critically ill patients. Optimally, pulse oximetry closely tracks arterial oxygen tension (PaO2 ), which provides guidance in oxygen titration. We investigated whether monitoring peripheral oxygen saturation (SpO2 ) could accurately guide oxygen titration in newborn infants. METHODS: Twenty seven thousand two hundred thirty seven SpO2 readings were retrospectively paired with arterial oxygen saturation (SaO2 ) and PaO2 results from blood gas analyses performed in infants with arterial catheters in place. RESULTS: SpO2 overestimated SaO2 readings by 2.9 ± 5.8%. When pulse oximetry readings were within the defined oxygen saturation target range, 7809 (20.9%) SaO2 values were below and 2830 (7.6%) exceeded the target range. In 57% of patients, PaO2 levels < 6 kPa was diagnosed while SpO2 readings were > 90%. PaO2  > 11 kPa was recorded in 19% of cases, when SpO2 readings were < 95%. Infants treated with supplemental oxygen showed a threefold increased risk of hypoxaemia compared to infants breathing room air. Sensitivity and specificity for detecting upper and lower target range limits were fair to good. For SpO2 values below 91%, ISO quality criteria were no longer fulfilled. CONCLUSIONS: Based on arterial blood gas analyses as reference, pulse oximetry readings did not fulfil the performance requirements for titrating oxygen in neonatal patients.

Swedish national guideline for prevention and treatment of neonatal hypoglycaemia in newborn infants with gestational age ≥35 weeks.

AIM: Postnatal hypoglycaemia in newborn infants remains an important clinical problem where prolonged periods of hypoglycaemia are associated with poor neurodevelopmental outcome. The aim was to develop an evidence-based national guideline with the purpose to optimise prevention, diagnosis and treatment of hypoglycaemia in newborn infants with a gestational age ≥35 + 0 weeks. METHODS: A PubMed search-based literature review was used to find actual and applicable evidence for all incorporated recommendations. The GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach was used for grading the evidence of the recommendations. RESULTS: Recommendations for the prevention of neonatal hypoglycaemia were extended and updated, focusing on promotion of breastfeeding as one prevention strategy. Oral dextrose gel as a novel supplemental therapy was incorporated in the treatment protocol. A new threshold-based screening and treatment protocol presented as a flow chart was developed. CONCLUSION: An updated and evidence-based national guideline for screening and treatment of neonatal hypoglycaemia will support standardised regimes, which may prevent hypoglycaemia and the risk for hypoglycaemia-related long-term sequelae.

Elevated levels of IL-6 and IGFBP-1 predict low serum IGF-1 levels during continuous infusion of rhIGF-1/rhIGFBP-3 in extremely preterm infants.

OBJECTIVE: Steady state insulin-like growth factor-1 (IGF-1) levels vary significantly during continuous intravenous infusion of recombinant human insulin-like growth factor-1/recombinant human insulin-like growth factor binding protein-3 (rhIGF-1/rhIGFBP-3) in the first weeks of life in extremely preterm infants. We evaluated interleukin-6 (IL-6) and insulin-like growth factor binding protein-1 (IGFBP-1) levels as predictors of low IGF-1 levels. METHODS: Nineteen extremely preterm infants were enrolled in a trial, 9 received rhIGF-1/rhIGFBP-3 and 10 received standard neonatal care. Blood samples were analyzed daily for IGF-1, IL-6 and IGFBP-1 during intervention with rhIGF-1/rhIGFBP-3. RESULTS: Thirty seven percent of IGF-1 values during active treatment were <20 µg/L. Among treated infants, higher levels of IL-6, one and two days before sampled IGF-1, were associated with IGF-1 < 20 µg/L, gestational age adjusted OR 1.30 (95% CI 1.03-1.63), p = .026, and 1.57 (95% CI 1.26-1.97), p < .001 respectively. Higher levels of IGFBP-1 one day before sampled IGF-1 was also associated with IGF-1 < 20 µg/L, gestational age adjusted OR 1.74 (95% CI 1.19-2.53), p = .004. CONCLUSION: In preterm infants receiving continuous infusion of rhIGF-1/rhIGFBP-3, higher levels of IL-6 and IGFBP-1 preceded lower levels of circulating IGF-1. These findings demonstrate a need to further evaluate if inflammation and/or infection suppress serum IGF-1 levels. The trial is registered at ClinicalTrials.gov (NCT01096784).

Dalteparin-sodium induced drug fever in a neonate.

Drug fever caused by dalteparin-sodium (DS), a low-molecular-weight derivative of heparin, is neither listed in the official drug information and nor published as a case report until today. A preterm infant, born at 26 weeks of gestation, developed fever 2 days after starting a treatment with DS for an intracardial thrombus. The fever reverses soon after changing the treatment to unfractionated heparin and reappeared after reintroduction of DS. Once again, after discontinuing DS, the infant regained normothermia. Bacterial and viral infections, tissue damage, impaired liver or kidney function, preservative agents and comedications could be ruled out as fever origin. By using the Naranjo adverse drug reaction (ADR) probability scale and the Liverpool ADR causality assessment tool, this case can be classified as 'probable ADR' and 'definite ADR'. This is the first case report of a drug fever caused by the low-molecular-weight heparin DS in a preterm infant.

Continuous subcutaneous glucose monitoring is accurate in term and near-term infants at risk of hypoglycaemia.

AIM: Postnatal hypoglycaemia increases the risk of adverse neurological outcomes in newborn infants, and adequate glucose control requires repetitive and painful blood sampling. This study evaluated a continuous glucose monitoring system (CGMS) that aims to improve glucose control and decrease the frequency of blood samples taken from neonates. METHODS: CGMS sensors, which measure glucose values every five minutes and require calibration twice a day, were placed on 20 infants at risk of hypoglycaemia. The infants also underwent blood glucose sampling, and the blood glucose values were compared with CGMS values six times during the first 30 minutes after sampling. RESULTS: We used 97/264 (37%) of the blood glucose values taken for the CGMS calibration. The highest accuracy, a mean of 0.22 (95% confidence interval 0.13-0.30 mmol/L), was found 15-19 minutes after sampling, due to the calibration process. No significant subcutaneous glucose time lag was detectable. CONCLUSION: The CGMS system was an accurate and feasible method for glucose control, provided earlier detection of hypoglycaemia in newborn infants and reduced their exposure to procedural pain. The delay in calibration in infants was a new finding and needs to be taken into account when comparing CGMS readings to blood glucose values.

Computer-aided nutrition - Effects on nutrition and growth in preterm infants <32 weeks of gestation.

BACKGROUND & AIMS: Preterm infants are often discharged from the NICU with suboptimal growth. The aim of our intervention study was to determine if a computer-aided nutrition calculation program could help to optimise the nutrition and secondary improve the growth of preterm infants. METHODS: Intake of macro- and micronutrients and anthropometric data was collected in 78 preterm infants with GA ≤32+0 from birth to postnatal week 7. The nutrition of 43 preterm infants was ordinated with help of the program Nutrium™â€‹ (IG). Before the introduction of the program 35 consecutive preterm infants served as control group (CG). Their data were collected in retrospect. RESULTS: Amino acid, carbohydrate, fluid intake and total energy intake were statistically different at all time points. Fatty acid intake was statistically different expect for week 2 and 4. Similar differences were found for magnesium, calcium and phosphorus, zinc, copper and selenium. In contrast vitamin intake was higher in the control group. At birth there were no differences between the groups with respect to anthropometric data. Weight, length and head circumference (HC) SDS decreased in both groups from birth to day 28 of life (CG -1.2 SDS; -1.2 SDS; -0.8 SDS vs IG -0.9 SDS; -0.8 SDS; -0.4 SDS). The infants in the CG showed until discharge a partial catch-up but remained below birth SDS for weight and length (-0.5 SDS; -0.9 SDS). In the IG, infants reached birth values for weight and length (-0.1 SDS; 0 SDS). For HC both groups showed similar values at the time point for birth and discharge (CG +0.3 SDS vs IG +0.5 SDS). CONCLUSION: By using a computer-aided nutrition calculation program better postnatal growth was achieved. Nutritional intake was increased in respect to nearly all micro- and macronutrients. There were no adverse effects. In contrast there was a tendency of decreased incidence of BPD, infection rate and PDA.