Relationship between Neonatal Cerebral Fuels and Neurosensory Outcomes at 3 Years in Well Babies: Follow-Up of the Glucose in Well Babies (GLOW) Study.

INTRODUCTION: We sought to investigate if the availability of cerebral fuels soon after birth in healthy term babies was associated with developmental progress at 3 years of age. METHODS: Healthy term babies had plasma glucose, lactate, and beta-hydroxybutyrate concentrations measured over the first 5 days. At 3 years, parents completed Ages and Stages (ASQ-3) questionnaires between December 2018 and August 2022. Developmental progress, analysed using structural equation modelling, was compared between children whose median fuel concentrations were above and below the mean neonatal concentrations of glucose (3.3 mmol/L) and total ATP-equivalents (140 mmol/L) in the first 48 h and over the first 5 days. RESULTS: Sixty-four (96%) families returned completed questionnaires. We found no differences between developmental progress in children who had median neonatal plasma glucose concentrations <3.3 or ≥3.3 mmol/L in the first 48 h (estimated mean difference in ASQ scores -1.0, 95% confidence interval: -5.8, 3.7, p = 0.66) or 120 h (-3.7, -12.0, 4.6, p = 0.39]). There were also no differences for any other measures of cerebral fuels including total ATP above and below the median over 48 and 120 h, any plasma or interstitial glucose concentration <2.6 mmol/L, or cumulative duration of interstitial glucose concentration <2.6 mmol/L. CONCLUSIONS: There was no detectable relationship between plasma concentrations of glucose, lactate, and beta-hydroxybutyrate soon after birth in healthy term babies and developmental progress at 3 years of age.

Role of beta-hydroxybutyrate measurement in the evaluation of plasma glucose concentrations in newborn infants.

OBJECTIVE: The Glucose in Well Babies (GLOW) Study showed that there are two phases of low glucose concentrations in healthy newborn infants: an initial phase in which plasma concentrations of ketones are low; and a second phase in which low glucose concentrations are accompanied by elevated concentrations of ketones. The implications of these two phases for the brain differ depending on whether ketones are available as alternative substrate for brain metabolism. The purpose of this study was to estimate the duration of these two phases of neonatal low glucose concentrations in 66 healthy breastfed newborns from the GLOW Study during the first 5 days of life. METHODS: The sum of glucose and beta-hydroxybutyrate (BOHB) was used as a proxy for the total concentrations of insulin-dependent fuels for the brain; a threshold value below 4 mmol/L was taken to indicate the presence of relative hyperinsulinism and a BOHB concentration above 0.5 mmol/L to indicate ketonaemia. RESULTS: The first phase of low glucose concentrations lasted a median of 40 hours and in 15% of infants, this persisted beyond 60 hours. Fifty (76%) of the 66 infants subsequently had ketonaemia, which resolved at a median age of 76 hours (range 41->120 hours). CONCLUSIONS: These data suggest that monitoring BOHB concentrations may be useful for interpreting glucose concentrations in newborns and screening for persistent hyperinsulinism.

Relationships between feeding and glucose concentrations in healthy term infants during the first five days after birth-the Glucose in Well Babies Study (GLOW).

Background: The World Health Organization recommends breastfeeding be commenced as soon as possible after birth. Amongst other benefits, early feeding is expected to support the metabolic transition after birth, but effects on blood glucose concentrations are controversial. We sought to describe the changes in interstitial glucose concentrations after feedings over the first five postnatal days. Participants and Methods: In healthy singleton term infants, all feeds were recorded using a smart phone app. Glucose concentrations were measured by blinded interstitial monitoring, calibrated by heel-prick capillary samples 2-4 times/d. Feeding sessions were included if a start and end time were recorded, and if the interval between the start of successive feeds was >90 min. The area under the glucose concentration curve (AUC) was calculated by trapezoidal addition from baseline (median of the 3 measurements before the beginning of the session). The maximum deviation (MD) was the greatest change in glucose concentration (positive or negative) from baseline to the next feeding session or 180 min, whichever came first. Data were analyzed using Stata V17 and are presented as mean (95% CI) in mmol/L. Results: Data were available for 62 infants and 1,770 feedings. The glucose response to breastfeeding was not different from zero on day 1 [day 1 AUC 0.05 (-0.00, 0.10), MD 0.06 (-0.05, 0.16)], but increased thereafter (day 3 (AUC 0.23 (0.18, 0.28), MD 0.41 (0.32, 0.50), day 5 AUC 0.11 (0.06, 0.16), MD 0.28 (0.18, 0.37), p < 0.001 for age effect). Glucose response increased with increased duration of breastfeeding (<30 min AUC 0.06 (0.02,0.09), MD 0.12 (0.04,0.19), >30 min AUC 0.20 (0.16, 0.23) MD 0.37 (0.30, 0.44), p < 0.001 for duration effect) and this was observed even in the first 2 days (<30 min AUC-0.02 (-0.06, 0.03), MD -0.06 (-0.15, 0.03), >30 min AUC 0.12 (0.08, 0.16), MD 0.19 (0.11, 0.27), overall p < 0.001 for age x duration interaction). In feeding sessions that were not breastfeeding, the glucose response was greater after formula than after expressed human milk [AUC 0.29 (0.15, 0.29), MD 0.48 (-0.12, 0.61)], and greater after feed volumes >20 ml than <10 ml [20-30 ml AUC 0.19 (0.01, 0.27), MD 0.23 (-0.01, 0.46)]. Conclusion: The glucose response to feeding in the days after birth increases with postnatal age and duration of the feeding episode. Breastfeeding for <30 min has little effect on glucose concentrations in the first two days.

Feeding Patterns of Healthy Term Newborns in the First 5 Days-The Glucose in Well Babies Study (GLOW).

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.

Oral dextrose gel for the treatment of hypoglycaemia in newborn infants.

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.

Alternative Cerebral Fuels in the First Five Days in Healthy Term Infants: The Glucose in Well Babies (GLOW) Study.

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.

Glucose Profiles in Healthy Term Infants in the First 5 Days: The Glucose in Well Babies (GLOW) Study.

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 <47 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). 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.

Limitations to exercise tolerance in type 1 diabetes: the role of pulmonary oxygen uptake kinetics and priming exercise.

We compared the time constant (τV̇O2) of the fundamental phase of pulmonary oxygen uptake (V̇o2) kinetics between young adult men with type 1 diabetes and healthy control subjects. We also assessed the impact of priming exercise on τV̇O2, critical power, and muscle deoxygenation in a subset of participants with type 1 diabetes. Seventeen men with type 1 diabetes and 17 healthy male control subjects performed moderate-intensity exercise to determine τV̇O2. A subset of seven participants with type 1 diabetes performed an additional eight visits, in which critical power, τV̇O2, and muscle deoxyhemoglobin + myoglobin ([HHb+Mb], via near-infrared spectroscopy) kinetics (described by a time constant, τ[HHb+Mb]) were determined with (PRI) and without (CON) a prior 6-min bout of heavy exercise. τV̇O2 was greater in participants with type 1 diabetes compared with control subjects (type 1 diabetes 50 ± 13 vs. control 32 ± 12 s; P < 0.001). Critical power was greater in PRI compared with CON (PRI 161 ± 25 vs. CON 149 ± 22 W; P < 0.001), whereas τV̇O2 (PRI 36 ± 15 vs. CON 50 ± 21 s; P = 0.006) and τ[HHb+Mb] (PRI 10 ± 5 vs. CON 17 ± 11 s; P = 0.037) were reduced in PRI compared with CON. Type 1 diabetes patients showed slower pulmonary V̇o2 kinetics compared with control subjects; priming exercise speeded V̇o2 and [HHb + Mb] kinetics and increased critical power in a subgroup with type 1 diabetes. These data therefore represent the first characterization of the power-duration relationship in type 1 diabetes and the first experimental evidence that τV̇O2 is an independent determinant of critical power in this population.NEW & NOTEWORTHY 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.

Parents of babies who participated in an invasive clinical study report a positive experience: the Glucose in Well Babies (GLOW) study.

OBJECTIVE: There 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 INTERVENTIONS: Eligible 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. RESULTS: All 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. CONCLUSIONS: Non-therapeutic studies involving invasive procedures in healthy term babies are feasible, and parents were positive about their experience.

Does a Good Quality Breastfeed Improve the Blood Glucose Concentration in Hypoglycaemic Babies?

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.

Point-of-care measurements of blood ketones in newborns.

OBJECTIVE: Babies 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 DESIGN: Eligible 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. RESULTS: One-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). CONCLUSION: Point-of-care measurement of blood beta-hydroxybutyrate concentrations is sufficiently accurate in newborns to be potentially useful in clinical care. CLINICAL TRIAL REGISTRATION NUMBER: Registered with the Australian and New Zealand Clinical Trials Registry ACTRN: 12616000784415. The study was registered before recruitment commenced.

What Happens to Blood Glucose Concentrations After Oral Treatment for Neonatal Hypoglycemia?

OBJECTIVE: To determine the change in blood glucose concentration after oral treatment of infants with hypoglycemia in the first 48 hours after birth. STUDY DESIGN: We analyzed data from 227 infants with hypoglycemia (blood glucose <46.8 mg/dL, 2.6 mmol/L) born at a tertiary hospital who experienced 295 episodes of hypoglycemia. Blood glucose concentrations were measured (glucose oxidase) within 90 minutes after randomization to dextrose or placebo gel plus feeding with formula, expressed breast milk, or breast feeding. RESULTS: The overall mean increase in blood glucose concentration was 11.7 mg/dL (95% CI 10.4-12.8). The increase was greater after buccal dextrose gel than after placebo gel (+3.0 mg/dL; 95% CI 0.7-5.3; P = .01) and greater after infant formula than after other feedings (+3.8 mg/dL; 95% CI 0.8-6.7; P = .01). The increase in blood glucose concentration was not affected by breast feeding (+2.0 mg/dL; 95% CI -0.3 to 44.2; P = .09) or expressed breast milk (-1.4 mg/dL; 95% CI -3.7 to 0.9; P = .25). However, breast feeding was associated with reduced requirement for repeat gel treatment (OR = 0.52; 95% CI 0.28-0.94; P = .03). CONCLUSIONS: Treatment of infants with hypoglycemia with dextrose gel or formula is associated with increased blood glucose concentration and breast feeding with reduced need for further treatment. Dextrose gel and breast feeding should be considered for first-line oral treatment of infants with hypoglycemia.

Dextrose gel treatment does not impair subsequent feeding.

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.

Oral dextrose gel for the treatment of hypoglycaemia in newborn infants.

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, given enterally with formula or intravenously with dextrose solution. This often requires that mother and baby are cared for in separate environments and may inhibit breast feeding. Dextrose gel is simple and inexpensive and can be administered directly to the buccal mucosa for rapid correction of hypoglycaemia, in association with continued breast feeding and maternal care. OBJECTIVES: To assess the effectiveness of dextrose gel in correcting hypoglycaemia and in reducing long-term neurodevelopmental impairment. SEARCH METHODS: We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), the Cumulative Index to Nursing and Allied Health Literature (CINAHL) and Web of Science from inception of the database to February 2016. We also searched international clinical trials networks and handsearched proceedings of specific scientific meetings. SELECTION CRITERIA: Randomised and quasi-randomised studies comparing dextrose gel versus placebo, no treatment or other therapies for treatment of neonatal hypoglycaemia. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted data and did not assess publications for which they themselves were study authors. MAIN RESULTS: We included two trials involving 312 infants. No data were available for correction of hypoglycaemia for each hypoglycaemic event. We found no evidence of a difference between dextrose gel and placebo gel for major neurosensory disability at two-year follow-up (risk ratio (RR) 6.27, 95% confidence interval (CI) 0.77 to 51.03; one trial, n = 184; quality of evidence very low). Dextrose gel compared with placebo gel or no gel did not alter the need for intravenous treatment for hypoglycaemia (typical RR 0.78, 95% CI 0.46 to 1.32; two trials, 312 infants; quality of evidence very low). Infants treated with dextrose gel were less likely to be separated from their mothers for treatment of hypoglycaemia (RR 0.54, 95% CI 0.31 to 0.93; one trial, 237 infants; quality of evidence moderate) and were more likely to be exclusively breast fed after discharge (RR 1.10, 95% CI 1.01 to 1.18; one trial, 237 infants; quality of evidence moderate). Estimated rise in blood glucose concentration following dextrose gel was 0.4 mmol/L (95% CI -0.14 to 0.94; one trial, 75 infants). Investigators in one trial reported no adverse outcomes (n = 237 infants). AUTHORS' CONCLUSIONS: Treatment of infants with neonatal hypoglycaemia with 40% dextrose gel reduces the incidence of mother-infant separation for treatment and increases the likelihood of full breast feeding after discharge compared with placebo gel. No evidence suggests occurrence of adverse effects during the neonatal period or at two years' corrected age. Oral dextrose gel should be considered first-line treatment for infants with neonatal hypoglycaemia.

A cost-benefit analysis of twice-daily consultant ward rounds and clinical input on investigation and pharmacy costs in a major teaching hospital in the UK.

OBJECTIVES: Misuse of investigations, medications and hospital beds is costing the National Health Service (NHS) billions of pounds with little evidence that approaches centred on reducing overuse are sustainable. Our previous study demonstrated that twice-daily consultant ward rounds reduce inpatient length of stay and suggested a reduction in overuse of investigations and medications. This study aims to assess the impact of daily consultant ward rounds on the use of investigations and medications and estimate the potential cost benefit. SETTINGS: The study was performed on two medical wards in a major city university teaching hospital in Liverpool, UK, receiving acute admissions from medical assessment and emergency departments. PARTICIPANTS AND INTERVENTION: The total number of patients admitted, investigations performed and pharmacy costs incurred were collected for 2 years before and following a change in the working practice of consultants from twice-weekly to twice-daily consultant ward rounds on the two medical wards. OUTCOME MEASURES: We performed a cost-benefit analysis to assess the net amount of money saved by reducing inappropriate investigations and pharmacy drug use following the intervention. RESULTS: Despite a 70% increase in patient throughput (p<0.01) the investigations and pharmacy, costs per patient reduced by 50% over a 12-month period (p<0.01) and were sustained for the next 12 months. The reduction in investigations and medication use did not have any effect on the readmission or mortality rate (p=NS), whereas, the length of stay was almost halved (p<0.01). Daily senior clinician input resulted in a net cost saving of £336,528 per year following the intervention. CONCLUSIONS: Daily consultant input has a significant impact on reducing the inappropriate use of investigations and pharmacy costs saving the NHS more than £650K on the two wards over a 2-year period.

Lactate, rather than ketones, may provide alternative cerebral fuel in hypoglycaemic newborns.

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, ß-hydroxybutyrate, lactate and insulin concentrations were measured in babies who had been hypoglycaemic (<2.6 mM) for >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 ß-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 ß-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.

Continuous glucose monitoring in newborn infants: how do errors in calibration measurements affect detected hypoglycemia?

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. The aim was to quantify the effect of timing delays and calibration BG measurement errors on hypoglycemia metrics in newborn infants. 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. 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. 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.

A survey of the management of neonatal hypoglycaemia within the Australian and New Zealand Neonatal Network.

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 <2.6 mmol/L. However, when provided with clinical scenarios, respondents reported a variety of interventions, including no treatment. CONCLUSION: Doctors within the ANZNN are consistent about definition and screening for neonatal hypoglycaemia. However, frequently, the diagnosis is made using unreliable analysers. There is also wide variation in treatment, suggesting a lack of reliable evidence on which to base practice.