Cardio-metabolic risk in 5-year-old children prenatally exposed to maternal psychosocial stress: the ABCD study

<p>Abstract</p> <p>Background</p> <p>Recent evidence, both animal and human, suggests that modifiable factors during fetal and infant development predispose for cardiovascular disease in adult life and that they may become possible future targets for prevention. One of these factors is maternal psychosocial stress, but so far, few prospective studies have been able to investigate the longer-term effects of stress in detail, i.e. effects in childhood. Therefore, our general aim is to study whether prenatal maternal psychosocial stress is associated with an adverse cardio-metabolic risk profile in the child at age five.</p> <p>Methods/design</p> <p>Data are available from the Amsterdam Born Children and their Development (ABCD) study, a prospective birth cohort in the Netherlands. Between 2003-2004, 8,266 pregnant women filled out a questionnaire including instruments to determine anxiety (STAI), pregnancy related anxiety (PRAQ), depressive symptoms (CES-D), parenting stress (PDH scale) and work stress (Job Content Questionnaire).</p> <p>Outcome measures in the offspring (age 5-7) are currently collected. These include lipid profile, blood glucose, insulin sensitivity, body composition (body mass index, waist circumference and bioelectrical impedance analysis), autonomic nervous system activity (parasympathetic and sympathetic measures) and blood pressure.</p> <p>Potential mediators are maternal serum cortisol, gestational age and birth weight for gestational age (intrauterine growth restriction). Possible gender differences in programming are also studied.</p> <p>Discussion</p> <p>Main strengths of the proposed study are the longitudinal measurements during three important periods (pregnancy, infancy and childhood), the extensive measurement of maternal psychosocial stress with validated questionnaires and the thorough measurement of the children's cardio-metabolic profile. The availability of several confounding factors will give us the opportunity to quantify the independent contribution of maternal stress during pregnancy to the cardio-metabolic risk profile of her offspring. Moreover, the mediating role of maternal cortisol, intrauterine growth, gestational age and potential gender differences can be explored extensively. If prenatal psychosocial stress is indeed found to be associated with the offspring's cardio-metabolic risk, these results support the statement that primary prevention of cardiovascular disease may start even before birth by reducing maternal stress during pregnancy.</p

Impact of primary kidney disease on the effects of empagliflozin in patients with chronic kidney disease: secondary analyses of the EMPA-KIDNEY trial

Background: The EMPA KIDNEY trial showed that empagliflozin reduced the risk of the primary composite outcome of kidney disease progression or cardiovascular death in patients with chronic kidney disease mainly through slowing progression. We aimed to assess how effects of empagliflozin might differ by primary kidney disease across its broad population. Methods: EMPA-KIDNEY, a randomised, controlled, phase 3 trial, was conducted at 241 centres in eight countries (Canada, China, Germany, Italy, Japan, Malaysia, the UK, and the USA). Patients were eligible if their estimated glomerular filtration rate (eGFR) was 20 to less than 45 mL/min per 1·73 m2, or 45 to less than 90 mL/min per 1·73 m2 with a urinary albumin-to-creatinine ratio (uACR) of 200 mg/g or higher at screening. They were randomly assigned (1:1) to 10 mg oral empagliflozin once daily or matching placebo. Effects on kidney disease progression (defined as a sustained ≥40% eGFR decline from randomisation, end-stage kidney disease, a sustained eGFR below 10 mL/min per 1·73 m2, or death from kidney failure) were assessed using prespecified Cox models, and eGFR slope analyses used shared parameter models. Subgroup comparisons were performed by including relevant interaction terms in models. EMPA-KIDNEY is registered with ClinicalTrials.gov, NCT03594110. Findings: Between May 15, 2019, and April 16, 2021, 6609 participants were randomly assigned and followed up for a median of 2·0 years (IQR 1·5–2·4). Prespecified subgroupings by primary kidney disease included 2057 (31·1%) participants with diabetic kidney disease, 1669 (25·3%) with glomerular disease, 1445 (21·9%) with hypertensive or renovascular disease, and 1438 (21·8%) with other or unknown causes. Kidney disease progression occurred in 384 (11·6%) of 3304 patients in the empagliflozin group and 504 (15·2%) of 3305 patients in the placebo group (hazard ratio 0·71 [95% CI 0·62–0·81]), with no evidence that the relative effect size varied significantly by primary kidney disease (pheterogeneity=0·62). The between-group difference in chronic eGFR slopes (ie, from 2 months to final follow-up) was 1·37 mL/min per 1·73 m2 per year (95% CI 1·16–1·59), representing a 50% (42–58) reduction in the rate of chronic eGFR decline. This relative effect of empagliflozin on chronic eGFR slope was similar in analyses by different primary kidney diseases, including in explorations by type of glomerular disease and diabetes (p values for heterogeneity all &gt;0·1). Interpretation: In a broad range of patients with chronic kidney disease at risk of progression, including a wide range of non-diabetic causes of chronic kidney disease, empagliflozin reduced risk of kidney disease progression. Relative effect sizes were broadly similar irrespective of the cause of primary kidney disease, suggesting that SGLT2 inhibitors should be part of a standard of care to minimise risk of kidney failure in chronic kidney disease. Funding: Boehringer Ingelheim, Eli Lilly, and UK Medical Research Council

Association of childhood adversities and home atmosphere with functioning in old age: the Helsinki birth cohort study

Objectivechildhood adversities have been linked with adverse health outcomes, but less is known about the long-term consequences of childhood home atmosphere. We investigated whether childhood adversities and home atmosphere were associated with physical and mental functioning in older age.Methodsin the Helsinki Birth Cohort Study 2003, participants born in the year 1934�44 had data available on nine childhood home atmosphere items, e.g. whether it was supportive and warm (sum score ranged between 0 and 36, higher score indicating better atmosphere), and nine childhood adversities, e.g. unemployment and divorce (sum score 0�9, coded into no; one; and two or more adversities) assessed in 2001�04. Of those, 835 had data on physical and mental functioning assessed using the Short Form 36 questionnaire in 2011�13.Resultsthose who had experienced two or more childhood adversities were more likely to have poorer physical and mental functioning in older age compared to those with no adversities. A better home atmosphere score was associated with better mental functioning (per one unit higher score β 0.24, 95% CI 0.16�0.32, P &lt; 0.001). In models including both childhood adversities and home atmosphere, a more favourable home atmosphere was associated with better mental functioning while the association for childhood adversities attenuated. There were no associations between childhood adversities or home atmosphere and physical functioning in the models that included both childhood exposures.Conclusionschildhood adversities and home atmosphere have long-term associations with physical and mental functioning in older age.</p

Characterization and testing of LAS: a prototype 'large area sensor' with performance characteristics suitable for medical imaging applications

The Large Area Sensor (LAS) is a 1350 x 1350 array of active pixels on a 40m pitch fabricated in a 0.35m CMOS process. Stitching technology is employed to achieve an area of 5.4 cm x 5.4 cm. The sensor includes 'regions of reset', whereby three different integration times can be set on the array to achieve a large imaging range for static scenes. Characterization of the noise performance included temporal and fixed pattern sources. LAS was found to have a read noise of 62 e -, a full well capacity of 61 x 10 3 e - and a conversion gain of 5 e - per digital number (DN). The fixed pattern noise (FPN) was evaluated at half saturation; within a single stitched section of the array, column-to-column FPN was found to be 0.6, while the pixel-to-pixel FPN was 3. Both FPN sources were found to be gain related and could be corrected via flat fielding. Based on the results of characterization, LAS was coupled to a structured CsI:Tl scintillator and included in an X-ray diffraction system developed for the analysis of breast biopsy samples. Data acquired with plastic test objects agrees with that acquired by a previous prototype sensor. It is demonstrated that an imaging output range of 140 dB can be achieved using integration times of 0.1 ms to record the transmitted X-ray beam and 2.3 s to record the lower intensity scattered radiation. © 2009 IEEE