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There is an increase in maternal metabolic burden due to the rise in pregnancies complicated by obesity, gestational diabetes, type 2 diabetes and polycystic ovary syndrome. Metabolic dysfunction during pregnancy is associated with increased risks of long-term morbidity and mortality for women and their offspring. Lifestyle interventions in pregnancy in women at risk of metabolic dysfunction have demonstrated short-term improvements such as reduced gestational weight gain and lowered risk of gestational diabetes. It is not known whether these interventions lead to sustained improvements in the metabolic health of the mother and baby. Pharmacological interventions have also shown benefits for the mother and baby in pregnancy, including improvements in glycaemic control, reduction in gestational weight gain and reduction in large for gestational age infants; however, there remains uncertainty over long-term outcomes for mother and child. Existing studies on interventions targeting metabolic health are limited to selected populations in the preconception and postpartum periods and lack follow-up beyond delivery of the intervention. The COVID-19 pandemic has refocused our attention on the effects of maternal metabolic ill-health that play a role in contributing to premature morbidity and mortality. There is an urgent need for strategies to accurately identify the growing number of women and offspring at risk of long-term adverse metabolic health. Strategies which focus on early identification and risk stratification using individualised risk scores in the pre and inter-conception periods must take priority if we are to target and improve the metabolic health of women and their offspring who are at highest risk.

Introduction: Although ultrasound to determine gestational age is fundamental to the optimum management of pregnancy and is recommended for all women by the World Health Organisation, it remains unavailable to many women in low-income countries where trained practitioners are scarce. This study aimed to evaluate a novel, context-specific education package to teach midwives basic obstetric ultrasound, including the determination of gestational age by measurement of fetal femur length., Methods: The study was conducted across six sites in Malawi in January 2021. Following a virtual "training of the trainers", local teams delivered a 10-day programme encompassing both didactic and "hands on" components. Matched pre and post course tests assessed participants' knowledge of key concepts, with Objective Structured Clinical Examinations used to evaluate practical skills. To achieve a pass, trainees were required to establish the gestational age to within ±7 days of an experienced practitioner and achieve an overall score of >65% on five consecutive occasions. A matched pre and post course survey explored participants' attitudes and confidence in performing ultrasound examinations., Results: Of the 29 midwives who participated, 28 finished the programme and met the criteria specified to pass. 22 midwives completed the matched knowledge tests, with the mean (SD) score increasing from 10.2 (3.3) to 18 (2.5) after training ( P <0.0001). Mean difference 7.9, 95% CI 6.5-9.2. Midwives passed 87% of the Observed Structured Clinical Examinations, establishing the gestational age to within ±7 days of an experienced practitioner in 89% of assessments. Beliefs regarding the importance of antenatal ultrasound increased post course ( p = 0.02), as did confidence in performing ultrasound examinations ( p <0.0001)., Conclusion: This study demonstrates not only that ultrasound-naive practitioners can be taught to perform basic obstetric ultrasound dating scans, confidently and competently, after 10 days of training, but also that local teams can be orientated to successfully deliver the programme virtually. Previous ultrasound training initiatives, while often more comprehensive in their syllabus, have been of considerably longer duration and this is likely to be a barrier to upscaling opportunities. We propose that this focused training increases the potential for widescale and sustainable implementation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Viner, Membe-Gadama, Whyte, Kayambo, Masamba, Makwakwa, Lissauer, Stock, Norman, Reynolds, Magowan, Freyne and Gadama.)

Background: Pregnant women with type 1 diabetes strive for tight glucose targets (3.5-7.8 mmol/L) to minimise the risks of obstetric and neonatal complications. Despite using diabetes technologies including continuous glucose monitoring (CGM), insulin pumps and contemporary insulin analogues, most women struggle to achieve and maintain the recommended pregnancy glucose targets. This study aims to evaluate whether the use of automated closed-loop insulin delivery improves antenatal glucose levels in pregnant women with type 1 diabetes., Methods/design: A multicentre, open label, randomized, controlled trial of pregnant women with type 1 diabetes and a HbA1c of ≥48 mmol/mol (6.5%) at pregnancy confirmation and ≤ 86 mmol/mol (10%) at randomization. Participants who provide written informed consent before 13 weeks 6 days gestation will be entered into a run-in phase to collect 96 h (24 h overnight) of CGM glucose values. Eligible participants will be randomized on a 1:1 basis to CGM (Dexcom G6) with usual insulin delivery (control) or closed-loop (intervention). The closed-loop system includes a model predictive control algorithm (CamAPS FX application), hosted on an android smartphone that communicates wirelessly with the insulin pump (Dana Diabecare RS) and CGM transmitter. Research visits and device training will be provided virtually or face-to-face in conjunction with 4-weekly antenatal clinic visits where possible. Randomization will stratify for clinic site. One hundred twenty-four participants will be recruited. This takes into account 10% attrition and 10% who experience miscarriage or pregnancy loss. Analyses will be performed according to intention to treat. The primary analysis will evaluate the change in the time spent in the target glucose range (3.5-7.8 mmol/l) between the intervention and control group from 16 weeks gestation until delivery. Secondary outcomes include overnight time in target, time above target (> 7.8 mmol/l), standard CGM metrics, HbA1c and psychosocial functioning and health economic measures. Safety outcomes include the number and severity of ketoacidosis, severe hypoglycaemia and adverse device events., Discussion: This will be the largest randomized controlled trial to evaluate the impact of closed-loop insulin delivery during type 1 diabetes pregnancy., Trial Registration: ISRCTN 56898625 Registration Date: 10 April, 2018., (© 2022. The Author(s).)

Introduction: Obstructive sleep apnoea (OSA), a condition characterised by intermittent hypoxia and reoxygenation during sleep, is associated with an increased risk of adverse pregnancy outcomes including gestational diabetes and hypertensive disorders of pregnancy. The biological mechanisms of these associations are poorly understood. The impact of OSA on placental function has not been well characterised., Methods: We performed 3' mRNA sequencing on placenta from women with obesity and OSA (n = 11) and women with obesity and no OSA (n = 9)., Results: After correcting for multiple testing, there were no statistically significant differences in gene expression between OSA and no OSA groups (adjusted p < 0.05). In unadjusted analyses, 101 genes were differentially expressed in OSA compared to no OSA placentae (p < 0.01). In Reactome pathway and GO term analysis, this included downregulation of genes involved in O-linked glycosylation (B3GNT5 and B3GNT8) and Wnt signalling (TRABD2B and FRZB) pathways. In gene set enrichment analysis, genes within 24 pathways had a non-random distribution in OSA compared to no OSA placentae (adjusted p < 0.05). This included an increase in genes relating to the reversible hydration of carbon dioxide in OSA placentae, a potential novel mechanism contributing to the development of adverse pregnancy outcomes in women with OSA., Discussion: There is overall similarity in the placental transcriptome of women with obesity who do and do not have OSA during pregnancy. Alterations in the reversible hydration of carbon dioxide are a potential mechanism contributing to the development of adverse pregnancy outcomes in maternal OSA, however this finding requires validation in larger cohorts., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objectives: To compare, in a population of women with gestational diabetes mellitus (GDM), the time to diagnosis of Type 2 diabetes in those with and without common mental disorder (CMD) (depression and/or anxiety) during pregnancy., Design and Setting: prospective study of the Born in Bradford cohort in Bradford, UK., Participants: 909 women diagnosed with GDM between 2007 and 2010, with linkage to their primary care records until 2017. The exposed population were women with an indicator of CMD during pregnancy in primary care records. The unexposed were those without an indicator., Outcome Measures: Time to diagnosis of type 2 diabetes as indicated by a diagnosis in primary care records., Analysis: time to event analysis using Cox regression was employed. Multiple imputation by chained equations was implemented to handle missing data. Models were adjusted for maternal age, ethnicity, education, preconception CMD and tobacco smoking during pregnancy., Results: 165 women (18%) were diagnosed with type 2 diabetes over a follow-up period of around 10 years. There was no evidence of an effect of antenatal CMD on the development of type 2 diabetes following GDM (adjusted HR 0.95; 95% CI 0.57 to 1.57)., Conclusions: Women with CMD were not at an increased risk of type 2 diabetes following GDM. This is reassuring for women with these co-morbidities but requires replication in other study populations., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Background and Aims: In 2017, the US Food and Drug Administration (FDA) proposed to reduce nicotine in cigarettes to minimally or non-addictive levels. This study qualitatively explored perceptions of nicotine and addiction, both independently and in response to messages communicating about nicotine reduction., Design: Qualitative study using focus groups. Participants described their perceptions of nicotine and addiction and their responses to messages about the nicotine reduction., Setting: Atlanta, GA and San Francisco, CA, USA. Semi-structured focus groups were conducted virtually in Spring 2020., Participants: Exclusive smokers (n = 27), dual users (of cigarettes and electronic cigarettes) (n = 25), former smokers (n = 32) and young adult non-smokers (n = 31)., Measurement: Inductive thematic analysis of transcripts was conducted, and results were compared across smoking status groups., Findings: Participants across all smoking status groups associated nicotine with tobacco products, but consistently misperceived that nicotine caused disease. Perceptions of addiction were largely negative and varied by smoking status. Experienced smokers (exclusive smokers, former smokers and dual users) differentiated tobacco use from other addictions and minimized their own experiences of addiction. Perceptions of addiction across experienced smokers included not only the chemical properties of nicotine, but also the behavioral aspects of tobacco use, including oral fixation, having a smoking routine and response to internal and external cues. In response to messages, many believed that removing the nicotine would not make cigarettes less addictive because of the multi-factorial nature of smoking addiction that includes non-pharmacological cues., Conclusions: Perceptions of nicotine and addiction among non-smokers, former smokers, exclusive smokers and dual users of cigarettes and e-cigarettes vary based on smoking status, but there is a common tendency to believe that nicotine is addictive, that addiction results from more than just nicotine, and that very low nicotine cigarettes will not necessarily reduce the addictiveness of cigarettes., (© 2021 Society for the Study of Addiction.)

Study Objectives: To determine the prevalence of obstructive sleep apnea (OSA) in a cohort of women with class III obesity, and a comparator lean group, in the second and third trimesters of pregnancy. Secondary objectives were to compare characteristics of women with obesity with and without OSA and to assess factors that were predictive of OSA., Methods: We performed a prospective cohort study involving 33 women with class III obesity (mean body mass index 43.5 ± 3.9 kg/m 2 ) and 39 lean women (body mass index 22.0 ± 1.7 kg/m 2 ) with singleton pregnancies. Participants completed 2 level 3 sleep studies between 12-22 weeks and 32-38 weeks gestation. OSA was defined as a respiratory event index ≥ 5 events/h (≥ 3% desaturation criteria). Levels of interleukin-6, glucose, and C-peptide were quantified in maternal blood. Logistic regression analysis was performed to determine predictors of OSA., Results: OSA was identified in 12 (37.5%) and 14 (50.0%) women with obesity and in 1 (2.6%) and 3 (9.1%) lean women in the second and third trimesters, respectively. Women with obesity with OSA were older than those with no OSA but otherwise had similar characteristics. In unadjusted analysis of women with obesity, increased age, body mass index, homeostatic model assessment of insulin resistance, and history of nonsmoking were associated with increased odds of OSA. In multivariable analysis, only increased age remained significantly associated with OSA., Conclusions: OSA is highly prevalent in pregnant women with class III obesity. Further research is required to establish effective management strategies for the growing number of women in this high-risk group., Citation: Johns EC, Hill EA, Williams S, et al. High prevalence of obstructive sleep apnea in pregnant women with class III obesity: a prospective cohort study. J Clin Sleep Med . 2022;18(2):423-432., (© 2022 American Academy of Sleep Medicine.)

Background: Public health officials have classified smoking as a risk factor for COVID-19 disease severity. Smokers generally have less trust in health experts than do nonsmokers, leading to reduced risk perceptions. This study addresses smokers' trust in information sources about COVID-19 and how trust is associated with perceived COVID-19 susceptibility and severity among smokers., Methods and Findings: A nationally representative sample of 1,223 current smokers were surveyed between October and November 2020, indicating their level of trust in COVID-19 information sources, and their perceptions of risk from COVID-19. Multiple differences in trustworthiness emerged; smokers trusted their personal doctor for information about COVID-19 more than other information sources, while news media were generally distrusted. In addition, the FDA was trusted less than the NIH and CDC. Several "trust gaps" were observed, indicating disparities in levels of trust associated with gender, ethnicity, education, and political orientation, which had the strongest association with trust of all factors. Political orientation was also a significant predictor of COVID-19 risk perceptions, but there was no independent effect of political orientation when accounting for trust, which was predictive of all risk perception outcomes., Conclusions: Trusted sources, such as personal doctors, may most effectively convey COVID-19 information across political orientations and sociodemographic groups. News media may be ineffective at informing smokers due to their low credibility. The results suggest that trust may explain the apparent effect of political orientation on COVID-19 risk perceptions. Implications for researchers, communication professionals, and policy makers are discussed., Competing Interests: The authors have declared that no competing interests exist.

Low total energy expenditure (TEE, MJ/d) has been a hypothesized risk factor for weight gain, but repeatability of TEE, a critical variable in longitudinal studies of energy balance, is understudied. We examine repeated doubly labeled water (DLW) measurements of TEE in 348 adults and 47 children from the IAEA DLW Database (mean ± SD time interval: 1.9 ± 2.9 y) to assess repeatability of TEE, and to examine if TEE adjusted for age, sex, fat-free mass, and fat mass is associated with changes in weight or body composition. Here, we report that repeatability of TEE is high for adults, but not children. Bivariate Bayesian mixed models show no among or within-individual correlation between body composition (fat mass or percentage) and unadjusted TEE in adults. For adults aged 20-60 y (N = 267; time interval: 7.4 ± 12.2 weeks), increases in adjusted TEE are associated with weight gain but not with changes in body composition; results are similar for subjects with intervals >4 weeks (N = 53; 29.1 ± 12.8 weeks). This suggests low TEE is not a risk factor for, and high TEE is not protective against, weight or body fat gain over the time intervals tested., (© 2022. The Author(s).)

Background: Reducing preterm birth and stillbirth and improving outcomes for babies born too soon is essential to reduce under-5 mortality globally. In the context of a rapidly evolving evidence base and problems with extrapolating efficacy data from high- to low-income settings, an assessment of the evidence for maternal and newborn interventions specific to low- and middle-income countries (LMICs) is required., Methods: A systematic review of the literature was done. We included all studies performed in LMICs since the Every Newborn Action Plan, between 2013 - 2018, which reported on interventions where the outcome assessed was reduction in preterm birth or stillbirth incidence and/or a reduction in preterm infant neonatal mortality. Evidence was categorised according to maternal or neonatal intervention groups and a narrative synthesis conducted., Results: 179 studies (147 primary evidence studies and 32 systematic reviews) were identified in 82 LMICs. 81 studies reported on maternal interventions and 98 reported on neonatal interventions. Interventions in pregnant mothers which resulted in significant reductions in preterm birth and stillbirth were (i) multiple micronutrient supplementation and (ii) enhanced quality of antenatal care. Routine antenatal ultrasound in LMICs increased identification of fetal antenatal conditions but did not reduce stillbirth or preterm birth due to the absence of services to manage these diagnoses. Interventions in pre-term neonates which improved their survival included (i) feeding support including probiotics and (ii) thermal regulation. Improved provision of neonatal resuscitation did not improve pre-term mortality rates, highlighting the importance of post-resuscitation care. Community mobilisation, for example through community education packages, was found to be an effective way of delivering interventions., Conclusions: Evidence supports the implementation of several low-cost interventions with the potential to deliver reductions in preterm birth and stillbirth and improve outcomes for preterm babies in LMICs. These, however, must be complemented by overall health systems strengthening to be effective. Quality improvement methodology and learning health systems approaches can provide important means of understanding and tackling implementation challenges within local contexts. Further pragmatic efficacy trials of interventions in LMICs are essential, particularly for interventions not previously tested in these contexts., Competing Interests: Competing interests: The authors completed the ICMJE Unified Competing Interest form (available upon request from the corresponding author), and declare no conflicts of interest., (Copyright © 2021 by the Journal of Global Health. All rights reserved.)

Objectives: The COVID-19 pandemic may impact cigarette smokers' behaviors. Among smokers, perceptions about the risks of contracting COVID-19 and the severity of COVID-19 illness likely vary, and perceptions may be associated with individual smoking behavior. Our study measured smokers' perceptions of COVID-19 risks and their association with smoking and quitting outcomes., Methods: A sample of 1,223 U.S. adult cigarette smokers participated in an online survey in October-November 2020 to assess their COVID-19-related risk perceptions and changes in smoking, readiness to quit, and quit attempts during the COVID-19 pandemic., Results: More smokers believed smoking could increase the severity of COVID-19 (43.6%, 95% CI: 40.1, 47.3) than believed smoking makes them more susceptible to COVID-19 (20.0%, 95% CI: 17.2, 23.0.). While there were no associations between perceptions of COVID-19 susceptibility and smoking behaviors or intentions, perceptions of greater smoking-related COVID-19 severity were associated with both higher likelihood of smoking increases (aOR: 2.16, 95% CI: 1.19, 3.93) and greater readiness to quit smoking (aOR: 1.65, 95% CI: 1.18, 2.30). Greater perceptions of general COVID-19 severity were associated with higher likelihood of smoking reductions (aOR: 1.12, 95% CI: 1.02, 1.22), greater readiness to quit smoking (aOR: 1.14, 95% CI: 1.07, 1.22), and higher likelihood of making a quit attempt (aOR: 1.12, 95% CI: 1.04, 1.22)., Conclusions: Smokers' perceptions about COVID-19 severity are related to their smoking behavior and likelihood of making a quit attempt. Providing smokers with accurate information on the relationship between smoking and the severity of COVID-19 may alter smoking behaviors., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Authors.)

Background: Physical activity may be a way to increase and maintain fat-free mass (FFM) in later life, similar to the prevention of fractures by increasing peak bone mass., Objectives: A study is presented of the association between FFM and physical activity in relation to age., Methods: In a cross-sectional study, FFM was analyzed in relation to physical activity in a large participant group as compiled in the International Atomic Energy Agency Doubly Labeled Water database. The database included 2000 participants, age 3-96 y, with measurements of total energy expenditure (TEE) and resting energy expenditure (REE) to allow calculation of physical activity level (PAL = TEE/REE), and calculation of FFM from isotope dilution., Results: PAL was a main determinant of body composition at all ages. Models with age, fat mass (FM), and PAL explained 76% and 85% of the variation in FFM in females and males < 18 y old, and 32% and 47% of the variation in FFM in females and males ≥ 18 y old, respectively. In participants < 18 y old, mean FM-adjusted FFM was 1.7 kg (95% CI: 0.1, 3.2 kg) and 3.4 kg (95% CI: 1.0, 5.6 kg) higher in a very active participant with PAL = 2.0 than in a sedentary participant with PAL = 1.5, for females and males, respectively. At age 18 y, height and FM-adjusted FFM was 3.6 kg (95% CI: 2.8, 4.4 kg) and 4.4 kg (95% CI: 3.2, 5.7 kg) higher, and at age 80 y 0.7 kg (95% CI: -0.2, 1.7 kg) and 1.0 kg (95% CI: -0.1, 2.1 kg) higher, in a participant with PAL = 2.0 than in a participant with PAL = 1.5, for females and males, respectively., Conclusions: If these associations are causal, they suggest physical activity is a major determinant of body composition as reflected in peak FFM, and that a physically active lifestyle can only partly protect against loss of FFM in aging adults., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Understanding the impacts of activity on energy balance is crucial. Increasing levels of activity may bring diminishing returns in energy expenditure because of compensatory responses in non-activity energy expenditures. 1-3 This suggestion has profound implications for both the evolution of metabolism and human health. It implies that a long-term increase in activity does not directly translate into an increase in total energy expenditure (TEE) because other components of TEE may decrease in response-energy compensation. We used the largest dataset compiled on adult TEE and basal energy expenditure (BEE) (n = 1,754) of people living normal lives to find that energy compensation by a typical human averages 28% due to reduced BEE; this suggests that only 72% of the extra calories we burn from additional activity translates into extra calories burned that day. Moreover, the degree of energy compensation varied considerably between people of different body compositions. This association between compensation and adiposity could be due to among-individual differences in compensation: people who compensate more may be more likely to accumulate body fat. Alternatively, the process might occur within individuals: as we get fatter, our body might compensate more strongly for the calories burned during activity, making losing fat progressively more difficult. Determining the causality of the relationship between energy compensation and adiposity will be key to improving public health strategies regarding obesity., Competing Interests: Declaration of interests The authors have no conflicts of interest to declare., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Context: Comprehensive assessment of metabolism in maternal obesity and pregnancy disorders can provide information about the shared maternal-fetal milieu and give insight into both maternal long-term health and intergenerational transmission of disease burden., Objective: To assess levels, profiles, and change in the levels of metabolic measures during pregnancies complicated by obesity, gestational diabetes (GDM), or hypertensive disorders., Design, Setting and Participants: A secondary analysis of 2 study cohorts, PREDO and RADIEL, including 741 pregnant women., Main Outcome Measures: We assessed 225 metabolic measures by nuclear magnetic resonance in blood samples collected at median 13 [interquartile range (IQR) 12.4-13.7], 20 (IQR 19.3-23.0), and 28 (27.0-35.0) weeks of gestation., Results: Across all 3 time points women with obesity [body mass index (BMI) ≥ 30kg/m2] in comparison to normal weight (BMI 18.5-24.99 kg/m2) had significantly higher levels of most very-low-density lipoprotein-related measures, many fatty and most amino acids, and more adverse metabolic profiles. The change in the levels of most metabolic measures during pregnancy was smaller in obese than in normal weight women. GDM, preeclampsia, and chronic hypertension were associated with metabolic alterations similar to obesity. The associations of obesity held after adjustment for GDM and hypertensive disorders, but many of the associations with GDM and hypertensive disorders were rendered nonsignificant after adjustment for BMI and the other pregnancy disorders., Conclusions: This study shows that the pregnancy-related metabolic change is smaller in women with obesity, who display metabolic perturbations already in early pregnancy. Metabolic alterations of obesity and pregnancy disorders resembled each other suggesting a shared metabolic origin., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society.)

Hypothalamic-pituitary-adrenal (HPA) axis dysregulation has been commonly reported in major depressive disorder (MDD), but with considerable heterogeneity of results; potentially due to the predominant use of acute measures of an inherently variable/phasic system. Chronic longer-term measures of HPA-axis activity have yet to be systematically examined in MDD, particularly in relation to brain phenotypes, and in the context of early-life/contemporaneous stress. Here, we utilise a temporally stable measure of cumulative HPA-axis function (hair glucocorticoids) to investigate associations between cortisol, cortisone and total glucocorticoids with concurrent measures of (i) lifetime-MDD case/control status and current symptom severity, (ii) early/current-life stress and (iii) structural neuroimaging phenotypes, in N = 993 individuals from Generation Scotland (mean age = 59.1 yrs). Increased levels of hair cortisol were significantly associated with reduced global and lobar brain volumes with reductions in the frontal, temporal and cingulate regions (β range  = -0.057 to -0.104, all P FDR  < 0.05). Increased levels of hair cortisone were significantly associated with MDD (lifetime-MDD status, current symptoms, and severity; β range  = 0.071 to 0.115, all P FDR  = < 0.05), with early-life adversity (β = 0.083, P = 0.017), and with reduced global and regional brain volumes (global: β = -0.059, P = 0.043; nucleus accumbens: β = -0.075, P FDR  = 0.044). Associations with total glucocorticoids followed a similar pattern to the cortisol findings. In this large community-based sample, elevated glucocorticoids were significantly associated with MDD, with early, but not later-life stress, and with reduced global and regional brain phenotypes. These findings provide important foundations for future mechanistic studies to formally explore causal relationships between early adversity, chronic rather than acute measures of glucocorticoids, and neurobiological associations relevant to the aetiology of MDD., (© 2021. The Author(s).)

Background: Children born preterm (before 37 weeks of gestation) are at risk for several adverse childhood outcomes. Parent priorities for research into these outcomes, and preferences for receiving information about these risks, have not previously been established. Here we report the results of an online survey designed to understand parent priorities for research and their preferences for receiving information about childhood outcomes. Methods: An online survey was circulated through social media and was completed by 148 parents of preterm children between the ages of 0 and 12 years from around the United Kingdom (UK). Survey questions were in the form of rating scale, multiple choice, ranking or open-ended free text questions. Descriptive analysis was applied to the quantitative data. Illustrative quotes were extracted from the qualitative free text data and a subset of these questions were analysed using framework analysis. Results: Parent priorities for research centre around identification of factors which can protect against or improve adverse cognitive or developmental outcomes. The majority of parents would prefer for communication to begin within the first year of the child's life. Parents reported a knowledge gap among health visitors, early years educators and schools. Conclusions: In order to align with parent preferences, research should prioritise identification of protective factors and the development of effective interventions to improve outcomes. Training for health visitors and educational professionals could improve the experiences of families and children., Competing Interests: No competing interests were disclosed., (Copyright: © 2021 Ginnell L et al.)

Context: Human and animal studies suggest that hypothalamic-pituitary-adrenal axis (HPA-A) function may be programmed in utero; however, these findings are inconsistent. Given the powerful metabolic actions of cortisol, it is important to clarify the influence of early life on adult HPA-A function., Objective: To determine the relationship between fetal growth and HPA-A stress response to a psychosocial stressor in young adults., Design: Multigenerational, prospective cohort study (the Raine Study) conducted between 1989 and 1991., Setting: King Edward Memorial Hospital, Perth, Western Australia, Australia., Participants: A total of 917 participants aged 18 years from Gen2 of the Raine Study., Main Outcome Measures: Measures of hypothalamic-pituitary-adrenal axis function before and after exposure to the Trier Social Stress Test., Results: In fully adjusted models, an inverse linear relationship was observed between birthweight and plasma measures of (1) baseline cortisol (β = -0.90%, 95% CI: -1.73 to -0.07; P = 0.03); (2) peak cortisol (β = -0.78%, 95% CI -1.51 to -0.06; P = 0.03); (3) area under the curve with respect to ground (β = -0.89%, 95% CI -1.60 to -0.18; P = 0.01); and (4) adrenal sensitivity (β = -1.02, 95% CI: -1.85 to -0.18; P = 0.02). Similar results were demonstrated for percent optimal birthweight. No consistent quadratic relationships were identified. No associations were found between measures of fetal adiposity and HPA-A function at age 18 years, or fetal growth and HPA-A response pattern. Removal of anticipatory responders from the models substantially attenuated the observed relationships., Conclusion: We observed an inverse linear relationship between fetal growth and HPA-A function at age 18 years. This differs from the inverse parabolic relationship (inverted U curve) reported in adults of advanced age. Altered adrenal sensitivity may underlie this relationship., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Total daily energy expenditure ("total expenditure") reflects daily energy needs and is a critical variable in human health and physiology, but its trajectory over the life course is poorly studied. We analyzed a large, diverse database of total expenditure measured by the doubly labeled water method for males and females aged 8 days to 95 years. Total expenditure increased with fat-free mass in a power-law manner, with four distinct life stages. Fat-free mass-adjusted expenditure accelerates rapidly in neonates to ~50% above adult values at ~1 year; declines slowly to adult levels by ~20 years; remains stable in adulthood (20 to 60 years), even during pregnancy; then declines in older adults. These changes shed light on human development and aging and should help shape nutrition and health strategies across the life span., (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Introduction: Currently, there are only 3 reported cases of central nervous system malignancies in patients with Noonan syndrome in the literature, all of which are intracranial pathologies. To our knowledge, there are no cases of spinal cord glioblastoma multiforme reported in the literature., Case Description: We describe the case of a 12-year-old girl with Noonan syndrome who presented with back pain and new onset neurological deficits and was found to have a spinal cord lesion. T10-L1 laminoplasty with safe maximal resection was done. Postoperative pathological analysis identified this lesion as a high-grade astrocytoma consistent with glioblastoma multiforme., Conclusions: Spinal cord glioblastoma multiforme is a rare occurrence in the general population, particularly in a patient with an underlying diagnosis of Noonan syndrome. Patients with spinal cord tumors can present with a multitude of clinical signs and symptoms and treatment should not be delayed., (Published by Elsevier B.V.)

Hypothalamic-pituitary-gonadal (HPG) axis suppression in exercising women can be caused by low energy availability (EA), but the impact of a real-world, multistressor training environment on reproductive and metabolic function is unknown. This study aimed to characterize reproductive and metabolic adaptation in women undertaking basic military training. A prospective cohort study in women undertaking 11-month initial military training ( n = 47) was carried out. Dynamic low-dose 1-h gonadotrophin-releasing hormone (GnRH) tests were completed after 0 and 7 mo of training. Urine progesterone was sampled weekly throughout. Body composition (dual X-ray absorptiometry), fasting insulin resistance (homeostatic modeling assessment 2, HOMA2), leptin, sex steroids, anti-Müllerian hormone (AMH), and inhibin B were measured after 0, 7, and 11 mo with an additional assessment of body composition at 3 mo. Luteinizing hormone (LH) and follicle-stimulating hormone (FSH) responses were suppressed after 7 mo (both P < 0.001). Among noncontraceptive users ( n = 20), 65% had regular (23-35 days) cycles preenrollment, falling to 24% by 7 mo of training. Of women in whom urine progesterone was measured ( n = 24), 87% of cycles showed no evidence of ovulation. There was little change in AMH, LH, and estradiol, although inhibin B and FSH increased ( P < 0.05). Fat mass fluctuated during training but at month 11 was unchanged from baseline. Fat-free mass did not change. Visceral adiposity, HOMA2, and leptin increased (all P < 0.001). HPG axis suppression with anovulation occurred in response to training without evidence of low EA. Increased insulin resistance may have contributed to the observed pituitary and ovarian dysfunction. Our findings are likely to represent an adaptive response of reproductive function to the multistressor nature of military training. NEW & NOTEWORTHY We characterized reproductive endocrine adaptation to prolonged arduous multistressor training in women. We identified marked suppression of hypothalamic-pituitary-gonadal (HPG) axis function during training but found no evidence of low energy availability despite high energy requirements. Our findings suggest a complex interplay of psychological and environmental stressors with suppression of the HPG axis via activation of the hypothalamic-pituitary adrenal (HPA) axis. The neuroendocrine impact of nonexercise stressors on the HPG axis during arduous training should be considered.

Maternal obesity in pregnancy predicts offspring psychopathology risk in childhood but it remains unclear whether maternal obesity or underweight associate with adult offspring mental disorders. We examined longitudinally whether maternal body mass index (BMI) in pregnancy predicted mental disorders in her offspring and whether the associations differed by offspring birth year among 68,571 mother-child dyads of Aberdeen Maternity and Neonatal Databank, Scotland. The offspring were born 1950-1999. Maternal BMI was measured at a mean 15.7 gestational weeks and classified into underweight, normal weight, overweight, moderate obesity and severe obesity. Mental disorders were identified from nationwide registers carrying diagnoses of all hospitalizations and deaths in Scotland in 1996-2017. We found that maternal BMI in pregnancy was associated with offspring mental disorders in a time-dependent manner: In offspring born 1950-1974, maternal underweight predicted an increased hazard of mental disorders [Hazard Ratio (HR) = 1.74; 95% Confidence Interval (CI) = 1.01-3.00)]. In offspring born 1975-1999, maternal severe obesity predicted increased hazards of any mental (HR 1.60; 95% CI 1.08-2.38) substance use (HR 1.91; 95% CI 1.03-3.57) and schizophrenia spectrum (HR 2.80; 95% CI 1.40-5.63) disorders. Our findings of time-specific associations between maternal prenatal BMI and adult offspring mental disorders may carry important public health implications by underlining possible lifelong effects of maternal BMI on offspring psychopathology., (© 2021. The Author(s).)

STratifying Resilience and Depression Longitudinally (STRADL) is a population-based study built on the Generation Scotland: Scottish Family Health Study (GS:SFHS) resource. The aim of STRADL is to subtype major depressive disorder (MDD) on the basis of its aetiology, using detailed clinical, cognitive, and brain imaging assessments. The GS:SFHS provides an important opportunity to study complex gene-environment interactions, incorporating linkage to existing datasets and inclusion of early-life variables for two longitudinal birth cohorts. Specifically, data collection in STRADL included: socio-economic and lifestyle variables; physical measures; questionnaire data that assesses resilience, early-life adversity, personality, psychological health, and lifetime history of mood disorder; laboratory samples; cognitive tests; and brain magnetic resonance imaging. Some of the questionnaire and cognitive data were first assessed at the GS:SFHS baseline assessment between 2006-2011, thus providing longitudinal measures relevant to the study of depression, psychological resilience, and cognition. In addition, routinely collected historic NHS data and early-life variables are linked to STRADL data, further providing opportunities for longitudinal analysis. Recruitment has been completed and we consented and tested 1,188 participants., Competing Interests: Competing interests: ISP-V and MRM are co-directors of Jericoe Ltd, a company that designs software for the assessment and modification of emotion recognition., (Copyright: © 2021 Habota T et al.)

Bone adapts to unaccustomed, high-impact loading but loses mechanosensitivity quickly. Short periods of military training (≤12 weeks) increase the density and size of the tibia in women. The effect of longer periods of military training, where the incidence of stress fracture is high, on tibial macrostructure and microarchitecture in women is unknown. This observational study recruited 51 women (age 19 to 30 years) at the start of 44 weeks of British Army Officer training. Tibial volumetric bone mineral density (vBMD), geometry, and microarchitecture were measured by high-resolution peripheral quantitative computed tomography (HRpQCT). Scans of the right tibial metaphysis (4% site) and diaphysis (30% site) were performed at weeks 1, 14, 28, and 44. Measures of whole-body areal bone mineral density (aBMD) were obtained using dual-energy X-ray absorptiometry (DXA). Blood samples were taken at weeks 1, 28, and 44, and were analyzed for markers of bone formation and resorption. Trabecular vBMD increased from week 1 to 44 at the 4% site (3.0%, p < .001). Cortical vBMD decreased from week 1 to 14 at the 30% site (-0.3%, p < .001). Trabecular area decreased at the 4% site (-0.4%); trabecular bone volume fraction (3.5%), cortical area (4.8%), and cortical thickness (4.0%) increased at the 4% site; and, cortical perimeter increased at the 30% site (0.5%) from week 1 to 44 (p ≤ .005). Trabecular number (3.5%) and thickness (2.1%) increased, and trabecular separation decreased (-3.1%), at the 4% site from week 1 to 44 (p < .001). Training increased failure load at the 30% site from week 1 to 44 (2.5%, p < .001). Training had no effect on aBMD or markers of bone formation or resorption. Tibial macrostructure and microarchitecture continued to adapt across 44 weeks of military training in young women. Temporal decreases in cortical density support a role of intracortical remodeling in the pathogenesis of stress fracture. © 2021 Crown copyright. Journal of Bone and Mineral Research © 2021 American Society for Bone and Mineral Research (ASBMR). This article is published with the permission of the Controller of HMSO and the Queen's Printer for Scotland., (© 2021 Crown copyright. Journal of Bone and Mineral Research © 2021 American Society for Bone and Mineral Research (ASBMR). This article is published with the permission of the Controller of HMSO and the Queen's Printer for Scotland.)

Introduction: Class III obesity (BMI ≥ 40 kg/m 2 ) during pregnancy predisposes mother and offspring to a range of adverse pregnancy complications and outcomes. Risk profiles vary between pregnancies and are affected by interpregnancy weight gain. We evaluated the risk of adverse outcomes in women with BMI ≥ 40 kg/m 2 in first and second pregnancies, and the impact of interpregnancy weight change on this risk., Materials and Methods: Data were extracted for all women with BMI ≥ 40 kg/m 2 at first antenatal visit, who completed antenatal and delivery care for first and second pregnancies in NHS Lothian between 1/1/2009-31/12/2018. Multiple pregnancies and recipients of bariatric surgery were excluded., Results: 442 pregnancies among 221 women were included. In first pregnancy, median (interquartile range) weight was 117 kg (108.5-126.7), age 28 years (24-31) and BMI 42 kg/m 2 (41.0-44.5), 14.4% had gestational diabetes (GDM), 11.3% had pregnancy-induced hypertension and 44.6% had a post-partum haemorrhage (PPH). 20.8% of babies were large for gestational age (LGA, ≥97% centile at birth). In second pregnancy, women were heavier with a median weight of 119.9 kg (109.0-130.0, p = 0.00) with 19.9% gaining over 10 kg. Women were more likely to develop GDM (21.6%, p = 0.02). Babies were heavier with 40% of babies LGA (p < 0.0001). Interpregnancy weight change had no significant impact on GDM, pregnancy induced hypertension, PPH, perinatal mortality or LGA., Conclusions: In a population of women with BMI ≥ 40 kg/m 2 , pregnancy complications are common and risk is higher in second pregnancy. The interpregnancy period is a critical time to engage women in health improvement and weight loss strategies to maximise outcomes for mother and offspring., (Copyright © 2021 Asia Oceania Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.)

Aims/hypothesis: The aim of this study was to determine the impact of the routine use of serum C-peptide in an out-patient clinic setting on individuals with a clinician-diagnosis of type 1 diabetes., Methods: In this single-centre study, individuals with type 1 diabetes of at least 3 years duration were offered random serum C-peptide testing at routine clinic review. A C-peptide ≥200 pmol/L prompted further evaluation of the individual using a diagnostic algorithm that included measurement of islet cell antibodies and genetic testing. Where appropriate, a trial of anti-diabetic co-therapies was considered., Results: Serum C-peptide testing was performed in 859 individuals (90% of the eligible cohort), of whom 114 (13.2%) had C-peptide ≥200 pmol/L. The cause of diabetes was reclassified in 58 individuals (6.8% of the tested cohort). The majority of reclassifications were to type 2 diabetes (44 individuals; 5.1%), with a smaller proportion of monogenic diabetes (14 individuals; 1.6%). Overall, 13 individuals (1.5%) successfully discontinued insulin, while a further 16 individuals (1.9%) had improved glycaemic control following the addition of co-therapies. The estimated total cost of the testing programme was £23,262 (~€26,053), that is, £27 (~€30) per individual tested. In current terms, the cost of prior insulin therapy in the individuals with monogenic diabetes who successfully stopped insulin was approximately £57,000 (~€64,000)., Conclusions/interpretation: Serum C-peptide testing can easily be incorporated into an out-patient clinic setting and could be a cost-effective intervention. C-peptide testing should be strongly considered in individuals with a clinician-diagnosis of type 1 diabetes of at least 3 years duration., (© 2021 Diabetes UK.)

Introduction: Metformin is among the most frequently prescribed drugs worldwide for a variety of indications. Although metformin has several important advantages, for example being easy to store and administer, it is associated with a high incidence of gastrointestinal side effects. Slower-release formulations of metformin may reduce the incidence of side effects while maintaining efficacy; however, there is a lack of systematic evidence available to guide head-to-head comparisons between different metformin formulations., Methods: PubMed, Web of Science, OVID EMBASE, MEDLINE, The Cochrane database and Clinicaltrials.gov were systematically searched (from inception to 25 January 2021). Trials that randomized adult participants to extended-release formulation of metformin (met-XR), delayed-release (met-DR) or immediate-release metformin (met-IR) were included. Two reviewers independently assessed articles for eligibility and risk-of-bias, with conflicts resolved by a third reviewer. Outcome measures were change in fasting plasma glucose (FPG), glycated haemoglobin (HbA1c), body weight, BMI, lipid profile and side effects. Meta-analyses were conducted using random-effects models., Results: Fifteen studies (n = 3765) met eligibility criteria. There was no significant difference between the efficacy of met-IR, met-XR or met-DR in changing FPG (p = 0.93). A non-significant reduction in mean body weight was observed in individuals randomized to met-XR vs. met-IR (- 1.03 kg, 95% CI - 2.12 to 0.05, p = 0.06). Individuals randomized to met-XR vs. met-IR had lower low-density lipoprotein (LDL) cholesterol levels (- 5.73 mg/dl, 95% CI - 7.91 to - 3.56, p < 0.00001). Gastrointestinal (GI) side effects were markedly reduced in patients randomised to met-DR vs. met-IR (OR 0.45, 95% CI 0.26-0.80, p = 0.006)., Conclusion: Our results demonstrate equal efficacy of longer-acting formulations (met-XR, met-DR) versus immediate-release metformin formulations in terms of glycaemic control. There were insufficient studies available to compare the efficacy of different metformin formulations outside of diabetes care. However met-XR was associated with reduced serum LDL cholesterol concentrations, while met-DR was strongly associated with reduced GI side effects, which could improve drug compliance.

Background: COVID-19 has had a significant impact on the economy, health care, and society as a whole. To prevent the spread of infection, local governments across the United States issued mandatory lockdowns and stay-at-home orders. In the surgical world, elective cases ceased to help "flatten the curve" and prevent the infection from spreading to hospital staff and patients. We explored the effect of the cancellation of these procedures on trainee operative experience at our high-volume, multihospital neurosurgical practice., Methods: Our department cancelled all elective cases starting March 16, 2020, and resumed elective surgical and endovascular procedures on May 11, 2020. We retrospectively reviewed case volumes for 54 days prelockdown and 54 days postlockdown to evaluate the extent of the decrease in surgical volume at our institution. Procedure data were collected and then divided into cranial, spine, functional, peripheral nerve, pediatrics, and endovascular categories., Results: Mean total cases per day in the prelockdown group were 12.26 ± 7.7, whereas in the postlockdown group, this dropped to 7.78 ± 5.5 ( P = 0.01). In the spine category, mean cases per day in the prelockdown group were 3.13 ± 2.63; in the postlockdown group, this dropped to 0.96 ± 1.36 ( P < 0.001). In the functional category, mean cases per day in the prelockdown group were 1.31 ± 1.51, whereas in the postlockdown group, this dropped to 0.11 ± 0.42 ( P < 0.001). For cranial ( P = 0.245), peripheral nerve ( P = 0.16), pediatrics ( P = 0.34), and endovascular ( P = 0.48) cases, the volumes dropped but were not statistically significant decreases., Conclusion: The impact of this outbreak on operative training does appear to be significant based solely on statistics. Although the drop in case volumes during this time can be accounted for by the pandemic, it is important to understand that this is a multifactorial effect. Further studies are needed for these results to be generalizable and to fully understand the effect this pandemic has had on trainee operative experience., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 Surgical Neurology International.)

Adult hair glucocorticoid concentrations reflect months of hypothalamic-pituitary-adrenal axis activity. However, little is known about the determinants of neonatal hair glucocorticoids. We tested associations between perinatal exposures and neonatal hair glucocorticoids. Cortisol and cortisone were measured by LC-MS/MS in paired maternal and infant hair samples collected within 10 days of birth (n = 49 term, n = 47 preterm), with neonatal samples collected at 6-weeks in n = 54 preterm infants. We demonstrate cortisol accumulation in hair increases with fetal maturity, with hair cortisol being higher in term than preterm born infants after delivery (median 401 vs 106 pg/mg; p < 0.001). In term born infants, neonatal hair cortisol is positively associated with maternal hair cortisol concentration (β = 0.240, p = 0.045) and negatively associated with birthweight z-score (β = -0.340, p = 0.006). Additionally, being born without maternal labour is associated with lower hair cortisol concentrations (β = -0.489, p < 0.001) and a lower ratio of cortisol to cortisone (β = -0.484, p = 0.001). In preterm infants, histological chorioamnionitis is associated with a higher cortisol to cortisone ratio in hair (β = 0.459, p = 0.001). In samples collected 6 weeks after preterm birth, hair cortisol concentration is associated with cortisol hair concentrations measured after birth (β = 0.523, p < 0.001), chorioamnionitis (β = 0.250, p = 0.049) and postnatal exposures including intravenous hydrocortisone therapy (β = 0.343, p < 0.007) and neonatal sepsis (β = 0.290, p = 0.017). In summary, neonatal hair cortisol is associated with birth gestation, maternal hair cortisol concentration and fetal growth. Additionally, exposures at delivery are important determinants of hair cortisol, and should be considered in the design of future research investigating how neonatal hair cortisol relates to prenatal exposures or fetal development., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: A negative association between obesity and pregnancy outcomes has been described, as well as between time sedentary and pregnancy outcomes. Most interventions based on physical activity involving obese pregnant women have failed in improving pregnancy outcomes. Exchanging time spent in sedentary activities with time spent in light-intensity activities, performed in a home-based setting, might help morbidly obese pregnant women. We aimed to assess the feasibility of an exercise intervention., Methods: An exercise intervention for morbidly obese pregnant women was designed involving morbidly obese pregnant women. Pregnant women with BMI ≥ 40 kg/m² with 20 or less weeks of gestation were invited to take part in the OPALS Feasibility Study. A home-based approach was employed. Participants were asked to perform the intervention for at least 12 weeks, and to register their performance in an activity diary. After the intervention, participants were asked to return the activity diary and answer a feasibility questionnaire., Results: In the intervention, 28 participants took part. Six women completed the intervention for 12 weeks or more. All declared they intended to keep on doing the intervention. All women reported that the exercises made them feel better., Conclusion: Empowering, and involving morbidly obese pregnant women in taking care of themselves and giving them realistic tasks to do on their own and around their environment helps to increase commitment, as does avoiding the effect of their own weight whilst exercising. A 20% of compliance was observed in this study, which might be explained by the difficulties that pregnancy and excess weight mean. Thus, for future studies, we suggest adding a supervision plan to increase that number.

Background: Type 2 diabetes (T2D) is associated with increased risk of progression to cirrhosis and hepatocellular carcinoma (HCC) in people with chronic liver diseases, particularly non-alcoholic fatty liver disease (NAFLD). However, the absolute risk of progression is low. So, it is crucial to accurately identify patients who would benefit most from hepatology referral and intensified management. Current risk-stratification tools are suboptimal and perform worse in people with diabetes., Aims: To determine whether the addition of complementary biomarker(s) to current NAFLD risk-stratification tools in people with T2D could improve the identification of people who are at increased risk of developing incident cirrhosis or HCC., Methods: The Edinburgh Type 2 diabetes Study (ET2DS) is a cohort study of men and women with T2D ( n  = 1066, age 60-75 at baseline). Cases of cirrhosis and HCC were identified over 11 years of follow-up. Biomarkers were measured at baseline and year 1 and association with incident disease was assessed using logistic regression., Results: Of existing risk-stratification scores tested, the Fibrosis-4 (FIB-4) index and the AST:platelet ratio index (APRI) performed best in this cohort. Addition of hyaluronic acid (cut-point ≥ 50  μ  g/L) to FIB-4 (cut-point ≥ 1.3) maintained a false negative rate of ≤25% and reduced the number of people incorrectly identified as "high risk" for incident disease by ∼50%., Conclusions: The addition of hyaluronic acid to FIB-4 reduced the proportion of people inappropriately identified as "high risk" for development of cirrhosis/HCC in a community population of otherwise asymptomatic people with T2D. These findings require a validation in independent cohorts., Competing Interests: Jonathan A. Fallowfield has served as a consultant or advisory board member for Novartis, Ferring Pharmaceuticals, Macrophage Pharma, Aquilla BioMedical, Galecto Biotech, Caldan Therapeutics, Cypralis, NorthSea Therapeutics, Rallybio, Tectonic, and has received research funding from Novartis and Intercept Pharmaceuticals, outside the submitted work. Peter C. Hayes has served as speaker or on advisory boards for the following AbbVie, BMS, Eisai Ltd, Falk, Ferring, Gilead, Gore, Janssen, Lundbeck, MSD, Norgine, Novartis, ONO Pharmaceuticals, Pfizer and Roche. Joanne R. Morling reports salary support from Diabetes UK for the ET2DS. Rachel M. Williamson reported salary funding by a research grant from Pfizer for 2 years. Brian M. Frier has participated in a Speakers' Bureau for: Lilly, Novo Nordisk, MSD, Sanofi, Roche, and Abbott and has served on advisory boards for Lilly, and Zucara. Mark W.J. Strachan has received consultancy fees from Servier and Novo Nordisk and speaking fees from Napp, Sanofi, Astra Zenica, Merck and Eli Lilly. No other potential conflicts of interest relevant to this article were reported., (© 2021 The Authors. Obesity Science & Practice published by World Obesity and The Obesity Society and John Wiley & Sons Ltd.)

Background: Burnout is a negative workplace syndrome of emotional exhaustion, cynicism, and perceived professional inefficacy that risks the patient-provider relationship, patient care, and physician well-being., Objective: To assimilate the neurosurgical burnout literature in order to classify burnout among domestic and international neurosurgeons and trainees, identify contributory factors, and appraise the impact of wellness programs., Methods: A scoping review identified the available literature, which was reviewed for key factors related to burnout among neurosurgeons. Two researchers queried PubMed, Embase, Google Scholar, Cochrane, and Web of Science for articles on burnout in neurosurgery and reduced 1610 results to 32 articles., Results: A total of 32 studies examined burnout in neurosurgery. A total of 26 studies examined prevalence and 8 studies detailed impact of wellness programs. All were published after 2011. Burnout prevalence was measured mostly through the Maslach Burnout Inventory (n = 21). In 4 studies, participants defined their own understanding of "burnout." Domestically, burnout prevalence was 11.2% to 67% among residents and 15% to 57% among attendings. Among trainees, poor operative experience, poor faculty relationships, and social stressors were burnout risks but not age, sex, or marital status. Among attendings, the literature identified financial or legal concerns, lack of intellectual stimulation, and poor work-life balance as risks. The impact of wellness programs on trainees is unclear but group exercises may offer the most benefit., Conclusion: Noticeable methodological differences in studies on trainee and attending burnout contribute to a wide range of neurosurgery burnout estimates and yield significant knowledge gaps. Environment may have greater impact on trainee burnout than demographics. Wellness programs should emphasize solidarity., (© Congress of Neurological Surgeons 2021.)

Introduction: Sodium-glucose co-transporter 2 inhibitors (SGLT2is) are licensed for the treatment of type 2 diabetes (T2D) and more recently for heart failure with or without diabetes. They have been shown to be safe (from the cardiovascular (CV) perspective) and effective (in terms of glycaemia, and in some cases, in reducing CV events) in extensive randomised controlled trials (RCTs). However, there remain concerns regarding the generalisability of these findings (to those ineligible for RCT participation) and about non-CV safety. For effectiveness, population-based pharmacoepidemiology studies can confirm and extend the findings of RCTs to broader populations and explore safety, for which RCTs are not usually powered, in more detail., Methods: A pre-planned and registered ((International PROSPEctive Register Of Systematic Reviews) PROSPERO registration CRD42019160792) systematic review of population-based studies investigating SGLT2i effectiveness and safety, following Meta-analyses Of Observational Studies in Epidemiology (MOOSE) guidelines was conducted., Results: A total of 37 studies were identified (total n = 1,300,184 adults; total follow-up 910,577 person-years; exposures: SGLT2i class, canagliflozin, dapagliflozin and empagliflozin) exploring CV disease (CVD) outcomes, acute kidney injury (AKI), lower limb amputation (LLA), diabetic ketoacidosis (DKA), bone fracture, urinary tract infection (UTI), genital mycotic infection (GMI), hypoglycaemia, pancreatitis and venous thromboembolism. For CV and mortality outcomes, studies confirmed the associated safety of these drugs and correlated closely with the findings from RCTs, which may extend to primary CVD prevention (major adverse cardiovascular events point estimate range (PER) hazard ratio (HR) 0.78-0.94; hospitalised heart failure PER HR 0.48-0.79). For safety outcomes, SGLT2i exposure was not associated with an increased risk of AKI (PER HR 0.40-0.96), fractures (PER HR 0.87-1.11), hypoglycaemia (PER HR 0.76-2.49) or UTI (PER HR 0.72-0.98). There was a signal for increased association for GMIs (PER HR 2.08-3.15), and possibly for LLA (PER HR 0.74-2.79) and DKA (PER HR 0.96-2.14), but with considerable uncertainty., Conclusion: In T2D, SGLT2is appear safe from the CV perspective and may have associated benefit in primary as well as secondary CVD prevention. For safety, they may be associated with an increased risk of GMI, LLA and DKA, although longer follow-up studies are needed.

Introduction: Low energy availability (EA) may impede adaptation to exercise, suppressing reproductive function and bone turnover. Exercise energy expenditure (EEE) measurements lack definition and consistency. This study aimed to compare EA measured from moderate and vigorous physical activity from accelerometry (EEEmpva) with EA from total physical activity (EEEtpa) from doubly labeled water in women. The secondary aim was to determine the relationship of EA with physical fitness, body composition by dual-energy x-ray absorptiometry, heart rate variability (HRV), and eating behavior (Brief Eating Disorder in Athletes Questionnaire [BEDA-Q])., Methods: This was a prospective, repeated-measures study, assessing EA measures and training adaptation during 11-month basic military training. Forty-seven women (23.9 ± 2.6 yr) completed three consecutive 10-d assessments of EEEmvpa, EEEtpa, and energy intake (EI). EA measures were compared using linear regression and Bland-Altman analyses; relationships of EA with fat mass, HRV, 1.5-mile run times, and BEDA-Q were evaluated using partial correlations., Results: EA from EEEmvpa demonstrated strong agreement with EA from EEEtpa across the measurement range (R2 = 0.76, r = 0.87, P < 0.001) and was higher by 10 kcal·kg-1 FFM·d-1. However, EA was low in absolute terms because of underreported EI. Higher EA was associated with improved 1.5-mile run time (r = 0.28, P < 0.001), fat mass loss (r = 0.38, P < 0.001), and lower BEDA-Q score (r = -0.37, P < 0.001) but not HRV (all P > 0.10)., Conclusion: Accelerometry-based EEE demonstrated validity against doubly labeled water during multistressor training, the difference representing 10 kcal·kg-1 FFM·d-1 EEE from nonexercise activity. Beneficial physical but not autonomic adaptations were associated with higher EA. EAmvpa and BEDA-Q warrant consideration for low EA assessment and screening., (Copyright © 2020 by the American College of Sports Medicine.)

Introduction: Glucagon-like peptide 1 receptor agonists (GLP1RAs) are licensed for the treatment of type 2 diabetes (T2D). They have been shown to be safe (from the cardiovascular (CV) perspective) and effective (in terms of glycaemia, and in some cases, reducing CV events) in extensive randomised controlled trials (RCTs). However, there remain concerns regarding the generalisability of these findings (to those ineligible for RCT participation) and about non-CV safety. For effectiveness, population-based pharmacoepidemiology studies can confirm and extend the findings of RCTs findings to broader populations and explore safety, for which RCTs are not usually powered, in more detail., Method: We did a pre-planned and registered (PROSPERO registration CRD42020165720) systematic review of population-based studies investigating GLP1RA effectiveness and safety, following Meta-analyses Of Observational Studies in Epidemiology (MOOSE) guidelines., Results: A total of 22 studies were identified (including 200,148 participants and 396,457 person-years of follow-up) exploring exposure to GLP1RA class, exenatide and liraglutide (the only individual drugs with treatment effect estimates identified) on mortality, cardiovascular disease (CVD), acute pancreatitis (AP), pancreatic cancer (PC), thyroid cancer (TC), acute renal failure (ARF), diabetic retinopathy (DR), breast cancer (BC) and hypoglycaemia. For CV and mortality outcomes, studies confirmed the associated safety of these drugs. For liraglutide, point estimate (PE) range (PER) major adverse cardiovascular events (MACE) (0.53-0.95) and PER heart failure (0.34-1.22) were similar in direction to the beneficial effect observed in RCTs for MACE but varied widely for heart failure. For safety outcomes, exposure was not associated with AP (PER 0.50-1.17), PC (PER 0.40-1.54), BC (PER 0.90-1.51) or hypoglycaemia (PER 0.59-1.06). Only one study was identified exploring each of TC (no evidence of association, hazard ratio (HR) 1.46, 95% confidence interval (CI) 0.98-2.19), renal outcomes (no evidence of association, HR 0.77, 95% CI 0.42-1.41) and DR (no evidence of association, HR 0.67, 95% CI 0.51-0.90)., Conclusion: In T2D, GLP1RAs appear safe from the CV perspective and (for liraglutide) may have associated benefit in primary as well as secondary CVD prevention. For non-CV safety, GLP1RA exposure was not associated with an increased risk of AP, PC, BC or hypoglycaemia; the other outcomes had too few studies to draw firm conclusions and should be explored further.

The doubly labeled water (DLW) method measures total energy expenditure (TEE) in free-living subjects. Several equations are used to convert isotopic data into TEE. Using the International Atomic Energy Agency (IAEA) DLW database (5,756 measurements of adults and children), we show considerable variability is introduced by different equations. The estimated rCO 2 is sensitive to the dilution space ratio (DSR) of the two isotopes. Based on performance in validation studies, we propose a new equation based on a new estimate of the mean DSR. The DSR is lower at low body masses (<10 kg). Using data for 1,021 babies and infants, we show that the DSR varies non-linearly with body mass between 0 and 10 kg. Using this relationship to predict DSR from weight provides an equation for rCO 2 over this size range that agrees well with indirect calorimetry (average difference 0.64%; SD = 12.2%). We propose adoption of these equations in future studies., Competing Interests: The authors declare no competing interests., (© 2021 The Authors.)

There are many unknowns for pregnant women during the coronavirus disease 2019 (COVID-19) pandemic. Clinical experience of pregnancies complicated with infection by other coronaviruses e.g., Severe Acute Respiratory Syndrome (SARS) and Middle Eastern Respiratory Syndrome, has led to pregnant woman being considered potentially vulnerable to severe SARS-CoV-2 infection. Physiological changes during pregnancy have a significant impact on the immune system, respiratory system, cardiovascular function, and coagulation. These may have positive or negative effects on COVID-19 disease progression. The impact of SARS-CoV-2 in pregnancy remains to be determined, and a concerted, global effort is required to determine the effects on implantation, fetal growth and development, labor, and neonatal health. Asymptomatic infection presents a further challenge regarding service provision, prevention, and management. Besides the direct impacts of the disease, a plethora of indirect consequences of the pandemic adversely affect maternal health, including reduced access to reproductive health services, increased mental health strain, and increased socioeconomic deprivation. In this review, we explore the current knowledge of COVID-19 in pregnancy and highlight areas for further research to minimize its impact for women and their children.

Background: Maternal antenatal stress, including symptoms of depression, anxiety and perceived stress, is associated with mental and behavioral problems in children. Whether it is associated with child mental and behavioral disorders remains uncertain. We examined if maternal antenatal symptoms of depression, anxiety and perceived stress were associated with mental and behavioral disorders in their children, if the associations varied according to gestational week, stress type, fluctuating or consistently high symptoms, and if they were driven by maternal or paternal lifetime mood or anxiety disorders., Methods: 3365 mothers participating in the Prediction and Prevention of Preeclampsia and Intrauterine Growth Restriction (PREDO) study completed the Center for Epidemiologic Studies Depression Scale, the State Anxiety Inventory and the Perceived Stress Scale up to 14 times throughout pregnancy. The Care Register for Health Care provided data on mental and behavioral (including neurodevelopmental) disorders for their children from birth (11/07/2006-07/24/2010) until 12/31/2016 and for parental lifetime mood and anxiety disorders until 12/31/2016., Results: The hazard of any childhood mental and behavioral disorder (HR=1.91, 95% CI: 1.39-2.51) was significantly higher for children whose mothers reported consistently high in comparison to consistently low levels of all types of stress throughout pregnancy. The associations remained significant when adjusted for maternal and paternal lifetime mood and anxiety disorders (and their comorbidity and timing and mood disorder type)., Conclusion: Maternal antenatal stress is associated with higher risk of childhood mental and behavioral disorders. Efforts to reduce maternal antenatal stress should be given a high priority to improve child mental health., (Copyright © 2020. Published by Elsevier B.V.)

Aim: To evaluate the diagnostic and prognostic performance of alternative diagnostic strategies to oral glucose tolerance tests, including random plasma glucose, fasting plasma glucose and HbA 1c , during the COVID-19 pandemic., Methods: Retrospective service data (Cambridge, UK; 17 736 consecutive singleton pregnancies, 2004-2008; 826 consecutive gestational diabetes pregnancies, 2014-2019) and 361 women with ≥1 gestational diabetes risk factor (OPHELIA prospective observational study, UK) were included. Pregnancy outcomes included gestational diabetes (National Institute of Health and Clinical Excellence or International Association of Diabetes and Pregnancy Study Groups criteria), diabetes in pregnancy (WHO criteria), Caesarean section, large-for-gestational age infant, neonatal hypoglycaemia and neonatal intensive care unit admission. Receiver-operating characteristic curves and unadjusted logistic regression were used to compare random plasma glucose, fasting plasma glucose and HbA 1c performance., Results: Gestational diabetes diagnosis was significantly associated with random plasma glucose at 12 weeks [area under the receiver-operating characteristic curve for both criteria 0.81 (95% CI 0.79-0.83)], fasting plasma glucose [National Institute of Health and Clinical Excellence: area under the receiver-operating characteristic curve 0.75 (95% CI 0.65-0.85); International Association of Diabetes and Pregnancy Study Groups: area under the receiver-operating characteristic curve 0.92 (95% CI 0.85-0.98)] and HbA 1c at 28 weeks' gestation [National Institute of Health and Clinical Excellence: 0.83 (95% CI 0.75-0.90); International Association of Diabetes and Pregnancy Study Groups: 0.84 (95% CI 0.77-0.91)]. Each measure predicts some, but not all, pregnancy outcomes studied. At 12 weeks, ~5% of women would be identified using random plasma glucose ≥8.5 mmol/l (sensitivity 42%; specificity 96%) and at 28 weeks using HbA 1c ≥39 mmol/mol (sensitivity 26%; specificity 96%) or fasting plasma glucose ≥5.2-5.4 mmol/l (sensitivity 18-41%; specificity 97-98%)., Conclusions: Random plasma glucose at 12 weeks, and fasting plasma glucose or HbA 1c at 28 weeks identify women with hyperglycaemia at risk of suboptimal pregnancy outcomes. These opportunistic laboratory tests perform adequately for risk stratification when oral glucose tolerance testing is not available., (© 2020 The Authors. Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.)

Objective: The global research group, DIPLOMATIC (Using eviDence, Implementation science, and a clinical trial PLatform to Optimise MATernal and newborn health in low Income Countries), aims to reduce stillbirths and preterm births and optimise outcomes for babies born preterm. Minimum datasets for routine data collection in healthcare facilities participating in DIPLOMATIC (initially in Malawi) were designed to assist understanding of baseline maternal and neonatal care processes and outcomes, and facilitate evaluation of improvement interventions and pragmatic clinical trials., Design: Published and grey literature was reviewed alongside extensive in-country consultation to define relevant clinical best practice guidance, and the existing local data and reporting infrastructure, to identify requirements for the minimum datasets. Data elements were subjected to iterative rounds of consultation with topic experts in Malawi and Scotland, the relevant Malawian professional bodies and the Ministry of Health in Malawi to ensure relevance, validity and feasibility., Setting: Antenatal, maternity and specialist neonatal care in Malawi., Results: The resulting three minimum datasets cover the maternal and neonatal healthcare journey for antenatal, maternity and specialist neonatal care, with provision for effective linkage of records for mother/baby pairs. They can facilitate consistent, precise recording of relevant outcomes (stillbirths, preterm births, neonatal deaths), risk factors and key care processes., Conclusions: Poor quality routine data on care processes and outcomes constrain healthcare system improvement. The datasets developed for implementation in DIPLOMATIC partner facilities reflect, and hence support delivery of, internationally agreed best practice for maternal and newborn care in low-income settings. Informed by extensive consultation, they are designed to integrate with existing local data infrastructure and reporting as well as meeting research data needs. This work provides a transferable example of strengthening data infrastructure to underpin a learning healthcare system approach in low-income settings.DIPLOMATIC is funded by the UK National Institute for Health Research., Competing Interests: Competing interests: SJS reports grants from NIHR HTA, non-financial support from HOLOGIC, non-financial support from PARSAGEN, non-financial support from MEDIX BIOCHEMICA, during the conduct of the study; and SJS declares being a member of the HTA general committee. JN reports membership of the following NIHR boards: Commissioning Priority Review decision-making committee (2015); Health Technology Assessment (HTA) Commissioning Board (2010–2016); HTA Commissioning Sub-Board (Expression of Interest) (2014); HTA Funding Boards Policy Group (2016–2019); HTA General Board (2016–2019); HTA Post-Board funding teleconference (2016–2019); NIHR Clinical Trials Unit Standing Advisory Committee (2018–present); NIHR HTA and Efficacy and Mechanism Evaluation Editorial Board (2014–2019); Pre-exposure Prophylaxis Impact Review Panel (2017). JEN reports being named as Principal Investigator on government and charitable research grants to her institution which aim to improve pregnancy outcome. In the last 3 years, she has provided consultancy to Pharma companies GSK and Dilafor: her institution was remunerated for this. Her institution has received travel and subsistence expenses from Merck to facilitate her speaking at a Merck-sponsored symposium on metformin. She is on Subpanel A1 for REF, and on a Wellcome Trust Science interview panel, and receive personal remuneration for each., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.)

The mechanisms linking maternal stress in pregnancy with infant neurodevelopment in a sexually dimorphic manner are poorly understood. We tested the hypothesis that maternal hypothalamic-pituitary-adrenal axis activity, measured by hair cortisol concentration (HCC), is associated with microstructure, structural connectivity, and volume of the infant amygdala. In 78 mother-infant dyads, maternal hair was sampled postnatally, and infants underwent magnetic resonance imaging at term-equivalent age. We found a relationship between maternal HCC and amygdala development that differed according to infant sex. Higher HCC was associated with higher left amygdala fractional anisotropy (β = 0.677, p=0.010), lower left amygdala orientation dispersion index (β = -0.597, p=0.034), and higher fractional anisotropy in connections between the right amygdala and putamen (β = 0.475, p=0.007) in girls compared to boys. Furthermore, altered amygdala microstructure was only observed in boys, with connectivity changes restricted to girls. Maternal cortisol during pregnancy is related to newborn amygdala architecture and connectivity in a sexually dimorphic manner. Given the fundamental role of the amygdala in the emergence of emotion regulation, these findings offer new insights into mechanisms linking maternal health with neuropsychiatric outcomes of children., Competing Interests: DS, MB, GS, PG, GL, GB, AQ, MT, MB, RR, JB No competing interests declared, (© 2020, Stoye et al.)

Background: Maternal depression and anxiety during pregnancy may enhance fetal exposure to glucocorticoids (GCs) and harm neurodevelopment. We tested whether a novel cross-tissue polyepigenetic biomarker indicative of in utero exposure to GC is associated with mental and behavioral disorders and their severity in children, possibly mediating the associations between maternal prenatal depressive and anxiety symptoms and these child outcomes., Methods: Children (n = 814) from the Prediction and Prevention of Preeclampsia and Intrauterine Growth Restriction (PREDO) study were followed-up from birth to age 7.1-10.7 years. A weighted polyepigenetic GC exposure score was calculated based on the methylation profile of 24 CpGs from umbilical cord blood. Child diagnosis of mental and behavioral disorder (n = 99) and its severity, defined as the number of days the child had received treatment (all 99 had received outpatient treatment and 8 had been additionally in inpatient treatment) for mental or behavioral disorder as the primary diagnosis, came from the Care Register for Health Care. Mothers (n = 408) reported on child total behavior problems at child's age of 2.3-5.8 years and their own depressive and anxiety symptoms during pregnancy (n = 583)., Results: The fetal polyepigenetic GC exposure score at birth was not associated with child hazard of mental and behavioral disorder (HR = 0.82, 95% CI 0.54; 1.24, p = 0.35) or total behavior problems (unstandardized beta = -0.10, 95% CI -0.31; 0.10, p = 0.33). However, for one standard deviation decrease in the polyepigenetic score, the child had spent 2.94 (95%CI 1.59; 5.45, p < 0.001) more days in inpatient or outpatient treatment with any mental and behavioral disorder as the primary diagnosis. Criteria for mediation tests were not met., Conclusions: These findings suggest that fetal polyepigenetic GC exposure score at birth was not associated with any mental or behavioral disorder diagnosis or mother-rated total behavior problems, but it may contribute to identifying children at birth who are at risk for more severe mental or behavioral disorders., Competing Interests: None., (© 2020 The Authors.)

Depression in older adults is associated with decreased physical, cognitive, and social functioning, which in turn, are associated with increased mortality. Research has found that robust social networks can protect against depression, yet it is unclear whether the relationship between social ties and depression is reciprocal. Moreover, links between network connections at different social layers are not well understood. This study uses a representative sample with panel data collected between 2005 and 2016 to identify the influence of social network composition on subsequent depression and explore how various layers of human relationships (e.g., community vs. interpersonal level) influence one another. Results demonstrate multiple links between social connection and depression, and that the evolution of social networks in older adults is complex, with distinct mechanisms leading to positive and negative outcomes. Specifically, community involvement showed consistent benefits in reducing depression. In contrast, intimate partnerships appear to increase susceptibility to depression among older adults through exposure to the severe outcomes of partner loss. In addition, intimate partnerships reduce future interpersonal connections, whereas community involvement increases future interpersonal connections for older adults. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Background: anxiety and depression are common in women with gestational diabetes but it is not clear whether they are more likely to precede the onset of gestational diabetes or to co-occur with it. Our aims were to compare the strength of association between common mental disorders of anxiety and depression (i) before pregnancy and (ii) during pregnancy in women with and without gestational diabetes., Methods: the sample comprised 12,239 women with 13,539 pregnancies from the UK's Born in Bradford cohort. Gestational diabetes was diagnosed by oral glucose tolerance test (OGTT). Indicators of common mental disorders were obtained from linked primary care records. Multivariable robust Poisson and logistic regression were employed. Multiple imputation by chained equations was implemented to handle missing data. Models were adjusted for maternal age, ethnicity, education and obstetric complications. Analyses of common mental disorders during pregnancy were additionally adjusted for maternal smoking, pre-pregnancy BMI, multiple pregnancy and common mental disorders prior to pregnancy., Results: there was no evidence for an association between common mental disorders prior to pregnancy and gestational diabetes (adjusted RR 0.96; 95% CI 0.80,1.15) or between gestational diabetes and common mental disorders during pregnancy (adjusted OR 0.91; 95% CI 0.73,1.12)., Limitations: high levels of deprivation and multi-ethnic composition of the cohort may limit generalisability of these findings to other populations., Conclusions: routine primary care records did not identify an increased risk of gestational diabetes in women with common mental disorders prior to pregnancy or of gestational diabetes in women with common mental disorders during pregnancy., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: The incidence of cirrhosis and hepatocellular carcinoma (HCC) is increased in Type 2 diabetes, primarily secondary to non-alcoholic fatty liver disease (NAFLD). European guidelines recommend screening for NAFLD in Type 2 diabetes. American guidelines, while not advocating a screening protocol, suggest using non-invasive markers of fibrosis for risk-stratification and guiding onward referral., Aims: To test the ability of individual fibrosis scores and the European screening algorithm to predict 11-year incident cirrhosis/HCC in an asymptomatic community cohort of older people with Type 2 diabetes., Methods: The Edinburgh Type 2 Diabetes Study investigated men and women with Type 2 diabetes (n = 1066, aged 60-75 at baseline). Liver markers were measured at baseline and year 1; steatosis and fibrosis markers were calculated according to independently published calculations. During 11 years of follow-up, cases of cirrhosis and HCC were identified., Results: Forty-three out of 1059 participants with no baseline cirrhosis/HCC developed incident disease. All scores were significantly associated with incident liver disease by odds ratio (P < .05). The ability of the risk-stratification tools to accurately identify those who developed incident cirrhosis/HCC was poor with low-positive predictive values (5-46%) and high false-negative and -positive rates (up to 60% and 77%) respectively. When fibrosis risk scores were used in conjunction with the European algorithm, they performed modestly better than when applied in isolation., Conclusions: In a cohort with a moderately low incidence of cirrhosis/HCC, existing risk scores did not reliably identify participants at high risk. Better prediction models for cirrhosis/HCC in people with Type 2 diabetes are required., (© 2020 The Authors. Liver International published by John Wiley & Sons Ltd.)

The Syrian conflict has created approximately five million refugees. Of these, more than one million have settled in Lebanon. This project aimed to determine the prevalence of psychological distress (PD) amongst Syrian refugee mothers compared to a control group of local mothers living in the same informal urban settlement in Beirut. A convenient sample was selected from a primary care center. The General Health Questionnaire-12 items (GHQ-12) was administered to determine PD amongst women who were pregnant within 2 years of the study. Data was analyzed using SPSS. Sixty women were enrolled; 35 were Syrian refugees. All women had PD. The mean GHQ-12 scores were 7.5 and 7.2 for the control and Syrian refugee mothers, respectively. When asked about stressors, 91.7% of the women stated poverty. Syrian refugee women had similar PD as women who were not displaced and did not experience direct war related hostilities.

This study investigates differences in pre- to post-expedition energy expenditure, substrate utilisation and body composition, between the all-male Spear17 (SP-17) and all-female Ice Maiden (IM) transantarctic expeditions (IM: N = 6, 61 days, 1700 km; SP-17: N = 5, 67 days, 1750 km). Energy expenditure and substrate utilisation were measured by a standardised 36 h calorimetry protocol; body composition was determined using air displacement plethysmography. Energy balance calculation were used to assess the physical challenge. There was difference in the daily energy expenditure (IM: 4,939 kcal day -1 ; SP-17: 6,461 kcal day -1 , p = 0.004); differences related to physical activity were small, but statistically significant (IM = 2,282 kcal day -1 ; SP-17 = 3,174 kcal day -1 ; p = 0.004). Bodyweight loss was modest (IM = 7.8%, SP-17 = 6.5%; p > 0.05) as was fat loss (IM = 30.4%, SP-17 = 40.4%; p > 0.05). Lean tissue weight change was statistically significant (IM = - 2.5%, SP-17 = + 1.0%; p = 0.05). No difference was found in resting or sleeping energy expenditure, normalised to lean tissue weight (p > 0.05); nor in energy expenditure when exercising at 80, 100 and 120 steps min -1 , normalised to body weight (p > 0.05). Similarly, no difference was found in the change in normalised substrate utilisation for any of the activities (p > 0.05). Analysis suggested that higher daily energy expenditures for the men in Spear-17 was the result of higher physical demands resulting in a reduced demand for energy to thermoregulate compared to the women in Ice Maiden. The lack of differences between men and women in the change in energy expenditure and substrate utilisation, suggests no sex difference in response to exposure to extreme environments.

Background: Maternal depression during pregnancy increases the risk for adverse developmental outcomes in children. However, the underpinning biological mechanisms remain unknown. We tested whether depression was associated with levels of and change in the inflammatory state during pregnancy, if early pregnancy overweight/obesity or diabetes/hypertensive pregnancy disorders accounted for/mediated these effects, and if depression added to the inflammation that typically accompanies these conditions., Methods: We analyzed plasma high-sensitivity C-reactive protein (hsCRP) and glycoprotein acetyls at three consecutive stages during pregnancy, derived history of depression diagnoses before pregnancy from Care Register for Healthcare (HILMO) (N = 375) and self-reports (N = 347) and depressive symptoms during pregnancy using the Center for Epidemiological Studies Depression Scale completed concurrently to blood samplings (N = 295). Data on early pregnancy body mass index (BMI) and diabetes/hypertensive pregnancy disorders came from medical records., Results: Higher overall hsCRP levels, but not change, during pregnancy were predicted by history of depression diagnosis before pregnancy [HILMO: mean difference (MD) = 0.69 standard deviation (s.d.) units; 95% confidence interval (CI) 0.26-1.11, self-report: MD = 0.56 s.d.; 95% CI 0.17-0.94] and higher depressive symptoms during pregnancy (0.06 s.d. per s.d. increase; 95% CI 0.00-0.13). History of depression diagnosis before pregnancy also predicted higher overall glycoprotein acetyls (HILMO: MD = 0.52 s.d.; 95% CI 0.12-0.93). These associations were not explained by diabetes/hypertensive disorders, but were accounted for and mediated by early pregnancy BMI. Furthermore, in obese women, overall hsCRP levels increased as depressive symptoms during pregnancy increased (p = 0.006 for interaction)., Conclusions: Depression is associated with a proinflammatory state during pregnancy. These associations are mediated by early pregnancy BMI, and depressive symptoms during pregnancy aggravate the inflammation related to obesity.