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Introduction: Glucagon is often used in neonatal hypoglycaemia, but its effects have not been systematically assessed. We undertook a systematic review to determine the efficacy and safety of glucagon treatment for neonatal hypoglycaemia. Methods: We searched MEDLINE, CINAHL, EMBASE, and CENTRAL from inception until May 2021. We included studies that reported one or more prespecified outcomes and compared glucagon with placebo or no glucagon. Studies were excluded if the majority (>70%) of participants were >1 month of age. Two authors independently extracted data. We used ROB-2/modified ROBINS-I to assess risk of bias, GRADE for certainty of evidence, and RevMan for meta-analysis. Results: 100 studies were screened, 37 reviewed in full, and seven single-arm non-randomised intervention studies, involving 348 infants, were included (no trials). Data were insufficient to undertake meta-analysis of the critical outcomes (time to blood glucose normalization, recurrent hypoglycaemia, neurocognitive impairment). In 3 studies, ≥80% of neonates achieved normoglycaemia within 4 h of glucagon administration. However, recurrent hypoglycaemia was common (up to 55%). Glucagon increased blood glucose concentration at 1–2 h by 2.3 mmol/L (95% CI 2.1, 2.5) (low certainty evidence, 6 studies, N = 323). There were few data for other important clinical outcomes. Conclusion: There is a paucity of evidence about the efficacy and safety of glucagon for treatment of neonatal hypoglycaemia. Low certainty evidence suggests that glucagon may increase blood glucose by ∼2.3 mmol/L but recurrent hypoglycaemia appears common. High-quality, randomized controlled trials are required to determine the role of glucagon in managing neonatal hypoglycaemia.

ObjectiveTo determine the effect of prophylactic dextrose gel on the infant gut microbiome.DesignObservational cohort study nested in a randomised trial.SettingThree maternity hospitals in New Zealand.PatientsInfants 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 measuresThe 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.ResultsWe 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.ConclusionsClinicians and consumers can be reassured that dextrose gel used for prophylaxis or treatment of neonatal hypoglycaemia does not alter the neonatal gut microbiome.Trial registration number12614001263684.

ImportanceNeonatal hypoglycemia is common, but its association with later neurodevelopment is uncertain.ObjectiveTo examine associations between neonatal hypoglycemia and neurocognitive outcomes at corrected age 2 years.Design, Setting, and ParticipantsExploratory cohort analysis of the Hypoglycaemia Prevention With Oral Dextrose (hPOD) randomized clinical trial was conducted. The trial recruited participants from January 9, 2015, to May 5, 2019, with follow-up between January 26, 2017, and July 31, 2021. Infants were recruited from 9 maternity hospitals in New Zealand and assessed at home or in a research clinic. Children born late preterm and at term at risk of neonatal hypoglycemia but without evidence of acute or imminent illness in the first hour after birth were screened and treated to maintain blood glucose concentrations greater than or equal to 47 mg/dL.ExposuresHypoglycemia was defined as any blood glucose concentration less than 47 mg/dL, recurrent as 3 or more episodes, and severe as less than 36 mg/dL.Main Outcomes and MeasuresNeurologic examination and tests of development (Bayley III) and executive function. The primary outcome was neurosensory impairment (any of the following: blindness, deafness, cerebral palsy, developmental delay, or executive function total score worse than 1.5 SD below the mean).ResultsA total of 1197 of 1321 (91%) eligible children were assessed at a mean of corrected age 24 months; 616 (52%) were male. Compared with the normoglycemia group, children who experienced hypoglycemia were more likely to have neurosensory impairment (111 [23%] vs 125 [18%]; adjusted risk ratio [aRR], 1.28; 95% CI, 1.01-1.60), particularly if they experienced severe episodes (30 [28%] vs 125 [18%]; aRR, 1.68; 95% CI, 1.20-2.36), but not recurrent episodes (12 [19%] vs 125 [18%]; aRR, 1.06; 95% CI, 0.63-1.80). The risk of cognitive, language, or motor delay was similar between groups, but children who experienced hypoglycemia had lower Bayley-III composite cognitive (adjusted mean difference [aMD], −1.48; 95% CI, −2.79 to −0.18) and motor scores (aMD, −2.05; 95% CI, −3.30 to −0.79).Conclusions and RelevanceIn children born at risk of hypoglycemia but otherwise well, those who experienced neonatal hypoglycemia were more likely to have neurosensory impairment at corrected age 2 years, with higher risks after severe episodes. Further research is required to determine causality.

ObjectiveTo determine if very low dose (VLD, 0.5% phenylephrine, 0.1% cyclopentolate) mydriatic microdrop (approximately 7 μL) administration (up to three doses) is non-inferior to low dose (LD, 1% phenylephrine, 0.2% cyclopentolate) mydriatic microdrop administration for ophthalmologist-determined successful retinopathy of prematurity eye examination (ROPEE).DesignMulticentre, prospective, randomised controlled, non-inferiority clinical trial.SettingFour neonatal intensive care units in Aotearoa, New Zealand from October 2019 to September 2021.PatientsInfants with a birth weight less than 1250 g or gestational age less than 30+6 weeks and who required a ROPEE.InterventionsThe intervention: microdrop (approximately 7 μL) of VLD (0.5% phenylephrine and 0.1% cyclopentolate) to both eyes, or the comparison: microdrop of LD (1% phenylephrine and 0.2% cyclopentolate) to both eyes. Up to three doses could be administered.Main outcome measuresThe primary outcome measure was an ophthalmologist-determined successful ROPEE.ResultsOne hundred and fifty preterm infants (LD mean GA=27.4±1.8 weeks, mean birth weight=1011±290 g, VLD mean GA=27.5±1.9 weeks, mean birth weight=1049±281 g,) were randomised. Non-inferiority for successful ROPEE was demonstrated for the VLD group compared with the LD group (VLD successful ROPEE=100%, LD successful ROPEE=100%, 95% CI no continuity correction −0.05 to 0.05) and for Māori (95% CI no continuity correction −0.02 to 0.19).ConclusionVLD microdrops enable safe and effective screening for ROPEE in both Māori and non-Māori preterm infants.Trial registration numberACTRN12619000795190.

To determine if consumers and clinicians believe intelligence or health outcomes are more important long-term outcomes for babies born preterm.Prospective, online survey of six outcomes ranked using a hierarchy ladder, Likert scale and a hypothetical scenario: education (complete secondary school); longevity (70 years of age or more); money (sufficient for rent and food); normal weight; good health and intelligence. Participants were clinicians taking care of preterm babies, parents of preterm babies, ex-preterm adults and adult controls.The survey was completed by 145 participants (35 controls, 36 clinicians, 39 parents and 35 ex-preterm adults). Health was the most frequently top-ranked variable on the hierarchy ladder (health; 99/145 (68.3%), money; 17/145 (11.7%), longevity; 10/145 (6.9%), education; 8/145 (5.5%), normal weight; 6/145 (4.1%), intelligence; 5/145 (3.4%), P 0.0001), with no statistical difference between the groups. On a 5-point Likert scale, participants were most likely to agree that sufficient money, health and finishing secondary school were important for preterm babies to have a good life (mean (SD): money 4.43 (0.81); health 4.39 (0.72); education 4.37 (0.81); normal weight 4.10 (0.81); intelligence 4.03 (0.94); longevity 4.01 (1.07), P 0.0001). In the scenario, the option of an ex-preterm adult having a healthy life with low socio-economic status (SES), was preferred over high SES with an unhealthy life (p 0.0001).Health was perceived as the most important long-term outcome for preterm babies. Future research should prioritise good health outcomes for babies born preterm.

ObjectiveTo determine the effect of prophylactic dextrose gel for prevention of neonatal hypoglycaemia on neurodevelopment and executive function at 2 years’ corrected age.DesignProspective follow-up of a randomised trial.SettingNew Zealand.PatientsParticipants from the pre-hypoglycaemia Prevention with Oral Dextrose (pre-hPOD) trial randomised to one of four dose regimes of buccal 40% dextrose gel or equivolume placebo.Main outcome measuresCoprimary outcomes were neurosensory impairment and executive function. Secondary outcomes were components of the primary outcomes, neurology, anthropometry and health measures.ResultsWe assessed 360 of 401 eligible children (90%) at 2 years’ corrected age. There were no differences between dextrose gel dose groups, single or multiple dose groups, or any dextrose and any placebo groups in the risk of neurosensory impairment or low executive function (any dextrose vs any placebo neurosensory impairment: relative risk (RR) 0.77, 95% CI 0.50 to 1.19, p=0.23; low executive function: RR 0.50, 95% CI 0.24 to 1.06, p=0.07). There were also no differences between groups in any secondary outcomes. There was no difference between children who did or did not develop neonatal hypoglycaemia in the risk of neurosensory impairment (RR 1.05, 95% CI 0.68 to 1.64, p=0.81) or low executive function (RR 0.73, 95% CI 0.34 to 1.59, p=0.43).ConclusionProphylactic dextrose gel did not alter neurodevelopment or executive function and had no adverse effects to 2 years’ corrected age, but this study was underpowered to detect potentially clinically important effects on neurosensory outcomes.

BACKGROUND Infants born moderate to late preterm constitute the majority of preterm births, yet guidelines for their nutritional care are unclear. Maternal milk is the most appropriate nutrition for these infants; however, its composition can be influenced by environmental factors. The present study therefore investigated perinatal predictors of human milk composition in a preterm cohort. METHODS Milk was collected during the DIAMOND trial (DIfferent Approaches to Moderate and late preterm Nutrition: Determinants of feed tolerance, body composition and development) from 169 mothers of 191 infants at three time-points (5 and 10 days post partum and 4 months' corrected age). Leptin, adiponectin and insulin-like growth factor-1 (IGF-1) were analysed by enzyme-linked immunosorbent assay. Generalised mixed models were used to evaluate associations between milk composition and maternal/infant/perinatal factors. RESULTS Most findings were independent of collection time-point. Gestational diabetes was associated with lower adiponectin. Higher adiponectin and lower leptin were associated with higher socioeconomic status, higher maternal education and ability to fully breastfeed at discharge from hospital. Higher leptin was associated with high perceived stress during hospital admission. Milk IGF-1 displayed sex-specific patterns in association with maternal social deprivation. CONCLUSION Maternal, infant and environmental factors during the perinatal period were associated with milk compositional profiles throughout lactation. Further clinical trials should investigate the impact of such changes in terms of long-term infant outcomes. IMPACT Human milk is the best nutrition for the infant. However, its composition may be susceptible to alterations determined by pathological conditions mother and infant may face throughout pregnancy and in the perinatal period. This study found that perinatal factors are associated with human milk composition from early to late lactation. If human milk composition throughout lactation is "programmed" during pregnancy or early lactation, infants who were exposed in utero to environmental insults may still be exposed to them during lactation. The impact of human milk compositional alteration on infant growth following perinatal pathological events requires further investigation.

IMPORTANCE: Prophylactic oral dextrose gel reduces neonatal hypoglycemia, but later benefits or harms remain unclear. OBJECTIVE: To assess the effects on later development of prophylactic dextrose gel for infants born at risk of neonatal hypoglycemia. DESIGN, SETTING, AND PARTICIPANTS: Prospective follow-up of a multicenter randomized clinical trial conducted in 18 Australian and New Zealand hospitals from January 2015 to May 2019. Participants were late preterm or term at-risk infants; those randomized in 9 New Zealand centers (n = 1359) were included and followed up between January 2017 and July 2021. INTERVENTIONS: Infants were randomized to prophylactic 40% dextrose (n = 681) or placebo (n = 678) gel, 0.5 mL/kg, massaged into the buccal mucosa 1 hour after birth. MAIN OUTCOMES AND MEASURES: The primary outcome of this follow-up study was neurosensory impairment at 2 years’ corrected age. There were 44 secondary outcomes, including cognitive, language, and motor composite Bayley-III scores (mean [SD], 100 [15]; higher scores indicate better performance). RESULTS: Of eligible infants, 1197 (91%) were assessed (581 females [49%]). Neurosensory impairment was not significantly different between the dextrose and placebo gel groups (20.8% vs 18.7%; unadjusted risk difference [RD], 2.09% [95% CI, −2.43% to 6.60%]; adjusted risk ratio [aRR], 1.13 [95% CI, 0.90 to 1.41]). The risk of cognitive and language delay was not significantly different between the dextrose and placebo groups (cognitive: 7.6% vs 5.3%; RD, 2.32% [95% CI, −0.46% to 5.11%]; aRR, 1.40 [95% CI, 0.91 to 2.17]; language: 17.0% vs 14.7%; RD, 2.35% [95% CI, −1.80% to 6.50%]; aRR, 1.19 [95% CI, 0.92 to 1.54]). However, the dextrose gel group had a significantly higher risk of motor delay (2.5% vs 0.7%; RD, 1.81% [95% CI, 0.40% to 3.23%]; aRR, 3.79 [95% CI, 1.27 to 11.32]) and significantly lower composite scores for cognitive (adjusted mean difference [aMD], −1.30 [95% CI, −2.55 to −0.05]), language (aMD, −2.16 [95% CI, −3.86 to −0.46]), and motor (aMD, −1.40 [95% CI, −2.60 to −0.20]) performance. There were no significant differences between groups in the other 27 secondary outcomes. CONCLUSIONS AND RELEVANCE: Among late preterm and term infants born at risk of neonatal hypoglycemia, prophylactic oral 40% dextrose gel at 1 hour of age, compared with placebo, resulted in no significant difference in the risk of neurosensory impairment at 2 years’ corrected age. However, the study may have been underpowered to detect a small but potentially clinically important increase in risk, and further research including longer-term follow-up is required. TRIAL REGISTRATION: anzctr.org.au Identifier: ACTRN12614001263684

ObjectiveTo establish the most effective and best tolerated dose of caffeine citrate for the prevention of intermittent hypoxaemia (IH) in late preterm infants.DesignPhase IIB, double-blind, five-arm, parallel, randomised controlled trial.SettingNeonatal units and postnatal wards of two tertiary maternity hospitals in New Zealand.ParticipantsLate preterm infants born at 34+0–36+6weeks’ gestation, recruited within 72 hours of birth.InterventionInfants were randomly assigned to receive a loading dose (10, 20, 30 or 40 mg/kg) followed by 5, 10, 15 or 20 mg/kg/day equivolume enteral caffeine citrate or placebo daily until term corrected age.Primary outcomeIH (events/hour with oxygen saturation concentration ≥10% below baseline for ≤2 min), 2 weeks postrandomisation.Results132 infants with mean (SD) birth weight 2561 (481) g and gestational age 35.7 (0.8) weeks were randomised (24–28 per group). Caffeine reduced the rate of IH at 2 weeks postrandomisation (geometric mean (GM): 4.6, 4.6, 2.0, 3.8 and 1.7 events/hour for placebo, 5, 10, 15 and 20 mg/kg/day, respectively), with differences statistically significant for 10 mg/kg/day (GM ratio (95% CI] 0.39 (0.20 to 0.76]; p=0.006) and 20 mg/kg/day (GM ratio (95% CI] 0.33 (0.17 to 0.68]; p=0.003) compared with placebo. The 20 mg/kg/day dose increased mean (SD) pulse oximetry oxygen saturation (SpO2) (97.2 (1.0) vs placebo 96.0 (0.8); p2ConclusionCaffeine reduces IH in late preterm infants at 2 weeks of age, with 20 mg/kg/day being the most effective dose.Trial registration numberACTRN12618001745235.

Background Treatment for gestational diabetes mellitus (GDM) aims to reduce maternal hyperglycaemia. The TARGET Trial assessed whether tighter compared with less tight glycaemic control reduced maternal and perinatal morbidity. Methods and findings In this stepped-wedge, cluster-randomised trial, identification number ACTRN12615000282583, 10 hospitals in New Zealand were randomised to 1 of 5 implementation dates. The trial was registered before the first participant was enrolled. All hospitals initially used less tight targets (fasting plasma glucose (FPG) P = 0.839). The composite serious health outcome for the infant of perinatal death, birth trauma, or shoulder dystocia was apparently reduced in the tighter group when adjusted for gestational age at diagnosis of GDM, BMI, ethnicity, and history of GDM compared with the less tight group (8/599, 1.3% versus 13/505, 2.6%, adjRR 0.23, 95% CI 0.06 to 0.88, P = 0.032). No differences were seen for the other infant secondary outcomes apart from a shorter stay in intensive care (P = 0.041). Secondary outcomes for the woman showed an apparent increase for the composite serious health outcome that included major haemorrhage, coagulopathy, embolism, and obstetric complications in the tighter group (35/595, 5.9% versus 15/501, 3.0%, adjRR 2.29, 95% CI 1.14 to 4.59, P = 0.020). There were no differences between the target groups in the risk for pre-eclampsia, induction of labour, or cesarean birth, but more women using tighter targets required pharmacological treatment (404/595, 67.9% versus 293/501, 58.5%, adjRR 1.20, 95% CI 1.00 to 1.44, P = 0.047). The main study limitation is that the treatment targets used may vary to those in use in some countries. Conclusions Tighter glycaemic targets in women with GDM compared to less tight targets did not reduce the risk of a large for gestational age infant, but did reduce serious infant morbidity, although serious maternal morbidity was increased. These findings can be used to aid decisions on the glycaemic targets women with GDM should use. Trial registration The Australian New Zealand Clinical Trials Registry (ANZCTR). ACTRN12615000282583.

Exclusive breastmilk is the desired enteral nutrition for babies born moderate- and late-preterm between 32A prospective cohort of babies 32A total of 151 eligible babies (60% boys) were included, 93 (63%) of whom successfully transitioned from IV fluids onto MOM only. Alternative sources of milk, mostly formula, were used to transition from IV fluids onto enteral feeds more often in multiples and Māori, and was commenced earlier in Māori than other ethnicities (Despite an intention to provide only MOM, significant numbers of moderate- and late-preterm babies received formula to transition from IV fluids, and this differed by ethnicity. The drivers underlying these decisions require further investigation. These data highlight an urgent need for quality initiatives to support and encourage mothers of moderate- and late-preterm babies in their lactation.

OBJECTIVES The aim of this study was to determine whether a new nutrition protocol designed to increase early protein intakes while reducing fluid volume in infants born very preterm was associated with altered neurodevelopment and growth in childhood. METHODS A retrospective, observational cohort study of children born

Although early nutrition is associated with neurodevelopmental outcome at 2 years’ corrected age in children born very preterm, it is not clear if these associations are different in girls and boys. Retrospective cohort study of infants born

Aim To assess local and individual factors that should be considered in the design of a pulse oximetry screening strategy in New Zealand's midwifery‐led maternity setting. Methods An intervention study was conducted over 2 years. Three hospitals and four primary maternity units participated in the study. Post‐ductal saturation levels were measured on well infants with a gestation of ≥35 weeks. Infant activity and age (hours) at the time of the test were recorded. Results Screening was performed on 16 644 of 27 172 (61%) eligible infants. The age at which the screening algorithm was initiated varied significantly among centres. The probability of achieving a pass result (saturations ≥95%) in the context of no underlying pathology ranged from .94 for an unsettled infant screened

IntroductionInfants with severe or recurrent transitional hypoglycaemia continue to have high rates of adverse neurological outcomes and new treatment approaches are needed that target the underlying pathophysiology. Diazoxide is one such treatment that acts on the pancreatic β-cell in a dose-dependent manner to decrease insulin secretion.Methods and analysisPhase IIB, double-blind, two-arm, parallel, randomised trial of diazoxide versus placebo in neonates ≥35 weeks’ gestation for treatment of severe (blood glucose concentration (BGC)Ethics and disseminationThis trial has been approved by the Health and Disability Ethics Committees of New Zealand (19CEN189). Findings will be disseminated in peer-reviewed journals, to clinicians and researchers at local and international conferences and to the public.Trial registration numberACTRN12620000129987.

Background Neonatal hypoglycaemia is a common condition that can be associated with brain injury. Current practice usually includes early identification of at-risk infants (e.g. infants of diabetic mothers; preterm, small- or large-for-gestational-age infants), and prophylactic measures are advised. However, these measures often involve use of formula milk or admission to the neonatal unit. Dextrose gel is non-invasive, inexpensive, and effective for treatment of neonatal hypoglycaemia. Use of prophylactic dextrose gel can prevent neonatal hypoglycaemia, thus potentially reducing separation of mother and baby and supporting breastfeeding, as well as preventing brain injury. Objectives To assess the effectiveness and safety of oral dextrose gel in preventing hypoglycaemia among newborn infants at risk of hypoglycaemia and in reducing long-term neurodevelopmental impairment. Search methods We used the standard search strategy of the Cochrane Neonatal Review Group to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 12), MEDLINE via PubMed (1966 to 23 January 2017), Embase (1980 to 23 January 2017), and the Cumulative Index to Nursing and Allied Health Literature (CINAHL; 1982 to 23 January 2017). We also searched clinical trials databases, conference proceedings, and reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials. Selection criteria We included randomised and quasi-randomised studies comparing dextrose gel versus placebo, no intervention, or other therapies for prevention of neonatal hypoglycaemia. Data collection and analysis We used standard methodological procedures as expected by the Cochrane Collaboration. Two review authors independently assessed trial quality and extracted data. We used the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach to assess the quality of evidence. Main results We included one trial comparing oral dextrose gel versus placebo in 416 infants at risk of hypoglycaemia. We judged this trial to be at low risk of bias. Using the GRADE method, we determined that evidence ranged from high quality to moderate quality. For outcomes selected for the GRADE analysis, we found the following. • Oral dextrose gel prophylaxis (any dose) is associated with reduced risk of neonatal hypoglycaemia compared with placebo (risk ratio (RR) 0.76, 95% confidence interval (CI) 0.62 to 0.94; one RCT; n = 415 infants; high-quality evidence). The risk difference (RD) is -0.13 (95% CI -0.23 to -0.03), and on average, 8.3 infants would have to receive prophylactic dextrose gel to prevent one additional case of neonatal hypoglycaemia. • Investigators found no statistically significant differences between dextrose gel and placebo groups in the number of adverse events (RR 1.09, 95% CI 0.55 to 2.17; one RCT; n = 413 infants; moderate-quality evidence); separation from mother for treatment of hypoglycaemia (RR 0.46, 95% CI 0.21 to 1.01; one RCT, n = 415 infants; moderate-quality evidence); exclusive breastfeeding at discharge (RR 1.00, 95% CI 0.86 to 1.15; one RCT; n = 415 women; moderate-quality evidence); or breastfeeding at six weeks postpartum (RR 1.06, 95% CI 0.88 to 1.29; one RCT; n = 386 women; moderate-quality evidence). • Researchers provided no data for the other prespecified GRADE outcomes for this review (major neurological disability at two years of age or older; receipt of treatment for hypoglycaemia during initial hospital stay; receipt of intravenous treatment for hypoglycaemia). Authors' conclusions Oral dextrose gel reduced the risk of neonatal hypoglycaemia in at-risk infants in a single trial. Results showed no statistically significant differences in the number of adverse events or in risk of separation of infant from mother for treatment of hypoglycaemia between babies who received oral dextrose gel and those given placebo. Caution is suggested in interpreting data for the latter two outcomes owing to low event rates. Available evidence is limited to a cohort of at-risk infants, most of whom were infants of diabetic mothers and were treated on the postnatal ward. Minimal data available for many of the prespecified outcomes of this review showed no long-term neurodevelopmental and disability outcomes. Additional evidence is needed to assess the efficacy and safety of dextrose gel for prevention 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.

We performed a case-control study to characterise infants with "prolonged transitional hypoglycaemia".Cases were born ≥36 weeks' gestation; had ≥1 hypoglycaemic episode72 h and ≥72 h; received ongoing treatment for hypoglycaemia ≥72 h; and were without congenital disorders or acute illness. Cases were compared to controls born ≥36 weeks' with brief transitional hypoglycaemia, resolving72 h.39/471 infants screened met case definition: 71.8% were male, 61.5% were small-for-gestational-age (SGA), and most were admitted6 h. Compared to controls (N = 75), key risk factors for prolonged transitional hypoglycaemia were SGA (OR = 6.4, 95%CI 2.7-15.1), severe/recurrent hypoglycaemia24 h (OR = 16.7, 95%CI 4.5-16.1), intravenous glucose bolus24 h (OR = 26.6, 95%CI 9.4-75.1) and maximum glucose delivery rate48 h of ≥8 mg/kg/min (OR = 25.5, 95%CI 7.7-84.1).Infants with prolonged transitional hypoglycaemia are predominantly male, SGA and have early severe/recurrent hypoglycaemia requiring glucose boluses and high glucose delivery rates in the first 24-48 h.

BACKGROUND: Magnesium sulphate given to women prior to very preterm birth protects the perinatal brain, so fewer babies die or develop cerebral palsy. How magnesium sulphate exerts these beneficial effects remains uncertain. The MagNUM Study aimed to assess the effect of exposure to antenatal magnesium sulphate on MRI measures of brain white matter microstructure at term equivalent age.METHODS: Nested cohort study within the Magnesium sulphate at 30 to FINDINGS: Of the 109 babies the demographics of the 49 babies exposed to magnesium sulphate were similar to the 60 babies exposed to placebo. In babies whose mothers were allocated to magnesium sulphate, fractional anisotropy was lower within the corticospinal tracts and corona radiata, the superior and inferior longitudinal fasciculi, and the inferior fronto-occipital fasciculi compared to babies whose mothers were allocated placebo (P < 0·05).INTERPRETATION: In babies born preterm after 30 weeks' gestation, antenatal magnesium sulphate exposure did not promote development of white matter microstructure in pathways affecting motor or cognitive function. This suggests that if the neuroprotective effect of magnesium sulphate treatment prior to preterm birth is confirmed at this gestation, the mechanisms are not related to accelerated white matter maturation inferred from fractional anisotropy.FUNDING: This study was funded by a project grant from the Health Research Council of New Zealand (HRC 14/153).

Introduction: Necrotizing enterocolitis (NEC) affects mainly preterm infants, has a multifactorial etiology and is associated with intestinal dysbiosis and disordered immunity. Use of probiotics for prophylaxis is beneficial with studies indicating reduction in NEC ≥ stage 2, late onset sepsis (LOS) and mortality. However, not all studies have shown a reduction, there are questions regarding which probiotic to use, whether infants

AIMS To determine the use of oral dextrose gel to treat neonatal hypoglycaemia in New Zealand (NZ), to identify barriers and enablers to the implementation of the guideline and to determine if there is variation in management between clinical disciplines caring for at-risk babies. METHODS An online survey was distributed to clinicians (including doctors, midwives and nurses) caring for babies with neonatal hypoglycaemia via stakeholders and maternity hospitals. RESULTS A total of 251 clinicians from all 20 District Health Boards (DHBs) completed the survey. Of the responding clinicians, 148 (59%) from 15 (75%) DHBs reported oral dextrose gel use in their hospital, and of these, 129 (87%) reported a local guideline. In 12 of 15 (80%) DHBs, oral dextrose gel could be prescribed by midwives. For a clinical scenario of a baby with neonatal hypoglycaemia, doctors were more likely to prescribe oral dextrose gel than midwives (odds ratio (95% confidence interval), 2.9 (2.2-3.8), P < 0.0001). Of 32 possible combinations of treatment options for this scenario, 31 were selected by one or more clinicians. A guideline was perceived to be the most useful enabler, and availability of oral dextrose gel was seen as the most important barrier. CONCLUSIONS Oral dextrose gel is widely used to treat neonatal hypoglycaemia in NZ. Increasing availability of dextrose gel and the clinical practice guideline are likely to further increase the use of oral dextrose gel.

Babies born at moderate-late preterm gestations account for > 80% of all preterm births. Although survival is excellent, these babies are at increased risk of adverse neurodevelopmental outcomes. They also are at increased risk of adverse long-term health outcomes, such as cardiovascular disease, obesity and diabetes. There is little evidence guiding optimal nutritional practices in these babies; practice, therefore, varies widely. This factorial design clinical trial will address the role of parenteral nutrition, milk supplementation and exposure of the preterm infant to taste and smell with each feed on time to tolerance of full feeds, adiposity, and neurodevelopment at 2 years. The DIAMOND trial is a multi-centre, factorial, randomised, controlled clinical trial. A total of 528 babies born between 32+ 0 and 35+ 6 weeks’ gestation receiving intravenous fluids and whose mothers intend to breastfeed will be randomised to one of eight treatment conditions that include a combination of each of the three interventions: (i) intravenous amino acid solution vs. intravenous dextrose solution until full milk feeds established; (ii) milk supplement vs. exclusive breastmilk, and (iii) taste/smell given or not given before gastric tube feeds. Babies will be excluded if a particular mode of nutrition is clinically indicated or there is a congenital abnormality. Primary study outcome: For parenteral nutrition and milk supplement interventions, body composition at 4 months’ corrected age. For taste/smell intervention, time to full enteral feeds defined as 150 ml.kg− 1.day− 1 or exclusive breastfeeding. Secondary outcomes: Days to full sucking feeds; days in hospital; body composition at discharge; growth to 2 years’ corrected age; development at 2 years’ corrected age; breastfeeding rates. This trial will provide the first direct evidence to inform feeding practices in moderate- to late-preterm infants that will optimise their growth, metabolic and developmental outcomes. Australian New Zealand Clinical Trials Registry - ACTRN12616001199404 . This trial is endorsed by the IMPACT clinical trials network ( https://impact.psanz.com.au ).

To determine the effects of different doses of prophylactic dextrose gel on glycemic stability assessed using continuous glucose monitoring in the first 48 hours when given to babies at risk of neonatal hypoglycemia.Continuous glucose monitoring was undertaken for the first 48 hours in 133 infants at risk of hypoglycemia who participated in the pre-hPOD randomized dosage trial of dextrose gel prophylaxis.Low glucose concentrations were detected in 41% of infants by blood glucose monitoring and 68% by continuous interstitial glucose monitoring. The mean ± SD duration of low interstitial glucose concentrations was 295 ± 351 minutes in the first 48 hours. Infants who received any dose of dextrose gel seemed to be less likely than those who received placebo gel to experience low glucose concentrations (47 mg/dL [2.6 mmol/L]; P = .08), particularly if they received a single dose of 200 mg/kg (relative risk, 0.70; 95% CI, 0.50-0.10; P = .049). They also spent a greater proportion of time in the central glucose concentration range of 54-72 mg/dL (3-4 mmol/L) (any dose, mean ± SD, 58.2 ± 20.3%; placebo, 50.0 ± 21.9%; mean difference, 8.20%; 95% CI, 0.43-15.9%; P = .038). Dextrose gel did not increase recurrent or severe episodes of low glucose concentrations and did not increase the peak glucose concentration. These effects were similar for all trial dosages.Low glucose concentrations were common in infants at risk of hypoglycemia despite blood glucose monitoring and treatment. Prophylactic dextrose gel reduced the risk of hypoglycemia without adverse effects on glucose stability.

To investigate relationships between early neonatal glycemia, neonatal characteristics, neonatal illness, and developmental outcomes in very preterm infants.A retrospective, observational cohort study of 443 infants born weighing1500 g or30 weeks of gestation, and admitted within 24 hours to National Women's Hospital, Auckland, New Zealand. Glucose variability was defined as the standard deviation around the mean after log transformation of all blood glucose concentrations. Absolute glycemic excursions in the first week were used to divide the infants into 4 groups: normoglycemic; hypoglycemic; hyperglycemic, and unstable.Compared with normoglycemic infants, hypoglycemic and unstable infants had lower birth weight z-scores, and hyperglycemic and unstable infants were of lower birth weight. Hypoglycemic infants had similar outcomes to normoglycemic infants. Hyperglycemic and unstable infants were less likely to survive without neonatal morbidity and less likely to survive without neurodevelopmental impairment at 2 years of age. Higher mean blood glucose concentration was seen in the hyperglycemic and unstable groups, and was associated with worse neonatal and 2-year outcomes. Greater glucose variability was seen in the hypoglycemic and unstable groups, and was associated with worse neonatal illness but not outcome at 2 years. No associations between measures of neonatal glycemia and neonatal or 2-year outcomes remained after correction for gestation, birth weight z-score, and socioeconomic status.In very preterm infants, measures of neonatal glycemia are markers of gestational age and intrauterine growth, and are not independent predictors of neonatal illness or outcomes at 2 years of age.

Background Models of human glucose–insulin physiology have been developed for a range of uses, with similarly different levels of complexity and accuracy. STAR (Stochastic Targeted) is a model-based approach to glycaemic control. Elevated blood glucose concentrations (hyperglycaemia) are a common complication of stress and prematurity in very premature infants, and have been associated with worsened outcomes and higher mortality. This research identifies and validates the model parameters for model-based glycaemic control in neonatal intensive care. Methods C-peptide, plasma insulin, and BG from a cohort of 41 extremely pre-term (median age 27.2 [26.2–28.7] weeks) and very low birth weight infants (median birth weight 839 [735–1000] g) are used alongside C-peptide kinetic models to identify model parameters associated with insulin kinetics in the NICING (Neonatal Intensive Care Insulin–Nutrition–Glucose) model. A literature analysis is used to determine models of kidney clearance and body fluid compartment volumes. The full, final NICING model is validated by fitting the model to a cohort of 160 glucose, insulin, and nutrition data records from extremely premature infants from two different NICUs (neonatal intensive care units). Results Six model parameters related to insulin kinetics were identified. The resulting NICING model is more physiologically descriptive than prior model iterations, including clearance pathways of insulin via the liver and kidney, rather than a lumped parameter. In addition, insulin diffusion between plasma and interstitial spaces is evaluated, with differences in distribution volume taken into consideration for each of these spaces. The NICING model was shown to fit clinical data well, with a low model fit error similar to that of previous model iterations. Conclusions Insulin kinetic parameters have been identified, and the NICING model is presented for glycaemic control neonatal intensive care. The resulting NICING model is more complex and physiologically relevant, with no loss in bedside-identifiability or ability to capture and predict metabolic dynamics.

Antenatal exogenous glucocorticoids (ANG) are standard management for women at risk of preterm birth but are reputed to impair glucose tolerance in preterm offspring. We compared lambs born preterm (137 days gestation) following labour induced with exogenous glucocorticoids (G-Prem, glucocorticoid-induced preterm group), or with a progesterone synthesis inhibitor (NG-Prem, non-glucocorticoid-induced preterm group), with term-born lambs (Term; 149 days). We assessed glucose tolerance, insulin secretion and sensitivity at 4 and 10 months n = 11–14/group) and pancreatic and hepatic gene and protein expression at 4 weeks post-term (4 weeks; n = 6/group) and 12 months (12 months; n = 12–13/group). NG-Prem had higher plasma glucose concentrations than G-Prem, but not Term, at 4 months (Mean[SEM] mM: NG-Prem = 4.1[0.1]; G-Prem = 3.4[0.1]; Term = 3.7[0.1]; p = 0.003) and 10 months (NG-Prem = 3.9[0.1]; G-Prem = 3.5[0.1]; Term = 3.7[0.1]; p = 0.01). Insulin sensitivity decreased from 4 to 10 months, in NG-Prem but not in Term (Mean[SEM] µmol·ml−1·kg−1·min−1·ng−1, 4 vs. 10 months: NG-Prem = 18.7[2.5] vs. 9.5[1.5], p < 0.01; Term: 12.1[2.8] vs. 10.4[1.5], p = 0.44). At 12 months, β-cell mass in NG-Prem was reduced by 30% vs. G-Prem (p < 0.01) and 75% vs. Term (p < 0.01) and was accompanied by an increased β-cell apoptosis: proliferation ratio at 12 months. At 12 months, pancreatic glucokinase, igf2 and insulin mRNA levels were reduced 21%–71% in NG-Prem vs. G-Prem and 42%–80% vs. Term. Hepatic glut2 mRNA levels in NG-Prem were 250% of those in G-Prem and Term. Thus, induction of preterm birth without exogenous glucocorticoids more adversely affected pancreas and liver than induction with exogenous glucocorticoids. These findings do not support that ANG lead to long-term adverse metabolic effects, but support an effect of preterm birth itself.

Background: We performed a case-control study to characterise infants with “prolonged transitional hypoglycaemia”. Methods: Cases were born ≥36 weeks’ gestation; had ≥1 hypoglycaemic episode Results: 39/471 infants screened met case definition: 71.8% were male, 61.5% were small-for-gestational-age (SGA), and most were admitted Conclusions: Infants with prolonged transitional hypoglycaemia are predominantly male, SGA and have early severe/ recurrent hypoglycaemia requiring glucose boluses and high glucose delivery rates in the first 24–48h.Published in Journal of Perinatology 2020 https://doi.org/10.1038/s41372-020-00891-wPublished data are available to approved researchers under the data sharing arrangements provided by the Clinical Data Research Hub (CCRH), based at the Liggins Institute, University of Auckland. Contact researchhub@auckland.ac.nzhttps://wiki.auckland.ac.nz/display/ontrack/Data+Sharing

ObjectivesThe aim of this study was to conduct New Zealand-specific research to inform the design of a pulse oximetry screening strategy that ensures equity of access for the New Zealand maternity population. Equity is an important consideration as the test has the potential to benefit some populations and socioeconomic groups more than others.SettingNew Zealand has an ethnically diverse population and a midwifery-led maternity service. One quaternary hospital and urban primary birthing unit (Region A), two regional hospitals (Region B) and three regional primary birthing units (Region C) from three Health Boards in New Zealand’s North Island participated in a feasibility study of pulse oximetry screening. Home births in these regions were also included.ParticipantsThere were 27 172 infants that satisfied the inclusion criteria; 16 644 (61%) were screened. The following data were collected for all well newborn infants with a gestation age ≥35 weeks: date of birth, ethnicity, type of maternity care provider, deprivation index and screening status (yes/no). The study was conducted over a 2-year period from May 2016 to April 2018.ResultsScreening rates improved over time. Infants born in Region B (adjusted OR=0.75; 95% CI 0.67 to 0.83) and C (adjusted OR=0.29; 95% CI 0.27 to 0.32) were less likely to receive screening compared with those born in Region A. There were significant associations between screening rates and deprivation, ethnicity and maternity care provider. Lack of human and material resources prohibited universal access to screening.ConclusionA pulse oximetry screening programme that is sector-led is likely to perpetuate inequity. Screening programmes need to be designed so that resources are distributed in the way most likely to optimise health outcomes for infants born with cardiac anomalies.Ethics approvalThis study was approved by the Health and Disability Ethics Committees of New Zealand (15/NTA/168).

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

Although early nutrition is associated with neurodevelopmental outcome at 2 years' corrected age in children born very preterm, it is not clear if these associations are different in girls and boys.Retrospective cohort study of infants born30 weeks' gestational age or1500 g birth weight in Auckland, NZ. Macronutrient, energy and fluid volumes per kg per day were calculated from daily nutritional intakes and averaged over days 1-7 (week 1) and 1-28 (month 1). Primary outcome was survival without neurodevelopmental impairment at 2 years corrected age.More girls (215/478) survived without neurodevelopmental impairment at 2 years (82% vs. 72%, P = 0.02). Overall, survival without neurodevelopmental impairment was positively associated with more energy, fat, and enteral feeds in week 1, and more energy and enteral feeds in month 1 (P = 0.005-0.03), but all with sex interactions (P = 0.008-0.02). In girls but not boys, survival without neurodevelopmental impairment was positively associated with week 1 total intakes of fat (OR(95% CI) for highest vs. lowest intake quartile 62.6(6.6-1618.1), P 0.001), energy (22.9(2.6-542.0), P = 0.03) and enteral feeds (1.9 × 10Higher early fat and enteral feed intakes are associated with improved outcome in girls, but not boys. Future research should determine sex-specific neonatal nutritional requirements.

AIM To determine if the routine use of automatically calculated birthweight centiles prior to discharge from the delivery unit is associated with improved adherence to the neonatal hypoglycaemia guideline. METHODS We conducted retrospective audits of adherence to the neonatal hypoglycaemia guideline in a tertiary maternity hospital in Auckland, New Zealand in a randomly selected cohort of newborn infants at risk of neonatal hypoglycaemia before (2011) and after (2015) the introduction of routine use of calculated birthweight centiles for all infants. The primary outcome was adherence to the guideline, defined as (i) blood glucose concentration screening in the first 48 h after birth; (ii) the initial measurement taken 1-2 h after birth; and (iii) at least three consecutive blood glucose concentrations ≥2.6 mmol/L, over 12 h, prior to cessation of screening. RESULTS The audits examined the records of 400 infants (200 each in 2011 and 2015) to determine guideline adherence. Adherence improved from 2011 to 2015 (59/200 (30%) vs. 95/200 (48%), P

Age- and sex-based BMI cut-offs are used to define overweight and obesity, but the relationship between BMI and body composition has not been very well studied in children or compared between children of different ethnic groups. Body size and composition in childhood are also influenced by size at birth. Our aim was to compare body size and composition at 2 years in children with different ethnicity and size at birth. We prospectively followed a multi-ethnic cohort of 300 children born with risk factors for neonatal hypoglycaemia (infants of diabetics, large or small at birth or late preterm) to 2 years corrected age. Complete data on weight, height and head circumference and body composition using bioelectrical impedance 24±1 months corrected age were available in 209 children. At birth, compared with European children, Chinese, Indian and other ethnicity children were lighter, and Indian children had smaller head circumferences, but birth lengths were similar in all ethnic groups. At 2 years, Pacific children were heavier and had higher BMI z scores, and Indian children had smaller head circumferences and lower BMI z scores than those from other ethnic groups. However, fat mass and fat-free mass indices were similar in all groups. At median BMI, fat mass:fat-free mass ratio was 23 % lower in Pacific than in Indian children (0·22 v. 0·27, P=0·03). BMI is not a good indicator of adiposity in this multi-ethnic cohort of 2-year-old New Zealand children.

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.

A mathematical model of the dynamics of insulin and glucose during a frequently sampled intravenous glucose tolerance test (IVGTT) in sheep was developed that characterizes the large second-phase insulin secretion response in sheep during IVGTT. The model was fit to measurements of the glucose and insulin dynamics during standard IVGTT ( = 42) and modified IVGTT ( = 40), where insulin was injected 60 min after the initiation of the IVGTT. The correlation between log insulin sensitivity determined by hyperglycemic clamps (HGC) and standard IVGTT was = 0.43 ( = 0.005). The correlation between log insulin sensitivity determined by HGC and modified IVGTT was = 0.51 ( = 0.002). The model, therefore, provides a method to determine insulin sensitivity through a cheaper and more easily performed IVGTT. We validated our estimation procedure using 2 independent experiments on the effect of 1) pregnancy and 2) being born preterm and exposed to dextrose or dextrose with insulin on HGC-derived insulin sensitivity. The IVGTT-derived insulin sensitivity was significantly greater in pregnant ewes than in prepregnant ewes (difference of 0.39 ± 0.12 log n ng mL; < 0.05), and this was consistent with the significantly greater hyperinsulinemic euglycemic clamp-derived insulin sensitivity in pregnant ewes than in prepregnant ewes (difference of 4.03 ± 0.66 µmol mL kg min ng; < 0.001). There was no significant effect of being born preterm on IVGTT/HGC-derived insulin sensitivity. Basal insulin, insulin sensitivity, insulin production, and insulin clearance were lower in prepregnant ewes ( < 0.05). That is, prepregnant ewes have a lower insulin equilibrium status and less responsive insulin turnover. There was also a significant effect of insulin therapy on the rate of insulin clearance in preterm lambs ( < 0.05). This effect was independently significant of its covariance with all other model parameters. Therefore, it can be interpreted as a direct effect on the rate of insulin clearance by the insulin treatment. All other parameter responses to the insulin treatment effect can be regarded as being due to the covariance between these parameters. These analyses demonstrate that treatment effects on insulin sensitivity can be detected using IVGTT experiments.

Aim To determine whether Bayley Scales of Infant and Toddler Development (3rd edition) (Bayley-III) motor scores and neurological examination at 2 years corrected age predict motor difficulties at 4.5 years corrected age. Method A prospective cohort study of children born at risk of neonatal hypoglycaemia in Waikato Hospital, Hamilton, New Zealand. Assessment at 2 years was performed using the Bayley-III motor scale and neurological examination, and at 4.5 years using the Movement Assessment Battery for Children (2nd edition) (MABC-2). Results Of 333 children, 8 (2%) had Bayley-III motor scores below 85, and 50 (15%) had minor deficits on neurological assessment at 2 years; 89 (27%) scored less than or equal to the 15th centile, and 54 (16%) less than or equal to the 5th centile on MABC-2 at 4.5 years. Motor score, fine and gross motor subtest scores, and neurological assessments at 2 years were poorly predictive of motor difficulties at 4.5 years, explaining 0 to 7% of variance in MABC-2 scores. A Bayley-III motor score below 85 predicted MABC-2 scores less than or equal to the 15th centile with a positive predictive value of 30% and a negative predictive value of 74% (7% sensitivity and 94% specificity). Interpretation Bayley-III motor scale and neurological examination at 2 years were poorly predictive of motor difficulties at 4.5 years.

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. Trial registration ACTRN 12614001263684., Jane E. Harding and colleagues present results from a trial of prophylactic dextrose gel in newborns at risk of hypoglycemia., Author summary Why was this study done? Hypoglycemia (low blood glucose level) is common in newborn babies and can cause brain injury, even if it is transient and treated. Dextrose (sugar) gel rubbed inside the baby’s cheek is widely used to treat hypoglycemia, and is noninvasive, inexpensive, and safe. One study previously has shown that dextrose gel can be used as a preventative to reduce the incidence of hypoglycemia, but it is not known if this improves clinically important outcomes like admission to newborn intensive care. What did the researchers do and find? We recruited from 18 centers in New Zealand and Australia 2,149 babies who were born at risk of neonatal hypoglycemia but who were not likely to need intensive care for other reasons. Babies were allocated at random to receive a single dose of dextrose gel or placebo gel at 1 hour after birth, and had blood glucose levels measured at 2 hours, followed by routine care. Preventative dextrose gel did not decrease admission to newborn intensive care but did decrease the incidence of hypoglycemia (secondary outcome), with 21 babies needing to be treated to prevent 1 case of hypoglycemia. There were no effects on breastfeeding, no high blood glucose levels, and no other adverse effects. What do these findings mean? Clinicians and clinical guideline groups should consider whether needing to treat 21 babies to prevent 1 case of hypoglycemia with no reduction in neonatal intensive care admission warrants introduction of this prevention strategy into practice at this time. Since the main reason for preventing hypoglycemia is to prevent brain injury, it will be important to assess the effect of this prevention strategy on the later development of children in this cohort.

IntroductionInfants born late preterm (34+0 to 36+6 weeks’ gestational age) have frequent episodes of intermittent hypoxaemia compared with term infants. Caffeine citrate reduces apnoea and intermittent hypoxaemia and improves long-term neurodevelopmental outcomes in infants born very preterm and may have similar effects in late preterm infants. Clearance of caffeine citrate increases with gestational age and late preterm infants are likely to need a higher dose than very preterm infants. Our aim is to determine the most effective and best-tolerated dose of caffeine citrate to reduce transient intermittent hypoxaemia events in late preterm infants.Methods and analysisA phase IIB, double-blind, five-arm, parallel, randomised controlled trial to compare the effect of four doses of oral caffeine citrate versus placebo on the frequency of intermittent hypoxaemia. Late preterm infants will be enrolled within 72 hours of birth and randomised to receive 5, 10, 15 or 20 mg/kg/day caffeine citrate or matching placebo daily until term corrected age. The frequency of intermittent hypoxaemia (events/hour where oxygen saturation concentration is ≥10% below baseline for ≤2 min) will be assessed with overnight oximetry at baseline, 2 weeks after randomisation (primary outcome) and at term corrected age. Growth will be measured at these timepoints, and effects on feeding and sleeping will be assessed by parental report. Data will be analysed using generalised linear mixed models.Ethics and disseminationThis trial has been approved by the Health and Disability Ethics Committees of New Zealand (reference 18/NTA/129) and the local institutional research review committees. Findings will be disseminated to peer-reviewed journals to clinicians and researchers at local and international conferences and to the public. The findings of the trial will inform the design of a large multicentre trial of prophylactic caffeine in late preterm infants, by indicating the most appropriate dose to use and providing information on feasibility.Trial registration numberACTRN12618001745235; Pre-results.

Children born very preterm are at higher risk of adverse neurocognitive and educational outcomes. However, how low intelligence (IQ) and low executive function may each contribute to poorer academic outcomes at school age requires clarification.To examine the associations between intelligence, executive function and academic achievement in children born very preterm.This cohort study assessed children born30 weeks' gestation or1500 g at age 7 years using the Wechsler Intelligence Scale for Children, Fourth Edition (WISC-IV) for IQ, and the Test of Everyday Attention for Children (TEA-Ch) and Behavior Rating Inventory of Executive Function (BRIEF) for executive function. Academic achievement was rated by teachers against curriculum standards.Of the 76 children (35 girls, 41 boys, mean age = 7.2 year), 22 (28%) were rated below expected level for reading, 32 (42%) for writing and 38 (50%) for mathematics. After adjustment for sex and socioeconomic status, low IQ (OR's 9.0-12.3) and most low executive function measures (OR's 4.1-9.3) were associated with below-expected achievement. After further adjustment for IQ, low cognitive flexibility (OR = 9.3, 95% CI = 1.2-71.5) and teacher ratings of executive function (OR = 5.3, 95% CI = 1.4-20.2) were associated with below-expected achievement. Mediation analysis showed IQ had indirect effects on writing (b = 1.5, 95% CI = 0.6-3.1) via attentional control; and on reading (b = 1.0, 95% CI = 0.2-3.2) and writing (b = 0.8, 95% CI = 0.1-2.5) via cognitive flexibility.Both low IQ and low executive function are associated with below-expected teacher-rated academic achievement in children born very preterm. IQ may influence academic achievement in part through executive function.

To determine whether neonatal hyperglycemia is associated with retinopathy of prematurity (ROP), visual outcomes, and ocular growth at 7 years of age.Children born preterm (30 weeks of gestational age) at a tertiary hospital in Auckland, New Zealand, who developed neonatal hyperglycemia (2 blood glucose concentrations ≥153 mg/dL [8.5 mmol/L] 4 hours apart) were matched with children who were not hyperglycemic (matching criteria: sex, gestational age, birth weight, age, socioeconomic status, and multiple birth) and assessed at 7 years of corrected age. The primary outcome, favorable overall visual outcome (visual acuity ≤0.3 logarithm of the minimum angle of resolution, no strabismus, stereoacuity ≤240 arcsec, not requiring spectacles) was compared between groups using generalized matching criteria-adjusted linear regression models.Assessments were performed on 57 children with neonatal hyperglycemia (hyperglycemia group) and 54 matched children without hyperglycemia (control group). There were no differences in overall favorable visual outcome (OR 0.95, 95% CI 0.42-2.13, P = .90) or severe ROP incidence (OR 2.20, 95% CI 0.63-7.63, P = .21) between groups. Children with hyperglycemia had poorer binocular distance visual acuity (mean difference 0.08, 95% CI 0.03-0.14 logarithm of the minimum angle of resolution, P .01), more strabismus (OR 6.22, 95% CI 1.31-29.45, P = .02), and thicker crystalline lens (mean difference 0.14, 95% CI 0.04-0.24 mm, P .01). Maximum blood glucose concentration was greater in the ROP-treated group compared with the ROP-not treated and no ROP groups after adjusting for sex, gestational age, and birth weight z score (P = .02).Neonatal hyperglycemia was not associated with overall visual outcomes at 7 years of age. However, there were between-group differences for specific outcome measures relating to interocular lens growth and binocular vision. Further follow-up is required to determine implications on long-term visual outcome.