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.

What are the barriers preventing the screening and management of neonatal hypoglycaemia in low-resource settings, and how can they be overcome?

Over 25 years ago, the World Health Organization (WHO) acknowledged the importance of effective prevention, detection and treatment of neonatal hypoglycaemia, and declared it to be a global priority. Neonatal hypoglycaemia is common, linked to poor neurosensory outcomes and, if untreated, can cause seizures and death. Neonatal mortality in low and lower-middle income countries constitutes an estimated 89% of overall neonatal deaths. Factors contributing to high mortality rates include malnutrition, infectious diseases, poor maternal wellbeing and resource constraints on both equipment and staff, leading to delayed diagnosis and treatment. The incidence of neonatal hypoglycaemia in low and lower-middle income countries remains unclear, as data are not collected.Data from high-resource settings shows that half of all at-risk babies will develop hypoglycaemia, using accepted clinical thresholds for treatment. Most at-risk babies are screened and treated, with treatment aiming to increase blood glucose concentration and, therefore, available cerebral fuel. The introduction of buccal dextrose gel as a first-line treatment for neonatal hypoglycaemia has changed the care of millions of babies and families in high-resource settings. Dextrose gel has now also been shown to prevent neonatal hypoglycaemia.In low and lower-middle income countries, there are considerable barriers to resources which prevent access to reliable blood glucose screening, diagnosis, and treatment, leading to inequitable health outcomes when compared with developed countries. Babies born in low-resource settings do not have access to basic health care and are more likely to suffer from unrecognised neonatal hypoglycaemia, which contributes to the burden of neurosensory delay and death.

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.

Mid-Childhood Outcomes after Dextrose Gel Treatment of Neonatal Hypoglycaemia: Follow-Up of the Sugar Babies Randomized Trial.

INTRODUCTION: Dextrose gel is widely used as first-line treatment for neonatal hypoglycaemia given its cost-effectiveness and ease of use. The Sugar Babies randomized trial first showed that 40% dextrose gel was more effective in reversing hypoglycaemia than feeding alone. Follow-up of the Sugar Babies Trial cohort at 2 and 4.5 years of age reported that dextrose gel appeared safe, with similar rates of neurosensory impairment in babies randomized to dextrose or placebo gel. However, some effects of neonatal hypoglycaemia may not become apparent until school age. METHODS: Follow-up of the Sugar Babies Trial cohort at 9-10 years of age was reported. The primary outcome was low educational achievement in reading or mathematics. Secondary outcomes included other aspects of educational achievement, executive function, visual-motor function, and psychosocial adaptation. RESULTS: Of 227 eligible children, 184 (81%) were assessed at a mean (SD) age of 9.3 (0.2) years. Low educational achievement was similar in dextrose and placebo groups (36/86 [42%] vs. 42/94 [45%]; RR 1.04, 95% CI 0.76, 1.44; p = 0.79). Children allocated to dextrose gel had lower visual perception standard scores (95.2 vs. 100.6; MD -5.68, 95% CI -9.79, -1.57; p = 0.006) and a greater proportion had low (<85) visual perception scores (20/88 [23%] vs. 10/95 [11%]; RR 2.23, 95% CI 1.13, 4.37; p = 0.02). Other secondary outcomes, including other aspects of visual-motor function, were similar in both groups. CONCLUSION: Treatment dextrose gel does not appear to result in any clinically significant differences in educational achievement or other neurodevelopmental outcomes at mid-childhood.

Outcome at 4.5 years after dextrose gel treatment of hypoglycaemia: follow-up of the Sugar Babies randomised trial.

OBJECTIVE: Dextrose gel is used to treat neonatal hypoglycaemia, but later effects are unknown. DESIGN AND SETTING: Follow-up of participants in a randomised trial recruited in a tertiary centre and assessed in a research clinic. PATIENTS: Children who were hypoglycaemic (<2.6 mmol/L) recruited to the Sugar Babies Study (>35 weeks, <48 hours old) and randomised to treatment with 40% dextrose or placebo gel. INTERVENTIONS: Assessment of neurological status, cognitive ability (Weschler Preschool and Primary Scale of Intelligence), executive function (five tasks), motor function (Movement Assessment Battery for Children-2 (MABC-2)), vision, visual processing (Beery-Buktenica Development Test of Visual Motor Integration (Beery VMI) and motion coherence thresholds) and growth at 2 years. MAIN OUTCOME MEASURES: Neurosensory impairment (cerebral palsy; visual impairment; deafness; intelligence quotient <85; Beery VMI <85; MABC-2 score <15th centile; low performance on executive function or motion coherence). RESULTS: Of 237 babies randomised, 185 (78%) were assessed; 96 randomised to dextrose and 89 to placebo gel. Neurosensory impairment was similar in both groups (dextrose 36/96 (38%) vs placebo 34/87 (39%), relative risk 0.96, 95% CI 0.66 to 1.34, p=0.83). Secondary outcomes were also similar, except children randomised to dextrose had worse visual processing scores (mean (SD) 94.5 (15.9) vs 99.8 (15.9), p=0.02) but no differences in the proportion with visual processing scores <85 or other visual test scores. Children randomised to dextrose gel were taller (z-scores 0.18 (0.97) vs -0.17 (1.01), p=0.001) and heavier (0.57 (1.07) vs 0.29 (0.92), p=0.01). CONCLUSIONS: Treatment of neonatal hypoglycaemia (<2.6 mol/L) with dextrose gel does not alter neurosensory impairment at 4.5 years. However, further assessment of visual processing and growth may be warranted. TRIAL REGISTRATION NUMBER: ACTRN1260800062392.

Securing peripheral intravenous catheters in babies without applying adhesive dressings to the skin: a proof-of-concept study.

BACKGROUND: Most babies admitted to a Neonatal Intensive Care Unit (NICU) require a peripheral intravenous catheter (PIVC). PIVCs are secured using splints and adhesive dressings applied to the skin. Removing the dressings causes skin injury, pain, and risks infection. We designed the Pepi Splint, which supports PIVCs without the application of adhesive dressings to the skin. We sought to determine the effectiveness and acceptability of the Pepi Splint using a proof-of-concept design. METHODS: Eligible babies were > 1000 g and > 30 weeks' corrected gestation admitted to Wellington Regional NICU and who required a PIVC. All babies received the same care as those not in the study, with the addition of the Pepi Splint. Primary outcomes were the proportion of babies in which the Pepi Splint secured the PIVC for the required time and proportion of babies who experience an adverse event. Secondary outcomes were the acceptability of the Pepi Splint as reported by the parents. RESULTS: Thirty-eight babies, median (range) birth weight 2625 g (396-4970) and gestation 37wk (22-41). When the Pepi was applied the postnatal weight was 2969 g (1145 - 4970) and gestation 37wk (29 - 41). The Pepi Splint held the PIVC secure for 34/38 babies (89%), for a duration of 37 h (6 to 97). There were no adverse events. Of the four babies reported to have unsecure PIVCs, two were due to the securement two were displaced during feeding. Fifty-eight parents responded to a questionnaire (32 mothers, 26 fathers). Of these parents 52 (90%) would participate again and 52 (90%) would recommend participating to others. Overall, clinicians reported the Pepi Splint was easy to use 33/38 (87%). CONCLUSION: The Pepi Splint safely secures PIVCs without adhesive dressings being applied to the skin and is acceptable to both parents and clinicians. Our findings provide support for a larger multicentred randomised controlled trial. TRIAL REGISTRATION: Registered with the Australian and New Zealand Clinical Trials Registry Reference ACTRN12620001335987 .

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.

Association of Neonatal Hypoglycemia With Academic Performance in Mid-Childhood.

Importance: Neonatal hypoglycemia is associated with increased risk of poor executive and visual-motor function, but implications for later learning are uncertain. Objective: To test the hypothesis that neonatal hypoglycemia is associated with educational performance at age 9 to 10 years. Design, Setting, and Participants: Prospective cohort study of moderate to late preterm and term infants born at risk of hypoglycemia. Blood and masked interstitial sensor glucose concentrations were measured for up to 7 days. Infants with hypoglycemic episodes (blood glucose concentration <47 mg/dL [2.6 mmol/L]) were treated to maintain a blood glucose concentration of at least 47 mg/dL. Six hundred fourteen infants were recruited at Waikato Hospital, Hamilton, New Zealand, in 2006-2010; 480 were assessed at age 9 to 10 years in 2016-2020. Exposures: Hypoglycemia was defined as at least 1 hypoglycemic event, representing the sum of nonconcurrent hypoglycemic and interstitial episodes (sensor glucose concentration <47 mg/dL for ≥10 minutes) more than 20 minutes apart. Main Outcomes and Measures: The primary outcome was low educational achievement, defined as performing below or well below the normative curriculum level in standardized tests of reading comprehension or mathematics. There were 47 secondary outcomes related to executive function, visual-motor function, psychosocial adaptation, and general health. Results: Of 587 eligible children (230 [48%] female), 480 (82%) were assessed at a mean age of 9.4 (SD, 0.3) years. Children who were and were not exposed to neonatal hypoglycemia did not significantly differ on rates of low educational achievement (138/304 [47%] vs 82/176 [48%], respectively; adjusted risk difference, -2% [95% CI, -11% to 8%]; adjusted relative risk, 0.95 [95% CI, 0.78-1.15]). Children who were exposed to neonatal hypoglycemia, compared with those not exposed, were significantly less likely to be rated by teachers as being below or well below the curriculum level for reading (68/281 [24%] vs 49/157 [31%], respectively; adjusted risk difference, -9% [95% CI, -17% to -1%]; adjusted relative risk, 0.72 [95% CI, 0.53-0.99; P = .04]). Groups were not significantly different for other secondary end points. Conclusions and Relevance: Among participants at risk of neonatal hypoglycemia who were screened and treated if needed, exposure to neonatal hypoglycemia compared with no such exposure was not significantly associated with lower educational achievement in mid-childhood.

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.

Improving the Quality of Patient Care and Healthcare Staff Well-Being through an Empathy Immersion Educational Programme in New Zealand: Protocol of a Feasibility and Pilot Study.

Empathy is positively related to healthcare workers and patients' wellbeing. There is, however, limited research on the effects of empathy education delivered in acute clinical settings and its impact on healthcare consumers. This research tests the feasibility and the potential efficacy outcomes of an immersive education programme developed by the research team in collaboration with clinical partners and a multidisciplinary advisory group. Healthcare worker participants in the intervention ward will receive an 8-week immersive empathy education. The primary outcome (feasibility) will be assessed by evaluating the acceptability of the intervention and the estimated resources. The secondary outcome (efficacy) will be assessed using a quasi-experimental study design. Non-parametric tests will be used to test healthcare worker participants' empathy, burnout, and organisational satisfaction (within-group and across groups), and healthcare consumer participants' satisfaction (between-group) over time. Despite growing interest in the importance of empathy in professional relationships, to our knowledge, the present pilot study is the first to explore the feasibility and efficacy of an immersive empathy education in New Zealand. Our findings will provide critical evidence to support the development of a randomised cluster trial and potentially provide preliminary evidence for the effectiveness of this type of empathy education.

Strategies to improve neurodevelopmental outcomes in babies at risk of neonatal hypoglycaemia.

Neonatal hypoglycaemia is associated with adverse development, particularly visual-motor and executive function impairment, in childhood. As neonatal hypoglycaemia is common and frequently asymptomatic in at-risk babies-ie, those born preterm, small or large for gestational age, or to mothers with diabetes, it is recommended that these babies are screened for hypoglycaemia in the first 1-2 days after birth with frequent blood glucose measurements. Neonatal hypoglycaemia can be prevented and treated with buccal dextrose gel, and it is also common to treat babies with hypoglycaemia with infant formula and intravenous dextrose. However, it is uncertain if screening, prophylaxis, or treatment improves long-term outcomes of babies at risk of neonatal hypoglycaemia. This narrative review assesses the latest evidence for screening, prophylaxis, and treatment of neonates at risk of hypoglycaemia to improve long-term neurodevelopmental outcomes.

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.

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.

Factors influencing glycaemic stability after neonatal hypoglycaemia and relationship to neurodevelopmental outcome.

Higher and unstable glucose concentrations in the first 48 hours in neonates at risk of hypoglycaemia have been associated with neurosensory impairment. It is unclear what defines and contributes to instability. This was a prospective study of term and late preterm babies (N = 139) born at risk of neonatal hypoglycaemia who had interstitial glucose (IG) monitoring and ≥1 hypoglycaemic episode <48 hours after birth (blood glucose concentration <2.6 mmol/l [<47 mg/dl]). For 6-hour epochs after each hypoglycaemic episode, masked IG parameters (time to reach maximum IG concentration [hours]; range, average, maximum and minimum IG concentrations; proportion of IG measurements outside the central band of 3-4 mmol/l [54-72 md/dl]; and total duration [hours] of IG concentrations <2.6 mmol/l) were analysed in tertiles and related to: (i) glycaemic instability in the first 48 hours (defined as the proportion of blood glucose concentrations outside the central band in the first 48 hours); (ii) risk factors and treatment for each episode; and (iii) risk of neurosensory impairment at 4.5 years, or at 2 years if a child was not seen at 4.5 years. Glycaemic instability in the first 48 hours was related to IG instability after hypoglycaemia. Risk factors for hypoglycaemia were not related to IG parameters. Treatment with intravenous dextrose was associated with higher IG maximum and range, and lower minimum compared to treatment with dextrose gel plus breast milk, breast milk alone or formula alone. The risk of neurosensory impairment was increased with both shorter and longer time to reach maximum epoch IG (P = 0.04; lower tertile [0.4-2.2 hours] vs middle [2.3-4.2 hours] OR 3.10 [95% CI 1.03; 9.38]; higher tertile [4.3-6.0 hours] vs middle OR 3.07; [95% CI 1.01; 9.24]). Glycaemic response to hypoglycaemia contributes to overall glycaemic instability in newborns and is influenced by treatment. Slow or rapid recovery of hypoglycaemia appears to be associated with neurosensory impairment.

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.