Hyperglycaemia and risk of adverse perinatal outcomes: Systematic review and meta-analysis

Objectives: To assess the association between maternal glucose concentrations and adverse perinatal outcomes in women without gestational or existing diabetes and to determine whether clear thresholds for identifying women at risk of perinatal outcomes can be identified. Design: Systematic review and meta-analysis of prospective cohort studies and control arms of randomised trials. Data sources: Databases including Medline and Embase were searched up to October 2014 and combined with individual participant data from two additional birth cohorts. Eligibility criteria for selecting studies: Studies including pregnant women with oral glucose tolerance (OGTT) or challenge (OGCT) test results, with data on at least one adverse perinatal outcome. Appraisal and data extraction: Glucose test results were extracted for OGCT (50 g) and OGTT (75 g and 100 g) at fasting and one and two hour post-load timings. Data were extracted on induction of labour; caesarean and instrumental delivery; pregnancy induced hypertension; pre-eclampsia; macrosomia; large for gestational age; preterm birth; birth injury; and neonatal hypoglycaemia. Risk of bias was assessed with a modified version of the critical appraisal skills programme and quality in prognostic studies tools. Results: 25 reports from 23 published studies and two individual participant data cohorts were included, with up to 207 172 women (numbers varied by the test and outcome analysed in the meta-analyses). Overall most studies were judged as having a low risk of bias. There were positive linear associations with caesarean section, induction of labour, large for gestational age, macrosomia, and shoulder dystocia for all glucose exposures across the distribution of glucose concentrations. There was no clear evidence of a threshold effect. In general, associations were stronger for fasting concentration than for post-load concentration. For example, the odds ratios for large for gestational age per 1 mmol/L increase of fasting and two hour post-load glucose concentrations (after a 75 g OGTT) were 2.15 (95% confidence interval 1.60 to 2.91) and 1.20 (1.13 to 1.28), respectively. Heterogeneity was low between studies in all analyses. Conclusions: This review and meta-analysis identified a large number of studies in various countries. There was a graded linear association between fasting and post-load glucose concentration across the whole glucose distribution and most adverse perinatal outcomes in women without pre-existing or gestational diabetes. The lack of a clear threshold at which risk increases means that decisions regarding thresholds for diagnosing gestational diabetes are somewhat arbitrary. Research should now investigate the clinical and cost-effectiveness of applying different glucose thresholds for diagnosis of gestational diabetes on perinatal and longer term outcomes

Genetic markers as instrumental variables: an application to child fat mass and academic achievement

Working Pape

Complex structure moduli stability in toroidal compactifications

In this paper we present a classification of possible dynamics of closed string moduli within specific toroidal compactifications of Type II string theories due to the NS-NS tadpole terms in the reduced action. They appear as potential terms for the moduli when supersymmetry is broken due to the presence of D-branes. We particularise to specific constructions with two, four and six-dimensional tori, and study the stabilisation of the complex structure moduli at the disk level. We find that, depending on the cycle on the compact space where the brane is wrapped, there are three possible cases: i) there is a solution inside the complex structure moduli space, and the configuration is stable at the critical point, ii) the moduli fields are driven towards the boundary of the moduli space, iii) there is no stable solution at the minimum of the potential and the system decays into a set of branes.Comment: 24 pages, JHEP3.cls, 19 figures. A few references adde

The identification and treatment of women with hyperglycaemia in pregnancy: an analysis of individual participant data, systematic reviews, meta-analyses and an economic evaluation

Background Gestational diabetes mellitus (GDM) is associated with a higher risk of important adverse outcomes. Practice varies and the best strategy for identifying and treating GDM is unclear. Aim To estimate the clinical effectiveness and cost-effectiveness of strategies for identifying and treating women with GDM. Methods We analysed individual participant data (IPD) from birth cohorts and conducted systematic reviews to estimate the association of maternal glucose levels with adverse perinatal outcomes; GDM prevalence; maternal characteristics/risk factors for GDM; and the effectiveness and costs of treatments. The cost-effectiveness of various strategies was estimated using a decision tree model, along with a value of information analysis to assess where future research might be worthwhile. Detailed systematic searches of MEDLINE® and MEDLINE In-Process & Other Non-Indexed Citations®, EMBASE, Cumulative Index to Nursing and Allied Health Literature Plus, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, Health Technology Assessment database, NHS Economic Evaluation Database, Maternity and Infant Care database and the Cochrane Methodology Register were undertaken from inception up to October 2014. Results We identified 58 studies examining maternal glucose levels and outcome associations. Analyses using IPD alone and the systematic review demonstrated continuous linear associations of fasting and post-load glucose levels with adverse perinatal outcomes, with no clear threshold below which there is no increased risk. Using IPD, we estimated glucose thresholds to identify infants at high risk of being born large for gestational age or with high adiposity; for South Asian (SA) women these thresholds were fasting and post-load glucose levels of 5.2 mmol/l and 7.2 mmol/l, respectively and for white British (WB) women they were 5.4 and 7.5 mmol/l, respectively. Prevalence using IPD and published data varied from 1.2% to 24.2% (depending on criteria and population) and was consistently two to three times higher in SA women than in WB women. Lowering thresholds to identify GDM, particularly in women of SA origin, identifies more women at risk, but increases costs. Maternal characteristics did not accurately identify women with GDM; there was limited evidence that in some populations risk factors may be useful for identifying low-risk women. Dietary modification additional to routine care reduced the risk of most adverse perinatal outcomes. Metformin (Glucophage,® Teva UK Ltd, Eastbourne, UK) and insulin were more effective than glibenclamide (Aurobindo Pharma – Milpharm Ltd, South Ruislip, Middlesex, UK). For all strategies to identify and treat GDM, the costs exceeded the health benefits. A policy of no screening/testing or treatment offered the maximum expected net monetary benefit (NMB) of £1184 at a cost-effectiveness threshold of £20,000 per quality-adjusted life-year (QALY). The NMB for the three best-performing strategies in each category (screen only, then treat; screen, test, then treat; and test all, then treat) ranged between –£1197 and –£1210. Further research to reduce uncertainty around potential longer-term benefits for the mothers and offspring, find ways of improving the accuracy of identifying women with GDM, and reduce costs of identification and treatment would be worthwhile. Limitations We did not have access to IPD from populations in the UK outside of England. Few observational studies reported longer-term associations, and treatment trials have generally reported only perinatal outcomes. Conclusions Using the national standard cost-effectiveness threshold of £20,000 per QALY it is not cost-effective to routinely identify pregnant women for treatment of hyperglycaemia. Further research to provide evidence on longer-term outcomes, and more cost-effective ways to detect and treat GDM, would be valuable

Response to 'Does smoking or alcohol cause early vascular damage in teenage years?'

This commentary refers to ‘Early vascular damage from smoking and alcohol in teenage years: the ALSPAC study’, by M. Charakida et al., 345–353

Conceptual learning : the priority for higher education

The common sense notion of learning as the all-pervasive acquisition of new behaviour and knowledge, made vivid by experience, is an incomplete characterisation, because it assumes that the learning of behaviour and the learning of knowledge are indistinguishable, and that acquisition constitutes learning without reference to transfer. A psychological level of analysis is used to argue that conceptual learning should have priority in higher education

Association of socioeconomic position with maternal pregnancy and infant health outcomes in birth cohort studies from Brazil and the UK

Background: Socioeconomic inequalities in health outcomes are dynamic and vary over time. Differences between countries can provide useful insights into the causes of health inequalities. The study aims to compare the associations between two measures of socioeconomic position (SEP)-maternal education and family income-and maternal and infant health outcomes between ALSPAC and Pelotas cohorts. Methods: Birth cohort studies were started in Avon, UK, in 1991 (ALSPAC) and in the city of Pelotas, Brazil, in 1982, 1993 and 2004. Maternal outcomes included smoking during pregnancy, caesarean section and delivery not attended by a doctor. Infant outcomes were preterm birth, intra-uterine growth restriction (IUGR) and breast feeding for <3 months. The relative index of inequality was used for each measure of SEP so that results were comparable between cohorts. Results: An inverse association (higher prevalence among the poorest and less educated) was observed for almost all outcomes, with the exception of caesarean sections where a positive association was found. Stronger income-related inequalities for smoking and education-related inequalities for breast feeding were found in the ALSPAC study. However, greater inequalities in caesarean section and education-related inequalities in preterm birth were observed in the Pelotas cohorts. Conclusions: Mothers and infants have more adverse health outcomes if they are from poorer and less well-educated socioeconomic backgrounds in both Brazil and the UK. However, our findings demonstrate the dynamic nature of the association between SEP and health outcomes. Examining differential socioeconomic patterning of maternal and infant health outcomes might help understanding of mechanisms underlying such inequalities.A Matijasevich, CG Victora, DA Lawlor, J Golding, AMB Menezes, CL Araújo, AJD Barros, IS Santos, FC Barros, G Davey Smit

Enhanced ionization of the Martian nightside ionosphere during solar energetic particle events

Electron densities in the Martian nightside ionosphere are more than 90% of time too low to be detected by the Mars Advanced Radar for Subsurface and Ionosphere Sounding radar sounder on board the Mars Express spacecraft. However, the relative number of ionograms with peak electron density high enough to be detected represents a good statistical proxy of the ionospheric density. We focus on solar energetic particle (SEP) events, and we analyze their effects on ionospheric formation. SEP time intervals were identified in situ using the background counts recorded by the ion sensor of the ASPERA-3 instrument on board Mars Express. We show that peak electron densities during the SEP events are large enough to be detected in more than 30% of measurements, and, moreover, the reflections of the sounding signal from the ground almost entirely disappear. Nightside electron densities during SEP events are thus substantially increased as compared to normal nightside conditions