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Find video protocols related to scientific articles indexed in Pubmed.
Obesity in pregnancy: could lifestyle interventions work?
BMC Med
PUBLISHED: 10-03-2014
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The increased prevalence of obesity has led to major health care issues in obstetric practice. Nevertheless, despite a major international effort, there is little evidence for interventions which can improve clinical outcome. Two reports from the LIMIT randomised controlled trial of more than 2,000 overweight and obese women, recently reported in BMC Medicine, show how a lifestyle intervention in Australian women changes dietary and physical activity behaviours without any evidence of harm to the health of the newborn infant and with some suggestion of benefit. The improvements in maternal lifestyle, albeit modest, may account for a previously reported reduction in the number of macrosomic infants born to LIMIT participants randomised to the intervention arm of the trial.Please see related articles: http://www.biomedcentral.com/1741-7015/12/161 and http://www.biomedcentral.com/1741-7015/12/163.
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Influences on adherence to diet and physical activity recommendations in women and children: insights from six European studies.
Ann. Nutr. Metab.
PUBLISHED: 10-02-2014
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Across Europe, poor health behaviours are associated with increased risks of non-communicable diseases. There is particular concern about young women, children and families, not least as health behaviours operating before and during pregnancy and in early postnatal life may have profound long-term consequences for children's health. Using findings drawn from 7 European countries, we aimed to identify barriers to the implementation and uptake of dietary and physical activity recommendations, and to consider how best to achieve changes in mothers' behaviours and thereby improve the adoption of health recommendations. Six studies across the 7 countries were used for this narrative synthesis of findings. Key Messages: A woman's education has a strong influence on her own and her children's health behaviours. Women's diets vary across ethnic groups and according to number of children, but psychological factors, such as self-efficacy and sense of control, which may be amenable to modification, are powerful, too, particularly in women with lower educational attainment. Maternal influences on children's behaviours are strong. Differences exist in infant feeding across countries, and there are apparent urban/rural differences in children's diets and physical activity.
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Association between Physical Activity in Obese Pregnant Women and Pregnancy Outcomes: The UPBEAT Pilot Study.
Ann. Nutr. Metab.
PUBLISHED: 10-02-2014
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Obesity in pregnancy is associated with fetal macrosomia, a raised neonatal fat mass and an increased risk of obesity and poor metabolic health in childhood which persists into adulthood. The offspring of obese women are more likely to be obese than the offspring of lean women when they become pregnant themselves, perpetuating a cycle of obesity and its associated negative metabolic consequences. Increasing physical activity during pregnancy could improve insulin sensitivity and reduce the risk of maternal and offspring adverse outcomes. The UK Pregnancy Better Eating and Activity Trial (UPBEAT) is a trial of a complex intervention designed to improve pregnancy outcomes through dietary changes and physical activity. Data from the pilot trial of 183 women were available for analysis. The relationship between the time spent at different physical activity levels and maternal and infant pregnancy outcomes was examined. Key Messages: Strong evidence exists that physical activity improves insulin sensitivity in non-pregnant populations, and lifestyle interventions of proven effectiveness in non-pregnant populations have been developed. Women who are active in pregnancy demonstrate better glucose control and favourable pregnancy outcomes. There is a lack of effective interventions to support obese pregnant women to be physically active.
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Dietary recommendations for obese pregnant women: current questions and controversies.
Acta Obstet Gynecol Scand
PUBLISHED: 09-12-2014
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With the increasing prevalence of obesity, maternal obesity is now one of the most common high-risk obstetric conditions. Obesity and excessive gestational weight gain are important modifiable risk factors for maternal and neonatal morbidity and mortality. Maternal obesity, associated with neonatal adiposity and high birthweight, has been implicated in increased risk of childhood obesity. Considerable effort has been directed towards improving clinical outcomes by lifestyle change in pregnant obese women, but there is at present no evidence-based intervention of adequate efficacy which can be recommended. The focus has been on preventing excessive weight gain, but studies have lacked the power to address effects on clinical outcomes; therefore preventing clinical practice translation. Adequately powered intervention studies devised to reduce neonatal adiposity by improvement of maternal glucose homeostasis, are needed to inform the optimal dietary and/or physical activity regimen.
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Early pregnancy prediction of preeclampsia in nulliparous women, combining clinical risk and biomarkers: the Screening for Pregnancy Endpoints (SCOPE) international cohort study.
Hypertension
PUBLISHED: 08-15-2014
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More than half of all cases of preeclampsia occur in healthy first-time pregnant women. Our aim was to develop a method to predict those at risk by combining clinical factors and measurements of biomarkers in women recruited to the Screening for Pregnancy Endpoints (SCOPE) study of low-risk nulliparous women. Forty-seven biomarkers identified on the basis of (1) association with preeclampsia, (2) a biological role in placentation, or (3) a role in cellular mechanisms involved in the pathogenesis of preeclampsia were measured in plasma sampled at 14 to 16 weeks' gestation from 5623 women. The cohort was randomly divided into training (n=3747) and validation (n=1876) cohorts. Preeclampsia developed in 278 (4.9%) women, of whom 28 (0.5%) developed early-onset preeclampsia. The final model for the prediction of preeclampsia included placental growth factor, mean arterial pressure, and body mass index at 14 to 16 weeks' gestation, the consumption of ?3 pieces of fruit per day, and mean uterine artery resistance index. The area under the receiver operator curve (95% confidence interval) for this model in training and validation cohorts was 0.73 (0.70-0.77) and 0.68 (0.63-0.74), respectively. A predictive model of early-onset preeclampsia included angiogenin/placental growth factor as a ratio, mean arterial pressure, any pregnancy loss <10 weeks, and mean uterine artery resistance index (area under the receiver operator curve [95% confidence interval] in training and validation cohorts, 0.89 [0.78-1.0] and 0.78 [0.58-0.99], respectively). Neither model included pregnancy-associated plasma protein A, previously reported to predict preeclampsia in populations of mixed parity and risk. In nulliparous women, combining multiple biomarkers and clinical data provided modest prediction of preeclampsia.
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Study protocol: differential effects of diet and physical activity based interventions in pregnancy on maternal and fetal outcomes-individual patient data (IPD) meta-analysis and health economic evaluation.
Syst Rev
PUBLISHED: 07-09-2014
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Pregnant women who gain excess weight are at risk of complications during pregnancy and in the long term. Interventions based on diet and physical activity minimise gestational weight gain with varied effect on clinical outcomes. The effect of interventions on varied groups of women based on body mass index, age, ethnicity, socioeconomic status, parity, and underlying medical conditions is not clear. Our individual patient data (IPD) meta-analysis of randomised trials will assess the differential effect of diet- and physical activity-based interventions on maternal weight gain and pregnancy outcomes in clinically relevant subgroups of women.
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Obesity and mental disorders during pregnancy and postpartum: a systematic review and meta-analysis.
Obstet Gynecol
PUBLISHED: 05-03-2014
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To evaluate the prevalence and risk of antenatal and postpartum mental disorders among obese and overweight women.
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No global consensus: a cross-sectional survey of maternal weight policies.
BMC Pregnancy Childbirth
PUBLISHED: 04-25-2014
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Growing evidence suggests that maternal prepregnancy weight and gestational weight gain are risk factors for perinatal complications and subsequent maternal and child health. Postpartum weight retention is also associated with adverse birth outcomes and maternal obesity. Clinical guidelines addressing healthy weight before, during, and after pregnancy have been introduced in some countries, but at present a systematic accounting for these policies has not been conducted. The objective of the present study was to conduct a cross-national comparison of maternal weight guidelines.
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Chronic hypertension and pregnancy outcomes: systematic review and meta-analysis.
BMJ
PUBLISHED: 04-17-2014
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To provide an accurate assessment of complications of pregnancy in women with chronic hypertension, including comparison with population pregnancy data (US) to inform pre-pregnancy and antenatal management strategies.
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Strategy for standardization of preeclampsia research study design.
Hypertension
PUBLISHED: 03-31-2014
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Preeclampsia remains a major problem worldwide for mothers and babies. Despite intensive study, we have not been able to improve the management or early recognition of preeclampsia. At least part of this is because of failure to standardize the approach to studying this complex syndrome. It is possible that within the syndrome there may be different phenotypes with pathogenic pathways that differ between the subtypes. The capacity to recognize and to exploit different subtypes is of obvious importance for prediction, prevention, and treatment. We present a strategy for research to study preeclampsia, which will allow discrimination of such possible subtypes and also allow comparison and perhaps combinations of findings in different studies by standardized data and biosample collection. To make studies relevant to current clinical practice, the definition of preeclampsia can be that currently used and accepted. However, more importantly, sufficient data should be collected to allow other diagnostic criteria to be used and applied retrospectively. To that end, we present what we consider to be the minimum requirements for a data set in a study of preeclampsia that will facilitate comparisons. We also present a comprehensive or optimal data set for in-depth investigation of pathophysiology. As we approach the definition of phenotypes of preeclampsia by clinical and biochemical criteria, adherence to standardized protocols will hasten our understanding of the causes of preeclampsia and development of targeted treatment strategies.
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Diet-induced obesity in mice reduces placental efficiency and inhibits placental mTOR signaling.
Physiol Rep
PUBLISHED: 02-01-2014
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As in humans, obesity during pregnancy in mice results in elevated maternal insulin levels and metabolic programming of offspring. mTOR signaling regulates amino acid transport and may function as a placental nutrient sensor. Because obesity is a condition with increased nutrient availability, we hypothesized that diet-induced obesity activates placental mTOR signaling. To test this hypothesis, female C57BL/6J mice were fed an obesogenic diet or standard chow prior to and throughout pregnancy. Fetuses and placentas were collected at gestational day 18. Using Western blot analysis, placental mTOR activity was determined along with energy, inflammatory, and insulin signaling pathways (upstream modulators of mTOR). At gestational day 18, fetal and placental weights did not differ, however, in obese dams, the fetal/placental weight ratio was lower (P <0.01). In placentas from obese dams, mTOR signaling was inhibited, as determined by decreased Rheb and S6K1 expression, and lower rpS6 phosphorylation (P <0.05). In contrast, energy, inflammatory, and insulin signaling pathways were unaffected. Contrary to our hypothesis, diet-induced obesity in pregnant mice was associated with inhibition of placental mTOR signaling. However, this finding is consistent with the lower fetal/placental weight ratio, indicating reduced placental efficiency.
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A complex intervention to improve pregnancy outcome in obese women; the UPBEAT randomised controlled trial.
BMC Pregnancy Childbirth
PUBLISHED: 01-28-2014
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Despite the widespread recognition that obesity in pregnant women is associated with adverse outcomes for mother and child, there is no intervention proven to reduce the risk of these complications. The primary aim of this randomised controlled trial is to assess in obese pregnant women, whether a complex behavioural intervention, based on changing diet (to foods with a lower glycemic index) and physical activity, will reduce the risk of gestational diabetes (GDM) and delivery of a large for gestational age (LGA) infant. A secondary aim is to determine whether the intervention lowers the long term risk of obesity in the offspring.
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Risk factors for excessive gestational weight gain in a healthy, nulliparous cohort.
J Obes
PUBLISHED: 01-09-2014
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Excessive gestational weight gain (GWG) is associated with adverse maternal and child outcomes and contributes to obesity in women. Our aim was to identify early pregnancy factors associated with excessive GWG, in a contemporary nulliparous cohort.
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Non-alcoholic fatty pancreas disease pathogenesis: a role for developmental programming and altered circadian rhythms.
PLoS ONE
PUBLISHED: 01-01-2014
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Emerging evidence suggests that maternal obesity (MO) predisposes offspring to obesity and the recently described non-alcoholic fatty pancreas disease (NAFPD) but involved mechanisms remain unclear. Using a pathophysiologically relevant murine model, we here investigated a role for the biological clock--molecular core circadian genes (CCG) in the generation of NAFPD.
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Association between maternal alcohol consumption in early pregnancy and pregnancy outcomes.
Obstet Gynecol
PUBLISHED: 10-03-2013
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To investigate the association between alcohol consumption and binge drinking before and during early pregnancy and adverse pregnancy outcomes.
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Pregnancy loss managed by cervical dilatation and curettage increases the risk of spontaneous preterm birth.
Hum. Reprod.
PUBLISHED: 09-19-2013
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Do women with a previous miscarriage or termination of pregnancy have an increased risk of spontaneous preterm birth and is this related to previous cervical dilatation and curettage?
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Experimental hyperleptinemia in neonatal rats leads to selective leptin responsiveness, hypertension, and altered myocardial function.
Hypertension
PUBLISHED: 07-08-2013
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The prevalence of obesity among pregnant women is increasing. Evidence from human cohort studies and experimental animals suggests that offspring cardiovascular and metabolic function is compromised through early life exposure to maternal obesity. Previously, we reported that juvenile offspring of obese rats develop sympathetically mediated hypertension associated with neonatal hyperleptinemia. We have now addressed the hypothesis that neonatal exposure to raised leptin in the immediate postnatal period plays a causal role. Pups from lean Sprague-Dawley rats were treated either with leptin (3 mg/kg IP) or with saline twice daily from postnatal day 9 to 15 to mimic the exaggerated postnatal leptin surge observed in offspring of obese dams. Cardiovascular function was assessed by radiotelemetry at 30 days, and 2 and 12 months. In juvenile (30 days) leptin-treated rats, hearts were heavier and night-time (active period) systolic blood pressure was raised (mm Hg; mean ± SEM: male leptin-treated, 132 ± 1 versus saline-treated, 119 ± 1, n=6, P<0.05; female leptin-treated, 132 ± 2 versus saline-treated, 119 ± 1, n=6, P<0.01), and the pressor response to restraint stress and leptin challenge increased compared with saline-treated rats. Heart rate variability demonstrated an increased low:high frequency ratio in 30-day leptin-treated animals, indicative of heightened sympathetic efferent tone. Echocardiography showed altered left ventricular structure and systolic function in 30-day female leptin versus saline-treated rats. These disorders persisted to adulthood. In isolated hearts, contractile function was impaired at 5 months in male leptin-treated rats. Exogenously imposed hyperleptinemia in neonatal rats permanently influences blood pressure and cardiac structure and function.
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Maternal obesity programs offspring nonalcoholic fatty liver disease by innate immune dysfunction in mice.
Hepatology
PUBLISHED: 05-31-2013
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The global prevalence of obesity-induced liver disease (nonalcoholic fatty liver disease; NAFLD) is rising. Suggested causes include a role for in utero influences of maternal obesity compounded by the availability of energy-dense foods throughout postnatal life. Using a physiologically relevant model, we investigated the role of the innate immune system in liver injury induced by maternal obesity followed by a postnatal obesogenic diet. Female C57BL/6J mice were fed a standard or obesogenic diet before and throughout pregnancy and during lactation. Female offspring were weaned onto a standard or obesogenic diet at 3 weeks postpartum. Biochemical and histological indicators of dysmetabolism, NAFLD and fibrosis, analysis of profibrotic pathways, liver innate immune cells, and reactive oxygen species (ROS) were investigated at 3, 6, and 12 months. Female offspring exposed to a postweaning obesogenic diet (OffCon-OD) demonstrated evidence of liver injury, which was exacerbated by previous exposure to maternal obesity (OffOb-OD), as demonstrated by raised alanine aminotransferase, hepatic triglycerides, and hepatic expression of interleukin (IL)-6, tumor necrosis factor alpha, transforming growth factor beta, alpha smooth muscle actin, and collagen (P < 0.01). Histological evidence of hepatosteatosis and a more-robust NAFLD phenotype with hepatic fibrosis was observed at 12 months in OffOb-OD. A role for the innate immune system was indicated by increased Kupffer cell numbers with impaired phagocytic function and raised ROS synthesis (P < 0.01), together with reduced natural killer T cells and raised interleukin (IL)-12 and IL-18. Conclusion: Maternal obesity in the context of a postnatal hypercalorific obesogenic diet aggressively programs offspring NAFLD associated with innate immune dysfunction, resulting in a comprehensive phenotype that accurately reflects the human disease.
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Developing a complex intervention for diet and activity behaviour change in obese pregnant women (the UPBEAT trial); assessment of behavioural change and process evaluation in a pilot randomised controlled trial.
BMC Pregnancy Childbirth
PUBLISHED: 03-07-2013
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Complex interventions in obese pregnant women should be theoretically based, feasible and shown to demonstrate anticipated behavioural change prior to inception of large randomised controlled trials (RCTs). The aim was to determine if a) a complex intervention in obese pregnant women leads to anticipated changes in diet and physical activity behaviours, and b) to refine the intervention protocol through process evaluation of intervention fidelity.
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Sucrose feeding in mouse pregnancy leads to hypertension, and sex-linked obesity and insulin resistance in female offspring.
Front Physiol
PUBLISHED: 01-18-2013
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Eating an unbalanced diet during pregnancy may induce long-term health consequences in offspring, in particular obesity, insulin resistance, and hypertension. We tested the hypothesis that a maternal diet rich in simple sugars predispose mouse offspring to obesity, glucose intolerance, and cardiovascular diseases in adulthood. Female C57BL/6J mice were fed either a standard chow or a sucrose-rich diet (26% of total energy) 6 weeks prior to mating, throughout pregnancy and lactation. Offspring of control dams (OC) and high sucrose fed dams (OSF) were weaned onto standard control chow, and metabolic and cardiovascular parameters determined at 3 months of age. Both male and female OSF were hyperphagic by 4 weeks of age and females were heavier than OC at 6 weeks. At 3 months, female OSF showed a significant increase in inguinal fat pad mass, whereas skeletal muscle mass (tibialis anterior) and locomotor activity were decreased relative to OC. A 10-fold increase in fasting serum insulin in female OSF vs. OC at 3 months (Insulin [pmol/L] mean ± SEM, OSF, 200.3 ± 16.1, vs. OC, 20.3 ± 1.8, n = 6 P < 0.001), was associated with impaired glucose tolerance (AUC [mmol/L min] mean ± SEM, OSF 1437.4 ± 124.2 vs. OC, 1076.8 ± 83.9, n = 6, P < 0.05). Both male and female OSF were hypertensive as assessed by radiotelemetry (night-time systolic arterial pressure (SAP) [mmHg] mean ± SEM, male OSF, 128 ± 1 vs. OC, 109 ± 1, n = 6, P < 0.01; female OSF, 130 ± 1 vs. OC, 118 ± 1, n = 6, P < 0.05). Analysis of heart rate variability (HRV) demonstrated an increased low:high frequency ratio in male and female OSF (P < 0.05), indicative of heightened sympathetic efferent tone. Renal tissue noradrenaline (NA) content was markedly raised in the OSF vs. OC (NA [pg/ml/mg tissue] mean ± SEM, male OSF, 2.28 ± 0.19 vs. OC 0.84 ± 0.09, n = 6, P < 0.01). Exposure to a maternal diet rich in sucrose led to obesity and glucose intolerance in female mice offspring, and hypertension in both sexes.
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Assessing early growth and adiposity: report from an earlynutrition academy workshop.
Ann. Nutr. Metab.
PUBLISHED: 01-07-2013
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This report provides a summary of a workshop organised by the European Commission-funded EarlyNutrition Project and the EarlyNutrition Academy. Accurate and reliable methods to assess body composition are needed in research on prenatal and early post-natal influences of nutrition on later health because common surrogate measures of maternal and offspring adiposity (body fat content), such as body mass index (BMI), have relatively poor predictive power for the risk of later disease. The key goals of the workshop were to discuss approaches to assess growth and body composition from pregnancy to adolescence, to summarise conclusions and to prepare a framework for research in the EarlyNutrition Project. The participants concluded that there is a pressing need to harmonise the methodologies for assessing body composition, recognising that each has advantages and limitations. Essential core measurements across studies assessing early growth and body composition were identified, including weight, length, BMI, waist and mid-upper arm circumference, subscapular and triceps skinfold thicknesses, and bioelectrical impedance analysis. In research settings with access to more sophisticated technologies, additional methods could include dual-energy X-ray absorptiometry, peripheral quantitative computed tomography, ultrasound assessment of regional body fat, magnetic resonance imaging (MRI), air displacement plethysmography (ADP), and deuterium dilution. These provide richer data to answer research questions in greater depth but also increase costs. Where overall whole-body composition is the primary outcome measure, ADP or tracer dilution should be used whenever possible. Where regional distribution of body fat is of greater interest, an imaging technique such as MRI is preferred.
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Maternal and paternal body mass index and offspring obesity: a systematic review.
Ann. Nutr. Metab.
PUBLISHED: 01-04-2013
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It has been hypothesized that the intrauterine environment is an independent factor in obesity development. If so, the maternal effect is likely to be a stronger influencing factor (fetal overnutrition hypothesis). We aimed to systematically evaluate the associations of offspring body mass index (BMI, or adiposity) with pre-pregnancy BMI (or adiposity) of the mother and the father.
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Association of proteinuria threshold in pre-eclampsia with maternal and perinatal outcomes: a nested case control cohort of high risk women.
PLoS ONE
PUBLISHED: 01-01-2013
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To evaluate occurrence of adverse maternal and perinatal outcomes with different thresholds of proteinuria (300-499 mg and ?500 mg/24 hours) in pre-eclamptic women, comparing outcomes against women with chronic and gestational hypertension.
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Clinical prediction in early pregnancy of infants small for gestational age by customised birthweight centiles: findings from a healthy nulliparous cohort.
PLoS ONE
PUBLISHED: 01-01-2013
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Small for gestational age (SGA) infants comprise up to 50% of all stillbirths and a minority are detected before birth. We aimed to develop and validate early pregnancy predictive models for SGA infants.
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Agreement between pedometer and accelerometer in measuring physical activity in overweight and obese pregnant women.
BMC Public Health
PUBLISHED: 06-27-2011
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Inexpensive, reliable objective methods are needed to measure physical activity (PA) in large scale trials. This study compared the number of pedometer step counts with accelerometer data in pregnant women in free-living conditions to assess agreement between these measures.
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Fostering in mice induces cardiovascular and metabolic dysfunction in adulthood.
J. Physiol. (Lond.)
PUBLISHED: 06-13-2011
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Cross-fostering is widely used in developmental programming studies to determine the relative contribution of the in utero and suckling periods in establishing the adult offspring phenotype in response to an environmental challenge. We have investigated whether the process of fostering per se influences cardiovascular and metabolic function in adult offspring of C57BL/6J mice in comparison with animals suckled by their biological dams. Cross-fostered (CF) mice demonstrated juvenile onset hyperphagia and significantly higher body weight (from weaning to 12 weeks: male control (CON) vs. CF: P < 0.01, female CON vs. CF: P < 0.001; RM ANOVA) accompanied by increased abdominal adiposity in males only (white adipose tissue mass (mg): CON 280.5 ± 13.4 [mean ± SEM] (n = 7) vs. CF, 549.8 ± 99.3 (n = 8), P < 0.01). Both male and female CF mice demonstrated significantly enhanced glucose tolerance. A marked increase in systolic blood pressure (SBP) was observed in male CF mice (SBP (mmHg), day: CON 100.5 ± 1.4 (n = 6) vs. CF 114.3 ± 0.7 (n = 6), P < 0.001; night: CON 108.0 ± 2.0 (n = 6) vs. CF 123.2 ± 1.1 (n = 6), P < 0.001). Endothelium-dependent relaxation was enhanced in male CF mice, and renal noradrenaline was increased in female CF mice. Concentration of serum triglycerides, cholesterol, insulin and leptin were increased in CF vs. CON. The process of cross-fostering profoundly affects cardiovascular and metabolic phenotype in mice. The findings have implications for the inclusion of appropriate controls in the design of future studies and in the interpretation of previous cross-fostering studies in mice.
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Role of oxidative stress and antioxidant supplementation in pregnancy disorders.
Am. J. Clin. Nutr.
PUBLISHED: 05-25-2011
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Oxidative stress is widely implicated in failed reproductive performance, including infertility, miscarriage, diabetes-related congenital malformations, and preeclampsia. Maternal obesity is a strong risk factor for preeclampsia, and in a recent study we observed oxidative stress in the oocytes of obese animals before pregnancy as well as in early-stage embryos. This adds to the growing evidence that investigators need to focus more on the preconceptual period in efforts to prevent pregnancy disorders, including those related to oxidative stress. Our research has also focused on the role of free radicals and antioxidant capacity in preeclampsia. By measuring markers of lipid peroxidation and antioxidant capacity, we obtained unequivocal evidence for oxidative stress in this disorder. Partial failure of the process of placentation has been implicated, and recent findings suggest that ischemia-reperfusion in the placenta may contribute to oxidative stress in trophoblasts. Endoplasmic reticulum stress in the placenta may also play a role. Randomized controlled trials have been conducted by our group as well as others to determine whether early supplementation with vitamins C and E in women at risk of preeclampsia is beneficial, but these trials have shown no evidence that these supplements can prevent preeclampsia. Whether this indicates that an inappropriate antioxidant strategy was used or supplementation was administered too late in gestation to be beneficial is not known. Other potential approaches for preventing preeclampsia through amelioration of oxidative stress include the use of supplements in the preconceptual period, selenium supplements, antiperoxynitrite strategies, and statins.
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Increased cardiovascular reactivity to acute stress and salt-loading in adult male offspring of fat fed non-obese rats.
PLoS ONE
PUBLISHED: 05-23-2011
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Diet-induced obesity in rat pregnancy has been shown previously to be associated with consistently raised blood pressure in the offspring, attributed to sympathetic over-activation, but the relative contributions to this phenotype of maternal obesity versus raised dietary fat is unknown. Sprague-Dawley female rats were fed either a control (4.3% fat, n = 11) or lard-enriched (23.6% fat, n = 16) chow 10 days prior to mating, throughout pregnancy and lactation. In conscious adult (9-month-old) offspring cardiovascular parameters were measured (radiotelemetry). The short period of fat-feeding did not increase maternal weight versus controls and the baseline blood pressure was similar in offspring of fat fed dams (OF) and controls (OC). However, adult male OF showed heightened cardiovascular reactivity to acute restraint stress (p<0.01; ? systolic blood pressure (SBP) and ?heart rate (HR)) with a prolonged recovery time compared to male OC. ?1/?-adrenergic receptor blockade normalised the response. Also, after dietary salt-loading (8%-NaCl ad libitum for 1 week) male OF demonstrated higher SBP (p<0.05) in the awake phase (night-time) and increased low/high frequency ratio of power spectral density of HR variability versus OC. Baroreflex gain and basal power spectral density components of the heart rate or blood pressure were similar in male OF and OC. Minor abnormalities were evident in female OF. Fat feeding in the absence of maternal obesity in pregnant rats leads to altered sympathetic control of cardiovascular function in adult male offspring, and hypertension in response to stressor stimuli.
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Obesity in pregnancy: implications for the mother and lifelong health of the child. A consensus statement.
Pediatr. Res.
PUBLISHED: 05-10-2011
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Obesity among pregnant women is becoming one of the most important womens health issues. Obesity is associated with increased risk of almost all pregnancy complications: gestational hypertension, preeclampsia, gestational diabetes mellitus, delivery of large-for-GA infants, and higher incidence of congenital defects all occur more frequently than in women with a normal BMI. Evidence shows that a child of an obese mother may suffer from exposure to a suboptimal in utero environment and that early life adversities may extend into adulthood. In September 2009, ILSI Europe convened a workshop with multidisciplinary expertise to review practices and science base of health and nutrition of obese pregnant women, with focus on the long-term health of the child. The consensus viewpoint of the workshop identified gaps and gave recommendations for future research on gestational weight gain, gestational diabetes, and research methodologies. The evidence available on short- and long-term health impact for mother and child currently favors actions directed at controlling prepregnancy weight and preventing obesity in women of reproductive ages. More randomized controlled trials are needed to evaluate the effects of nutritional and behavioral interventions in pregnancy outcomes. Moreover, suggestions that maternal obesity may transfer obesity risk to child through non-Mendelian (e.g. epigenetic) mechanisms require more long-term investigation.
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Clinical risk prediction for pre-eclampsia in nulliparous women: development of model in international prospective cohort.
BMJ
PUBLISHED: 04-09-2011
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To develop a predictive model for pre-eclampsia based on clinical risk factors for nulliparous women and to identify a subgroup at increased risk, in whom specialist referral might be indicated.
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A prospective cohort study investigating associations between hyperemesis gravidarum and cognitive, behavioural and emotional well-being in pregnancy.
PLoS ONE
PUBLISHED: 04-06-2011
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To investigate the association between hyperemesis gravidarum and altered cognitive, behavioural and emotional well-being in pregnancy.
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Selenium in reproductive health.
Am. J. Obstet. Gynecol.
PUBLISHED: 04-06-2011
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Selenium is an essential trace element of importance to human biology and health. Increasing evidence suggests that this mineral plays an important role in normal growth and reproduction in animals and humans, and selenium supplementation is now recommended as part of public health policy in geographical areas with severe selenium deficiency in soil. This review addresses the biological functions of selenium followed by a detailed review of associations between selenium status and reproductive health. In many countries, selenium dietary intake falls below the recommended nutrient intakes and is inadequate to support maximal expression of the selenoenzymes. Numerous reports implicate selenium deficiency in several reproductive and obstetric complications including male and female infertility, miscarriage, preeclampsia, fetal growth restriction, preterm labor, gestational diabetes, and obstetric cholestasis. Currently, there is inadequate information from the available small intervention studies to inform public health strategies. Larger intervention trials are required to reinforce or refute a beneficial role of selenium supplementation in disorders of reproductive health.
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Influence of maternal nutritional status on vascular function in the offspring.
Microcirculation
PUBLISHED: 03-23-2011
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Suboptimal maternal nutritional status has been implicated in the development of cardiovascular risk in the child. Initially inferred from studies of low-birthweight children, investigations in cohorts of women subjected to famine provide direct evidence for an independent influence of the mothers diet on the cardiovascular health of her child. Animal studies from rodents and sheep have shown associations between maternal undernutrition and raised blood pressure, as well as abnormalities in resistance artery function, particularly in endothelium-dependent responses. Early life exposure to the influences of maternal over nutritional states, e.g. obesity and excessive gestational weight gain, has also been associated with markers of cardiovascular risk in man, and animal models have shown raised blood pressure and endothelial dysfunction in offspring of diet-induced obese dams. Increased sympathetic tone is commonly associated with hypertension in animal models of both under nutritional and over nutritional states. This and several other similarities may indicate commonality of mechanism and could reflect supranormal nutritional status in postnatal life in both conditions.
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Adverse maternal and perinatal outcomes in women with previous preeclampsia: a prospective study.
Am. J. Obstet. Gynecol.
PUBLISHED: 02-02-2011
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The purpose of this study was to assess recurrence rates of preeclampsia and neonatal outcomes in women with a history of preeclampsia that required preterm delivery.
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Pregnancy outcome in women with chronic kidney disease: a prospective cohort study.
Reprod Sci
PUBLISHED: 02-01-2011
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To evaluate pregnancy outcome in women with chronic kidney disease (CKD) or proteinuria in early pregnancy with concomitant risk for preeclampsia (PE).
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Maternal plasma fatty acid composition and pregnancy outcome in adolescents.
Br. J. Nutr.
PUBLISHED: 01-29-2011
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Adolescents are at a greater risk of adverse pregnancy outcome, including spontaneous preterm delivery and fetal growth restriction, and typically have a poorer-quality diet than adults have. In the present study, we addressed the hypothesis that low maternal dietary intake of n-3 long-chain PUFA (LCP) status adversely influences pregnancy outcome. A total of 500 adolescents (14-18 years) were recruited at ? 20 weeks gestation. The frequency of consumption of oily fish was determined by questionnaire (at recruitment and during the third trimester). The fatty acid composition of plasma lipids during the third trimester was determined in 283 subjects. Principal components analysis (PCA) was used to derive components, which were divided into tertiles. The pregnancy outcomes were then compared by tertile, adjusting for potentially confounding variables. Of the participants, 69% reported never eating oily fish during pregnancy, although consumption was not associated with a shorter duration of gestation (P=0·33), lower customised birth weight (P=0·82) or higher incidence of small-for-gestational age (SGA) birth (P=0·55). PCA of the fatty acid composition of maternal plasma lipids identified a low PUFA:SFA (P:S) ratio component and a high n-3 LCP component. There were no differences between tertiles of the high n-3 LCP component and gestational age at delivery (P=0·62), customised birth weight (P=0·38) or incidence of SGA birth (P=0·25), nor were there any associations between the low P:S ratio component and pregnancy outcome. Lower proportions of n-3 LCP in plasma lipids are not associated with greater risk of adverse pregnancy outcomes in UK adolescents.
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Urinary proteomics for prediction of preeclampsia.
Hypertension
PUBLISHED: 01-03-2011
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Preeclampsia is a major determinant of fetal and maternal morbidity and mortality. We used a proteomic strategy to identify urinary biomarkers that predict preeclampsia before the onset of disease. We prospectively collected urine samples from women throughout pregnancy. Samples from gestational weeks 12 to 16 (n=45), 20 (n=50), and 28 (n=18) from women who subsequently had preeclampsia develop were matched to controls (n=86, n=49, and n=17, respectively). We performed capillary electrophoresis online coupled to micro-time-of-flight mass spectrometry. Disease-specific peptide patterns were generated using support vector machine-based software. Candidate biomarkers were sequenced by liquid chromatography-tandem mass spectrometry. From comparison with nonpregnant controls, we defined a panel of 284 pregnancy-specific proteomic biomarkers. Subsequently, we developed a model of 50 biomarkers from specimens obtained at week 28 that was associated with future preeclampsia (classification factor in cases, 1.032 ± 0.411 vs controls, -1.038 ± 0.432; P<0.001). Classification factor increased markedly from week 12 to 16 to 28 in women who subsequently had preeclampsia develop (n=16; from -0.392 ± 0.383 to 1.070 ± 0.383; P<0.001) and decreased slightly in controls (n=16; from -0.647 ± 0.437 to -1.024 ± 0.433; P=0.043). Among the biomarkers are fibrinogen alpha chain, collagen alpha chain, and uromodulin fragments. The markers appear to predict preeclampsia at gestational week 28 with good confidence but not reliably at earlier time points (weeks 12-16 and 20). After prospective validation in other cohorts, these markers may contribute to better prediction, monitoring, and accurate diagnosis of preeclampsia.
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Paternal contribution to small for gestational age babies: a multicenter prospective study.
Obesity (Silver Spring)
PUBLISHED: 12-02-2010
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Our aims were to investigate whether men who fathered small for gestational age (SGA) infants themselves had lower birthweight, were more likely to be obese, have central adiposity and elevated blood pressure in adult life compared with men who fathered non-SGA infants. A total of 2,002 couples participating in the Screening for Pregnancy Endpoints (SCOPE) study were enrolled in early pregnancy and pregnancy outcome data collected prospectively. SGA was defined as birthweight <10th customized centile, obesity as BMI ?30 kg/m(2), central adiposity as waist circumference >102 cm. Logistic regression was used to compare rates of obesity, and central adiposity between men who fathered SGA infants compared with those with non-SGA infants and the final model was adjusted for maternal and paternal confounders. The men who fathered an SGA infant (209 (10.4%)) themselves had lower mean birthweight (3,291 (530) g vs. 3,472 (584) g, P < 0.0001), were more likely to be obese (50 (24.8%) vs. 321 (18.3%), adjusted odds ratio (OR) 1.50, 95% confidence interval 1.05-2.16, adjusted for maternal and paternal factors) and to have central adiposity (52 (25.1%) vs. 341 (19.2%), adjusted OR 1.53, 95% confidence interval 1.06-2.20) compared with men who fathered a non-SGA infant. Elevated paternal blood pressure was not associated with SGA. In conclusion, we report a novel relationship between paternal obesity/central adiposity and birth of an SGA infant, which appears to be independent of maternal factors associated with fetal growth restriction.
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Respiratory outcomes in early childhood following antenatal vitamin C and E supplementation.
Thorax
PUBLISHED: 10-01-2010
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Prenatal antioxidant supplementation might influence fetal lung growth and development and reduce infant respiratory morbidity. The aim of this study was to test the hypothesis that infants of mothers at risk of pre-eclampsia who were randomised to receive high-dose vitamins C and E (1000 mg vitamin C and 400 IU RRR ?-tocopherol daily) during pregnancy would have better respiratory outcomes than infants whose mothers were randomised to receive placebo.
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Developmental programming and diabetes - The human experience and insight from animal models.
Best Pract. Res. Clin. Endocrinol. Metab.
PUBLISHED: 09-14-2010
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Children born to mothers, rather than to fathers, with type 1 diabetes (type 1 DM) or type 2 diabetes (type 2 DM) may have a greater susceptibility to diabetes and obesity in later life, inferring a role for in utero or early post-natal influences on the developing child. This review summarises the studies contributing to this hypothesis, noting some of the controversies including the potential for residual confounding and the influence of maternal BMI. Animal models demonstrate that maternal hyperglycaemia leads to persistent disorders of offspring pancreatic ? cell secretory capacity, abnormal insulin signaling in insulin-sensitive tissues and abnormal development of the hypothalamus, associated with aberrant control of energy regulation and obesity in adult life. Prospective studies, particularly follow-up of children born to diabetic mothers participating in RCTs of improved glycemic control are needed to accurately assess the transgenerational influences of maternal diabetes and to evaluate mechanisms inferred from animal data.
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Intergenerational transmission of insulin resistance and type 2 diabetes.
Prog. Biophys. Mol. Biol.
PUBLISHED: 07-26-2010
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Studies in women with type 1 or type 2 diabetes mellitus (DM) and their children suggest that the in utero diabetic environment in which the fetus develops can increase the risk of diabetes in the child, in a non-genetic but heritable fashion. Studies in rodents provide strong evidence for maternal transmission of diabetes, but are based primarily on a model type 1 DM and there is no standard animal model of type 2 DM in pregnancy or of gestational diabetes mellitus (GDM), although those reported uniformly show glucose intolerance in the offspring. Rodent models of diet-induced obesity have relevance to current upward trends in maternal obesity and GDM, although maternal glucose homeostasis is not always assessed and elements of the diet may have an independent influence. The mechanisms by which maternal type 2DM evokes a higher risk of the disorder in the offspring are likely to result from epigenetic modification in early life of pathways of pancreatic ? cells and of liver and muscle insulin signalling pathways. Also, epigenetic processes associated with hormonal imbalance may lead to irreversible reordering of hypothalamic neural networks in fetal/neonatal life, permanently alter energy balance and lead to obesity with associated insulin resistance.
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Maternal obesity during pregnancy and lactation programs the development of offspring non-alcoholic fatty liver disease in mice.
J. Hepatol.
PUBLISHED: 04-01-2010
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Obesity induced, non-alcoholic fatty liver disease (NAFLD), is now the major cause in affluent countries, of the spectrum of steatosis-to-cirrhosis. Obesity and NAFLD rates in reproductive age women, and adolescents, are rising worldwide. Our hypothesis was that maternal obesity and lactation transmit to the offspring a pre-disposition to dysmetabolism, obesity and NAFLD.
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Maternal diet-induced obesity alters mitochondrial activity and redox status in mouse oocytes and zygotes.
PLoS ONE
PUBLISHED: 03-17-2010
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The negative impact of obesity on reproductive success is well documented but the stages at which development of the conceptus is compromised and the mechanisms responsible for the developmental failure still remain unclear. Recent findings suggest that mitochondria may be a contributing factor. However to date no studies have directly addressed the consequences of maternal obesity on mitochondria in early embryogenesis.Using an established murine model of maternal diet induced obesity and a live cell dynamic fluorescence imaging techniques coupled with molecular biology we have investigated the underlying mechanisms of obesity-induced reduced fertility. Our study is the first to show that maternal obesity prior to conception is associated with altered mitochondria in mouse oocytes and zygotes. Specifically, maternal diet-induced obesity in mice led to an increase in mitochondrial potential, mitochondrial DNA content and biogenesis. Generation of reactive oxygen species (ROS) was raised while glutathione was depleted and the redox state became more oxidised, suggestive of oxidative stress. These altered mitochondrial properties were associated with significant developmental impairment as shown by the increased number of obese mothers who failed to support blastocyst formation compared to lean dams. We propose that compromised oocyte and early embryo mitochondrial metabolism, resulting from excessive nutrient exposure prior to and during conception, may underlie poor reproductive outcomes frequently reported in obese women.
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Maternal obesity programmes offspring development of non-alcoholic fatty pancreas disease.
Biochem. Biophys. Res. Commun.
PUBLISHED: 01-22-2010
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The prevalence of pancreatic adenocarcinoma (PAC) parallels rising rates of obesity and dysmetabolism, a possible link being non-alcoholic fatty pancreas disease (NAFPD). We have recently shown that maternal obesity programmes the development of a dysmetabolic and fatty liver (non-alcoholic fatty liver disease, NAFLD) phenotype in adult offspring. Since the pancreas and liver originate from the same embryonic bud, it is plausible that maternal obesity may similarly programme the development of NAFPD. Our objective was to determine the effect of maternal obesity on development of NAFPD in offspring and ascertain contributions of the intra/extra-uterine periods.
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Maternal metabolism and obesity: modifiable determinants of pregnancy outcome.
Hum. Reprod. Update
PUBLISHED: 12-04-2009
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Obesity among pregnant women is highly prevalent worldwide and is associated in a linear manner with markedly increased risk of adverse outcome for mother and infant. Obesity in the mother may also independently confer risk of obesity to her child. The role of maternal metabolism in determining these outcomes and the potential for lifestyle modification are largely unknown.
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Evidence for sympathetic origins of hypertension in juvenile offspring of obese rats.
Hypertension
PUBLISHED: 11-09-2009
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Maternal obesity in rodents is associated with increased adiposity, impaired glucose tolerance, and hypertension in adult offspring. In this study we investigated the influence of maternal obesity in the rat on blood pressure and blood pressure regulatory pathways in juvenile and adult offspring. Obesity was induced before pregnancy in female Sprague-Dawley rats by feeding a highly palatable energy-dense diet. In juvenile animals (30 days of age), before the onset of obesity and hyperleptinemia, basal nighttime mean arterial pressure was significantly raised in the offspring of obese dams (OffOb) relative to offspring of controls (OffCon; mean arterial pressure, males: OffOb, 121.8+/-0.6 mm Hg versus OffCon, 115.0+/-0.5 mm Hg, n=6, P<0.01; females: OffOb, 125.4+/-0.4 mm Hg versus OffCon, 114.4+/-0.5 mm Hg, n=6, P<0.001), as was the mean arterial pressure response to restraint stress (P<0.01). The pressor response to a leptin challenge was enhanced in OffOb rats (Deltamean arterial pressure: OffOb, 9.7+/-0.8 mm Hg versus OffCon, 5.3+/-1.3 mm Hg; n=8; P<0.05). Renal tissue norepinephrine content (P<0.001) and renin expression (P<0.05) were markedly raised. Analysis of heart rate variability revealed an increased low:high frequency ratio in OffOb versus OffCon rats (P<0.05). At 90 days, hypertension in OffOb rats persisted and was abolished by alpha1- and beta-adrenergic blockade, and cardiovascular responses to phenylephrine or sodium nitroprusside indicated altered baroreceptor function. The exaggerated pressor response to leptin in OffOb rats was maintained. Hypertension in the offspring of obese rats may arise from persistent sympathoexcitatory hyperresponsiveness acquired in early stages of development.
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Maternal high-fat feeding primes steatohepatitis in adult mice offspring, involving mitochondrial dysfunction and altered lipogenesis gene expression.
Hepatology
PUBLISHED: 10-10-2009
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Nonalcoholic fatty liver disease (NAFLD) describes an increasingly prevalent spectrum of liver disorders associated with obesity and metabolic syndrome. It is uncertain why steatosis occurs in some individuals, whereas nonalcoholic steatohepatitis (NASH) occurs in others. We have generated a novel mouse model to test our hypothesis: that maternal fat intake contributes to the development of NAFLD in adult offspring. Female mice were fed either a high-fat (HF) or control chow (C) diet before and during gestation and lactation. Resulting offspring were fed either a C or a HF diet after weaning, to generate four offspring groups; HF/HF, HF/C, C/HF, C/C. At 15 weeks of age, liver histology was normal in both the C/C and HF/C offspring. Kleiner scoring showed that although the C/HF offspring developed nonalcoholic fatty liver, the HF/HF offspring developed NASH. At 30 weeks, histological analysis and Kleiner scoring showed that both the HF/C and C/HF groups had NAFLD, whereas the HF/HF had a more severe form of NASH. Therefore, exposure to a HF diet in utero and during lactation contributes toward NAFLD progression. We investigated the mechanisms by which this developmental priming is mediated. At 15 weeks of age, hepatic mitochondrial electron transport chain (ETC) enzyme complex activity (I, II/III, and IV) was reduced in both groups of offspring from HF-fed mothers (HF/C and HF/HF). In addition, measurement of hepatic gene expression indicated that lipogenesis, oxidative stress, and inflammatory pathways were up-regulated in the 15-week-old HF/C and HF/HF offspring.
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Effects of pre- and periconceptional undernutrition on arterial function in adult female sheep are vascular bed dependent.
Exp. Physiol.
PUBLISHED: 06-26-2009
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The nutritional environment during development and even prior to conception may contribute to cardiovascular risk. In mature adult female sheep, we investigated the effect of preconceptional and periconceptional maternal nutritional restriction on the vascular reactivity of arteries from four vascular beds supplying the heart, thorax, kidney and hindlimb. Welsh Mountain ewes received 100% of nutrient requirements throughout gestation (control group, C, n = 18), or 50% of nutrient requirements for 30 days prior to conception (preconceptional group, PRE, n = 20) or for 15 days either side of conception (periconceptional group, PERI, n = 31) and 100% thereafter. In 3.5-year-old female offspring, the left anterior descending coronary (LAD), left internal thoracic (LITA), right renal and second and third order femoral arteries were dissected and their reactivity was assessed by organ bath or wire myography. Vasoconstrictor responses were greater in both LAD and LITA from PERI offspring compared with C (P < 0.01), while vasoconstriction was unaffected by maternal diet in arteries from the renal and femoral circulations (P = n.s.). Endothelium-dependent and -independent vasodilatation was attenuated in third order femoral arteries of PRE and PERI groups compared with C (P < 0.05). Endothelium-independent vasodilatation was attenuated in both the LAD and renal arteries in the PERI group compared with C (P < 0.05). These data show that moderate maternal undernutrition either prior to or around conception affects vascular function of adult offspring. The effect depends on the timing of the insult, but also on the vascular bed studied and vessel hierarchy in the vascular tree.
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Altered skeletal muscle insulin signaling and mitochondrial complex II-III linked activity in adult offspring of obese mice.
Am. J. Physiol. Regul. Integr. Comp. Physiol.
PUBLISHED: 06-17-2009
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We recently reported insulin resistance in adult offspring of obese C57BL/6J mice. We have now evaluated whether parameters of skeletal muscle structure and function may play a role in insulin resistance in this model of developmental programming. Obesity was induced in female mice by feeding a highly palatable sugar and fat-rich diet for 6 wk prior to pregnancy, and during pregnancy and lactation. Offspring of obese dams were weaned onto standard laboratory chow. At 3 mo of age, skeletal muscle insulin signaling protein expression, mitochondrial electron transport chain activity (ETC), muscle fiber type, fiber density, and fiber cross-sectional area were compared with that of offspring of control dams weaned onto the chow diet. Female offspring of obese dams demonstrated decreased skeletal muscle expression of p110beta, the catalytic subunit of PI3K (P < 0.01), as well as reduced Akt phosphorylation at Serine residue 473 compared with control offspring. Male offspring of obese dams demonstrated increased skeletal muscle Akt2 and PKCzeta expression (P < 0.01; P < 0.001, respectively). A decrease in mitochondrial-linked complex II-III was observed in male offspring of obese dams (P < 0.01), which was unrelated to CoQ deficiency. This was not observed in females. There were no differences in muscle fiber density between offspring of obese dams and control offspring in either sex. Sex-related alterations in key insulin-signaling proteins and in mitochondrial ETC may contribute to a state of insulin resistance in offspring of obese mice.
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Developmental programming resulting from maternal obesity in mice: effects on myocardial ischaemia-reperfusion injury.
Exp. Physiol.
PUBLISHED: 04-24-2009
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A comprehensive number of epidemiological and animal studies suggest that prenatal and early life events are important determinants for disorders later in life. Among them, prenatal stress (i.e. stress experienced by the pregnant mother with impact on the fetal ontogeny) has clear programming effects on the cardiovascular system. A fetus developing in adverse conditions becomes an adult who is susceptible to disease, which may include hypertension, insulin resistance, altered blood lipid levels and cardiovascular disease. Recent evidence demonstrates that maternal programming can occur in the absence of other adverse environmental factors. Obesity, which is becoming a problem of large proportions in Western countries, is a possible cause of programming. With over 30% of the population of the USA currently obese, many mothers suffer from obesity during their child-bearing years (in fact, these conditions are often aggravated during pregnancy). One of the targets of programming is the cardiovascular system, and reported consequences include hypertension, endothelial dysfunction and vascular abnormalities. The overall goal of our study was to investigate the susceptibility of the heart to ischaemia-reperfusion in an animal model of maternal obesity. Our data demonstrate that normal (non-mutant) offspring from obese agouti mouse dams had an increased susceptibility to ischaemia-reperfusion injury. These data may provide insights into the long-term cardiovascular consequences of programming.
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Acute and chronic modulation of placental chorionic plate artery reactivity by reactive oxygen species.
Free Radic. Biol. Med.
PUBLISHED: 04-01-2009
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Control of vascular resistance and blood flow in the fetoplacental circulation is incompletely understood. Reactive oxygen species (ROS), physiological and pathophysiological regulators of vascular tone, are elevated in preeclampsia (PE), a disease of pregnancy characterized by increased fetoplacental vascular resistance. We tested the hypothesis that ROS modulate vascular reactivity in placental chorionic plate arteries. Wire myography was used to examine (1) the effects of acute exposure to ROS on arterial function in normal pregnancy and (2) the effects of maternal antioxidant supplementation on arterial reactivity in women at high risk for PE participating in the Vitamins in Pre-eclampsia (VIP) trial. ROS generated by xanthine plus xanthine oxidase enhanced basal tension, vasoconstriction in response to the thromboxane mimetic U46619, and relaxation in response to sodium nitroprusside. Hydrogen peroxide and peroxynitrite increased basal tone and relaxed preconstricted arteries (U44619), respectively. In women at risk for PE, chorionic plate artery constriction in response to U46619 was greater in the women receiving placebo compared to the women supplemented with the antioxidant vitamins C and E. ROS may regulate fetoplacental vascular resistance and blood flow in the short term, and chronic exposure to raised ROS could contribute to elevated fetoplacental vascular resistance in PE and fetal growth restriction (FGR).
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A randomized controlled trial of cervical scanning vs history to determine cerclage in women at high risk of preterm birth (CIRCLE trial).
Am. J. Obstet. Gynecol.
PUBLISHED: 03-06-2009
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We sought to compare history-indicated placement of cervical cerclage based on history- vs ultrasound-indicated placement in women at risk of preterm birth.
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A prospective study of micronutrient status in adolescent pregnancy.
Am. J. Clin. Nutr.
PUBLISHED: 02-25-2009
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Adolescents are more likely than adults to consume energy-dense, micronutrient-poor diets and to experience adverse pregnancy outcomes.
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Maternal obesity induced by diet in rats permanently influences central processes regulating food intake in offspring.
PLoS ONE
PUBLISHED: 02-15-2009
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Hypothalamic systems which regulate appetite may be permanently modified during early development. We have previously reported hyperphagia and increased adiposity in the adult offspring of rodents fed an obesogenic diet prior to and throughout pregnancy and lactation. We now report that offspring of obese (OffOb) rats display an amplified and prolonged neonatal leptin surge, which is accompanied by elevated leptin mRNA expression in their abdominal white adipose tissue. At postnatal Day 30, before the onset of hyperphagia in these animals, serum leptin is normal, but leptin-induced appetite suppression and phosphorylation of STAT3 in the arcuate nucleus (ARC) are attenuated; the level of AgRP-immunoreactivity in the hypothalamic paraventricular nucleus (PVH), which derives from neurones in the ARC and is developmentally dependent on leptin, is also diminished. We hypothesise that prolonged release of abnormally high levels of leptin by neonatal OffOb rats leads to leptin resistance and permanently affects hypothalamic functions involving the ARC and PVH. Such effects may underlie the developmental programming of hyperphagia and obesity in these rats.
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A prospective study of pregnancy outcome and biomarkers of oxidative stress in nulliparous obese women.
Am. J. Obstet. Gynecol.
PUBLISHED: 02-06-2009
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We sought to investigate pregnancy outcome and biomarkers of oxidative stress in nulliparous obese pregnant women.
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Quantitative fetal fibronectin screening in asymptomatic high-risk patients and the spectrum of risk for recurrent preterm delivery.
Am. J. Obstet. Gynecol.
PUBLISHED: 01-20-2009
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We sought to determine whether a single quantitative vaginal fetal fibronectin (fFN) test at 24 weeks gestational age (GA) can delineate the spectrum of risk of spontaneous preterm delivery (sPTD) in an asymptomatic high-risk population comprised of patients with a prior preterm birth.
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Perinatal outcomes in large infants using customised birthweight centiles and conventional measures of high birthweight.
Paediatr Perinat Epidemiol
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Large-for-gestational-age (LGA) or macrosomic infants are associated with adverse maternal and neonatal outcomes. It is unclear if these associations are stronger using customised birthweight centiles. We compared outcomes between term infants defined macrosomic by birthweight >4000 g (Macro(4000) ) or LGA by population centiles (LGA(pop) ) with those defined LGA by customised centiles (LGA(cust) ).
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Maternal obesity, gestational weight gain and diet as determinants of offspring long term health.
Best Pract. Res. Clin. Endocrinol. Metab.
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This review addresses the increasingly prolific literature from studies in man and animals suggesting that maternal obesity, a diet rich in calories or excess gestational weight gain may, through perturbation of the intrauterine environment, lead to lifelong risk of obesity and related disorders in the child. In addressing maternal- child obesity relationships it remains a challenge to distinguish the influence of the intrauterine environment from the contribution of shared genetic traits, and to adequately adjust for postnatal determinants of childhood obesity. Studies in genetically identical rodents convincingly show that maternal obesity, as well as elements of a hypercalorific diet can permanently influence offspring risk of obesity, and are these are supported by studies in larger mammals. Importantly, dissection of the mechanism in animals has led to description of novel interactive pathways between maternal environment and fetus which are amenable to investigation in humans.
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Maternal selenium, copper and zinc concentrations in pregnancy associated with small-for-gestational-age infants.
Matern Child Nutr
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Pregnancy during adolescence increases the risk of adverse pregnancy outcome, especially small-for-gestational-age (SGA) birth, which has been linked to micronutrient deficiencies. Smoking has been shown to be related to lower micronutrient concentrations. Different ethnicities have not been examined. We used a subset from a prospective observational study, the About Teenage Eating study consisting of 126 pregnant adolescents (14-18-year-olds) between 28 and 32 weeks gestation. Micronutrient status was assessed by inductively coupled mass spectrometry. Smoking was assessed by self-report and plasma cotinine, and SGA was defined as infants born <10th corrected birthweight centile. The main outcome measures were as follows: (1) maternal plasma selenium, copper and zinc concentrations in adolescent mothers giving birth to SGA vs. appropriate-for-gestational-age (AGA) infants; and (2) comparison of micronutrient concentrations between women of different ethnicities and smoking habits. The plasma selenium {mean?±?standard deviation (SD) [95% confidence interval (CI)]} concentration was lower in the SGA [n?=?19: 49.4?±?7.3 (CI: 45.9, 52.9) µg?L(-1) ] compared with the AGA [n?=?107: 65.1?±?12.5 (CI: 62.7, 67.5) µg?L(-1) ; P?
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Early nutrition programming of long-term health.
Proc Nutr Soc
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Increasing evidence from the EU Project EARNEST and many other investigators demonstrates that early nutrition and lifestyle have long-term effects on later health and the risk of common non-communicable diseases (known as developmental programming). Because of the increasing public health importance and the transgenerational nature of the problem, obesity and associated disorders are the focus of the new EU funded project EarlyNutrition. Currently, three key hypotheses have been defined: the fuel mediated in utero hypothesis suggests that intrauterine exposure to an excess of fuels, most notably glucose, causes permanent changes of the fetus that lead to obesity in postnatal life; the accelerated postnatal weight gain hypothesis proposes an association between rapid weight gain in infancy and an increased risk of later obesity and adverse outcomes; and the mismatch hypothesis suggests that experiencing a developmental mismatch between a sub-optimal perinatal and an obesogenic childhood environment is related to a particular predisposition to obesity and corresponding co-morbidities. Using existing cohort studies, ongoing and novel intervention studies and a basic science programme to investigate those key hypotheses, project EarlyNutrition will provide the scientific foundations for evidence-based recommendations for optimal nutrition considering long-term health outcomes, with a focus on obesity and related disorders. Scientific and technical expertise in placental biology, epigenetics and metabolomics will provide understanding at the cellular and molecular level of the relationships between early life nutritional status and the risk of later adiposity. This will help refine strategies for intervention in early life to prevent obesity.
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Lifestyle interventions for overweight and obese pregnant women to improve pregnancy outcome: systematic review and meta-analysis.
BMC Med
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Overweight and obesity pose a big challenge to pregnancy as they are associated with adverse maternal and perinatal outcome. Evidence of lifestyle intervention resulting in improved pregnancy outcome is conflicting. Hence the objective of this study is to determine the efficacy of antenatal dietary, activity, behaviour or lifestyle interventions in overweight and obese pregnant women to improve maternal and perinatal outcomes.
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Gestational weight gain: influences on the long-term health of the child.
Curr Opin Clin Nutr Metab Care
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To address the recent evidence which suggests that inappropriate gestational weight gain (GWG) may have consequences that extend to the longer term health of the child.
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