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Low blood concentrations of glucose (hypoglycaemia) soon after birth are common because of the delayed metabolic transition from maternal to endogenous neonatal sources of glucose. Because glucose is the main energy source for the brain, severe hypoglycaemia can cause neuroglycopenia (inadequate supply of glucose to the brain) and, if severe, permanent brain injury. Routine screening of infants at risk and treatment when hypoglycaemia is detected are therefore widely recommended. Robust evidence to support most aspects of management is lacking, however, including the appropriate threshold for diagnosis and optimal monitoring. Treatment is usually initially more feeding, with buccal dextrose gel, followed by intravenous dextrose. In infants at risk, developmental outcomes after mild hypoglycaemia seem to be worse than in those who do not develop hypoglycaemia, but the reasons for these observations are uncertain. Here, the current understanding of the pathophysiology of neonatal hypoglycaemia and recent evidence regarding its diagnosis, management, and outcomes are reviewed. Recommendations are made for further research priorities.

Measurement of body composition is increasingly important in research and clinical settings but is difficult in very young children. Bioelectrical impedance analysis (BIA) and air displacement plethysmography (ADP) are well-established but require specialist equipment so are not always feasible. Our aim was to determine if anthropometry and skinfold thickness measurements can be used as a substitute for BIA or ADP for assessing body composition in very young New Zealand children. We used three multi-ethnic cohorts: 217 children at a mean age of 24·2 months with skinfold and BIA measurements; seventy-nine infants at a mean age of 20·9 weeks and seventy-three infants at a mean age of 16·2 weeks, both with skinfold and ADP measurements. We used Bland–Altman plots to compare fat and fat-free mass calculated using all potentially relevant equations with measurements using BIA or ADP. We also calculated the proportion of children in the same tertile for measured fat or fat-free mass and tertiles (i) calculated using each equation, (ii) each absolute skinfold, and (iii) sum of skinfold thicknesses. We found that even for the best equation for each cohort, the 95 % limits of agreement with standard measures were wide (25–200 % of the mean) and the proportion of children whose standard measures fell in the same tertile as the skinfold estimates was ≤69 %. We conclude that none of the available published skinfold thickness equations provides good prediction of body composition in multi-ethnic cohorts of very young New Zealand children with different birth history and growth patterns.

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.

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 is also influenced by size at birth. Our aim was to compare body size and composition at two years in children with different ethnicity and size at birth. We prospectively followed to two years’ corrected age 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). Complete data on weight, height and head circumference, and body composition using bioelectrical impedance at 24 ± 1 months’ corrected age was available in 209 children. At birth, compared to 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 two 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 vs. 0.27, p = 0.03). BMI is not a good indicator of adiposity in this multi-ethnic cohort of New Zealand two-year-old children.

Background For the follow-up of participants in randomised trials, data linkage is thought a more cost-efficient method for assessing outcomes. However, researchers often encounter technical and budgetary challenges. Data requests often require a significant amount of information from researchers, and can take several years to process. This study aimed to determine the feasibility, direct costs and the total time required to access administrative datasets for assessment of outcomes in a follow-up study of two randomised trials. Methods We applied to access administrative datasets from New Zealand government agencies. All actions of study team members, along with their corresponding dates, were recorded prospectively for accessing data from each agency. Team members estimated the average time they spent on each action, and invoices from agencies were recorded. Additionally, we compared the estimated costs and time required for data linkage with those for obtaining self-reported questionnaires and conducting in-person assessments. Results Eight agencies were approached to supply data, of which seven gave approval. The time from first enquiry to receiving an initial dataset ranged from 96 to 854 days. For 859 participants, the estimated time required to obtain outcome data from agencies was 1,530 min; to obtain completed self-reported questionnaires was 11,025 min; and to complete in-person assessments was 77,310 min. The estimated total costs were 20,827 NZD for data linkage, 11,735 NZD for self-reported questionnaires, and 116,085 NZD for in-person assessments. Using this data, we estimate that for a cohort of 100 participants, the costs would be similar for data linkage and in-person assessments. For a cohort of 5,000 participants, we estimate that costs would be similar for data linkage and questionnaires, but ten-fold higher for in-person assessments. Conclusions Obtaining administrative datasets demands a substantial amount of time and effort. However, data linkage is a feasible method for outcome ascertainment in follow-up studies in New Zealand. For large cohorts, data linkage is likely to be less costly, whereas for small cohorts, in-person assessment has similar costs but is likely to be faster and allows direct assessment of outcomes.

Background Early onset fetal growth restriction secondary to placental insufficiency can lead to severe maternal and neonatal morbidity and mortality. Pre-clinical studies and a few small randomised clinical trials have suggested that phosphodiesterase type 5 (PDE-5) inhibitors may have protective effects against placental insufficiency in this context; however, robust evidence is lacking. The STRIDER Consortium conducted four randomised trials to investigate the use of a PDE-5 inhibitor, sildenafil, for the treatment of early onset fetal growth restriction. We present a protocol for the pre-planned systematic review with individual participant data meta-analysis, aggregate meta-analysis, and trial sequential analysis of these and other eligible trials. The main objective of this study will be to evaluate the effects of PDE-5 inhibitors on neonatal morbidity compared with placebo or no intervention among pregnancies with fetal growth restriction. Methods We will search the following electronic databases with no language or date restrictions: OVID MEDLINE, OVID EMBASE, the Cochrane Controlled Register of Trials (CENTRAL), and the clinical trial registers Clinicaltrials.gov and World Health Organisation International Clinical Trials Registry Platform (ICTRP). We will identify randomised trials of PDE-5 inhibitors in singleton pregnancies with growth restriction. Two reviewers will independently screen all citations, full-text articles, and abstract data. Our primary outcome will be infant survival without evidence of serious adverse neonatal outcome. Secondary outcomes will include gestational age at birth and birth weight z -scores. We will assess bias using the Cochrane Risk of Bias 2 tool. We will conduct aggregate meta-analysis using fixed and random effects models, Trial Sequential Analysis, and individual participant data meta-analysis using one- and two-stage approaches. The certainty of evidence will be assessed with GRADE. Discussion This pre-defined protocol will minimise bias during analysis and interpretation of results, toward the goal of providing robust evidence regarding the use of PDE-5 inhibitors for the treatment of early onset fetal growth restriction. Systematic review registration PROSPERO (CRD42017069688).

High-sensitivity cardiac troponin assays permit use of lower thresholds for the diagnosis of myocardial infarction, but whether this improves clinical outcomes is unknown. We aimed to determine whether the introduction of a high-sensitivity cardiac troponin I (hs-cTnI) assay with a sex-specific 99th centile diagnostic threshold would reduce subsequent myocardial infarction or cardiovascular death in patients with suspected acute coronary syndrome. In this stepped-wedge, cluster-randomised controlled trial across ten secondary or tertiary care hospitals in Scotland, we evaluated the implementation of an hs-cTnI assay in consecutive patients who had been admitted to the hospitals' emergency departments with suspected acute coronary syndrome. Patients were eligible for inclusion if they presented with suspected acute coronary syndrome and had paired cardiac troponin measurements from the standard care and trial assays. During a validation phase of 6–12 months, results from the hs-cTnI assay were concealed from the attending clinician, and a contemporary cardiac troponin I (cTnI) assay was used to guide care. Hospitals were randomly allocated to early (n=5 hospitals) or late (n=5 hospitals) implementation, in which the high-sensitivity assay and sex-specific 99th centile diagnostic threshold was introduced immediately after the 6-month validation phase or was deferred for a further 6 months. Patients reclassified by the high-sensitivity assay were defined as those with an increased hs-cTnI concentration in whom cTnI concentrations were below the diagnostic threshold on the contemporary assay. The primary outcome was subsequent myocardial infarction or death from cardiovascular causes at 1 year after initial presentation. Outcomes were compared in patients reclassified by the high-sensitivity assay before and after its implementation by use of an adjusted generalised linear mixed model. This trial is registered with ClinicalTrials.gov, number NCT01852123. Between June 10, 2013, and March 3, 2016, we enrolled 48 282 consecutive patients (61 [SD 17] years, 47% women) of whom 10 360 (21%) patients had cTnI concentrations greater than those of the 99th centile of the normal range of values, who were identified by the contemporary assay or the high-sensitivity assay. The high-sensitivity assay reclassified 1771 (17%) of 10 360 patients with myocardial injury or infarction who were not identified by the contemporary assay. In those reclassified, subsequent myocardial infarction or cardiovascular death within 1 year occurred in 105 (15%) of 720 patients in the validation phase and 131 (12%) of 1051 patients in the implementation phase (adjusted odds ratio for implementation vs validation phase 1·10, 95% CI 0·75 to 1·61; p=0·620). Use of a high-sensitivity assay prompted reclassification of 1771 (17%) of 10 360 patients with myocardial injury or infarction, but was not associated with a lower subsequent incidence of myocardial infarction or cardiovascular death at 1 year. Our findings question whether the diagnostic threshold for myocardial infarction should be based on the 99th centile derived from a normal reference population. The British Heart Foundation.

Logged and disturbed forests are often viewed as degraded and depauperate environments compared with primary forest. However, they are dynamic ecosystems1 that provide refugia for large amounts of biodiversity2,3, so we cannot afford to underestimate their conservation value4. Here we present empirically defined thresholds for categorizing the conservation value of logged forests, using one of the most comprehensive assessments of taxon responses to habitat degradation in any tropical forest environment. We analysed the impact of logging intensity on the individual occurrence patterns of 1,681 taxa belonging to 86 taxonomic orders and 126 functional groups in Sabah, Malaysia. Our results demonstrate the existence of two conservation-relevant thresholds. First, lightly logged forests (<29% biomass removal) retain high conservation value and a largely intact functional composition, and are therefore likely to recover their pre-logging values if allowed to undergo natural regeneration. Second, the most extreme impacts occur in heavily degraded forests with more than two-thirds (>68%) of their biomass removed, and these are likely to require more expensive measures to recover their biodiversity value. Overall, our data confirm that primary forests are irreplaceable5, but they also reinforce the message that logged forests retain considerable conservation value that should not be overlooked.

AbstractObjectiveTo evaluate the impact of implementing a high sensitivity assay for cardiac troponin I on long term outcomes in patients with suspected acute coronary syndrome.DesignSecondary observational analysis of a stepped wedge, cluster randomised controlled trial.Setting10 secondary and tertiary care centres in Scotland, UK.Participants48 282 consecutive patients with suspected acute coronary syndrome. Myocardial injury was defined as any high sensitivity assay result for cardiac troponin I >99th centile of 16 ng/L in women and 34 ng/L in men.InterventionHospital sites were randomly allocated to either early (n=5 hospitals) or late (n=5 hospitals) implementation of a high sensitivity cardiac troponin I assay with sex specific diagnostic thresholds.Main outcome measureThe main outcome was myocardial infarction or death at five years.Results10 360 patients had cardiac troponin concentrations greater than the 99th centile, of whom 1771 (17.1%) were reclassified by the high sensitivity assay. The five year incidence of subsequent myocardial infarction or death before and after implementation of the high sensitivity assay was 29.4% (5588/18 978) v 25.9% (7591/29 304), respectively, in all patients (adjusted hazard ratio 0.97, 95% confidence interval 0.93 to 1.01), and 63.0% (456/720) v 53.9% (567/1051), respectively, in those reclassified by the high sensitivity assay (0.82, 0.72 to 0.94). After implementation of the high sensitivity assay, a reduction in subsequent myocardial infarction or death was observed in patients with non-ischaemic myocardial injury (0.83, 0.75 to 0.91) but not in those with type 1 or type 2 myocardial infarction (0.92, 0.83 to 1.01 and 0.98, 0.84 to 1.14).ConclusionsImplementation of a high sensitivity cardiac troponin I assay in the assessment of patients with suspected acute coronary syndrome was associated with a reduced risk of subsequent myocardial infarction or death at five years in those reclassified by the high sensitivity assay. Improvements in outcome were greatest in patients with non-ischaemic myocardial injury, suggesting a broader benefit beyond the identification of myocardial infarction.Trial registrationClinicalTrials.gov NCT01852123.

A combination of self-reported questionnaire and administrative data could potentially enhance ascertainment of outcomes and alleviate the limitations of both in follow up studies. However, it is uncertain how access to only one of these data sources to assess outcomes impact study findings. Therefore, this study aimed to determine whether the study findings would be altered if the outcomes were assessed by different data sources alone or in combination. At 50-year follow-up of participants in a randomized trial, we assessed the effect of antenatal betamethasone exposure on the diagnosis of diabetes, pre-diabetes, hyperlipidemia, hypertension, mental health disorders, and asthma using a self-reported questionnaire, administrative data, a combination of both, or any data source, with or without adjudication by an expert panel of five clinicians. Differences between relative risks derived from each data source were calculated using the Bland-Altman approach. There were 424 participants (46% of those eligible, aged 49 years, SD 1, 50% male). There were no differences in study outcomes between participants exposed to betamethasone and those exposed to placebo when the outcomes were assessed using different data sources. When compared to the study findings determined using adjudicated outcomes, the mean difference (limits of agreement) in relative risks derived from other data sources were: self-reported questionnaires 0.02 (-0.35 to 0.40), administrative data 0.06 (-0.32 to 0.44), both questionnaire and administrative data 0.01 (-0.41 to 0.43), and any data source, 0.01 (-0.08 to 0.10). Utilizing a self-reported questionnaire, administrative data, both questionnaire and administrative data, or any of these sources for assessing study outcomes had no impact on the study findings compared with when study outcomes were assessed using adjudicated outcomes.