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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.)

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.)

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.)

Sleep disordered breathing (SDB) is a common obesity-related co-morbidity with strong associations to cardiometabolic disease. The risk of SDB is increased during pregnancy, particularly among obese pregnant women. Accumulating evidence suggests that an association exists between maternal SDB and the development of adverse pregnancy outcomes, particularly gestational diabetes and hypertensive disorders of pregnancy. Intermittent hypoxia, a central characteristic of SDB, has been shown in animal and clinical studies to dysregulate several biological pathways. This includes the promotion of oxidative stress, increased inflammation, activation of the hypothalamic-pituitary-adrenal axis, increased sympathetic activity and impaired glucose and insulin metabolism. This review considers how, during pregnancy, these pathophysiological processes are plausible mechanisms through which SDB may contribute to an increased risk of adverse outcomes, for the mother and perhaps also the offspring. However, a lack of robust evidence specific to the pregnant population, including limited evaluation of the placental function in affected pregnancies, limits our ability to draw definite conclusions on mechanisms contributing to adverse pregnancy outcomes and, indeed, the strength of association between SDB and certain pregnancy complications., (© 2020 The Authors. Acta Physiologica published by John Wiley & Sons Ltd on behalf of Scandinavian Physiological Society.)

Maternal obesity is the most common metabolic disturbance in pregnancy affecting >1 in 5 women in some countries. Babies born to obese women are heavier with more adiposity at birth, and are vulnerable to obesity and metabolic disease across the lifespan suggesting offspring health is 'programmed' by fetal exposure to an obese intra-uterine environment. The placenta plays a major role in dictating the impact of maternal health on prenatal development. Maternal obesity impacts the function of integral placental receptors and transporters for glucocorticoids and nutrients, key drivers of fetal growth, though mechanisms remain poorly understood. This review aims to summarise current knowledge in this area, and considers the impact of obesity on the epigenetic machinery of the placenta at this vital juncture in offspring development. Further research is required to advance understanding of these areas in the hope that the trans-generational cycle of obesity can be alleviated., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Gestational diabetes mellitus (GDM) is the most common metabolic disturbance during pregnancy. The prevalence is rising and correlates with the increase in maternal obesity over recent decades. The etiology of GDM is complex, with genetic and environmental factors implicated in mechanistic and epidemiological studies. GDM begets important short- and long-term health risks for the mother, developing fetus, and offspring. This includes the high likelihood of subsequent maternal type 2 diabetes (T2DM), and possible adverse cardiometabolic phenotypes in the offspring. The most clinically and cost-effective methods of screening for GDM remain uncertain. Whilst treatments with lifestyle and pharmacological interventions have demonstrated short-term benefits, the long-term impact for the offspring of intrauterine exposure to antidiabetic medication remains unclear., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Aims: Evidence suggests that screening for gestational diabetes (GDM) occurs too late in pregnancy, when changes in glucose metabolism and fetal growth rates can already be detected. In August 2016 NHS Lothian began screening women with risk factors for GDM during early pregnancy (11-13 weeks). We hypothesised that an earlier identification and treatment of dysglycaemia would improve pregnancy outcomes compared to previous standard care., Methods: We compared management and outcomes for singleton pregnancies with GDM delivering at Royal Infirmary Edinburgh, UK, diagnosed through routine or early screening from 01/01/2015-31/10/2017 (routine screening n = 335, early screening n = 241)., Results: Early screening increased the proportion of women diagnosed before 24 weeks' gestation (n = 59/335, 17.6% vs n = 103/241, 42.7%, p < 0.001) but did not change the average monthly rate of diagnosis. Early screening increased the median duration of GDM during pregnancy (71 vs 93 days of gestation, p < 0.001) with no significant changes in the pharmacological management. Early screening improved the primary composite outcome (emergency caesarean section, neonatal hypoglycaemia and macrosomia; n = 138/335, 41.2% vs n = 73/241, 30.3%, adjusted Odds Ratio [95% confidence interval] 0.62 [0.43-0.91]., Conclusions: There is a role for early screening and management of GDM however it is unclear whether this represents a cost-effective intervention., (Copyright © 2018 Elsevier B.V. All rights reserved.)

We present a method for data storage in continuous ferroelectric (FE) media, applicable to storage systems based on one or more scanning probes. Written FE domains are read back in a destructive fashion by applying a constant voltage of magnitude greater than the coercive voltage, as is done in FE random access memory (FeRAM). The resulting flow of screening charges through the readback amplifier provides sufficient signal to allow readback of domains of minimum dimension of the order of 10 nm at MHz rates, orders of magnitude faster than previously demonstrated techniques for readback of domains in continuous FE media.

Cardiac hypertrophy in the guinea-pig is not accompanied by a large shift in the expression of the predominant isoform of myosin in the left ventricle; however, in this species, thin filament proteins do change. We examined the relaxation, following laser flash photolysis of the photolabile caged Ca2+ chelator diazo-2, of a skinned trabecular preparation from the left ventricle of guinea-pigs that had undergone abdominal aortic banding. Sham-operated animals were used as controls; no guinea-pigs showed any signs of heart failure. We report that mild cardiac hypertrophy does not affect the relaxation rate of Triton-skinned trabeculae from the guinea-pig. However, there was a 35% reduction in the maximum force generated by trabeculae from the left ventricle of the abdominal aortic-banded animals. Additionally, alterations in key troponin subunits occur in the left ventricle of guinea-pigs with mild hypertrophy. We conclude that the thin filament protein changes do not influence trabecular relaxation rates, even though they probably affect maximal force generation. The cellular membrane systems of the intact guinea-pig heart, which were not a factor in this present study, appear to have an important role in the altered cardiac relaxation rates seen in hypertrophy.

The aim of this study was to examine the effect of the metabolites H+, ADP, and Pi on the rate of cardiac relaxation. We used guinea pig right ventricular trabeculae that had been chemically skinned, allowing the myofilaments to be studied in isolation. Laser-flash photolysis of the caged Ca2+ chelator diazo 2, causing a rapid fall in intracellular Ca2+, enabled investigation of relaxation independently of the rate of Ca2+ diffusion. On the photolysis of diazo 2, the trabeculae relaxed biphasically with exponential rate constants (k1 and k2) of 10.07 and 4.23 s-1, respectively, at 12 degrees C and 18.35 and 2.52 s-1, respectively, at a nominal 20 degrees C. Increasing the concentration of both protons (pH 7.2-6.8) and MgADP (0.5-3.4 mM) slowed the two phases of the relaxation transients. Raising the concentration of Pi from the control level of 1.36 mM to 15.2 mM increased the rate of both phases, with relaxation becoming monoexponential at 19.4 mM Pi (with a k of 20.31 s-1 at 12 degrees C). Cardiac muscle was compared with skeletal muscle under identical conditions; in cardiac muscle 19.4 mM Pi increased the rate of relaxation, whereas in skeletal muscle this concentration of Pi slowed relaxation. We conclude that the mechanism of relaxation differs between cardiac and skeletal muscle. This study is a direct demonstration of the effects of ATP metabolites on cardiac myofilament processes during relaxation.

Rat models of cardiac hypertrophy are characterised by a shift in left ventricular myosin isoform from V1 (adult) to V3 (foetal), the latter being associated with a slowing of the acto-myosin ATPase rate. The aim of this study was to examine hypertrophy effects on relaxation by investigating a chemically skinned cardiac preparation from the SHR, where all the cellular membranes are rendered non-functional allowing the myofibrils to be studied in isolation. On comparison, following photolysis of the photolabile caged Ca2+ chelator diazo-2, it can be seen that the SHR fibres relax at a slower rate than their age-matched WKY counterparts. We suggest that, since the thin filament regulatory proteins seem not to be affected by cardiac hypertrophy in the rat, this result can be attributed to the shift in left ventricular myosin isoforms. The reduced relaxation rate in the SHR could be the result of a slowing of the dissociation of actin and myosin during the cross-bridge cycle. These results have previously been published in abstract form [1].

In vivo, two effects of beta-adrenergic stimulation in cardiac muscle are phosphorylation of troponin I and an increase in relaxation rate. In vitro, cardiac TnI can be phosphorylated by protein kinase A (PKA). We have used the technique of laser flash photolysis of the calcium chelator diazo-2 to investigate the effect of phosphorylation of TnI on the relaxation rate of skinned trabeculae from the guinea-pig at 12 degrees C. The fibres were phosphorylated by PKA, and double exponential curve fits of the average relaxation transients showed no significant difference between the rate constants of the phosphorylated and control cases. We conclude that TnI phosphorylation has no effect on the rate of relaxation in skinned trabeculae from the guinea-pig following diazo-2 photolysis.