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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).)

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.)

Introduction: Preterm birth is closely associated with altered brain development and is a leading cause of neurodevelopmental, cognitive and behavioural impairments across the life course. We aimed to investigate neuroanatomic variation and adverse outcomes associated with preterm birth by studying a cohort of preterm infants and controls born at term using brain MRI linked to biosamples and clinical, environmental and neuropsychological data., Methods and Analysis: Theirworld Edinburgh Birth Cohort is a prospective longitudinal cohort study at the University of Edinburgh. We plan to recruit 300 infants born at <33 weeks of gestational age (GA) and 100 healthy control infants born after 37 weeks of GA. Multiple domains are assessed: maternal and infant clinical and demographic information; placental histology; immunoregulatory and trophic proteins in umbilical cord and neonatal blood; brain macrostructure and microstructure from structural and diffusion MRI (dMRI); DNA methylation; hypothalamic-pituitary-adrenal axis activity; social cognition, attention and processing speed from eye tracking during infancy and childhood; neurodevelopment; gut and respiratory microbiota; susceptibility to viral infections; and participant experience. Main analyses include creation of novel methods for extracting information from neonatal structural and dMRI, regression analyses of predictors of brain maldevelopment and neurocognitive outcome associated with preterm birth, and determination of the quantitative predictive performance of MRI and other early life factors for childhood outcome., Ethics and Dissemination: Ethical approval has been obtained from the National Research Ethics Service (NRES), South East Scotland Research Ethics Committee (NRES numbers 11/55/0061 and 13/SS/0143 (phase I) and 16/SS/0154 (phase II)), and NHS Lothian Research and Development (2016/0255). Results are disseminated through open access journals, scientific meetings, social media, newsletters anda study website (www.tebc.ed.ac.uk), and we engage with the University of Edinburgh public relations and media office to ensure maximum publicity and benefit., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.)

Background: The prevalence of sleep problems among pregnant women is over 50%, and daytime sleepiness is among the most common sleep problems. Previous studies have associated antenatal sleep problems with adverse maternal health and neonatal outcomes, but the consequences of antenatal sleep problems and particularly daytime sleepiness on child psychological development have not been assessed prospectively., Methods: In this prospective cohort study including 111 mother-child dyads, we examined the associations of maternal daytime sleepiness during pregnancy, assessed at 17 and 28 weeks of gestation using the Epworth Sleepiness Scale, with child neuropsychiatric problems and neuropsychological development, assessed with mother-rated questionnaires and individually administered neuropsychological tests, at child age 2.6-5.7 years (mean = 4.3 years)., Results: Independently of sociodemographic and perinatal covariates and maternal depressive and anxiety symptoms during and/or after pregnancy, maternal antenatal daytime sleepiness was associated with increased total [unstandardized regression coefficient (B) = 0.25 standard deviation (s.d.) units; 95% confidence interval (CI) 0.01-0.48] and internalizing (B = 0.25 s.d.s: 95% CI 0.01-0.49) psychiatric problems and ADHD symptoms (B = 0.27 s.d.s: 95% CI 0.04-0.50) in children, and with poorer executive function, particularly in the areas of attention, working memory and inhibitory control (B = -0.39 s.d.s: 95% CI -0.69 to -0.10)., Conclusions: Maternal antenatal daytime sleepiness carries adverse consequences for offspring psychological development. The assessment of sleep problems may be an important addition to standard antenatal care.

Aims/hypothesis: Maternal obesity in pregnancy is associated with cardiovascular disease and mortality rate in the offspring. We aimed to determine whether maternal obesity is also associated with increased incidence of type 2 and type 1 diabetes in the offspring, independently of maternal diabetes as a candidate mechanistic pathway., Methods: Birth records of 118,201 children from 1950 to 2011 in the Aberdeen Maternity and Neonatal Databank were linked to Scottish Care Information-Diabetes, the national register for diagnosed diabetes in Scotland, to identify incident and prevalent type 1 and type 2 diabetes up to 1 January 2012. Maternal BMI was calculated from height and weight measured at the first antenatal visit. The effect of maternal obesity on offspring outcomes was tested using time-to-event analysis with Cox proportional hazards regression to compare outcomes in offspring of mothers in underweight, overweight or obese categories of BMI, compared with offspring of women with normal BMI., Results: Offspring of obese (BMI ≥30 kg/m 2 ) and overweight (BMI 25-29.9 kg/m 2 ) mothers had an increased hazard of type 2 diabetes compared with mothers with normal BMI, after adjustment for gestation when weight was measured, maternal history of diabetes before pregnancy, maternal history of hypertension, age at delivery, parity, socioeconomic status, and sex of the offspring: HR 3.48 (95% CI 2.33, 5.06) and HR 1.39 (1.06, 1.83), respectively., Conclusions/interpretation: Maternal obesity is associated with increased incidence of type 2 diabetes in the offspring. Evidence-based strategies that reduce obesity among women of reproductive age and that might reduce the incidence of diabetes in their offspring are urgently required.

Introduction: The optimal surgical approach for caesarean section is uncertain in women with very severe obesity (body mass index (BMI) >40kg/m2). We aimed to assess maternal and surgical predictors of surgical site skin infection (SSSI) in very severely obese women and to undertake an exploratory evaluation of clinical outcomes in women with a supra-panniculus transverse compared to an infra-panniculus transverse skin incision., Material and Methods: Using a retrospective cohort design, case-records were reviewed of very severely obese women with a singleton pregnancy delivered by caesarean between August 2011 and December 2015 (n = 453) in two maternity hospitals in Scotland. Logistic regression analysis was used to determine predictors for SSSI. Outcomes were compared between women who had a supra-panniculus transverse compared to infra-panniculus transverse skin incision., Results: Lower maternal age was predictive of SSSI, with current smoking status and longer wound open times being marginally significant. Maternal BMI, suture method and material demonstrated univariate associations with SSSI but were not independent predictors. Women with a supra-panniculus transverse skin incision were older (32.9 (4.4), vs. 30.6 (5.7), p = 0.002), had higher BMI (49.2 (7.1), vs. 43.3 (3.3), p<0.001), shorter gestation at delivery (days) (267.7 (14.9), vs. 274.8 (14.5), p<0.001) and higher prevalence of gestational diabetes mellitus (42.6% vs. 21.9%, p = 0.002). SSSI rates did not differ between supra-panniculus transverse (13/47; 27.7%) and infra-panniculus transverse (90/406; 22.2%; p = 0.395) skin incisions., Conclusion: SSSI rates are high in very severely obese women following caesarean section, regardless of location of skin incision., Competing Interests: The authors have declared that no competing interests exist.

The process of ovarian aging is influenced by a complex and poorly understood interplay of endocrine, metabolic, and environmental factors. The purpose of this study was to explore the feasibility of using latent class analysis to identify subgroups based on cardiometabolic, psychological, and reproductive parameters of health and to describe patterns of anti-Müllerian hormone levels, a biomarker of the ovarian reserve, within these subgroups. Sixty-nine lean (body mass index [BMI] ⩽ 25 kg/m 2 ) and severely obese (BMI ⩾ 40 kg/m 2 ) postpartum women in Edinburgh, Scotland, were included in this exploratory study. The best fitting model included three classes: Class 1, n = 23 (33.5%); Class 2, n = 30 (42.2%); Class 3, n = 16 (24.3%). Postpartum women with lower ovarian reserve had less favorable cardiometabolic and psychological profiles. Examining the ovarian reserve within distinct subgroups based on parameters of health that affect ovarian aging may facilitate risk stratification in the context of ovarian aging.

One in 5 pregnant women is obese but the impact on later health is unknown. We aimed to determine whether maternal obesity during pregnancy associates with increased premature mortality and later life major cardiovascular events. Maternity records of women who gave birth to their first child between 1950 and 1976 (n=18 873) from the Aberdeen Maternity and Neonatal databank were linked to the National Register of Deaths, Scotland and Scottish Morbidity Record. The effect of maternal obesity at first antenatal visit on death and hospital admissions for cardiovascular events was tested using time-to-event analysis with Cox proportional hazard regression to compare outcomes of mothers in underweight, overweight, or obese body mass index (BMI) categories compared with normal BMI. Median follow-up was at 73 years. All-cause mortality was increased in women who were obese during pregnancy (BMI>30 kg/m(2)) versus normal BMI after adjustment for socioeconomic status, smoking, gestation at BMI measurement, preeclampsia, and low birth weight (hazard ratio, 1.35; 95% confidence interval, 1.02-1.77). In adjusted models, overweight and obese mothers had increased risk of hospital admission for a cardiovascular event (1.16; 1.06-1.27 and 1.26; 1.01-1.57) compared with normal BMI mothers. Adjustment for parity largely unchanged the hazard ratios (mortality: 1.43, 1.09-1.88; cardiovascular events overweight: 1.17, 1.07-1.29; and obese: 1.30, 1.04-1.62). In conclusion, maternal obesity is associated with increased risk of premature death and cardiovascular disease. Pregnancy and early postpartum could represent an opportunity for interventions to identify obesity and reduce its adverse consequences., (© 2015 American Heart Association, Inc.)

Background and Aims: The last study of screening practices for gestational diabetes (GDM) in the UK concluded that a lack of consensus about screening was due to a lack of clinical guidelines. We aimed to determine current practices in Scotland since new guidelines recommended that diagnosis should be made at a lower level of hyperglycaemia., Method and Results: An online questionnaire designed to investigate the screening and management of GDM was distributed to all maternity units in Scotland managing women with GDM (n = 15) for completion by relevant clinical team members. The response rate was 100%. Considerable variation in clinical practice existed between units. Thirteen units (86.7%) had adopted the lower glucose tolerance values for diagnosis of GDM (fasting ≥5.1 mmol/L; 2-h ≥8.5 mmol/L) recommended by the Scottish Intercollegiate Guidelines Network in 2010. Available data from units using this guideline (n = 3) revealed a significant increase in the percentage of women diagnosed with GDM between 2010 and 2012 (2010: 1.28%, 2012: 2.54%; p < 0.0001)., Conclusion: Despite provision of clinical guidelines, there are still inconsistencies in screening and management of GDM in Scotland. If a similar increase in the prevalence of GDM is experienced across Scotland, there will be major implications for health care provision and resource allocation., (© The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.)

Background & Aims: Type 2 diabetes is an established risk factor for the presence and progression of fatty liver. Little is known about the distributions and correlates of hepatic non-invasive biomarkers in community-based populations with diabetes, unselected for liver disease. We aimed to identify the distribution of, and metabolic risk factors associated with serum cytokeratin-18 (CK18) and the Enhanced Liver Fibrosis score (ELF), in a large, representative cohort of people with type 2 diabetes (the Edinburgh Type 2 Diabetes Study, ET2DS)., Methods: Nine hundred and thirty-nine ET2DS participants, aged 60-74 years underwent physical examination including ultrasound for assessment of liver fat. Representative subgroups were assessed for markers of chronic liver disease (CK18 and ELF)., Results: CK18 values ranged from 29-993 U/L (median 102, IQR 76-137 U/L) and ELF scores ranged from 6.9-11.6 (mean 8.9, SD 0.8). Statistically significant associations were found between both biomarkers and a number of metabolic risk factors. Neither CK18 nor ELF was consistently or strongly associated with established hepatic risk factors (alcohol excess, hepatotoxic medication use and positive immunology titres)., Conclusions: We identified the distribution of CK18 and ELF in a large cohort of older people with type 2 diabetes and showed that these markers are associated with an adverse metabolic risk factor profile, although much of the variation in biomarkers remained unexplained. Prospective studies are required to determine the extent to which CK18 and/or ELF predict the development of symptomatic liver disease and to identify additional risk factors which may influence the development of advanced liver disease in people with type 2 diabetes., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objectives: To determine whether maternal obesity during pregnancy is associated with increased mortality from cardiovascular events in adult offspring., Design: Record linkage cohort analysis., Setting: Birth records from the Aberdeen Maternity and Neonatal databank linked to the General Register of Deaths, Scotland, and the Scottish Morbidity Record systems., Population: 37 709 people with birth records from 1950 to present day., Main Outcome Measures: Death and hospital admissions for cardiovascular events up to 1 January 2012 in offspring aged 34-61. Maternal body mass index (BMI) was calculated from height and weight measured at the first antenatal visit. The effect of maternal obesity on outcomes in offspring was tested with time to event analysis with Cox proportional hazard regression to compare outcomes in offspring of mothers in underweight, overweight, or obese categories of BMI compared with offspring of women with normal BMI., Results: All cause mortality was increased in offspring of obese mothers (BMI >30) compared with mothers with normal BMI after adjustment for maternal age at delivery, socioeconomic status, sex of offspring, current age, birth weight, gestation at delivery, and gestation at measurement of BMI (hazard ratio 1.35, 95% confidence interval 1.17 to 1.55). In adjusted models, offspring of obese mothers also had an increased risk of hospital admission for a cardiovascular event (1.29, 1.06 to 1.57) compared with offspring of mothers with normal BMI. The offspring of overweight mothers also had a higher risk of adverse outcomes., Conclusions: Maternal obesity is associated with an increased risk of premature death in adult offspring. As one in five women in the United Kingdom is obese at antenatal booking, strategies to optimise weight before pregnancy are urgently required.

Objective: FFQ are popular instruments for assessing dietary intakes in epidemiological studies but have not been validated for use in severely obese pregnancy. The aim of the present study was to compare nutrient intakes assessed by an FFQ with those obtained from a food diary among severely obese pregnant women., Design: Comparison of an FFQ containing 170 food items and a food diary for 4 d (three weekdays and one weekend day); absolute agreement was assessed using the paired t test and relative agreement by Pearson/Spearman correlation, crossclassification into tertiles and weighted kappa values., Setting: Antenatal metabolic clinic for severely obese women., Subjects: Thirty-one severely obese (BMI at booking ≥ 40.0 kg/m2) and thirty-two lean control (BMI520.0–24.9 kg/m2) pregnant women., Results: The findings showed that nutrient intakes estimated by the FFQ were significantly higher than those from the food diary; average correlation was 0.32 in obese and 0.43 in lean women. A mean of 48.5% of obese and 47.3% of lean women were correctly classified, while 12.9% (obese) and 10.0% (lean) were grossly misclassified. Weighted k values ranged from 20.04 to 0.79 in obese women and from 0.16 to 0.78 in lean women., Conclusions: Overall, the relative agreement between the FFQ and food diary was lower in the obese group than in the lean group, but was comparable with earlier studies conducted in pregnant women. The validity assessments suggest that the FFQ is a useful tool for ranking severely obese pregnant women according to the levels of their dietary intake.

Objective: Both type 2 diabetes and glucocorticoid therapy are highly prevalent. Although people with type 2 diabetes may be more susceptible to adverse effects of glucocorticoids, and it is recommended that glucocorticoid therapy is avoided for fear of worsening glycaemic control, the extent to which this advice is followed and the consequences when glucocorticoids are prescribed are poorly documented. The aim was to assess the characteristics of people with type 2 diabetes prescribed glucocorticoids in a real-world setting and to quantify resulting adverse effects., Design: Cross-sectional cohort study., Methods: Cardiometabolic variables, body fat distribution, cognitive function and mood were studied in the 1066 participants of the Edinburgh Type 2 Diabetes Study, of whom 162 (15%) were taking systemic, topical or inhaled glucocorticoids., Results: Glucocorticoid therapy was more common in women and in smokers but was not avoided in patients with diabetic complications or cardiovascular risk factors. People taking glucocorticoids were more centrally obese with slightly higher HbA1c and total serum cholesterol but were no more likely to have hepatic steatosis or hypertension. Glucocorticoid treatment was associated with substantially lower mood and greater anxiety. Women taking glucocorticoid therapy were twice as likely to report depressive symptoms compared with those not taking treatment. Glucocorticoid therapy was also associated with poorer cognitive function among those with subclinical atherosclerosis, as indicated by low ankle-brachial pressure index., Conclusions: Glucocorticoids are prescribed commonly for people with type 2 diabetes despite being associated with adverse indices of glycaemic control, cardiovascular risk factors, mood and cognitive function.

Objective: Depression in Type 2 diabetes is associated with obesity, cardiovascular disease, and mortality. Leptin is a plausible mediating factor because it has been related to obesity, depression, and cardiovascular disease in nondiabetic populations. We sought to assess whether leptin is related to depressive symptoms in people with Type 2 diabetes., Methods: One thousand fifty-seven subjects (48.5% women, mean [standard deviation] age = 67.9 [4.2] years) with Type 2 diabetes were assessed for depressive symptoms using the Hospital Anxiety and Depression Scale and other clinical variables by interview and physical examination. Plasma leptin was determined by radioimmunoassay. Multiple linear regression was performed to assess the relationship between depressive symptoms and ln leptin while adjusting for other covariates. A mediation analysis was performed to test whether depressive symptoms mediated the relationship between obesity and leptin., Results: In univariate analyses, symptoms of depression were related to leptin in men (r = 0.214, p < .001) and women (r = 0.146, p = .007). When adjusting for other covariates including body mass index, ischemic heart disease, glycated hemoglobin, duration of diabetes, and treatment with antidepressants, insulin, or glucocorticoids, using a hierarchical multiple linear regression, depressive symptoms (ln Hospital Anxiety and Depression Scale-depression score) were significant only in men (B = 0.083, standard error = 0.037, p = .03). In the mediation analysis, depressive symptoms partially mediated the effect of obesity (body mass index) on leptin in men but not in women., Conclusions: There is a sex difference in the relationship between depressive symptoms and leptin in people with Type 2 diabetes, with a positive association in men but not in women. Adipocyte-derived factors are associated with depressive symptoms in Type 2 diabetes.

Objective: Cerebral microvascular disease associated with type 2 diabetes may exacerbate the effects of aging on cognitive function. A considerable homology exists between the retinal and cerebral microcirculations; a hypothesized association between diabetic retinopathy (DR) and cognitive decline was examined in older people with type 2 diabetes., Research Design and Methods: In the population-based Edinburgh Type 2 Diabetes Study, 1,046 men and women aged 60-75 years with type 2 diabetes underwent standard seven-field binocular digital retinal photography and a battery of seven cognitive function tests. A general cognitive ability score (g) was generated by principal components analysis. The Mill-Hill Vocabulary Scale was used to estimate premorbid cognitive ability. DR was graded using a modification of the Early Treatment of Diabetic Retinopathy Scale., Results: After age and sex adjustment, a significant relationship was observed with increasing severity of DR (none, mild, and moderate to severe) for most cognitive measures. Participants with moderate-to-severe retinopathy had the worst g and the worst performances on the individual tests. There was a significant interaction between sex and retinopathy for g. In male subjects, the associations of retinopathy with g (and with tests of verbal fluency, mental flexibility, and processing speed but not memory and nonverbal reasoning) persisted (P < 0.05) when further adjusted for vocabulary (to estimate lifetime cognitive decline), depression, sociodemographic characteristics, cardiovascular risk factors, and macrovascular disease., Conclusions: DR was independently associated with estimated lifetime cognitive decline in older men with type 2 diabetes, supporting the hypothesis that cerebral microvascular disease may contribute to their observed accelerated age-related cognitive decline. A sex interaction with stronger findings in men requires further confirmation.

Context: Increased activity of the hypothalamic-pituitary-adrenal (HPA) axis may underlie the metabolic syndrome, but whether circulating cortisol levels predict cardiovascular end points is less clear. People with type 2 diabetes are at increased cardiovascular disease risk and thus are suitable to study associations of plasma cortisol with cardiovascular risk., Objective: We aimed to assess whether altered HPA axis activity was associated with features of the metabolic syndrome and ischemic heart disease in people with type 2 diabetes., Design and Setting: We conducted a cross-sectional cohort study in the general community, including 919 men and women aged 67.9 (4.2) yr with type 2 diabetes (the Edinburgh Type 2 Diabetes Study)., Intervention: We measured fasting morning plasma cortisol., Main Outcome Measurement: Associations between cortisol levels, features of the metabolic syndrome, obesity, and ischemic heart disease were determined., Results: Elevated plasma cortisol levels were associated with raised fasting glucose and total cholesterol levels (P < 0.001). These findings remained significant after adjustment for potential confounding factors (P < 0.001). Elevated cortisol levels were associated with prevalent ischemic heart disease (>800 vs. <600 nmol/liter; odds ratio, 1.58; P = 0.02). This association remained significant after adjustment for duration and control of diabetes and other cardiovascular risk factors (P = 0.03)., Conclusions: The previously described associations between HPA axis activation and features of the metabolic syndrome are present among people with type 2 diabetes. Elevated plasma cortisol is also associated with a greater prevalence of ischemic heart disease, independent of conventional risk factors. Understanding the role of cortisol in the pathogenesis of ischemic heart disease merits further exploration.

Objective: To determine whether low serum cortisol concentrations are associated with adverse prognosis in patients with acute myocardial infarction. Low serum cortisol concentrations have been associated with adverse prognosis in critical illness of diverse etiology., Design: Nested case-control study., Setting: Prospective cohort study of consecutive patients admitted with acute myocardial infarction to nine Scottish hospitals., Patients: A total of 100 patients who survived 30 days (controls) and 100 patients who died within 30 days (cases)., Measurements and Main Results: Admission cortisol concentrations were lower in patients who died than those who survived (median, 1189 nmol/L vs. 1355 nmol/L; p < .001). A cortisol concentration in the bottom quartile (<1136 nmol/L) was a strong predictor of death within 30 days and remained so after adjustment for age and cardiac troponin concentration (adjusted odds ratio, 8.78; 95% confidence interval, 3.09-24.96; p < .001)., Conclusions: Patients who mount a lesser cortisol stress response to acute myocardial infarction have a poorer early prognosis.

Objective: To determine whether circulating levels of the inflammatory markers C-reactive protein (CRP), interleukin (IL)-6, and tumor necrosis factor (TNF)-alpha are associated with cognitive ability and estimated lifetime cognitive decline in an elderly population with type 2 diabetes., Research Design and Methods: A cross-sectional study of 1,066 men and women aged 60-75 years with type 2 diabetes and living in Lothian, Scotland (the Edinburgh Type 2 Diabetes Study), was performed. Seven cognitive tests were used to measure abilities in memory, nonverbal reasoning, information processing speed, executive function, and mental flexibility. The results were used to derive a general intelligence factor (g). A vocabulary-based test was administered as an estimate of peak prior cognitive ability. Results on the cognitive tests were assessed for statistical association with inflammatory markers measured in a venous blood sample at the time of cognitive testing., Results: Higher IL-6 and TNF-alpha levels were associated with poorer age- and sex-adjusted scores on the majority of the individual cognitive tests. They were also associated with g using standardized regression coefficients -0.074 to -0.173 (P < 0.05). After adjusting for vocabulary, education level, cardiovascular dysfunction, duration of diabetes, and glycemic control, IL-6 remained associated with three of the cognitive tests and with g., Conclusions: In this representative population of people with type 2 diabetes, elevated circulating levels of inflammatory markers were associated with poorer cognitive ability. IL-6 levels were also associated with estimated lifetime cognitive decline.

Objective: To investigate the effect of maternal body mass index (BMI) on minor complications, associated additional medication use during pregnancy and the consequent cost implications., Design: Retrospective analysis of case notes., Setting: Labour wards, tertiary referral hospital, Royal Infirmary Edinburgh, UK. Population Six hundred and fifty-one women with a singleton pregnancy over four separate time periods in 2007 and 2008., Methods: Descriptive statistics, univariate and multivariate logistic regression analysis and cost analysis using standard techniques and inflation indices., Main Outcome Measures: Minor complications, use of medications during pregnancy and consequent incremental costs from the perspective of the National Health Service (NHS)., Results: 42.4% of women were overweight or obese (BMI > or = 25 kg/m(2)). Higher BMI during the first trimester (BMI > or = 30 kg/m(2) compared with BMI < 25 kg/m(2)) was associated with an increased risk of minor complications including symphysis pubis dysfunction (OR 3.97; 95% CI 2.19-7.18), heartburn (OR 2.65; 95% CI 1.42-4.94) and chest infection (OR 8.71; 95% 2.20-34.44) and with drugs used to treat these complications including Gaviscon (OR 3.52; 95% CI 1.78-6.96). The mean incremental (additional) NHS costs per woman for treating minor complications increased with maternal BMI were 15.45 pounds/woman, 17.64 pounds/woman and 48.66 pounds/woman for BMI < 25 kg/m(2), BMI > or = 25 to <30 kg/m(2) and BMI > or = 30 kg/m(2) respectively., Conclusions: Increased maternal BMI is associated with increased risk of developing minor complications during pregnancy; use of medications associated with treating these conditions and has significant NHS costs.

Objective: The incidence of thyroid cancer is increasing in several countries. The aim was to investigate trends in the incidence and mortality of thyroid cancer in Scotland, where thyroid cancer is relatively uncommon, between 1960 and 2002., Design: Descriptive epidemiological study., Methods: Thyroid cancer registrations between 1960 and 2000 were obtained from the Scottish Cancer Registry. Mortality data (1960-2002) and population estimates were supplied by the Registrar General for Scotland. Incidence and mortality data are expressed as age-specific rates and European age-standardized rates (EASRs)., Results: Thyroid cancer was three times more common in females than in males and was more common in older than younger age groups. Between 1960 and 2000, the annual EASR of thyroid cancer increased from 1.76 to 3.54 per 100,000 for females (P < 0.001) and from 0.83 to 1.25 per 100,000 in males (P < 0.001). The overall thyroid cancer increase between 1975 and 2000 was primarily caused by an increase in papillary thyroid cancer, particularly over the most recent decade. The incidence of follicular thyroid cancer also increased while the incidence of anaplastic and medullary thyroid cancer did not change significantly. Mortality from thyroid cancer fell progressively between 1960 and 2002. EASR for females decreased from 1.05 to 0.28 (P < 0.001) and in males from 0.73 to 0.34 (P < 0.001). For both sexes, in general, survival at 1-, 5- and 10-year follow-up intervals from diagnosis improved steadily over the study period. In both females and males, survival from thyroid cancer was better if the diagnosis was made under the age of 50 years., Conclusions: Thyroid cancer incidence has increased in Scotland over the past 40 years. This is accompanied by a change in the distribution of histological type with a particular increase in papillary carcinoma. The reasons for this may relate partly to changes in clinical practice and histological criteria. Falling mortality in the face of increasing incidence reflects improvements in survival, which should improve further with the introduction and implementation of standardized treatment protocols.