How to assess and manage hypertension during and after pregnancy.

Hypertensive disorders of pregnancy are increasingly important complications of which clinicians should have an up-to-date knowledge to facilitate prompt recognition, diagnosis and management. These disorders affect a growing number of pregnancies worldwide, with incidence rates likely to increase in the future commensurate with increasing maternal age and maternal comorbidities independent of age, with consequent effects on maternal and fetal/neonatal morbidity and mortality rates. This article mainly focuses on management within the UK of these disorders, examining their current working definitions, detection methods and recent developments in screening tool development. The current NICE-recommended strategies for treating these disorders and minimizing their occurrence in pregnancy are also explored. In addition, the association between adverse pregnancy outcome and increased risk of future maternal and offspring cardiovascular disease is described, with comments on future strategies to help minimize these potential risks

Anatomical fat distribution and accumulation and lipotoxicity in lean and obese pregnancy

Maternal obesity has been at the forefront of pregnancy-related research in recent times. The impact of this chronic health condition has been highlighted in reports on maternal mortality (CEMACH, 2007, CEMACH, 2011), where 30% of mothers who died from pregnancy related causes were obese (CEMACH, 2011). The importance of maternal obesity and how it affects maternal adaptation to pregnancy is well documented with obese women exhibiting low grade inflammation, greater coagulability and poorer improvement in vascular function during pregnancy compared to lean women (Stewart et al., 2007a). These findings suggest that obese women display similar characteristics to the non-pregnant adult metabolic syndrome and these attributes may be important in explaining why obese pregnancies have higher rates of obstetric complications including gestational diabetes (GDM) and pre-eclampsia (PET). In non-pregnant adult obesity it has been found that central or truncal adiposity is associated with increased NEFA (non-esterified fatty acids) turnover and ectopic fat (especially liver) deposition. It has been suggested that obese pregnant women may also preferentially gain fat in central depots and this may be the mechanism by which poor vascular improvement and inflammation are initiated. The aims of this thesis were to assess subcutaneous fat accumulation and distribution throughout pregnancy in both lean and OW/OB women. Furthermore this thesis aimed to acquire a better understanding of the impact of anatomical fat deposition on metabolic and vascular function during pregnancy. A final aim was to assess vascular function and evidence of lipotoxicity during pregnancy and test whether the site of fat accumulation and distribution was associated with gestational improvement of vascular function. A longitudinal study was performed and anthropometric data was collected from 26 lean and 16 OW/OB women at three antenatal time points (15, 25 and 35 weeks’ gestation) during pregnancy. Direct measurements of energy metabolism (basal metabolic rate, substrate utilisation, physical activity and diet) were also collected to assess the impact of energy metabolism on fat accumulation and distribution. A comprehensive panel of plasma markers of carbohydrate and lipid metabolism (fasting glucose, fasting insulin, total cholesterol [TC], total triglyceride [TG], high density lipoprotein [HDL] and NEFA) and inflammatory (C-reactive protein [CRP], interleukin-6 [IL6] and tumour necrosis factor alpha [TNF]) were quantitated at each study appointment. Endothelial function was measured using laser Doppler imaging (LDI). Measurement of plasma and urinary biomarkers of endothelial function and lipotoxicity including soluble intracellular adhesion molecule 1 (sICAM-1), soluble vascular adhesion molecule-1 (sVCAM-1), oxidised low density lipoprotein (oxLDL), plasma superoxide and urinary isoprostanes were undertaken. Lean and OW/OB women gained similar amounts of total body weight and fat mass during pregnancy. Only in lean women was there an anatomical preference for site of fat storage and this was in the upper peripheral subcutaneous depots. In healthy OW/OB pregnancy no such anatomical preference of fat deposition was found. The study of energy metabolism found that OW/OB women had higher basal metabolic rate and higher fat oxidation than lean women, whilst lean women had higher rates of carbohydrate oxidation and physical activity than OW/OB women. In the lean and OW/OB groups dietary macronutrient intakes were similar. Overall the parameters of energy metabolism were not associated with overall fat mass accumulation or distribution. During pregnancy, OW/OB women were more insulin resistant and pro-inflammatory (CRP and TNFα) than lean women and lean women had higher concentrations of plasma HDL. Interestingly the lean group had higher plasma concentrations of IL6 which may be a result of higher rates of vascular remodelling and may reflect a physiological rather than pathological process. In both lean and OW/OB pregnancies the gestational increase in subcutaneous adipose depots was not associated with the gestational changes in markers of carbohydrate, lipid or inflammatory profiles. Both lean and OW/OB women exhibited similar gestational improvement in endothelial microvascular function. During pregnancy both groups showed an increase in markers of lipotoxicity but levels were not associated with vascular function. Changes in anatomical subcutaneous fat distribution were also not associated with the changes in vascular function during pregnancy. In conclusion, in pregnancy, only lean women exhibit an anatomical site-specific fat accumulation. Although the OW/OB group displayed some aspects of the metabolic syndrome in general the OW/OB women studied here adapted to pregnancy in a similar way to lean women in terms of vascular function and levels of lipotoxicity. However, visceral adiposity was not assessed and OW/OB women with larger visceral adipose stores may exhibit a more lipotoxic phenotype and more pathological adaptation to pregnancy that may make them susceptible to metabolic complications of pregnancy. This study highlights the heterogeneity of maternal obesity and suggests that further studies into ‘metabolically healthy’ and ‘metabolically unhealthy’ lean and OW/OB women is warranted

Natural gas at thermodynamic equilibrium Implications for the origin of natural gas

It is broadly accepted that so-called 'thermal' gas is the product of thermal cracking, 'primary' thermal gas from kerogen cracking, and 'secondary' thermal gas from oil cracking. Since thermal cracking of hydrocarbons does not generate products at equilibrium and thermal stress should not bring them to equilibrium over geologic time, we would not expect methane, ethane, and propane to be at equilibrium in subsurface deposits. Here we report compelling evidence of natural gas at thermodynamic equilibrium. Molecular compositions are constrained to equilibrium

Lipotoxicity in obese pregnancy and its potential role in adverse pregnancy outcome and obesity in the offspring

Increasing maternal obesity is a challenge that has an impact on all aspects of female reproduction. Lean and obese pregnant women gain similar fat mass, but lean women store fat in the lower-body compartment and obese women in central compartments. In the non-pregnant, central storage of fat is associated with adipocyte hypertrophy and represents a failure to adequately store excess fatty acids, resulting in metabolic dysregulation and ectopic fat accumulation (lipotoxicity). Obese pregnancy is associated with exaggerated metabolic adaptation, endothelial dysfunction and increased risk of adverse pregnancy outcome. We hypothesize that the preferential storage of fat in central rather than ‘safer’ lower-body depots in obese pregnancy leads to lipotoxicity. The combination of excess fatty acids and oxidative stress leads to the production of oxidized lipids, which can be cytotoxic and influence gene expression by acting as ligands for nuclear receptors. Lipid excess and oxidative stress provoke endothelial dysfunction. Oxidized lipids can inhibit trophoblast invasion and influence placental development, lipid metabolism and transport and can also affect fetal developmental pathways. As lipotoxicity has the capability of influencing both maternal endothelial function and placental function, it may link maternal obesity and placentally related adverse pregnancy outcomes such as miscarriage and pre-eclampsia. The combination of excess/altered lipid nutrient supply, suboptimal in utero metabolic environment and alterations in placental gene expression, inflammation and metabolism may also induce obesity in the offspring

Pregnancy and neonatal outcomes of COVID-19: The PAN-COVID study

Objective To assess perinatal outcomes for pregnancies affected by suspected or confirmed SARS-CoV-2 infection. Methods Prospective, web-based registry. Pregnant women were invited to participate if they had suspected or confirmed SARS-CoV-2 infection between 1st January 2020 and 31st March 2021 to assess the impact of infection on maternal and perinatal outcomes including miscarriage, stillbirth, fetal growth restriction, pre-term birth and transmission to the infant. Results Between April 2020 and March 2021, the study recruited 8239 participants who had suspected or confirmed SARs-CoV-2 infection episodes in pregnancy between January 2020 and March 2021. Maternal death affected 14/8197 (0.2%) participants, 176/8187 (2.2%) of participants required ventilatory support. Pre-eclampsia affected 389/8189 (4.8%) participants, eclampsia was reported in 40/ 8024 (0.5%) of all participants. Stillbirth affected 35/8187 (0.4 %) participants. In participants delivering within 2 weeks of delivery 21/2686 (0.8 %) were affected by stillbirth compared with 8/4596 (0.2 %) delivering ≥ 2 weeks after infection (95 % CI 0.3–1.0). SGA affected 744/7696 (9.3 %) of livebirths, FGR affected 360/8175 (4.4 %) of all pregnancies. Pre-term birth occurred in 922/8066 (11.5%), the majority of these were indicated pre-term births, 220/7987 (2.8%) participants experienced spontaneous pre-term births. Early neonatal deaths affected 11/8050 livebirths. Of all neonates, 80/7993 (1.0%) tested positive for SARS-CoV-2. Conclusions Infection was associated with indicated pre-term birth, most commonly for fetal compromise. The overall proportions of women affected by SGA and FGR were not higher than expected, however there was the proportion affected by stillbirth in participants delivering within 2 weeks of infection was significantly higher than those delivering ≥ 2 weeks after infection. We suggest that clinicians’ threshold for delivery should be low if there are concerns with fetal movements or fetal heart rate monitoring in the time around infection

Maternal adipose tissue expansion, a missing link in the prediction of birth weight centile

Context Maternal body mass index (BMI) is associated with increased birth weight but does not explain all the variance in fetal adiposity. Objective To assess the contribution of maternal body fat distribution to offspring birth weight and adiposity. Design Longitudinal study throughout gestation and at delivery. Setting Women recruited at 12 weeks of gestation and followed up at 26 and 36 weeks. Cord blood was collected at delivery. Patients Pregnant women (n = 45) with BMI 18.0 to 46.3 kg/m2 and healthy pregnancy outcome. Methods Maternal first trimester abdominal subcutaneous and visceral adipose tissue thickness (SAT and VAT) was assessed by ultrasound. Main Outcome Measures Maternal body fat distribution, maternal and cord plasma glucose and lipid concentrations, placental weight, birth weight, and fetal adiposity assessed by cord blood leptin. Results VAT was the only anthropometric measure independently associated with birth weight centile (r2 adjusted 15.8%, P = .002). BMI was associated with trimester 2 and trimesters 1 through 3 area under the curve (AUC) glucose and insulin resistance (Homeostatic Model Assessment). SAT alone predicted trimester 2 lipoprotein lipase (LPL) mass (a marker of adipocyte insulin sensitivity) (11.3%, P = .017). VAT was associated with fetal triglyceride (9.3%, P = .047). Placental weight was the only independent predictor of fetal adiposity (48%, P \u3c .001). Maternal trimester 2 and AUC LPL were inversely associated with fetal adiposity (r = -0.69, P = .001 and r = -0.58, P = .006, respectively). Conclusions Maternal VAT provides additional information to BMI for prediction of birth weight. VAT may be a marker of reduced SAT expansion and increased availability of maternal fatty acids for placental transport

Sexualidades intermedias en la prensa colonial hispanoamericana: Tres estudios de caso

Context: Maternal body mass index (BMI) is associated with increased birth weight but does not explain all the variance in fetal adiposity. Objective: To assess the contribution of maternal body fat distribution to offspring birth weight and adiposity. Design: Longitudinal study throughout gestation and at delivery. Setting: Women recruited at 12 weeks of gestation and followed up at 26 and 36 weeks. Cord blood was collected at delivery. Patients: Pregnant women (n=45) with BMI 18.0-46.3 kg/m2 and healthy pregnancy outcome. Methods: Maternal first trimester abdominal subcutaneous and visceral adipose tissue thickness (SAT and VAT) was assessed by ultrasound. Results: VAT was the only anthropometric measure independently associated with birth weight centile (r2 adjusted 15.8%, P=0.002). BMI was associated with trimester 2 and trimester 1 – 3 area under the curve (AUC) glucose and insulin resistance (HOMA). SAT alone predicted trimester 2 lipoprotein lipase (LPL) mass (a marker of adipocyte insulin sensitivity) (11.3%, P=0.017). VAT was associated with fetal triglyceride (9.3%, P=0.047). Placental weight was the only independent predictor of fetal adiposity (48%, P<0.001). Maternal trimester 2 and AUC LPL were inversely associated with fetal adiposity (r=-0.69, P=0.001 and r=-0.58, P=0.006 respectively). Conclusions: Maternal VAT provides additional information to BMI for prediction of birth weight. VAT may be a marker of reduced SAT expansion and increased availability of maternal fatty acids for placental transport