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Background: The feeding patterns of healthy newborns have been poorly described. Research Aim: To determine the feeding patterns of healthy term newborns soon after birth, and if these differed with sex, gestation, and mode of birth. Methods: This study was a prospective, longitudinal observational cohort study. Term, appropriately grown newborns ( N = 66) were fed according to maternal choice and details were recorded. Data were analyzed using generalized Poisson regression for feeding frequencies, and mixed model regression of log-transformed data for durations. Results: The participants completing the study had a M = 3589 g ( SD = 348 g) birthweight, with a gestation age of M = 40.1 (1.2) weeks. All participants were breastfed; 23 (35%) also received expressed human milk and 10 (15%) received formula. Participants had fewer feeding sessions on Day 1, ( M = 7.3 [1.9] sessions/day) increasing to ( M = 9.4 [2.4] sessions/day) by Day 3, then reducing to ( M = 9.0 [2.2] sessions/day) on Day 5, p < .001. The overall duration of breastfeeding sessions varied widely ( Mdn = 29 [range = 1–447] min). Feed frequency but not duration was higher in males than females ( M = 8.9, SE = 0.2 vs. 8.1, 02, sessions/day, p = .03), in newborns born ≥ 40 weeks’ gestation ( M = 8.9, SE = 0.3 vs. 8.2, 02, sessions/day, p = .04), and in newborns born by Caesarean section ( M = 9.4, SE = 0.3 vs. 8.4, 02, sessions/day, for vaginal birth, p = .003). Conclusion: Feeding patterns of healthy term newborns vary widely, but frequency increases during the first 3 days, and is greater in males, newborns born late term, and born by Caesarean section. Clinical Trial Registration: The Australian and New Zealand Clinical Trials Registry Ref: ACTRN12615000986572. The study protocol is available online: http://hdl.handle.net/2292/32066

Diabetes secondary to pancreatic disease accounts for 0.5% of all cases of diabetes mellitus. These conditions are associated with exocrine as well as endocrine pancreatic failure and present a complex management challenge. Diabetes in patients with haemochromatosis is associated with micro- and macrovascular complications and most patients require insulin therapy. Regular venesection to reduce the iron overload is associated with improvements in glycaemic control. Secondary haemochromatosis occurring in patients with haematological conditions requiring frequent blood transfusions is also associated with diabetes. Diabetes secondary to pancreatic disease is commonly seen and can present complex management problems which are best managed by a multidisciplinary team. Treating the underlying condition, as well as the associated hyperglycaemia, is essential.

Objectives To determine postnatal changes in plasma and interstitial glucose concentrations of healthy infants receiving current recommended care and to compare the incidence of low concentrations with recommended thresholds for treatment of at-risk infants. Study design A prospective masked observational study in Hamilton, New Zealand. Healthy, term, appropriately grown singletons had continuous glucose monitoring and repeated heel-prick plasma glucose measurements (4 in the first 24 hours then twice daily using the glucose oxidase method) from birth to 120 hours. Results The 67 infants had a mean birth weight of 3584 ± 349 g, and gestational age of 40.1 ± 1.2 weeks. The mean glucose concentrations increased over the first 18 hours, remained stable to 48 hours (59 ± 11 mg/dL; 3.3 ± 0.6 mmol/L)] before increasing to a new plateau by the fourth day (89 ± 13 mg/dL; 4.6 ± 0.7 mmol/L). Plasma glucose concentrations of 47 mg/dL (2.6 mmol/L) approximated the 10th percentile in the first 48 hours, and 39% of infants had ≥1 episode below this threshold. Early term infants had lower mean glucose concentrations than those born at later gestational ages and were more likely to have episodes Conclusions Healthy infants seem to complete their metabolic transition by day 4. Many have glucose concentrations below the accepted thresholds for treatment of hypoglycemia. Trial registration ACTRN: 12615000986572.

Patients with type 1 diabetes demonstrated slower oxygen uptake (V̇o2) kinetics compared with healthy control subjects. Furthermore, a prior bout of high-intensity exercise speeded V̇o2 kinetics and increased critical power in people with type 1 diabetes. Prior exercise speeded muscle deoxygenation kinetics, indicating that V̇o2 kinetics in type 1 diabetes are limited primarily by oxygen extraction and/or intracellular factors. These findings highlight the potential for interventions that decrease metabolic inertia for enhancing exercise tolerance in this condition.

ObjectiveBabies may use alternative cerebral fuels including ketones when blood glucose concentrations are low, but laboratory ketone measurements are slow and expensive. Point-of-care measurement of ketone concentrations, if sufficiently accurate, may provide useful information for clinical care.Patients and designEligible babies were 35–42 weeks’ gestation, ≤10 days old and admitted to the newborn intensive care unit. At the time of clinically indicated blood tests, additional samples were taken to measure beta-hydroxybutyrate using a point-of-care analyser and the laboratory method.ResultsOne-hundred and fifty babies had 142 paired samples. Overall point-of-care accuracy was excellent (mean difference 0.00 mmol/L) and precision was moderate (SD 0.18 mmol/L). A point-of-care measurement ≥0.4 mmol/L was highly predictive of a laboratory measurement ≥0.4 mmol/L (area under the curve 0.98).ConclusionPoint-of-care measurement of blood beta-hydroxybutyrate concentrations is sufficiently accurate in newborns to be potentially useful in clinical care.Clinical trial registration numberRegistered with the Australian and New Zealand Clinical Trials Registry ACTRN: 12616000784415. The study was registered before recruitment commenced.

ObjectiveThere is a paucity of data about normal blood metabolite concentrations in healthy babies, in part because of a reluctance to undertake non-therapeutic invasive testing in newborns. The Glucose in Well Babies study (GLOW) sought to describe blood glucose, lactate and beta-hydroxybutyrate concentrations in healthy term babies over the first 5 postnatal days. We also sought to understand both parents’ experience of participation in this invasive non-therapeutic study.Design, setting, patients and interventionsEligible babies were healthy, term, appropriately grown singletons born in a birthing centre, hospital or home within the greater Hamilton area and then discharged home. Babies had subcutaneous continuous glucose monitoring placed soon after birth, up to 14 heel-prick blood samples, twice-daily home visits and parents were asked to record all feeds. At study completion, both parents were asked to independently complete a questionnaire about their experience.ResultsAll eligible babies completed the study and every parent completed the questionnaire (65 fathers, 66 mothers). Parents reported they liked contributing to improving healthcare (126/131, 96%) and support from the GLOW team (119/131, 91%). Nearly all (127/131, 97%) would participate in GLOW again if they had another eligible baby, and all would recommend GLOW to family and friends. Two-thirds of parents (87/131, 66%) reported that participation had made them more likely to contribute to clinical research in the future.ConclusionsNon-therapeutic studies involving invasive procedures in healthy term babies are feasible, and parents were positive about their experience.

Objectives To determine plasma lactate and beta-hydroxybutyrate (BHB) concentrations of healthy infants in the first 5 days and their relationships with glucose concentrations. Study design Prospective masked observational study in Hamilton, New Zealand. Term, appropriately grown singletons had heel-prick blood samples, 4 in the first 24 hours then twice daily. Results In 67 infants, plasma lactate concentrations were higher in the first 12 hours (median, 20; range, 10-55 mg/dL [median, 2.2 mmol/L; range, 1.1-6.2 mmol/L]), decreasing to 12 mg/dL (range, 7-29 mg/dL [median, 1.4 mmol/L; range, 0.8-3.3 mmol/L]) after 48 hours. Plasma BHB concentrations were low in the first 12 hours (median, 0.9 mg/dL; range, 0.5-5.2 mg/dL [median, 0.1 mmol/L; range, 0.05-0.5 mmol/L]), peaked at 48-72 hours (median, 7.3 mg/dL; range, 1.0-25.0 mg/dL [median, 0.7 mmol/L; range, 0.05-2.4 mmol/L]), and decreased by 96 hours (median, 0.9 mg/dL; range, 0.5-16.7 mg/dL [median, 0.1 mmol/L; range, 0.05-1.6 mmol/L]). Compared with infants with plasma glucose concentrations above the median (median, 67 mg/dL [median, 3.7 mmol/L]), those with lower glucose had lower lactate concentrations in the first 12 hours and higher BHB concentrations between 24 and 96 hours. Lower interstitial glucose concentrations were also associated with higher plasma BHB concentrations, but only if the lower glucose lasted greater than 12 hours. Glucose contributed 72%-84% of the estimated potential adenosine triphosphate throughout the 5 days, with lactate contributing 25% on day 1 and BHB 7% on days 2-3. Conclusions Lactate on day 1 and BHB on days 2-4 may contribute to cerebral fuels in healthy infants, but are unlikely to provide neuroprotection during early or acute hypoglycemia. Trial registration The Australian and New Zealand Clinical Trials Registry: ACTRN12615000986572.

To determine postnatal changes in plasma and interstitial glucose concentrations of healthy infants receiving current recommended care and to compare the incidence of low concentrations with recommended thresholds for treatment of at-risk infants.A prospective masked observational study in Hamilton, New Zealand. Healthy, term, appropriately grown singletons had continuous glucose monitoring and repeated heel-prick plasma glucose measurements (4 in the first 24 hours then twice daily using the glucose oxidase method) from birth to 120 hours.The 67 infants had a mean birth weight of 3584 ± 349 g, and gestational age of 40.1 ± 1.2 weeks. The mean glucose concentrations increased over the first 18 hours, remained stable to 48 hours (59 ± 11 mg/dL; 3.3 ± 0.6 mmol/L)] before increasing to a new plateau by the fourth day (89 ± 13 mg/dL; 4.6 ± 0.7 mmol/L). Plasma glucose concentrations of 47 mg/dL (2.6 mmol/L) approximated the 10th percentile in the first 48 hours, and 39% of infants had ≥1 episode below this threshold. Early term infants had lower mean glucose concentrations than those born at later gestational ages and were more likely to have episodes47 mg/dL (2.6 mmol/L) (19/32 [59%] vs 7/35 [20%]; relative risk, 3.0; 95% CI, 1.4-6.1; P = .001).Healthy infants seem to complete their metabolic transition by day 4. Many have glucose concentrations below the accepted thresholds for treatment of hypoglycemia.ACTRN: 12615000986572.

Background: Feeding is often used for the initial treatment of hypoglycaemia, but it is not known if pre-feed alertness and observed quality of breastfeeding are related to the subsequent change in blood glucose concentration. Objective: We sought to determine if assessment of pre-feed alertness and the observed quality of the breastfeed were related to the subsequent change in blood glucose concentration in hypoglycaemic babies. Methods: Babies were ≥35 weeks, ≤48 h old, identified as being at-risk for hypoglycaemia (infants of diabetic mothers, small [< 2,500 g or < 10th centile] or large [birthweight > 4,500 g or > 90th centile] birthweight) and hypoglycaemic (< 2.6 mM). Midwives assessed pre-feed alertness and quality of feeding at each hypoglycaemic episode. Change in blood glucose concentration was assessed within 15–90 min. Results: One hundred and thirty-one babies had 163 hypoglycaemic episodes. Babies assessed as alert had a greater increase in blood glucose concentration than sleepy babies (mean [95% CI] awake 0.71 [0.61–0.82] vs. sleepy 0.51 [0.35–0.66] mM, p = 0.04). The change in blood glucose concentration was similar after feeds of different observed quality (offered, 0.50 [0.29–0.72], latched, 0.66 [0.52–0.81], swallowing 0.65 [0.54–0.76] mM, p = 0.13). Conclusions: Observed quality of breastfeeding is not a useful predictor of the change in blood glucose concentration in hypoglycaemic babies.

Background Model-based glycaemic control protocols have shown promise in neonatal intensive care units (NICUs) for reducing both hyperglycaemia and insulin-therapy driven hypoglycaemia. However, current models for the appearance of glucose from enteral feeding are based on values from adult intensive care cohorts. This study aims to determine enteral glucose appearance model parameters more reflective of premature infant physiology. Methods Peaks in CGM data associated with enteral milk feeds in preterm and term infants are used to fit a two compartment gut model. The first compartment describes glucose in the stomach, and the half life of gastric emptying is estimated as 20 min from literature. The second compartment describes glucose in the small intestine, and absorption of glucose into the blood is fit to CGM data. Two infant cohorts from two NICUs are used, and results are compared to appearances derived from data in highly controlled studies in literature. Results The average half life across all infants for glucose absorption from the gut to the blood was 50 min. This result was slightly slower than, but of similar magnitude to, results derived from literature. No trends were found with gestational or postnatal age. Breast milk fed infants were found to have a higher absorption constant than formula fed infants, a result which may reflect known differences in gastric emptying for different feed types. Conclusions This paper presents a methodology for estimation of glucose appearance due to enteral feeding, and model parameters suitable for a NICU model-based glycaemic control context.

Background Dextrose gel is increasingly used as first-line treatment for neonatal hypoglycaemia. Treatment with 400 mg/kg previously has been reported to impair subsequent feeding. We sought to determine if the recommended dose of 200 mg/kg altered feeding. Methods Hypoglycaemic babies were randomised to 200 mg/kg dextrose gel or placebo and fed. Prefeed alertness, quality and duration of breast feeding, and the volume of formula taken were assessed on the next feeding. Results Prefeed alertness scores were similar in babies (n=211) treated with dextrose or placebo gel (124 episodes, OR=1.30 (95% CI 0.62 to 2.77), p=0.49). Breastfed babies were more likely to have good feeding scores after dextrose gel (160 episodes, OR=3.54 (95% CI 1.30 to 9.67), p=0.01) but similar breastfeeding duration (57 episodes, median (range) 20 (3–90) vs 25 (2–80) min, p=0.62). Formula volumes taken were also similar (24 episodes, median (range) 4.6 (2.2–11.3) vs 6.4 (2.0–8.9) mL/kg, p=0.30). Conclusions Treating hypoglycaemic babies with dextrose gel 200 mg/kg does not depress subsequent feeding and may improve breastfeeding quality. Trial registration number ACTRN 12608000623392.

Extremely immature newborns develop a self-limiting normal anion gap metabolic acidosis in early life. This study examined the natural history of this acidosis in a population of infants of gestation less than 26 weeks in the first 14 days of life. The acidosis was maximal on day 4 with a mean base deficit of 10.6 mmol/l and had resolved in 90 % of infants by day 11. Dopamine usage was the only independent predictor of the acidosis. Its use was associated with a greater degree of acidosis. Conclusion: Extremely preterm infants experience a self-limiting normal anion gap metabolic acidosis in the first 2 weeks of life which is consistent with renal tubular immaturity.

Randomized trials are essential for improving outcomes, but researchers can be hesitant about undertaking clinical trials in newborn babies because of perceived vulnerability of the baby and risk of increasing parental anxiety. There is a paucity of evidence about the parental experience. We investigated mothers’ experiences of having their newborn baby participate in a randomized double-blind placebo-controlled trial soon after birth. Eligible mothers had consented to their baby’s participation in the Sugar Babies Study. Mothers of potentially eligible babies were invited to join the study antenatally, but others were approached postnatally. Babies were enrolled in the study soon after birth and remained in the study for 48 h. After 2 weeks the birth mothers were interviewed by phone about their experience. Four hundred and eighty-one mothers were enrolled, of whom 310 (64%) gave consent antenatally. All mothers were contacted and 477 (99%) were interviewed. The majority of mothers (458, 96%) reported they would consent to participating again, if they had another eligible baby, and 460 mothers (96%) reported they would recommend participation to family and friends. Nineteen mothers (4%) reported they did not like the heel lance blood tests, which were part of routine clinical care and not part of the trial protocol. Most mothers reported the experience of having their newborn baby participate in a clinical trial as positive. Most negative responses were related to aspects of routine care rather than the trial protocol.

BACKGROUND: Neonatal hypoglycaemia, a common condition, can be associated with brain injury. It is frequently managed by providing infants with an alternative source of glucose, often given enterally with milk‐feeding or intravenously with dextrose solution, which may decrease breastfeeding success. Intravenous dextrose also often requires that mother and baby are cared for in separate environments. Oral dextrose gel is simple and inexpensive, and can be administered directly to the buccal mucosa for rapid correction of hypoglycaemia, in association with continued breastfeeding and maternal care. This is an update of a previous review published in 2016. OBJECTIVES: To assess the effectiveness of oral dextrose gel in correcting hypoglycaemia in newborn infants from birth to discharge home and reducing long‐term neurodevelopmental impairment. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials, MEDLINE, and Embase from database inception to October 2021. We also searched international clinical trials networks, the reference lists of included trials, and relevant systematic reviews identified in the search. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi‐RCTs comparing oral dextrose gel versus placebo, no treatment, or other therapies for the treatment of neonatal hypoglycaemia in newborn infants from birth to discharge home. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed study quality and extracted data; they did not assess publications for which they were study authors. We contacted investigators to obtain additional information. We used fixed‐effect models and the GRADE approach to assess the certainty of evidence. MAIN RESULTS: We included two studies conducted in high‐income countries, involving 312 late preterm and at‐risk term infants and comparing oral dextrose gel (40% concentration) to placebo gel. One study was at low risk of bias, and the other (an abstract) was at unclear to high risk of bias. Oral dextrose gel compared with placebo gel probably increases correction of hypoglycaemic events (rate ratio 1.08, 95% confidence interval (CI) 0.98 to 1.20; rate difference 66 more per 1000, 95% CI 17 fewer to 166 more; 1 study; 237 infants; moderate‐certainty evidence), and may result in a slight reduction in the risk of major neurological disability at age two years or older, but the evidence is uncertain (risk ratio (RR) 0.46, 95% CI 0.09 to 2.47; risk difference (RD) 24 fewer per 1000, 95% CI 41 fewer to 66 more; 1 study, 185 children; low‐certainty evidence). The evidence is very uncertain about the effect of oral dextrose gel compared with placebo gel or no gel on the need for intravenous treatment for hypoglycaemia (RR 0.78, 95% CI 0.46 to 1.32; RD 37 fewer per 1000, 95% CI 91 fewer to 54 more; 2 studies, 312 infants; very low‐certainty evidence). Investigators in one study of 237 infants reported no adverse events (e.g. choking or vomiting at the time of administration) in the oral dextrose gel or placebo gel group (low‐certainty evidence). Oral dextrose gel compared with placebo gel probably reduces the incidence of separation from the mother for treatment of hypoglycaemia (RR 0.54, 95% CI 0.31 to 0.93; RD 116 fewer per 1000, 95% CI 174 fewer to 18 fewer; 1 study, 237 infants; moderate‐certainty evidence), and increases the likelihood of exclusive breastfeeding after discharge (RR 1.10, 95% CI 1.01 to 1.18; RD 87 more per 1000, 95% CI 9 more to 157 more; 1 study, 237 infants; moderate‐certainty evidence). AUTHORS' CONCLUSIONS: Oral dextrose gel (specifically 40% dextrose concentration) used to treat hypoglycaemia in newborn infants (specifically at‐risk late preterm and term infants) probably increases correction of hypoglycaemic events, and may result in a slight reduction in the risk of major neurological disability at age two years or older. Oral dextrose gel treatment probably reduces the incidence of separation from the mother for treatment and increases the likelihood of exclusive breastfeeding after discharge. No adverse events have been reported. Oral dextrose gel is probably an effective and safe first‐line treatment for infants with neonatal hypoglycaemia in high‐income settings. More evidence is needed about the effects of oral dextrose gel treatment on later neurological disability and the need for other treatments for hypoglycaemia. Future studies should be conducted in low‐and middle‐income settings, in extremely and moderately preterm infants, and compare oral dextrose gel with other therapies such as intravenous dextrose. There are two ongoing studies that may alter the conclusions of this review when published.

Neonatal hypoglycemia is common and may cause serious brain injury. Diagnosis is by blood glucose (BG) measurements, often taken several hours apart. Continuous glucose monitoring (CGM) could improve hypoglycemia detection, while reducing the number of BG measurements. Calibration algorithms convert sensor signals into CGM output. Thus, these algorithms directly affect measures used to quantify hypoglycemia. This study was designed to quantify the effects of recalibration and filtering of CGM data on measures of hypoglycemia (BG2.6 mmol/L) in neonates.CGM data from 50 infants were recalibrated using an algorithm that explicitly recognized the high-accuracy BG measurements available in this study. CGM data were analyzed as (1) original CGM output, (2) recalibrated CGM output, (3) recalibrated CGM output with postcalibration median filtering, and (4) recalibrated CGM output with precalibration median filtering. Hypoglycemia was classified by number of episodes, duration, severity, and hypoglycemic index.Recalibration increased the number of hypoglycemic events (from 161 to 193), hypoglycemia duration (from 2.2% to 2.6%), and hypoglycemic index (from 4.9 to 7.1 μmol/L). Median filtering postrecalibration reduced hypoglycemic events from 193 to 131, with little change in duration (from 2.6% to 2.5%) and hypoglycemic index (from 7.1 to 6.9 μmol/L). Median filtering prerecalibration resulted in 146 hypoglycemic events, a total duration of hypoglycemia of 2.6%, and a hypoglycemic index of 6.8 μmol/L.Hypoglycemia metrics, especially counting events, are heavily dependent on CGM calibration BG error, and the calibration algorithm. CGM devices tended to read high at lower levels, so when high accuracy calibration measurements are available it may be more appropriate to recalibrate the data.

SUMMARY The dead in bed syndrome describes the sudden death of patients with Type 1 diabetes in characteristic circumstances. The victims are found dead in undisturbed beds having previously been in good health. Post-mortem examinations in these patients consistently reveal no anatomical cause for death. The initial reason for investigating these deaths was to look for an association with human insulin. No link was found but there was circumstantial evidence to suggest that the deaths were due to hypoglycemia. Only a small minority of these patients had ante-mortem complications of diabetes. These devastating deaths and the pathophysiology associated with the deaths have been studied in some detail over the intervening years and the outcomes of those studies will be described in this review.

Background: Neonatal hypoglycaemia is a common problem linked to both brain damage and death. There is controversy regarding both the definition of and best treatment for neonatal hypoglycaemia. Aim: To determine current management of neonatal hypoglycaemia within the Australian and New Zealand Neonatal Network (ANZNN). Methods: Four questionnaires were sent to the Director of each of the 45 nurseries within the ANZNN. The Director was asked to complete one questionnaire and give the remaining three to other doctors involved with the management of babies with hypoglycaemia in the nursery. Results: One hundred and eighty surveys were sent and 127 were returned (71%), including at least one from each nursery. Almost all respondents (120, 94%) reported using a protocol to treat hypoglycaemia. Only 2 (2%) reported screening all babies for neonatal hypoglycaemia, with the remainder screening babies at risk. Only 67, (53%) reported that blood glucose levels were tested on an analyser generally considered to be reliable at low levels. Most respondents (99, 78%) reported the clinical threshold for treatment was

Background: The optimal approach to detection and management of neonatal hypoglycaemia remains unclear. Objectives: We sought to demonstrate whether electro-encephalography (EEG) changes could be detected on the amplitude-integrated EEG monitor during induced hypoglycaemia in newborn lambs, and also to determine the accuracy of continuously measured interstitial glucose in this situation. Methods: Needle electrodes were placed in the P3-P4, O1-O2 montages. The interstitial glucose sensor was placed subcutaneously. After 30 min baseline recordings, hypoglycaemia was induced by insulin infusion and blood glucose levels were monitored every 5 min. The infusion was adjusted to reduce blood glucose levels by 0.5 mmol/l every 15 min and then maintain a blood glucose level Results: All lambs (n = 15, aged 3–11 days) became hypoglycaemic, with median blood glucose levels falling from 6.5 to 1.0 mmol/l, p < 0.0001. There were no detectable changes in any of the measured EEG parameters related to hypoglycaemia, although seizures occurred in 2 lambs. There was moderate agreement between the intermittent blood glucose and continuous interstitial glucose measurements in the baseline, decline, and hypoglycaemia periods (mean difference –0.7 mmol/l, 95% confidence interval, CI, –2.8 to 1.4 mmol/l). However, agreement was poor during reversal of hypoglycaemia (mean difference 4.5 mmol/l, 95% CI –1.1 to 10.7 mmol/l). Conclusions: The cot-side EEG may not be a useful clinical tool in the detection of neurological changes induced by hypoglycaemia. However, continuous interstitial glucose monitoring may be useful in the management of babies at risk of hypoglycaemia.

Although people with diabetes have decreased lung function, the dose-response relation between measures of glucose control and lung function in nondiabetic people is not known. The authors used data from the Third National Health and Nutrition Examination Survey (1988-1994) to investigate the relation between glucose tolerance test response and other measures of glucose homeostasis and lung function in an adult population without a clinical diagnosis of diabetes. Plasma glucose level 2 hours after oral administration of 75 g of glucose was inversely related to forced expiratory volume in 1 second (FEV(1)), with a difference of -144.7 ml (95% confidence interval: -231.9, -57.4) for persons in the highest quintile of postchallenge glucose compared with the lowest. Similar inverse associations with FEV(1) were found for other measures of glucose autoregulation. Lung function did not appear to be related to fasting glucose level. Similar associations were seen for forced vital capacity (FVC) but not for the FEV(1):FVC ratio. In the total study population, persons with previously diagnosed diabetes had an FEV(1) 119.1 ml (95% confidence interval: -161.5, -76.6) lower than persons without diabetes. This effect was greater in those with poorly controlled diabetes. These findings suggest that impaired glucose autoregulation is associated with impaired lung function.

Objective Alternative cerebral fuels are reputed to provide neuroprotection during hypoglycaemia, particularly in breastfed babies. We measured concentrations of alternative cerebral fuels in hypoglycaemic babies in the first 48 h. Patient and methods Babies were ≥35 weeks, ≤48 h old and at risk of hypoglycaemia (infant of diabetic, preterm, small or large). Plasma glucose, β-hydroxybutyrate, lactate and insulin concentrations were measured in babies who had been hypoglycaemic ( 1 h. Results Samples were taken from 35 hypoglycaemic babies at 3.7; 1.8–39.6 (median; range) hours after birth. Concentrations of glucose and β-hydroxybutyrate were low (2.03; 0.19–3.39 mM and 0.06; 0.00–1.20 mM), but lactate concentrations varied widely (3.06; 0.02–7.96 mM). Infants of diabetics had lower β-hydroxybutyrate and higher insulin concentrations, but mode of feeding did not influence plasma concentrations of alternative cerebral fuels. Conclusions Hypoglycaemic babies within the first 48 h after birth are unlikely to receive neuroprotection from ketones. However, lactate may provide an alternative cerebral fuel for many. Lactate, rather than ketones, may provide alternative cerebral fuel in hypoglycaemic newborns. Trial registration number ACTRN12608000623392.

Background:Neonatal hypoglycemia is common and can cause serious brain injury. Continuous glucose monitoring (CGM) could improve hypoglycemia detection, while reducing blood glucose (BG) measurements. Calibration algorithms use BG measurements to convert sensor signals into CGM data. Thus, inaccuracies in calibration BG measurements directly affect CGM values and any metrics calculated from them.Aim:The aim was to quantify the effect of timing delays and calibration BG measurement errors on hypoglycemia metrics in newborn infants.Methods:Data from 155 babies were used. Two timing and 3 BG meter error models (Abbott Optium Xceed, Roche Accu-Chek Inform II, Nova Statstrip) were created using empirical data. Monte-Carlo methods were employed, and each simulation was run 1000 times. Each set of patient data in each simulation had randomly selected timing and/or measurement error added to BG measurements before CGM data were calibrated. The number of hypoglycemic events, duration of hypoglycemia, and hypoglycemic index were then calculated using the CGM data and compared to baseline values.Results:Timing error alone had little effect on hypoglycemia metrics, but measurement error caused substantial variation. Abbott results underreported the number of hypoglycemic events by up to 8 and Roche overreported by up to 4 where the original number reported was 2. Nova results were closest to baseline. Similar trends were observed in the other hypoglycemia metrics.Conclusions:Errors in blood glucose concentration measurements used for calibration of CGM devices can have a clinically important impact on detection of hypoglycemia. If CGM devices are going to be used for assessing hypoglycemia it is important to understand of the impact of these errors on CGM data.

Background: Low selenium (SE) status has been documented in preterm infants and has been suggested to be a risk factor for chronic lung disease. Methods: A total of 534 infants with birth weight Results: No significant differences were seen between the groups with respect to primary or secondary outcome measures, with the exception that fewer supplemented infants had an episode of sepsis after the first week of life ( P P Conclusions: Postnatal SE supplementation in very low birth weight infants did not improve neonatal outcome. Further investigation of SE supplementation of mothers from the second half of pregnancy is warranted.(J Pediatr 2000;136:473-80)

Summary Background Neonatal hypoglycaemia is common, and a preventable cause of brain damage. Dextrose gel is used to reverse hypoglycaemia in individuals with diabetes; however, little evidence exists for its use in babies. We aimed to assess whether treatment with dextrose gel was more effective than feeding alone for reversal of neonatal hypoglycaemia in at-risk babies. Methods We undertook a randomised, double-blind, placebo-controlled trial at a tertiary centre in New Zealand between Dec 1, 2008, and Nov 31, 2010. Babies aged 35–42 weeks' gestation, younger than 48-h-old, and at risk of hypoglycaemia were randomly assigned (1:1), via computer-generated blocked randomisation, to 40% dextrose gel 200 mg/kg or placebo gel. Randomisation was stratified by maternal diabetes and birthweight. Group allocation was concealed from clinicians, families, and all study investigators. The primary outcome was treatment failure, defined as a blood glucose concentration of less than 2·6 mmol/L after two treatment attempts. Analysis was by intention to treat. The trial is registered with Australian New Zealand Clinical Trials Registry, number ACTRN12608000623392. Findings Of 514 enrolled babies, 242 (47%) became hypoglycaemic and were randomised. Five babies were randomised in error, leaving 237 for analysis: 118 (50%) in the dextrose group and 119 (50%) in the placebo group. Dextrose gel reduced the frequency of treatment failure compared with placebo (16 [14%] vs 29 [24%]; relative risk 0·57, 95% CI 0·33–0·98; p=0·04). We noted no serious adverse events. Three (3%) babies in the placebo group each had one blood glucose concentration of 0·9 mmol/L. No other adverse events took place. Interpretation Treatment with dextrose gel is inexpensive and simple to administer. Dextrose gel should be considered for first-line treatment to manage hypoglycaemia in late preterm and term babies in the first 48 h after birth. Funding Waikato Medical Research Foundation, the Auckland Medical Research Foundation, the Maurice and Phyllis Paykel Trust, the Health Research Council of New Zealand, and the Rebecca Roberts Scholarship.

1. Autonomic neuropathy is a common complication of diabetes mellitus and is a major risk factor for sudden death. 2. A group of 30 patients with insulin-dependent diabetes mellitus and 30 age-, sex- and blood pressure-matched control subjects underwent traditional tests of autonomic function. Resting supine R—R interval and systolic blood pressure variability were assessed using spectral analysis methods. In addition, we assessed the baroreceptor—cardiac reflex from the linear relation of the change in R—R interval to the increasing systolic blood pressure measured noninvasively with the Finapres monitor during phase 4 of the Valsalva manoeuvre and from resting heart rate and systolic blood pressure power spectra. 3. Whereas standard tests of autonomic function revealed no differences between patients with insulin-dependent diabetes mellitus and control subjects, there was a significant reduction in power spectral density of heart rate variability around the high-frequency region (125.2 ± 112.9 versus 459.3 ± 189.8 ms2, mean ± SD). Furthermore, reductions in baroreflex sensitivity calculated from the Valsalva manoeuvre were detected in diabetics compared with controls (3.3 ± 1.6 versus 9.5 ± 2.5 ms/mmHg, mean ± SD, P > 0.00001). There were significant relations between impairment of the baroreflex and duration of diabetes (P > 0.001) and poor diabetic control (P > 0.05). 4. In summary, autonomic dysfunction occurs much more frequently in diabetic patients than conventional tests would suggest. Abnormal baroreceptor—cardiac reflex sensitivity in patients with insulin-dependent diabetes mellitus may in part be explained by abnormal parasympathetic function. This unrecognized abnormality may have a role in the increased incidence of sudden death seen in young diabetic subjects.

The effect of a 21-day (reducing dose) course of dexamethasone upon platelet numbers, neutrophil numbers and neutrophil morphology in ventilator-dependent preterm infants with chronic lung disease is reported. Forty-one infants, who were sepsis-free throughout the treatment period, received 46 courses of dexamethasone. In these infants the circulating platelet count increased significantly from 235 +/- 157 to 476 +/- 208 X 10(9)/L. Both total neutrophil numbers (7.94 +/- 7.16 to 19.56 +/- 12.40 X 10(9)/L) and immature neutrophil numbers (1.19 +/- 1.22 to 2.68 +/- 2.58 X 10(9)/L) also showed a significant increase reaching a peak on day 7 of treatment and decreasing thereafter. The immature:total (I:T) neutrophil ratio remained essentially unchanged. Eight other infants who developed serious sepsis during the treatment period showed a fall in both platelets (293 +/- 236 to 140 +/- 170 X 10(9)/L) and total neutrophil numbers (18.61 +/- 10.83 to 15.76 +/- 10.53 X 10(9)/L), together with an increase in immature neutrophils (2.30 +/- 2.80 to 8.22 +/- 13.91 X 10(9)/L) and consequent increase in I:T ratio.

Increased prevalence of hypertension and cardiovascular mortality have been reported in hypopituitary patients who had been appropriately replaced with conventional pituitary hormones except GH. Growth hormone replacement (GHR) results in improvement of surrogate markers of cardiovascular function. Data on effects of GHR on blood pressure (BP) in adult growth hormone deficiency (AGHD), however, remain contradictory. There are as yet no reports on BP circadian rhythms in untreated or treated AGHD. Therefore, in a 12-month follow-up study, we evaluated the effects of GHR on ambulatory blood pressure (ABP) in AGHD patients.A prospective, open treatment design study to determine the effects of GHR on ABP and heart rate in AGHD patients. GH was commenced at a daily dose of 0.5 IU, and titrated up by increments of 0.25 IU at 4-weekly intervals to achieve and maintain IGF-I standard deviation score (IGF-I SD) between the median and upper end of the age-related reference range.Twenty-two, post-pituitary surgery, severe AGHD patients (11 men), defined as peak GH response9 mU/l to provocative testing were recruited. The mean age +/- SEM was 48.8 +/- 2.5 years. Twenty-one patients required additional pituitary replacement hormones following pituitary surgery and were on optimal doses at recruitment.Twenty-four-hour ABP and heart rate (HR), body mass index (BMI), waist hip ratio (WHR) and total body water (TBW) were measured before and after 12 months on GHR. Cosinor analysis was used to analyse BP and HR circadian rhythm parameter estimates.Target IGF-I SD was achieved within 3 months of commencement of GHR in all patients (-3.5 +/- 0.4 at baseline vs. 0.8 +/- 0.2 at 3 months, P0.001) and remained within range at 12 months (1.1 +/- 0.2, P0.001 compared to baseline). A significant increase in TBW (45.8 +/- 1.2 vs. 47.8 +/- 1.5 kg, P0.05) but no significant change in BMI (30.7 +/- 2.2 vs. 31.8 +/- 2.7, P = NS) or WHR (0.95 +/- 0.02 vs. 0.93 +/- 0.02, P = NS) was observed after 12 months on GHR. The 24-h mean systolic ABP (SBP; 126.2 +/- 2.8 vs. 120.1 +/- 2.7 mmHg, P0.001) and diastolic ABP (DBP; 78.2 +/- 1.6 vs. 71.4 +/- 1.8 mmHg, P0.001) significantly decreased following GHR with a parallel increase in 24-h mean HR (69.6 +/- 2.5 vs. 73.8 +/- 2.5 beats/min; P0.001). A significant nocturnal decrease in SBP and DBP was observed both before (SBP; daytime, 129.1 +/- 2.8 vs. night time, 115.9 +/- 3.0 mmHg, P0.001 and DBP; daytime, 80.7 +/- 1.6 vs. night time, 69.2 +/- 1.8 mmHg, P0.001) and following GHR (SBP; daytime, 122.8 +/- 2.6 vs. night time, 110.0 +/- 3.6 mmHg, P0.001 and DBP; daytime, 73.9 +/- 1.8 vs. night time, 62.0 +/- 2.3 mmHg, P0.001). Individual and population-mean cosinor analysis demonstrated significant circadian rhythms for SBP, DBP and HR before and after 12 months on GHR (P0.001), suggesting that SBP, DBP and HR circadian rhythms were not altered by GHR. There was, however, a significant reduction in SBP (124.2 +/- 2.8 vs. 118.4 +/- 2.8 mmHg, P0.001) and DBP (77.0 +/- 1.6 vs. 70.2 +/- 1.8 mmHg, P0.001) MESOR with an increase in HR MESOR (68.9 +/- 2.5 vs. 72.2 +/- 2.4 beats/min, P0.01) following GHR.Systolic and diastolic BP and HR circadian rhythms are preserved in AGHD following 12 months of GHR. However, there is a significant decrease in 24-h mean SBP and DBP and increase in 24-h mean HR after 12 months on GHR. We postulate that this decrease in 24-h mean SBP and DBP may result in a reduction of cardiovascular morbidity and mortality and may explain the beneficial effects of GHR on cardiovascular system previously reported in AGHD patients.

Background Neonatal hypoglycaemia is linked to poor developmental outcome. Dextrose gel reverses hypoglycaemia, but its long term effects are unknown. Aim To determine two year outcomes of children randomised to dextrose or placebo gel for treatment of neonatal hypoglycaemia 1 . Methods At risk babies who became hypoglycaemic ( Results 184 children were assessed; 90/118 (76%) randomised to dextrose and 94/119 (79%) to placebo gel. Mean birth weight was 3093 (803) g and gestation 37.7 (1.6) wk. 67 children (36%) had neurosensory disability (1 severe, 9 moderate, 57 mild) with similar rates in both groups (dextrose 35 (39%) vs placebo 32 (34%), RR 1.14, 0.78–1.67). Processing difficulty was also similar in both groups (dextrose 8 (10%) vs placebo 16 (18%), RR 0.52, 0.23–1.15). Discussion Neurosensory disability is common amongst children treated for neonatal hypoglycaemia. Treatment with dextrose gel does not change the incidence of disability or processing problems. Reference Harris DL, et al . Dextrose gel for neonatal hypoglycaemia (the Sugar Babies Study). Lancet 2013;382:2077–83

AIM—To compare the efficacy of hydrocortisone with dopamine for the treatment of hypotensive, very low birthweight (VLBW) infants. METHODS—Forty infants were randomly allocated to receive either hydrocortisone (n=21) or dopamine (n=19). RESULTS—All 19 infants randomised to dopamine responded; 17 of 21 (81%) did so in the hydrocortisone group. Three of the four non-responders in the hydrocortisone group had clinically significant left to right ductal shunting. The incidence of bronchopulmonary dysplasia, retinopathy of prematurity, intraventricular haemorrhage, necrotising enterocolitis, symptomatic patent ductus arteriosus, hyperglycaemia, sepsis (bacterial or fungal) or survival did not differ between groups. The adrenocorticotrophic hormone (ACTH) stimulated plasma cortisol activity, either before or after treatment, did not differ between the two groups of infants. Although a significant difference in efficacy between dopamine and hydrocortisone was not noted (P = 0.108), there were four treatment failures in the hydrocortisone group, compared with none in the dopamine group. CONCLUSION—Both hydrocortisone and dopamine are effective treatments for hypotension in very low birthweight infants. Keywords: hydrocortisone; dopamine; hypotension; very low birthweight; plasma cortisol

Dextrose Gel and Infant Formula are More Effective than Breast Milk for Reversing Neonatal Hypoglycaemia

Randomised Trial of Dextrose Gel for Treating Neonatal Hypoglycaemia: The Sugar Babies Study

To determine whether there is a relationship between electroencephalography patterns and hypoglycemia, by using simultaneous cot-side amplitude integrated electroencephalography (aEEG) and continuous interstitial glucose monitoring, and whether non-glucose cerebral fuels modified these patterns.Eligible babies were ≥ 32 weeks gestation, at risk for hypoglycemia, and admitted to the neonatal intensive care unit. Electrodes were placed in C3-P3, C4-P4 O1-O2 montages. A continuous interstitial glucose sensor was placed subcutaneously, and blood glucose was measured by using the glucose oxidase method. Non-glucose cerebral fuels were measured at study entry, exit, and during recognized hypoglycemia.A total of 101 babies were enrolled, with a median weight of 2179 g and gestation of 35 weeks. Twenty-four of the babies had aEEG recordings, and glucose concentrations were low (2.6 mM). There were 103 episodes of low glucose concentrations lasting 5 to 475 minutes, but no observable changes in aEEG variables. Plasma concentrations of lactate, beta-hydroxybutyrate, and glycerol were low and did not alter during hypoglycemia.Cot-side aEEG was not useful for the detection of neurological changes during mild hypoglycemia. Plasma concentrations of non-glucose cerebral fuels were low and unlikely to provide substantial neuroprotection.

La hipoglucemia (HG) es un problema muy frecuente en el periodo neonatal, que conlleva riesgo de secuelas neurologicas. Su frecuencia podria estar mal estimada debido, por una parte, a la falta de consenso sobre la defi nicion analitica de HG en el recien nacido (RN) y, por otra, a la difi cultad tecnica de la medicion de la glucemia en los rangos mas bajos. El gold standard consiste en determinar la glucosa plasmatica por metodos enzimaticos en el laboratorio, pero esto requiere multiples extracciones. En los neonatos con riesgo incrementado de HG, esta se mide habitualmente de manera intermitente y en sangre capilar. Aunque la correlacion de los niveles de glucosa –determinados mediante glucemia capilar o monitorizacion continua de glucosa intersticial (MCGI)– con los resultados del laboratorio es aceptable, en los rangos inferiores esta correlacion no es tan buena. En la actualidad existen dos tipos de metodos de determinacion continua de glucosa: el metodo «ciego» o retrospectivo y el «abierto» o prospectivo (que permite la vision continuada de la glucosa en tiempo real). Determinados cambios introducidos en el algoritmo de calibracion de algunos de estos sistemas (Paradigm Veo, Medtronic, Northridge, California, Estados Unidos) han mejorado la sensibilidad en rangos hipoglucemicos. Ya en 2005, Beardsall et al., en su estudio de MCGI con un sistema «ciego» CGMS (MiniMed, Medtronic, Northridge, California, Estados Unidos) realizado en 16 RN de 32 semanas de gestacion ingresados en la UCI, mediante la determinacion intermitente de glucemia capilar, comparandola con un sistema «ciego» de MCGI (CGMS System GoldTM, Medtronic, Northridge, California, Estados Unidos). Los RN fueron monitorizados desde las primeras horas de vida hasta que desaparecio el riesgo de HG, o en su defecto hasta los 7 dias (tiempo medio 80 horas), defi niendose las HG por debajo de 47 mg/dL (2,6 mmol/L). Estos autores encontraron una buena correlacion entre glucosa sanguinea e intersticial. Detectaron HG en el 32% mediante determinacion sanguinea y en el 44% con MCGI, y constataron que el 81% de los episodios de HG no se detectaban con mediciones sanguineas. En 107 episodios de HG evidenciados en 34 ninos la duracion fue superior a 30 minutos. Ademas, senalaron que la incidencia de niveles bajos de glucemia fue similar en ninos con diferentes factores de riesgo, pero no mostraron los datos. Este estudio, ademas de mostrar que la MCGI con CGMS System GoldTM fue segura y bien tolerada en un grupo mayor de pacientes y en todo tipo de recien nacidos, demuestra que dicha monitorizacion puede prolongarse con el mismo sensor hasta 7 dias, lo que permite reducir el gasto y las molestias al paciente. El trabajo tambien evidencia que los episodios de HG fueron frecuentes y recurrentes, tambien en RN >32 semanas de gestacion. Un punto debil del estudio es que se incluyo una poblacion muy heterogenea, lo que difi culta la valoracion del riesgo de HG, pues este puede variar segun el peso, la edad gestacional y la existencia de determinadas patologias neonatales. En relacion con trabajos similares previos, Harris et al. encontraron una mejor correlacion entre la glucosa intersticial y la glucosa capilar. Aunque existen algunos estudios en animales y personas adultas que sugieren la precision de los metodos de MCGI en los rangos bajos, esta precision sigue estando cuestionada, lo que podria condicionar una sobrestimacion de la hipoglucemia. Estas dudas razonables deberian ser resueltas con nuevos estudios prospectivos utilizando ya las nuevas tecnologias de MCGI en tiempo real, mas sensibles, que ademas permitirian un diagnostico y tratamiento mas precoz de las hipoglucemias. Es evidente que las alteraciones de la homeostasis de la glucosa son clinicamente relevantes en el periodo neonatal. Sin embargo, quedaria por defi nir de manera precisa su signifi cacion patologica ulterior, para lo cual son esenciales el seguimiento y la valoracion evolutiva del desarrollo neurocognitivo de los ninos con HG neonatal. ■ Fecha de recepcion: 17 de mayo de 2010 Fecha de aceptacion: 20 de mayo de 2010

Aim: To compare the efficacy of hydrocortisone with dopamine in the treatment of hypotensive, very low birthweight (VLBW) infants (< 1500 grams).