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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.

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.

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