Dr Deborah Harris

Background: Faltering postnatal growth in preterm babies is associated with adverse neurodevelopment. However, which growth reference is most helpful for predicting neurodevelopment is unknown. We examined associations between faltering growth and developmental delay in extremely low birthweight (ELBW) infants. Methods: We categorized faltering growth (z-score decrease =0.8 for weight/length, >1 for head circumference) between birth, 4 weeks, 36 weeks' postmenstrual age and 2 years' corrected age using fetal (Fenton, UK-WHO and Olsen) and healthy preterm (INTERGROWTH-21st) references. Associations between faltering growth and developmental delay were examined using binary logistic regression and area under the receiver operating curve (AUC). Results: In 327 infants, Olsen charts identified the highest prevalence of faltering growth (weight 37%, length 63%, head 45%). Agreement in classification was higher amongst fetal references (kappa coefficient, ¿ = 0.46¿0.94) than between INTERGROWTH-21st and fetal references (¿ = 0.10¿0.81). Faltering growth in all measures between 4¿36 weeks (odds ratio, OR 2.0¿4.7) compared with other time intervals (OR 1.7¿2.7) were more strongly associated with developmental delay, particularly motor delay (OR 2.0¿4.7). All growth references were poorly predictive of developmental delay at 2 years (AUC = 0.62). Conclusions: Faltering postnatal growth in ELBW infants is associated with, but is poorly predictive of, developmental delay at 2 years. Impact: In babies born preterm, different growth references result in wide variation in categorization of faltering postnatal growth. Faltering growth in weight, length, and head circumference from 4 weeks to 36 weeks' postmenstrual age are associated with developmental delay at 2 years' corrected age, particularly motor delay. However, postnatal growth is a poor predictor of later developmental delay in extremely low birthweight infants irrespective of the growth reference used.

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.

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.

Background: Neonatal hypoglycaemia can lead to brain damage and neurocognitive impairment. Neonatal hypoglycaemia is associated with smaller caudate volume in the mid-childhood. We investigated the relationship between neurodevelopmental outcomes and caudate volume and whether this relationship was influenced by neonatal hypoglycaemia. Methods: Children born at risk of neonatal hypoglycaemia =36 weeks' gestation who participated in a prospective cohort study underwent neurodevelopmental assessment (executive function, academic achievement, and emotional-behavioural regulation) and MRI at age 9¿10 years. Neonatal hypoglycaemia was defined as at least one hypoglycaemic episode (blood glucose concentration <2.6 mmol/L or at least 10 min of interstitial glucose concentrations <2.6 mmol/L). Caudate volume was computed using FreeSurfer. Results: There were 101 children with MRI and neurodevelopmental data available, of whom 70 had experienced neonatal hypoglycaemia. Smaller caudate volume was associated with greater parent-reported emotional and behavioural difficulties, and poorer prosocial behaviour. Caudate volume was significantly associated with visual memory only in children who had not experienced neonatal hypoglycaemia (interaction p = 0.03), but there were no other significant interactions between caudate volume and neonatal hypoglycaemia. Conclusion: Smaller caudate volume is associated with emotional behaviour difficulties in the mid-childhood. Although neonatal hypoglycaemia is associated with smaller caudate volume, this appears not to contribute to clinically relevant neurodevelopmental deficits. Impact: At 9¿10 years of age, caudate volume was inversely associated with emotional-behavioural difficulties and positively associated with prosocial behaviour but was not related to executive function or educational achievement. Previous studies have suggested that neonatal hypoglycaemia may contribute to smaller caudate volume but exposure to neonatal hypoglycaemia did not appear to influence the relationship between caudate volume and behaviour. Among children not exposed to neonatal hypoglycaemia, caudate volume was also positively associated with visual memory, but no such association was detected among those exposed to neonatal hypoglycaemia. Understanding early-life factors that affect caudate development may provide targets for improving behavioural function.

Objective: The aim of this project was to find and put in place a functional skin assessment tool that would be specific to neonates of any gestational age. The purpose was to find a skin assessment tool that would; ¿ Assess and optimise the preservation of the neonate's skin integrity. ¿ Highlight babies that are at possible risk of skin breakdown. ¿ Assist nurses to assess neonatal skin on a regular basis, thus to prevent skin damage and help care for neonates with skin damage, in delivering a recommend bundle of care. Design: Showing the development and introduction of a neonatal skin assessment tool. The Neonatal Intensive Care Unit (NICU), where this project took place was in Wellington Hospital, based in Wellington, New Zealand (NZ). This NICU is one of the six tertiary NICU's within NZ, it has a yearly average of 875 admissions.

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.

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.

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.

We aimed to investigate whether gestation at birth, birth weight, and head circumference at birth are still associated with brain volume and white matter microstructure at 9¿10¿years in children born late-preterm and at term. One hundred and eleven children born at = 36¿weeks gestation from the CHYLD Study cohort underwent brain magnetic resonance imaging at 9 to 10¿years. Images were analysed using FreeSurfer for volumetric data and tract-based spatial statistics for diffusion data. Of the cohort, 101 children were included for volumetric analysis [boys, 49(49%); median age, 9.5 (range: 8.9¿12.4) years]. Shorter gestation at birth, lower birthweight, and smaller birth head circumference were associated with smaller brain volumes at 9 to 10¿years, both globally and regionally. Amongst the perinatal factors studied, head circumference at birth was the strongest predictor of later brain volumes. Gestation at birth and absolute birthweight were not associated with diffusion metrics of white matter skeleton. However, lower birthweight z-score was associated with higher fractional anisotropy and lower radial diffusivity. Our findings suggest that even in children born late preterm and at term, growth before birth and timing of birth are still associated with brain development 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.

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.

Objective To determine the effect of prophylactic dextrose gel on the infant gut microbiome. Design Observational cohort study nested in a randomised trial. Setting Three maternity hospitals in New Zealand. Patients Infants at risk of neonatal hypoglycaemia whose parents consented to participation in the hypoglycaemia Prevention in newborns with Oral Dextrose trial (hPOD). Infants were randomised to receive prophylactic dextrose gel or placebo gel, or were not randomised and received no gel (controls). Stool samples were collected on days 1, 7 and 28. Main outcome measures The primary outcome was microbiome beta-diversity at 4 weeks. Secondary outcomes were beta-diversity, alpha-diversity, bacterial DNA concentration, microbial community stability and relative abundance of individual bacterial taxa at each time point. Results We analysed 434 stool samples from 165 infants using 16S rRNA gene amplicon sequencing. There were no differences between groups in beta-diversity at 4 weeks (p=0.49). There were also no differences between groups in any other microbiome measures including beta-diversity (p=0.53 at day 7), alpha-diversity (p=0.46 for day 7 and week 4), bacterial DNA concentration (p=0.91), microbial community stability (p=0.52) and microbial relative abundance at genus level. There was no evidence that exposure to any dextrose gel (prophylaxis or treatment) had any effect on the microbiome. Mode of birth, type of milk fed, hospital of birth and ethnicity were all associated with differences in the neonatal microbiome. Conclusions Clinicians and consumers can be reassured that dextrose gel used for prophylaxis or treatment of neonatal hypoglycaemia does not alter the neonatal gut microbiome.

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 mot...

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.

Severe and prolonged neonatal hypoglycemia can cause brain injury, while the long-term consequences of mild or transitional hypoglycemia are uncertain. As neonatal hypoglycemia is often asymptomatic it is routine practice to screen infants considered at risk, including infants of mothers with diabetes and those born preterm, small or large, with serial blood tests over the first 12¿24 h after birth. However, to prevent brain injury, the gold standard would be to determine if an infant has neuroglycopenia, for which currently there is not a diagnostic test. Therefore, screening of infants at risk for neonatal hypoglycemia with blood glucose monitoring does not meet several screening test principles. Specifically, the long-term neurodevelopmental outcomes of transient neonatal hypoglycemia are not well understood and there is no direct evidence from randomized controlled trials that treatment of hypoglycemia improves long-term neurodevelopmental outcomes. There have been no studies that have compared the long-term neurodevelopmental outcomes of at-risk infants screened for neonatal hypoglycemia and those not screened. However, screening infants at risk of hypoglycemia and treating those with hypoglycaemic episodes to maintain the blood glucose concentrations =2.6 mmol/L appears to preserve cognitive function compared to those without episodes. This narrative review explores the evidence for screening for neonatal hypoglycemia, the effectiveness of blood glucose screening as a screening test and recommend future research areas to improve screening for neonatal hypoglycemia. Screening babies at-risk of neonatal hypoglycemia continues to be necessary, but as over a quarter of all infants may be screened for neonatal hypoglycemia, further research is urgently needed to determine the optimal method of screening and which infants would benefit from screening and treatment.

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.

COVID-19 has plunged us into times of loss¿loss of friends and family, loss of purpose, and loss of a sense of certainty about the immediate future. As we traverse this time of anomie and loss between pre-and post-COVID-19 times, through pandemic surges that threaten to exhaust our resources and seemingly endless troughs of calm, we need to care for each other. Care provided to those in need of hospitalization due to COVID-19 should undoubtedly be prioritized, but we should not forget to care for those who are physically well but suffering, by recognizing the fear and sorrow that flavor changed experiences due to COVID-19. Narratives that reveal challenges and triumphs are central to this kind of care. Frank (2007) argues that care is about "helping people find their stories." We find comfort in telling these stories and in hearing them; recognizing ourselves in another's tale allows us to find meaning in our own suffering. This paper tells the narratives of three health professionals on the COVID-19 frontline.

This study aimed to explore Neonatal nurses and midwives opinion regarding global research priorities. A prospective descriptive study was completed using survey methodology. Responses (n = 596) were received from 42 countries. Countries were divided into geographical areas: Africa 18 (3%), Asia 36 (6%), North America 156 (26%), South America 26 (4%), Europe 169 (28%) and Oceania 191 (32%). Sixteen research priorities were identified and categorised under two main themes with two key priorities being identified for each theme: 1) Improving clinical care of new-borns; key priorities are: Training and education needs of neonatal nurses, midwives and health workers; and Implementation of existing evidence into nursing practice: 2) The management and long-term outcomes of neonates; two key priorities are: Extreme prematurity: management and improving outcomes; and Pain: prevention management, and long-term outcomes of pain. Collaboration and research are needed to improve the dissemination of not only research evidence but practice methodologies that enable nurses to implement best practice.

Background Neonatal hypoglycemia is common and can cause brain injury. Buccal dextrose gel is effective for treatment of neonatal hypoglycemia, and when used for prevention may reduce the incidence of hypoglycemia in babies at risk, but its clinical utility remains uncertain. Methods and findings We conducted a multicenter, double-blinded, placebo-controlled randomized trial in 18 New Zealand and Australian maternity hospitals from January 2015 to May 2019. Babies at risk of neonatal hypoglycemia (maternal diabetes, late preterm, or high or low birthweight) without indications for neonatal intensive care unit (NICU) admission were randomized to 0.5 ml/kg buccal 40% dextrose or placebo gel at 1 hour of age. Primary outcome was NICU admission, with power to detect a 4% absolute reduction. Secondary outcomes included hypoglycemia, NICU admission for hypoglycemia, hyperglycemia, breastfeeding at discharge, formula feeding at 6 weeks, and maternal satisfaction. Families and clinical and study staff were unaware of treatment allocation. A total of 2,149 babies were randomized (48.7% girls). NICU admission occurred for 111/1,070 (10.4%) randomized to dextrose gel and 100/1,063 (9.4%) randomized to placebo (adjusted relative risk [aRR] 1.10; 95% CI 0.86, 1.42; p = 0.44). Babies randomized to dextrose gel were less likely to become hypoglycemic (blood glucose < 2.6 mmol/l) (399/1,070, 37%, versus 448/1,063, 42%; aRR 0.88; 95% CI 0.80, 0.98; p = 0.02) although NICU admission for hypoglycemia was similar between groups (65/1,070, 6.1%, versus 48/1,063, 4.5%; aRR 1.35; 95% CI 0.94, 1.94; p = 0.10). There were no differences between groups in breastfeeding at discharge from hospital (aRR 1.00; 95% CI 0.99, 1.02; p = 0.67), receipt of formula before discharge (aRR 0.99; 95% CI 0.92, 1.08; p = 0.90), and formula feeding at 6 weeks (aRR 1.01; 95% CI 0.93, 1.10; p = 0.81), and there was no hyperglycemia. Most mothers (95%) would recommend the study to friends. No adverse effects, including 2 deaths in each group, were attributable to dextrose gel. Limitations of this study included that most participants (81%) were infants of mothers with diabetes, which may limit generalizability, and a less reliable analyzer was used in 16.5% of glucose measurements. Conclusions In this placebo-controlled randomized trial, prophylactic dextrose gel 200 mg/kg did not reduce NICU admission in babies at risk of hypoglycemia but did reduce hypoglycemia. Long-term follow-up is needed to determine the clinical utility of this strategy.

The COVID-19 pandemic has resulted in inestimable morbidity and mortality across the globe. The healthcare and political leadership of the pandemic within Aotearoa New Zealand has been internationally recognised. The pivotal role of nurses and nursing practice in the establishment of National Close Contact Service (NCCS) has been fundamental in protecting the health of our nation. Using exemplars, and the themes of shared human vulnerability and professional authority, this critical discussion draws on theoretical and philosophical nursing perspectives to demonstrate the authors' involvement in the establishment of the NCCS.

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.

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.

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.

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.

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.

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.

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.

Objective: To evaluate the costs of using dextrose gel as a primary treatment for neonatal hypoglycemia in the first 48 hours after birth compared with standard care. Study design: We used a decision tree to model overall costs, including those specific to hypoglycemia monitoring and treatment and those related to the infant's length of stay in the postnatal ward or neonatal intensive care unit, comparing the use of dextrose gel for treatment of neonatal hypoglycemia with placebo, using data from the Sugar Babies randomized trial. Sensitivity analyses assessed the impact of dextrose gel cost, neonatal intensive care cost, cesarean delivery rate, and costs of glucose monitoring. Results: In the primary analysis, treating neonatal hypoglycemia using dextrose gel had an overall cost of NZ$6863.81 and standard care (placebo) cost NZ$8178.25; a saving of NZ$1314.44 per infant treated. Sensitivity analyses showed that dextrose gel remained cost saving with wide variations in dextrose gel costs, neonatal intensive care unit costs, cesarean delivery rates, and costs of monitoring. Conclusions: Use of buccal dextrose gel reduces hospital costs for management of neonatal hypoglycemia. Because it is also noninvasive, well tolerated, safe, and associated with improved breastfeeding, buccal dextrose gel should be routinely used for initial treatment of neonatal hypoglycemia. Trial registration: Australian New Zealand Clinical Trials Registry: ACTRN12608000623392.

Background: Studies in animals and in humans have suggested that docosahexaenoic acid (DHA), an n-3 long-chain polyunsaturated fatty acid, might reduce the risk of bronchopulmonary dysplasia, but appropriately designed trials are lacking. Methods: We randomly assigned 1273 infants born before 29 weeks of gestation (stratified according to sex, gestational age [<27 weeks or 27 to <29 weeks], and center) within 3 days after their first enteral feeding to receive either an enteral emulsion providing DHA at a dose of 60 mg per kilogram of body weight per day or a control (soy) emulsion without DHA until 36 weeks of postmenstrual age. The primary outcome was bronchopulmonary dysplasia, defined on a physiological basis (with the use of oxygen-saturation monitoring in selected infants), at 36 weeks of postmenstrual age or discharge home, whichever occurred first. Results: A total of 1205 infants survived to the primary outcome assessment. Of the 592 infants assigned to the DHA group, 291 (49.1% by multiple imputation) were classified as having physiological bronchopulmonary dysplasia, as compared with 269 (43.9%) of the 613 infants assigned to the control group (relative risk adjusted for randomization strata, 1.13; 95% confidence interval [CI], 1.02 to 1.25; P = 0.02). The composite outcome of physiological bronchopulmonary dysplasia or death before 36 weeks of postmenstrual age occurred in 52.3% of the infants in the DHA group and in 46.4% of the infants in the control group (adjusted relative risk, 1.11; 95% CI, 1.00 to 1.23; P = 0.045). There were no significant differences between the two groups in the rates of death or any other neonatal illnesses. Bronchopulmonary dysplasia based on a clinical definition occurred in 53.2% of the infants in the DHA group and in 49.7% of the infants in the control group (P = 0.06). Conclusions: Enteral DHA supplementation at a dose of 60 mg per kilogram per day did not result in a lower risk of physiological bronchopulmonary dysplasia than a control emulsion among preterm infants born before 29 weeks of gestation and may have resulted in a greater risk.

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.

Neonatal hypoglycaemia is common, and screening and treatment of babies considered at risk is widespread, despite there being little reliable evidence upon which to base management decisions. Although there is now evidence about which babies are at greatest risk, the threshold for diagnosis, best approach to treatment and later outcomes all remain uncertain. Recent studies suggest that treatment with dextrose gel is safe and effective and may help support breast feeding. Thresholds for intervention require a wide margin of safety in light of information that babies with glycaemic instability and with low glucose concentrations may be associated with a higher risk of later higher order cognitive and learning problems. Randomised trials are urgently needed to inform optimal thresholds for intervention and appropriate treatment strategies.

Hospitals are challenged to implement measures to improve health outcomes, decrease costly interventions, and increase patient satisfaction. By following a nurse-driven protocol, our institution has successfully met these three challenges in our treatment of newborns diagnosed with neonatal hypoglycemia (NH). Based on results of a randomized clinical trial,1 a multidisciplinary team trialed glucose gel as a standard treatment for NH. During the first year, admission rates to the NICU for NH decreased by 73 percent. Exclusive breastfeeding rates for this population increased to 49 percent and 40 additional families remained together on the mother baby unit. This practice change is improving health outcomes, decreasing expensive interventions, and increasing satisfaction among the population of infants at risk for NH.

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.

IMPORTANCE: Hypoglycemia is common during neonatal transition and may cause permanent neurological impairment, but optimal intervention thresholds are unknown. OBJECTIVE: To test the hypothesis that neurodevelopment at 4.5 years is related to the severity and frequency of neonatal hypoglycemia. DESIGN, SETTING, AND PARTICIPANTS: The Children With Hypoglycemia and Their Later Development (CHYLD) Study is a prospective cohort investigation of moderate to late preterm and term infants born at risk of hypoglycemia. Clinicians were masked to neonatal interstitial glucose concentrations; outcome assessors were masked to neonatal glycemic status. The setting was a regional perinatal center in Hamilton, New Zealand. The study was conducted from December 2006 to November 2010. The dates of the follow-up were September 2011 to June 2015. Participants were 614 neonates born from 32 weeks' gestation with at least 1 risk factor for hypoglycemia, including diabetic mother, preterm, small, large, or acute illness. Blood and masked interstitial glucose concentrations were measured for up to 7 days after birth. Infants with hypoglycemia (whole-blood glucose concentration <47 mg/dL) were treated to maintain blood glucose concentration of at least 47 mg/dL. EXPOSURES: Neonatal hypoglycemic episode, defined as at least 1 consecutive blood glucose concentration less than 47 mg/dL, a severe episode (<36 mg/dL), or recurrent (3 episodes). An interstitial episode was defined as an interstitial glucose concentration less than 47 mg/dL for at least 10 minutes. MAIN OUTCOMES AND MEASURES: Cognitive function, executive function, visual function, and motor function were assessed at 4.5 years. The primary outcome was neurosensory impairment, defined as poor performance in one or more domains. RESULTS: In total, 477 of 604 eligible children (79.0%) were assessed. Their mean (SD) age at the time of assessment was 4.5 (0.1) years, and 228 (47.8%) were female. Those exposed to neonatal hypoglycemia (280 [58.7%]) did not have increased risk of neurosensory impairment (risk difference [RD], 0.01; 95% CI, -0.07 to 0.10 and risk ratio [RR], 0.96; 95% CI, 0.77 to 1.21). However, hypoglycemia was associated with increased risk of low executive function (RD, 0.05; 95% CI, 0.01 to 0.10 and RR, 2.32; 95% CI, 1.17 to 4.59) and visual motor function (RD, 0.03; 95% CI, 0.01 to 0.06 and RR, 3.67; 95% CI, 1.15 to 11.69), with highest risk in children exposed to severe, recurrent, or clinically undetected (interstitial episodes only) hypoglycemia. CONCLUSIONS AND RELEVANCE: Neonatal hypoglycemia was not associated with increased risk of combined neurosensory impairment at 4.5 years but was associated with a dose-dependent increased risk of poor executive function and visual motor function, even if not detected clinically, and may thus influence later learning. Randomized trials are needed to determine optimal screening and intervention thresholds based on assessment of neurodevelopment at least to school age.

Objective To determine neurodevelopmental outcome at 2 years' corrected age in children randomized to treatment with dextrose gel or placebo for hypoglycemia soon after birth (The Sugar Babies Study). Study design This was a follow-up study of 184 children with hypoglycemia (<2.6 mM [47 mg/dL]) in the first 48 hours and randomized to either dextrose (90/118, 76%) or placebo gel (94/119, 79%). Assessments were performed at Kahikatea House, Hamilton, New Zealand, and included neurologic function and general health (pediatrician assessed), cognitive, language, behavior, and motor skills (Bayley Scales of Infant and Toddler Development, Third Edition), executive function (clinical assessment and Behaviour Rating Inventory of Executive Function-Preschool Edition), and vision (clinical examination and global motion perception). Coprimary outcomes were neurosensory impairment (cognitive, language or motor score below -1 SD or cerebral palsy or blind or deaf) and processing difficulty (executive function or global motion perception worse than 1.5 SD from the mean). Statistical tests were two sided with 5% significance level. Results Mean (±SD) birth weight was 3093 ± 803 g and mean gestation was 37.7 ± 1.6 weeks. Sixty-six children (36%) had neurosensory impairment (1 severe, 6 moderate, 59 mild) with similar rates in both groups (dextrose 38% vs placebo 34%, relative risk 1.11, 95% CI 0.75-1.63). Processing difficulty also was similar between groups (dextrose 10% vs placebo 18%, relative risk 0.52, 95% CI 0.23-1.15). Conclusions Dextrose gel is safe for the treatment of neonatal hypoglycemia, but neurosensory impairment is common among these children. Trial registration Australian New Zealand Clinical Trials Registry: 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, 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.