Search

Objective: Hyperglycemia in preterm infants is usually treated with adjustment of glucose intake and, if persistent, with continuous insulin infusion. However, hypoglycemia is a well-known complication of intravenous (iv) insulin treatment. The aim of this study was to evaluate the feasibility of continuous subcutaneous insulin infusion (CSII) in extremely preterm infants. Methods: Clinical data from extremely premature infants (<28 weeks of gestation) undergoing CSII treatment for severe hyperglycemia in the neonatal intensive care unit were included. Blood glucose levels during CSII, as well as the nutritional intake and insulin intake were recorded. Data were analyzed and compared to a control group of very preterm infants receiving iv insulin therapy. Results: Normoglycemia rates were best in the iv insulin-cohort (n=22, 50.3%) compared to the CSII group (n=15, 15.6%). Hypoglycemia was very rare in both groups (0.4% vs. 0.0%). CSII therapy appears to require higher insulin doses compared to continuous iv therapy to achieve a similar effect. Subcutaneous Insulin therapy in extremely preterm infants is feasible, at least for prevention of hypoglycemia. However, dose control needs to be improved. Conclusion: The results justify further model validation and clinical trial research to explore a model-based protocol and the use of CSII in this population. [ABSTRACT FROM AUTHOR]

A preterm infant, whose course was complicated by sepsis, necrotizing enterocolitis with jejunal perforation, intraventricular hemorrhage and cerebellar hemorrhage, suffered permanent and total paralysis below the neck from extravasation of parenteral nutrition fluids through a femoral venous catheter. MRI imaging revealed extravasation of fluid into the paraspinus musculature with extension into the spinal canal. This fluid was identified as hyperalimentation and intralipid. Postmortem examination found evidence of necrosis of the spinal cord as well as perforation of the right iliac vein.

The cause of hyperglycemia in extremely-low-birth-weight (ELBW) infants is not well understood. We studied infants weighing <1,000 g to investigate the relationship of hyperglycemia to blood levels of insulin-like growth factor (IGF)-I and IGF-II. We also compared two methods of treatment for hyperglycemia: continuous insulin infusion and reduction of glucose intake. Fifty-six ELBW infants were enrolled on day 2 of life. Intravenous glucose intake was increased incrementally to a maximum of 12 mg/kg/min on day 6. Infants who developed hyperglycemia were randomly assigned to receive reduced glucose intake (n = 11) or insulin infusion (n = 12). Infants whose blood sugar remained normal served as controls (n = 33). Blood was drawn on days 3, 8 and 15 in all infants, and again when they developed hyperglycemia. Nutritional intake and laboratory results for the treatment groups were compared with controls. Hyperglycemic infants had lower birth weights than controls. Hyperglycemic infants treated with glucose reduction remained <60 kcal/kg/day longer than control or insulin infusion groups (8.6 +/- 1.3 days vs. 4.1 +/- 0.2 and 5.5 +/- 0.6 days). No infants became hypoglycemic during insulin infusion. There was no difference in baseline blood levels of IGF-I or IGF-II among the groups, and these growth factors did not change in response to hyperglycemia. Hyperglycemic infants had baseline levels of insulin which were similar to normal controls, and endogenous insulin increased in response to hyperglycemia in 15 of the 23 infants who developed hyperglycemia. IGF-I and IGF-II are not related to hyperglycemia. In our population, hyperglycemic infants did not have baseline insulin deficiency and most had a normal insulin response to hyperglycemia. Insulin infusion appears safe in these infants and helped to maintain normal caloric intake, whereas glucose reduction was associated with a prolonged caloric deprivation.

Neonatal hypoglycemia is a major source of concern for pediatricians since it has commonly been related to poor neurodevelopmental outcomes. Diagnosis is challenging, considering the different operational thresholds provided by each guideline. Screening of infants at risk plays a crucial role, considering that most hypoglycemic infants show no clinical signs. New opportunities for prevention and treatment are provided by the use of oral dextrose gel. Continuous glucose monitoring systems could be a feasible tool in the next future. Furthermore, there is still limited evidence to underpin the current clinical practice of administering, in case of hypoglycemia, an intravenous "mini-bolus" of 10% dextrose before starting a continuous dextrose infusion. This brief review provides an overview of the latest advances in this field and neurodevelopmental outcomes according to different approaches. Conclusion: To adequately define if a more permissive approach is risk-free for neurodevelopmental outcomes, more research on continuous glucose monitoring and long-term follow-up is still needed. What is Known: • Neonatal hypoglycemia (NH) is a well-known cause of brain injury that could be prevented to avoid neurodevelopmental impairment. • Diagnosis is challenging, considering the different suggested operational thresholds for NH (<36, <40, <45, <47 or <50 mg/dl). What is New: • A 36 mg/dl threshold seems to be not associated with a worse psychomotor development at 18 months of life when compared to the "traditional" threshold (47 mg/dl). • Further studies on long-term neurodevelopmental outcomes are required before suggesting a more permissive management of NH. [ABSTRACT FROM AUTHOR]

Considerable evidence suggests that glucocorticoids (GCs) play an important role in neurodegeneration. Chronic elevated levels of GCs can result in neuronal degeneration of the hippocampal pyramidal neurons, which are paralleled by cognitive deficits. Moreover, GCs potentiate stress or ischemia-induced accumulation of excitatory amino acids (EAA) in the extracellular space of the hippocampus. ACEA 1021 (licostinel), a selective antagonist of the allosteric glycine site of the N-methyl-D-aspartate (NMDA) receptor complex, has been reported to prevent the excitotoxic action of high extracellular glutamate levels. The aim of this study was to investigate the effect of ACEA 1021 on the neurotoxic effect of dexamethasone (DEX, a synthetic GCs receptor agonist). The experiments were carried out on Albino Swiss mice (25-30 g). ACEA 1021 (1.25 and 2.5 mg/kg/day, ip) was administered 15 min before DEX (16 mg/kg/day, ip). Long-term memory acquisition (passive avoidance test) and motor performance ("chimney" test) were evaluated 14 days after drug administration. A prolongation of climbing time in the "chimney" test and a decrease in retention time in the memory task were observed in mice treated with DEX. ACEA 1021 at both doses reduced the climbing time in the "chimney" test and improved memory acquisition especially at the dose of 1.25 mg/kg in mice subjected to DEX for 14 days. The above findings suggest that ACEA 1021 could prevent the neurotoxic effects induced by DEX, but further studies need to be conducted to explain this effect. [ABSTRACT FROM AUTHOR]

Background: This study aimed to find an association between infants who had hyperglycemia and those who did not, those treated with insulin or not and several prenatal and postnatal variables or the suboptimal prescription of parenteral nutrition. Methods: We conducted a retrospective study, which included extremely premature infants (<28 weeks of gestation) admitted to the tertiary NICU, University Medical Centre Ljubljana, between 1 January 2021 and 31 December 2021. Blood glucose measurements, insulin treatment, general characteristics, nutritional data and complications of prematurity were obtained retrospectively from hospital data. RESULTS: There were 21 infants included in the study who did not receive insulin and 17 who were treated with insulin. Infants receiving insulin were younger and lighter compared to the non-insulin treatment group (mean gestational age 178 vs. 188 days; median birth weight 680 g vs. 990 g). The younger insulin group of infants received the same daily number of total macronutrients per kg per day compared to the older non-insulin group, i.e., glucose, lipids and amino acids, as recommended for the gestational age and birth weight. After adjusting for gestational age, no significant association with complications of prematurity was found. Conclusions: The postulated explanation (with the prescription of a higher amount of macronutrients during the first seven days) for hyperglycemia and treatment with insulin in the less mature and lighter infants cannot be supported by the data given. [ABSTRACT FROM AUTHOR]

Aim: To study the outcomes of very preterm infants with hyperglycaemia treated with Insulin. Methods: This is a systematic review of randomised controlled trials (RCTs) and observational studies. PubMed, Medline, EMBASE, Cochrane Library, EMCARE and MedNar databases were searched in May 2022. Data were pooled separately for adjusted and unadjusted odds ratios (ORs) using random‐effects model. Main outcome measures: Mortality and morbidities (e.g. Necrotising enterocolitis [NEC], retinopathy of prematurity [ROP]) in very preterm (<32 weeks) or very low birth weight infants (<1500 g) after treatment of hyperglycaemia with insulin. Results: Sixteen studies with data from 5482 infants were included. Meta‐analysis of unadjusted ORs from cohort studies showed that insulin treatment was significantly associated with increased mortality [OR 2.98 CI (1.03 to 8.58)], severe ROP [OR 2.23 CI (1.34 to 3.72)] and NEC [OR 2.19 CI (1.11 to 4)]. However, pooling of adjusted ORs did not show significant associations for any outcomes. The only included RCT found better weight gain in the insulin group, but no effect on mortality or morbidities. Certainty of evidence was 'Low' or 'Very low'. Conclusion: Very low certainty evidence suggests that Insulin therapy may not improve outcomes of very preterm infants with hyperglycaemia. [ABSTRACT FROM AUTHOR]

Neonatal hyperglycemia is a common metabolic disorder seen in very low birth weight (VLBW) and critically ill newborns. Hyperglycemia is a recognized cause for mortality and morbidity in the neonatal period. Incidence in preterm infants is around 45%–80%. The mechanism of increased risk of hyperglycemia in preterm infants is not well understood, but different possible mechanisms have been reported. Plasma glucose values more than 180–200 mg/dl (10–11.1 mmol) are of concern as this can lead to complications. Hyperglycemia was found to predispose to severe intraventricular hemorrhage, retinopathy of prematurity, necrotizing enterocolitis, and increased mortality. It is important to recognize and manage this condition early to avoid serious complications. Multiple etiologies with different management strategies are mentioned in the literature. Here, we discuss a complete understanding on practical management of hyperglycemia and we propose a simplified practical approach for the diagnosis and management of neonatal hyperglycemia. [ABSTRACT FROM AUTHOR]

Introduction: There is limited comprehensive literature focussing on the range of patient safety incidents related to parenteral nutrition (PN). Objective: The aim of this review was to examine patient safety incidents related to the use of PN in all patient age groups. Methods: Literature published in the English language between January 2000 and April 2020 were searched across the MEDLINE, CINHAL and Embase databases. Articles were included if they contained PN-related patient safety incidents related to an avoidable event. No restrictions were applied to patient populations. The screening process was undertaken independently by two authors. Results: In total, 108 records were included in the review: 52 case studies, 54 observation studies (e.g. prevalence studies, surveys) and two experimental studies. All age groups were represented, with 62% of studies in paediatrics (of which two-thirds were neonates) and 23% in adults. They included all medication processes: prescribing, dispensing, compounding, administration and monitoring. Incidents were related to microbial contamination, venous access and specific components (e.g. lipid emulsion, amino acids, glucose, micronutrients and electrolytes) or the whole product. Incident outcomes ranging from near miss to death were reported. Intervention studies looked at the impact on patient safety incidents of computerised tools, healthcare processes, e.g. pharmacist screening, and standardisation. One study demonstrated more severe outcomes with paediatric than with adult PN. Conclusions: This review demonstrates the vast range of PN-related patient safety incidents in all patient age groups and all medication process stages. The need for a national study looking at patient safety incidents related to PN in England is highlighted. [ABSTRACT FROM AUTHOR]

Through a meta-analysis, we aimed to investigate whether neonatal hyperglycemia was associated with an increased risk of retinopathy of prematurity (ROP) by summarizing all available observational evidence. We searched online databases for studies published prior to December 2020; 26745 neonates with 3227 cases of ROP in 11 case–control studies and 997 neonates with 496 cases of hyperglycemia in 5 cohort studies were included. The results showed that the association between hyperglycemia and the occurrence of ROP was statistically significant in case–control studies (OR 3.93, 95% CI 2.36–6.53) and cohort studies (OR 1.70, 95% CI 1.11–2.60). Besides, the borderline significant association between the duration of hyperglycemia and ROP was observed in case–control studies (MD = 1.96, 95% CI 0.90–3.03; adjusted OR = 1.08, 95% CI 1.01–1.15). Furthermore, we found that the mean blood glucose level is higher in the ROP group than the non-ROP group in case–control studies (MD = 14.86, 95% CI 5.06–24.66) and the mean blood glucose level is higher in the hyperglycemia group than in the non-hyperglycemia group (MD = 86.54, 95% CI 11.03–162.05). However, after adjusting other confounders, the association between the mean blood glucose level and ROP varied in cohort studies (OR 1.96, 95% CI 1.23–3.13) and case–control studies (OR 1.02, 95% CI 1.00–1.05). Conclusion: This meta-analysis demonstrates that preterm infants with hyperglycemia have a tendency to increase the risk of ROP. Further studies will be required to achieve a firm conclusion for hyperglycemia and ROP and promote a better understanding of the prevention of ROP. Trial registration: CRD42021228733 What is Known: • Hyperglycemia including the duration and daily mean blood glucose concentration has been associated with the risk of developing ROP in some clinical studies. Current evidence cannot reach a consensus on whether neonatal hyperglycemia is a risk factor for ROP. What is New: • This meta-analysis demonstrates that preterm infants with hyperglycemia have a tendency to increase the risk of ROP. • While the association between the mean blood glucose level and ROP remains inconclusive. [ABSTRACT FROM AUTHOR]

Background: Hyperglycemia in preterm infants may be associated with severe retinopathy of prematurity (ROP) and other morbidities. However, it is uncertain which concentration of blood glucose is associated with increased risk of tissue damage, with little consensus on the cutoff level to treat hyperglycemia. The objective of our study was to examine the association between hyperglycemia and severe ROP in premature infants. Methods and findings: In 2 independent, monocentric cohorts of preterm infants born at <30 weeks' gestation (Nantes University Hospital, 2006–2016, primary, and Lyon-HFME University Hospital, 2009–2017, validation), we first analyzed the association between severe (stage 3 or higher) ROP and 2 markers of glucose exposure between birth and day 21—maximum value of glycemia (MaxGly1–21) and mean of daily maximum values of glycemia (MeanMaxGly1–21)—using logistic regression models. In both the primary (n = 863 infants, mean gestational age 27.5 ± 1.4 weeks, boys 52.5%; 38 with severe ROP; 54,083 glucose measurements) and the validation cohort (n = 316 infants, mean gestational age 27.4 ± 1.4 weeks, boys 51.3%), MaxGly1–21 and MeanMaxGly1–21 were significantly associated with an increased risk of severe ROP: odds ratio (OR) 1.21 (95% CI 1.14–1.27, p < 0.001) and OR 1.70 (95% CI 1.48–1.94, p < 0.001), respectively, in the primary cohort and OR 1.17 (95% CI 1.05–1.32, p = 0.008) and OR 1.53 (95% CI 1.20–1.95, p < 0.001), respectively, in the validation cohort. These associations remained significant after adjustment for confounders in both cohorts. Second, we identified optimal cutoff values of duration of exposure above each concentration of glycemia between 7 and 13 mmol/l using receiver operating characteristic curve analyses in the primary cohort. Optimal cutoff values for predicting stage 3 or higher ROP were 9, 6, 5, 3, 2, 2, and 1 days above a glycemic threshold of 7, 8, 9, 10, 11, 12, and 13 mmol/l, respectively. Severe exposure was defined as at least 1 exposure above 1 of the optimal cutoffs. Severe ROP was significantly more common in infants with severe exposure in both the primary (10.9% versus 0.6%, p < 0.001) and validation (5.2% versus 0.9%, p = 0.030) cohorts. Finally, we analyzed the association between insulin therapy and severe ROP in a national population-based prospectively recruited cohort (EPIPAGE-2, 2011, n = 1,441, mean gestational age 27.3 ± 1.4, boys 52.5%) using propensity score weighting. Insulin use was significantly associated with severe ROP in overall cohort crude analyses (OR 2.51 [95% CI 1.13–5.58], p = 0.024). Adjustment for inverse propensity score (gestational age, sex, birth weight percentile, multiple birth, spontaneous preterm birth, main pregnancy complications, surfactant therapy, duration of oxygen exposure between birth and day 28, digestive state at day 7, caloric intake at day 7, and highest glycemia during the first week) and duration of oxygen therapy had a large but not significant effect on the association between insulin treatment and severe ROP (OR 0.40 [95% CI 0.13–1.24], p = 0.106). Limitations of this study include its observational nature and, despite the large number of patients included compared to earlier similar studies, the lack of power to analyze the association between insulin use and retinopathy. Conclusions: In this study, we observed that exposure to high glucose concentration is an independent risk factor for severe ROP, and we identified cutoff levels that are significantly associated with increased risk. The clinical impact of avoiding exceeding these thresholds to prevent ROP deserves further evaluation. In this cohort study, Elsa Kermorvant-Duchemin and colleagues examine the association between hyperglycemia and severe retinopathy of prematurity in infants. Author summary: Why was this study done?: Hyperglycemia, i.e., elevated blood glucose, is common in preterm babies, due to the immaturity of glucose regulation mechanisms; it is often treated with insulin infusion, based on weak evidence. A number of studies, with heterogeneity in both setting and design, have suggested that hyperglycemia may be associated with increased risk of morbidity in premature infants, especially severe retinopathy of prematurity, a condition characterized by an abnormal development of the retinal vessels that can lead to blindness. However, current published evidence does not rule out that hyperglycemia may only be a marker of severity of illness and not an independent risk factor for retinopathy of prematurity because not all potential confounding factors were taken into account. It is also uncertain which concentration of blood glucose could be associated with tissue damage in preterm infants, with little consensus on the cutoff level to treat hyperglycemia. What did the researchers do and find?: We used 2 independent cohorts of 863 (primary cohort) and 316 (validation cohort) preterm infants born at <30 weeks' gestation to study the association between severe retinopathy of prematurity and 2 markers of glucose exposure between birth and day 21. We used a third cohort—a prospective, nationwide population-based cohort of 1,441 preterm infants born at <30 weeks' gestation, representing a large variation of practices regarding neonatal management—to examine the impact of strategies to avoid or reduce hyperglycemia on the risk of severe retinopathy of prematurity. Strengthened by multiple sensitivity analyses and external validation, our results support the hypothesis that hyperglycemia is an independent risk factor for severe retinopathy of prematurity and not a mere marker of illness. More importantly, we identified thresholds of combined severity and duration of hyperglycemia above which the risk of severe retinopathy increases significantly. In the nationwide population-based cohort, the analysis of insulin as a protective factor against severe retinopathy of prematurity found a large but not significant effect after controlling for confounding factors. What do these findings mean?: The results suggest that overall average exposure and duration of hyperglycemia matter more than a single high glucose value when determining risk of retinopathy. The thresholds of combined severity and duration of exposure that were identified may help physicians to determine treatment strategies in hyperglycemic premature infants. The clinical impact of avoiding exceeding these thresholds to prevent severe retinopathy of prematurity deserves evaluation. [ABSTRACT FROM AUTHOR]

Hyperglycemia in extremely low-birth weight infants (ELBWIs) is frequently observed during the acute perinatal phase, (i.e., first 1–2 weeks postnatal period); however it can occasionally persists for >2 weeks, extending to the post-acute phase. Since such prolonged hyperglycemia (PH) is not typical for ELBWIs, the aim of the present study was to further understand the clinical details of PH. Twenty-five hyperglycemic ELBWIs born before 28 weeks of gestation from 2015 to 2018 were included in the study. Based on the duration of hyperglycemia, we separated the subjects into two groups: non-prolonged hyperglycemia (NPH) who achieved remission within ≤2 weeks [n = 18, median 3.0 (range, 2.0–4.0) days], and PH, whose hyperglycemia persisted for >2 weeks [n = 7, median 50.0 (range, 33.5–66.0) days]. Compared to the NPH group, glucose metabolism of the PH group was more deteriorate. The peak blood glucose level was significantly higher in the PH group [PH: median 472 mg/dL, NPH: median 275 mg/dL, p < 0.001], and a higher proportion of subjects in the PH group required insulin therapy [PH: 100% (7/7) vs. NPH: 22% (4/22)]. Multivariate analysis revealed that among perinatal factors, prematurity was the only independent risk factor for PH (glucocorticoid therapy: p = 0.884, gestational age: p = 0.006), with a cutoff of 23W4D determined by receiver operating characteristic analysis. Our data revealed distinctive clinical features of PH, suggesting a type different from the previously reported hyperglycemia in ELBWIs. Specifically, extreme prematurity, less than 24 weeks of gestation, is a risk for PH, and aggressive interventions, such as insulin would be required. [ABSTRACT FROM AUTHOR]

Background: Stress‐induced hyperglycemia is a frequent complication of neonatal sepsis. Hyperglycemia induces oxidative stress and immunosuppression. We investigated the glucose kinetics and effect of insulin administration during stress‐induced hyperglycemia in a neonatal sepsis mouse model. Methods: A stock cecal slurry (CS) solution was prepared from adult cecums and 3.0 mg of CS/g (LD40) was administered intraperitoneally to 4‐day‐old FVB mouse pups. Blood glucose levels were measured at 1.5, 3, 6, and 9 h post‐sepsis induction and compared with basal levels. Two different doses of ultrafast‐acting insulin were administered subcutaneously, and blood glucose levels and survival rates were monitored. Results: Blood glucose levels were significantly higher than those of baseline levels with a peak at 3 h, which progressively decreased from 6 to 9 h post‐sepsis induction. Insulin treatment reduced post‐sepsis‐induced hyperglycemia at 1.5 and 3 h. The mortality rate of CS‐only pups (39%) was similar to that of CS + 1 U/kg insulin pups (60%). However, the mortality rate of CS + 5 U/kg insulin pups (82%) was significantly higher than that of CS‐only pups. Conclusions: Marked hyperglycemia was induced immediately after post‐sepsis induction, and the high‐dose insulin treatment increased mortality post‐induction. Stress‐induced hyperglycemia could therefore be a physiological and protective response for preterm sepsis, and aggressive treatment of this hyperglycemia might be contraindicated. [ABSTRACT FROM AUTHOR]

The goal of nutrition of the preterm infant is to "provide nutrients to approximate the rate of growth and composition of weight gain for a normal fetus of the same postmenstrual age and to maintain normal concentrations of blood and tissue nutrients" (American Academy of Pediatrics 2014). Failure to provide the necessary amounts of all of the essential nutrients to preterm infants has produced not only growth failure, but also increased morbidity and less than optimal neurodevelopment. This continues to be true despite many efforts to increase nutrition of the preterm infants. In contrast, enhanced nutrition of very preterm infants, both intravenous and enteral, beginning right after birth, promotes positive energy and protein balance and improves longer term neurodevelopmental outcomes. The benefits are long lasting too, particularly for prevention of later life chronic diseases. [ABSTRACT FROM AUTHOR]

Aim: We evaluated a strict strategy that aimed to avoid fluctuations in glucose infusion rates (GIRs) and assessed the independent effects of maximal daily GIRs on the hyperglycaemia risk among extremely low birth weight (ELBW) infants receiving early enhanced parenteral nutrition.Methods: This study comprised all ELBW infants admitted to the neonatal intensive care unit of Oslo University Hospital Rikshospitalet, Norway, before (2007-2009) and after (2012-2013) implementing a strict GIR strategy. Severe hyperglycaemia was defined as two consecutive blood glucose values over 12 mmol/L. Maximum daily GIRs (mg/kg/min) were categorised into low (<5.1), intermediate (5.1-7.0) or high (>7.0). Mixed effects logistic regression modelling for repeated measurements was applied to investigate independent determinants of hyperglycaemia.Results: We included 1293 treatment days for 195 infants. The maximum daily GIR decreased (6.3 versus 5.8 mg/kg/min), while mean daily glucose and energy intakes were maintained in the post-strategy period. The prevalence of severe hyperglycaemia (48% versus 23%), insulin use (39% versus 16%) and mortality (26% versus 10%) fell. Intermediate GIR (odds ratio 2.11) and high GIR (odds ratio 2.85) were significant independent predictors of severe hyperglycaemia compared to low GIR.Conclusion: A strict GIR strategy reduced the risk of severe hyperglycaemia and adverse outcomes. [ABSTRACT FROM AUTHOR]

Human breast milk (BM) amino acid (AA) composition may be impacted by lactation stage or factors related to geographical location. The present cross-sectional study is aimed at assessing the temporal changes of BMAA over lactation stages in a large cohort of urban mothers in China. Four hundred fifty BM samples, collected in three Chinese cities covering eight months of lactation were analyzed for free (FAA) and total (TAA) AA by o-phthalaldehyde/ fluorenylmethylchloroformate (OPA/FMOC) derivatization. Concentrations and changes over lactation were aligned with previous reports. Both the sum and the individual TAA values significantly decreased during the first periods of lactation and then generally leveled off. Leucine and methionine were respectively the most and the least abundant indispensable amino acids across all the lactation stages, whereas glutamic acid + glutamine (Glx) was the most and cystine the least abundant dispensable AA. The contribution of FAA to TAA levels was less than 2%, except for free Glx, which was the most abundant FAA. In conclusion, the AA composition of the milk from our cohort of urban Chinese mothers was comparable to previous studies conducted in other parts of the world, suggesting that this is an evolutionary conserved trait largely independent of geographical, ethnic, or dietary factors. [ABSTRACT FROM AUTHOR]

Compartment syndrome is a rare but devastating condition that can result in permanent neuromuscular or soft tissue injuries. Extravasation injuries, among the iatrogenic causes of compartment syndrome, occur under a wide variety of circumstances in the inpatient setting. Total parenteral nutrition via a peripheral route is an effective alternative for the management of critically ill children who do not obtain adequate nutrition via the oral route. However, there is an inherent risk of extravasation, which can cause compartment syndrome, especially when detected at a later stage. Herein, we report a rare case of compartment syndrome and skin necrosis due to extravasation, requiring emergency fasciotomy and skin graft in a 7-month-old boy who was treated with peripheral parenteral nutrition via a pressurized infusion pump. Although we cannot estimate the exact time at which extravasation occurred, the extent and degree of the wound suggest that the ischemic insult was prolonged, lasting for several hours. Pediatric clinicians and medical teams should carefully examine the site of insertion of the intravenous catheter, especially in patients receiving parenteral nutrition via a peripheral intravenous catheter with a pressurized infusion pump. [ABSTRACT FROM AUTHOR]

An abnormal plasma glucose concentration is one of the most commonly encountered metabolic problems in the intensive care of premature infants. Compared with term infants, glycogen reserves are lower in the preterm neonatal liver. Despite this, preterm infants are at a greater risk of hyperglycemia than term infants are, which is owing to comparable production rate of endogenous glucose and impaired ability to reduce glucose production rate in response to hyperglycemia. Debate continues about the normal plasma glucose concentrations and the guideline for glucose control in premature infants. Some randomized controlled trials in very low birth weight infants demonstrated little clinical benefit of tight glycemic control with early insulin therapy and higher calorie intake in terms of mortality, morbidities and growth parameters. Compared with term infants, preterm infants have limited endocrine and metabolic adaptation to hypoglycemia. In any case, hypoglycemia in premature infants should not be considered a physiologic condition. The operational criteria for intervention of hypoglycemia should be different from that in term infants. Continuous non-invasive glucose monitoring is a promising tool considering the principle of minimal handling of extremely premature infants. However, the clinical implication of abnormal glucose concentrations, previously undetected on intermittent measurements, is unclear. [ABSTRACT FROM AUTHOR]

Standardised parenteral nutrition formulations are routinely used in the neonatal intensive care units in Australia and New Zealand. In 2010, a multidisciplinary group was formed to achieve a consensus on the formulations acceptable to majority of the neonatal intensive care units. Literature review was undertaken for each nutrient and recommendations were developed in a series of meetings held between November 2010 and April 2011. Three standard and 2 optional amino acid/dextrose formulations and one lipid emulsion were agreed by majority participants in the consensus. This has a potential to standardise neonatal parenteral nutrition guidelines, reduce costs and prescription errors. [ABSTRACT FROM AUTHOR]

Neonatal diabetes mellitus (NDM) is a rare form of diabetes characterized by hyperglycemia occurring in the first few months of life. It can present as either transient NDM (TNDM), which resolves by a few months, or permanent NDM (PNDM), which continues throughout life. The etiology of this disease remained unclear until recently, when advances in molecular genetic techniques illuminated the mechanisms involved in the pathogenesis of the disease. Having delineated the genes involved in insulin production and secretion and their association with NDM, we currently understand the molecular basis of this disease. While most TNDM cases are caused by the overexpression of chromosome 6q24, the majority of PNDM cases are due to mutations in the adenosine triphosphate-sensitive potassium (KATP) channel. The improved understanding of the etiology of the disease had revolutionized the diagnosis and its management with oral sulfonylureas. The primary objective of this study was to review the current understanding of neonatal diabetes, including its genetic etiologies, clinical presentation, diagnosis, acute treatment, and long-term management. [ABSTRACT FROM AUTHOR]

A systematic review was undertaken to assess the effect of using insulin therapy in the treatment for stress hyperglycaemia in children without preexisting diabetes in: achieving normoglycaemia, improving symptoms associated with hyperglycaemia and survival, and to determine if any adverse effects were associated with the use of insulin therapy. Conclusion There is currently insufficient evidence for the routine use of insulin therapy in stress hyperglycaemia compared with conventional care in children without preexisting diabetes. [ABSTRACT FROM AUTHOR]

OBJECTIVE:To investigate the association between early hyperglycemia and growth and development from hospital discharge to 2 years corrected age (CA) in very low birth weight (VLBW) infants.STUDY DESIGN:Blood glucose levels during the first 14 days after birth, weight, length and occipital-frontal circumference (OFC) at birth, hospital discharge and 4, 12 and 24 months CA, Bayley developmental scores at 12 and 24 months CA, and information on multiple clinical variables were recorded on VLBW preterm infants (N=80). The relationships between hyperglycemia, growth and developmental scores were determined using linear mixed effects regression.RESULT:Hyperglycemia was a strong predictor of poor rate of increase in weight, length and OFC until 24 months CA. Hyperglycemia was not associated with lower scores on the Bayley scales.CONCLUSION:Neonatal hyperglycemia was associated with poor physical growth until at least 2 years CA in this cohort of VLBW preterm infants. [ABSTRACT FROM AUTHOR]

Background: Hyperglycaemic preterm babies suffer increased mortality and morbidity, but it is not known if these associations are causal or if treatment with insulin improves outcome. Objectives: We aimed to investigate the effect of neonatal hyperglycaemia, and its treatment with insulin, on mortality and morbidity in preterm lambs. Methods: Preterm lambs (137 days' gestation; term = 148 days) were randomised to a 12-day intravenous infusion of saline (PremC; n = 39), 50% dextrose (HYPER; n = 47), or 50% dextrose + insulin (INS; n = 21). Term controls (TermC; n = 19) received saline. Dextrose and insulin infusions were titrated to maintain blood glucose concentrations (BGC) at 10-12 mmol·l-1 (HYPER) or 4-6 mmol·l-1 (INS). Results: HYPER lambs had higher BGC (mean (SEM); TermC: 5.6 (0.1), PremC: 5.5 (0.1), HYPER: 10.8 (0.6), INS: 6.2 (0.3) mmol·l-1; p < 0.0001), higher mortality (n (%); TermC: 0, PremC: 2 (5), HYPER: 11 (23), INS: 0; p < 0.001), higher incidence of fever (n (%); TermC: 3 (16), PremC: 13 (33), HYPER: 26 (55), INS: 6 (29); p = 0.01) and lower weight gain (mean (SEM); TermC: 45.9 (2.9), PremC: 44.2 (2.1), HYPER: 28.4 (1.9), INS: 28.7 (2.8) g·kg-1·day-1; p < 0.0001). Conclusions: Neonatal hyperglycaemia in preterm lambs causes increased mortality and morbidity, and decreases growth. Insulin treatment to restore euglycaemia attenuated the increased mortality and morbidity, but not the decreased growth. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Hyperglycemia often occurs in premature, very low birthweight infants (VLBW) due to immaturity of endogenous regulatory systems and the stress of their condition. Hyperglycemia in neonates has been linked to increased morbidities and mortality and occurs at increasing rates with decreasing birthweight. In this cohort, the emerging use of insulin to manage hyperglycemia has carried a significant risk of hypoglycemia. The efficacy of blood glucose control using a computer metabolic system model to determine insulin infusion rates was assessed in very-low-birth-weight infants. Methods: Initial short-term 24-hour trials were performed on 8 VLBW infants with hyperglycemia followed by longterm trials of several days performed on 22 infants. Median birthweight was 745 g and 760 g for short-term and long-term trial infants, and median gestational age at birth was 25.6 and 25.4 weeks respectively. Blood glucose control is compared to 21 retrospective patients from the same unit who received insulin infusions determined by sliding scales and clinician intuition. This study was approved by the Upper South A Regional Ethics Committee, New Zealand (ClinicalTrials.gov registration NCT01419873). Results: Reduction in hyperglycemia towards the target glucose band was achieved safely in all cases during the short-term trials with no hypoglycemic episodes. Lower median blood glucose concentration was achieved during clinical implementation at 6.6 mmol/L (IQR: 5.5 - 8.2 mmol/L, 1,003 measurements), compared to 8.0 mmol/L achieved in similar infants previously (p < 0.01). No significant difference in incidence of hypoglycemia during longterm trials was observed (0.25% vs 0.25%, p = 0.51). Percentage of blood glucose within the 4.0 - 8.0 mmol/L range was increased by 41% compared to the retrospective cohort (68.4% vs 48.4%, p < 0.01). Conclusions: A computer model that accurately captures the dynamics of neonatal metabolism can provide safe and effective blood glucose control without increasing hypoglycemia. Trial Registration: ClinicalTrials.gov registration NCT01419873 [ABSTRACT FROM AUTHOR]

In the newborn infant, insulin secretion has to adjust in response to the switch from a regulated and continuous placental supply of glucose in utero to the delivery of intermittent oral feeds postnatally. Changes in insulin secretion must reflect its primary role for maintaining glucose homeostasis, but also its roles in promoting growth and anabolism and in the newborn disorders of insulin secretion or sensitivity, which present with hyperglycemia and impaired growth. Recent elucidation of the genetic basis of neonatal diabetes has helped to provide valuable insights into the molecular mechanisms of β-cell function and the potential for treatment of some patients with oral hypoglycemic agents, although the majority require prolonged subcutaneous insulin treatment, which may prove challenging. The recent development of insulin pump therapy has significantly improved the clinical management of these infants. Although they do not have neonatal diabetes, the preterm or very-low-birthweight infant, subjected to the combined effects of insulin resistance owing to the impact of intensive care, and relative insulin deficiency related to prematurity, may have long periods of hyperglycemia and impaired growth, which have been associated with adverse clinical outcomes. Although these infants often require insulin treatment, the optimal management of glucose control and use of insulin has not been determined and remains controversial. INSET: Key issues. [ABSTRACT FROM AUTHOR]

Background: Hyperglycemia in premature infants is associated with increased morbidity and mortality, but data on long-term outcome are limited. We investigated the effects of neonatal hyperglycemia (blood glucose ≥ 10 mmol/l, treated with insulin for ≥ 12 hours) on growth and neurobehavioral outcome at 2 years of age. Methods: Retrospective follow-up study at 2 years of age among 859 infants ≤32 weeks of gestation admitted to a tertiary neonatal center between January 2002 and December 2006. Thirty-three survivors treated with insulin for hyperglycemia and 63 matched controls without hyperglycemia were evaluated at a corrected age of 2 years. Outcome measures consisted of growth (weight, length, and head circumference) and neurological and behavioural development. Results: 66/859 (8%) infants ≤ 32 weeks of gestation developed hyperglycemia. Mortality during admission was 27/66 (41%) in the hyperglycemia group versus 62/793 (8%) in those without hyperglycemia (p < 0.001). Mortality was higher in infants with hyperglycemia with a birth weight ≤1,000 gram (p = 0.005) and/or gestational age of 24-28 weeks (p = 0.009) than in control infants without hyperglycemia. Sepsis was more prominent in infants with hyperglycemia and a birth weight of >1,000 gram (p = 0.002) and/or gestational age of 29-32 weeks (p = 0.009) than in control infants without hyperglycemia. Growth at 2 years of age was similar, but neurological and behavioural development was more frequently abnormal among those with neonatal hyperglycemia (p = 0.036 and 0.021 respectively). Conclusions: Mortality was higher in very preterm infants with hyperglycemia treated with insulin during the neonatal period. At 2 years of age survivors showed normal growth, but a higher incidence of neurological and behavioural problems. Better strategies to manage hyperglycemia may improve outcome of very preterm infants. [ABSTRACT FROM AUTHOR]

AbstractObjectives:To evaluate the feasibility and efficacy of a continuous glucose monitoring system (CGMS) in a population of infants of very low birth weight (VLBW). Study Design:Infants weighing ≤1,500 g and of ≤32 weeks of gestation were recruited within 24 h of delivery. A subcutaneous sensor connected to a CGMS was inserted and maintained for 7 days or until dysfunction. Therapeutic management followed the usual standard protocols. Results:38 patients (21 male) were included over 17 months. Their mean gestational age was 27.5 ± 2.0 weeks and their mean birth weight was 958.3 ± 205.5 g. Their perinatal histories and complications during admission were unremarkable for extremely premature babies. Continuous monitoring lasted an average of 7.84 ± 1.99 days per patient. Hyperglycaemia was detected in 22 (57.90) patients and it lasted a mean of 20.33 ± 30.13 h, while 14 (36.8) presented with hypoglycaemia for a mean of 2.45 ± 2.3 h. Conclusions:The CGMS gave a safe and useful estimate of glucose levels in VLBW infants, revealing abnormal glucose levels at a much higher rate than expected by usual sampling. However, it was not able to provide real-time glucose concentration data. CGMS may be very useful in providing information on the role of hyper- and hypoglycaemia on short- and long-term outcomes in VLBW infants.Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Hyperglycemia is a common problem in newborns undergoing intensive care, especially extremely low birth weight (ELBW) infants. There is a lack of consensus with regard to various aspects of management of neonatal hyperglycemia including definition, optimal management strategy as well as short and long term implications. We reviewed the current evidence in this regard. Recent studies suggest that adequate control of hyperglycemia may be beneficial but long-term implications of hyperglycemia and insulin therapy in the ELBW infants are not known. Awaiting further research, it may be pragmatic to use a more operational definition of hyperglycemia and limit insulin therapy to neonates with high risk of osmolar derangement as per the proposed guideline. [ABSTRACT FROM AUTHOR]

Aim: Hyperglycaemia is a common problem in very low birthweight (VLBW) preterm neonates and has been associated with an increase in intraventricular haemorrhage and mortality. There are few data to guide clinicians on the best range of blood glucose levels to aim for when treating hyperglycaemic preterm babies with insulin. The aim of this study was to survey all Australasian tertiary neonatal intensive care units for their current practice in the definition and management of neonatal hyperglycaemia to aid in the design of a randomised controlled trial of the effect of tight glycaemic control on long-term outcome in VLBW babies. Methods: An online survey was sent to the 27 tertiary neonatal units in Australasia asking the respondents for details of their unit’s definition and management of hyperglycaemia in VLBW infants. Results: Twenty-three tertiary neonatal units responded to the questionnaire. There were six different definitions of hyperglycaemia, with most units defining neonatal hyperglycaemia as a blood glucose level greater than 10 mM. There were large variations in the criteria for commencing insulin (blood glucose level 8–15 mM ± glycosuria) and target blood glucose ranges for babies on insulin (ranging from 2.5–8 mM to 8–15 mM). Conclusions: There is a wide variation in the management of neonatal hyperglycaemia between tertiary neonatal units in Australasia. This reflects the paucity of data available in this area. Further research on the management of neonatal hyperglycaemia is needed. [ABSTRACT FROM AUTHOR]

Background Delayed sepsis, systemic inflammatory response syndrome (SIRS) and multiorgan failure remain major causes of morbidity and mortality on intensive care units. One factor thought to be important in the aetiology of SIRS is failure of the intestinal barrier resulting in bacterial translocation and subsequent sepsis. Aim This review summarizes the current knowledge about bacterial translocation and methods to prevent it. Methods Relevant studies during 1966–2006 were identified from a literature search. Factors, which detrimentally affect intestinal barrier function, are discussed, as are methods that may attenuate bacterial translocation in the critically ill patient. Results Methodological problems in confirming bacterial translocation have restricted investigations to patients undergoing laparotomy. There are only limited data available relating to specific interventions that might preserve intestinal barrier function or limit bacterial translocation in the intensive care setting. These can be categorized broadly into pre-epithelial, epithelial and post-epithelial interventions. Conclusions A better understanding of factors that influence translocation could result in the implementation of interventions which contribute to improved patient outcomes. Glutamine supplementation, targeted nutritional intervention, maintaining splanchnic flow, the judicious use of antibiotics and directed selective gut decontamination regimens hold some promise of limiting bacterial translocation. Further research is required. [ABSTRACT FROM AUTHOR]

Background: Studies in adult intensive care have highlighted the importance of insulin and improved glucose control on survival, with 32% reduction in mortality, 22% reduction in intensive care stay and halving of the incidence of bacteraemia. Very low birth weight infants requiring intensive care also have relative insulin deficiency often leading to hyperglycaemia during the first week of life. The physiological influences on insulin secretion and sensitivity, and the potential importance of glucose control at this time are not well established. However there is increasing evidence that the early postnatal period is critical for pancreatic development. At this time a complex set of signals appears to influence pancreatic development and β cell survival. This has implications both in terms of acute glucose control but also relative insulin deficiency is likely to play a role in poor postnatal growth, which has been associated with later motor and cognitive impairment, and fewer β cells are linked to risk of type 2 diabetes later in life. Methods: A multi-centre, randomised controlled trial of early insulin replacement in very low birth weight babies (VLBW, birth weight < 1500 g). 500 infants will be recruited from 10 centres in the UK and Europe. Babies will be randomised to receive a continuous insulin infusion (0.05 units/kg/h) or to receive standard neonatal care from the first day of life and for the next 7 days. If blood glucose (BG) levels fall infants will receive 20% dextrose titrated to maintain normoglycaemia 4-8 mmol/l). If BG is consistently above 10 mmol/l babies will receive standard treatment with additional insulin infusion. The primary end point will be mortality on or before expected date of delivery, secondary end points will be markers of morbidity and include episodes of sepsis, severity of retinopathy, chronic lung disease and growth. Trial Registration: Current Controlled Trials ISRCTN78428828. EUDRACT Number 2004-002170-34. [ABSTRACT FROM AUTHOR]

Objective:The purpose of this study was to determine the association between hyperglycemia and mortality and late-onset infections (>72 h) in extremely low birth weight (ELBW) infants.Study design:Retrospective analysis of a prospective cohort study of 201 ELBW infants who survived greater than 3 days after birth. Mean morning glucose levels were categorized as normoglycemia (<120 mg/dl), mild-moderate hyperglycemia (120 to 179 mg/dl) and severe hyperglycemia (180 mg/dl). Hyperglycemia was further divided into early (first 3 days of age) and persistent (first week of age). Logistic regression was performed to assess whether hyperglycemia was associated with either mortality or late-onset culture-proven infection, measured after 3 and 7 days of age.Results:Adjusting for age, the odds ratio (OR) for either dying or developing a late infection was 5.07 (95% confidence interval (CI): 1.06 to 24.3) for infants with early severe hyperglycemia and 6.26 (95% CI: 0.73 to 54.0) for infants with persistent severe hyperglycemia. Adjusting for age, both severe early and persistent hyperglycemia were associated with increased mortality. Among survivors, there was no significant association between hyperglycemia and length of mechanical ventilation or length of hospital stay. Persistent severe hyperglycemia was associated with the development of Stage II/III necrotizing enterocolitis, after adjusting for age and male gender (OR: 9.49, 95% CI: 1.52 to 59.3).Conclusion:Severe hyperglycemia in the first few days after birth is associated with increased odds of death and sepsis in ELBW infants.Journal of Perinatology (2006) 26, 730–736. doi:10.1038/sj.jp.7211593; published online 24 August 2006 [ABSTRACT FROM AUTHOR]

Aim: The incidence of invasive fungal infection in preterm newborns is rising steadily. Early recognition and treatment are imperative, but diagnosis is difficult as data from microbiological investigations are often poor, and clinical and laboratory signs do not help in differentiating bacterial from fungal infections. We evaluated whether glucose intolerance could represent a possible surrogate marker predictor of invasive fungal infection in preterm neonates. Methods: We performed a case-control study on neonates with birthweight less than 1250 g admitted to our tertiary-level unit during the years 1998–2004 ( n =383), comparing those with invasive fungal infection ( n = 45, group A) to matched controls with late-onset sepsis caused by bacterial agents ( n =46, group B). We investigated in both groups the occurrence of hyperglycaemia (serum glycaemia > 215 mg/dl, i.e. 12 mmol/l) in the first month of life, and its temporal relationship with the episodes of sepsis. Results: Hyperglycaemia occurred significantly more often in group A (21/45, 46.6%) than in group B neonates (11/46, 23.9%) (OR 1.95, 95% CI 1.235–4.432, p =0.008). Moreover, in 19 of 21 (90.4%) neonates with hyperglycaemia in group A, the carbohydrate intolerance episode typically occurred 72 h prior to the onset of invasive fungal infection; in contrast, no temporal relationship was found in neonates with bacterial sepsis ( p =0.002). Correction of hyperglycaemia was successfully achieved in all neonates of both groups, with no significant differences in the number of days of insulin treatment needed to normalize glycaemia ( p = 0.15). Conclusions: Hyperglycaemia is significantly more frequent in neonates who subsequently develop fungal rather than bacterial late-onset sepsis, with a typical 3-d interval. We suggest that a preterm neonate whose birthweight is less than 1250 g in its first month of life should be carefully evaluated for systemic fungal infection whenever signs of carbohydrate intolerance occur. [ABSTRACT FROM AUTHOR]

The article presents information on a report related to the nutrition in hyperglycaemic very low birth weight infants. The article presents information on a report related to the nutrition in hyperglycaemic very low birth weight infants. Usually hyperglycaemia develops when the premature infants are given parenteral nutrition in amounts necessary to meet requirements for adequate growth. But it may lead to theosmotic diuresis with resultant dehydration and electrolyte imbalance. The subsequent hyperosmolar state has been associated with an increased risk of intraventricular haemorrhage. according to the recent studies involving the use of insulin for rigid blood glucose control in hyperglycaemic adult intensive care patients have shown significant decrease in their mortality, intensive care stay, and incidence of sepsis.