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Parasuraman R.,Wessex Maternal and Fetal Medicine Unit | Osmond C.,Epidemiology Resource Center | Howe D.T.,Wessex Maternal and Fetal Medicine Unit
Journal of Obstetrics and Gynaecology Research | Year: 2012

Aim: Ejection force of the fetal cardiac ventricles has previously been described from 18 weeks of gestation.We aimed to establish gestation-specific reference intervals for ventricular ejection force (VEF) from 12 to 40 weeks of pregnancy. Material and Methods: In a cross-sectional observational study of singleton pregnancies, examinations were performed in 236 women evenly distributed across each week of pregnancy from 12 to 40 weeks. Each mother was scanned once. For the aortic and pulmonary valves, the time to peak velocity (TPV) and the average (TAV) and peak flow velocity in systole (PSV) was measured. For each we averaged values from three consecutive complexes. The outlet valve diameters were measured and the VEF on both the right and left sides were calculated using the formula VEF = (1.055 × valve area × time to peak velocity × TAV) × (PSV/TPV) where 1.055 represents the density of blood. Measurements were repeated in 40 women to assess intraobserver reproducibility and in 19 women for interobserver variability. Results: We present reference intervals for right and left VEF. We demonstrated that the ventricular force on both right and left sides increases with advancing gestational age. Conclusion: Fetal cardiac physiology can be studied and Doppler indices reliably measured as early as the late first trimester of pregnancy. Ventricular ejection force and its relationship with fetal growth could be explored in future studies and this may eventually provide better understanding of changes which may predispose to adult cardiac disease. © 2011 Japan Society of Obstetrics and Gynecology.


Godfrey K.M.,University of Southampton | Godfrey K.M.,NIHR Biomedical Research Unit in Nutrition | Godfrey K.M.,Epidemiology Resource Center | Gluckman P.D.,University of Auckland | And 3 more authors.
Trends in Endocrinology and Metabolism | Year: 2010

Recent evidence demonstrates important maternal effects on an offspring's risk of developing metabolic disease. These effects extend across the full range of maternal environments and partly involve epigenetic mechanisms. The maternal effects can be explained in evolutionary terms, and there is some evidence for their transmission into succeeding generations. Unbalanced maternal diet or body composition, ranging from poor to rich environments, adversely influences the offspring's response to later challenges such as an obesogenic diet or physical inactivity, increasing the risk of disease. Adopting a life course approach that takes into account intergenerational effects has important implications for prevention of non-communicable diseases, particularly in populations undergoing rapid economic transition. © 2010.


Groenwold R.H.H.,University Utrecht | de Vries F.,University Utrecht | de Vries F.,Epidemiology Resource Center | de Boer A.,University Utrecht | And 4 more authors.
Pharmacoepidemiology and Drug Safety | Year: 2011

Purpose: Propensity score (PS) methods aim to control for confounding by balancing confounders between exposed and unexposed subjects with the same PS. PS balance measures have been compared in simulated data but limited in empirical data. Our objective was to compare balance measures in clinical data and assessed the association between long-acting inhalation beta-agonist (LABA) use and myocardial infarction. Methods: We estimated the relationship between LABA use and myocardial infarction in a cohort of adults with a diagnosis of asthma or chronic obstructive pulmonary disorder from the Utrecht General Practitioner Research Network database. More than two thousand PS models, including information on the observed confounders age, sex, diabetes, cardiovascular disease and chronic obstructive pulmonary disorder status, were applied. The balance of these confounders was assessed using the standardised difference (SD), Kolmogorov-Smirnov (KS) distance and overlapping coefficient. Correlations between these balance measures were calculated. In addition, simulation studies were performed to assess the correlation between balance measures and bias. Results: LABA use was not related to myocardial infarction after conditioning on the PS (median heart rate=1.14, 95%CI=0.47-2.75). When using the different balance measures for selecting a PS model, similar associations were obtained. In our empirical data, SD and KS distance were highly correlated balance measures (r=0.92). In simulations, SD, KS distance and overlapping coefficient were similarly correlated to bias (e.g. r=0.55, r=0.52 and r=-0.57, respectively, when conditioning on the PS). Conclusions: We recommend using the SD or the KS distance to quantify the balance of confounder distributions when applying PS methods. © 2011 John Wiley & Sons, Ltd.


De Vries F.,Medicines and Healthcare Products Regulatory Agency | De Vries F.,University Utrecht | De Vries F.,Epidemiology Resource Center | Setakis E.,Medicines and Healthcare Products Regulatory Agency | And 2 more authors.
British Journal of Clinical Pharmacology | Year: 2010

AIMS To evaluate and compare the risk of specific safety outcomes in patients prescribed ibuprofen and paracetamol concomitantly with those in patients prescribed ibuprofen or paracetamol alone. The outcomes were evaluated according to dose, duration and exposure. METHODS The study used a retrospective longitudinal cohort design with data from the UK General Practice Research Database (GPRD). The study population included patients aged 18 years or over who were prescribed ibuprofen alone, paracetamol alone or concomitant ibuprofen and paracetamol (tablets or capsules only). The safety outcomes evaluated were upper gastrointestinal events, myocardial infarction, stroke, renal failure (excluding chronic), congestive heart failure, intentional or accidental overdose, suicidal behaviour and mortality. Time-dependent Cox regression was used to estimate relative rates for the safety outcomes, by treatment group. A further analysis evaluated whether the hazard rates (i.e. absolute risks) varied over time with changes in drug exposure. RESULTS The study population included 1.2 million patients. There was considerable heterogeneity in both patient and exposure characteristics. When comparing with past users, for most safety outcomes, current users of concomitant paracetamol and ibuprofen had relative rates between those for current users of ibuprofen alone and paracetamol alone. The hazard rates were generally proportional over time, from current to past exposure, following a prescription for concomitant paracetamol and ibuprofen compared with ibuprofen alone or paracetamol alone. CONCLUSIONS The known risk of the safety outcomes examined does not appear to be modified by concomitant use of ibuprofen and paracetamol compared with paracetamol or ibuprofen alone. © 2010 The British Pharmacological Society.


Watkins A.J.,University of Southampton | Lucas E.S.,University of Southampton | Torrens C.,University of Southampton | Cleal J.K.,University of Southampton | And 6 more authors.
British Journal of Nutrition | Year: 2010

Environmental perturbations during early mammalian development can affect aspects of offspring growth and cardiovascular health. We have demonstrated previously that maternal gestational dietary protein restriction in mice significantly elevated adult offspring systolic blood pressure. Therefore, the present study investigates the key mechanisms of blood pressure regulation in these mice. Following mating, female MF-1 mice were assigned to either a normal-protein diet (NPD; 18% casein) or an isocaloric low-protein diet throughout gestation (LPD; 9% casein), or fed the LPD exclusively during the pre-implantation period (3.5d) before returning to the NPD for the remainder of gestation (Emb-LPD). All offspring received standard chow. At 22 weeks, isolated mesenteric arteries from LPD and Emb-LPD males displayed significantly attenuated vasodilatation to isoprenaline (P=0.04 and P=0.025, respectively), when compared with NPD arteries. At 28 weeks, stereological analysis of glomerular number in female left kidneys revealed no significant difference between the groups. Real-time RT-PCR analysis of type 1a angiotensin II receptor, Na+/K+ ATPase transporter subunits and glucocorticoid receptor expression in male and female left kidneys revealed no significant differences between the groups. LPD females displayed elevated serum angiotensin-converting enzyme (ACE) activity (P=0.044), whilst Emb-LPD males had elevated lung ACE activity (P=0.001), when compared with NPD offspring. These data demonstrate that elevated offspring systolic blood pressure following maternal gestational protein undernutrition is associated with impaired arterial vasodilatation in male offspring, elevated serum and lung ACE activity in female and male offspring, respectively, but kidney glomerular number in females and kidney gene expression in male and female offspring appear unaffected. © 2010 The Authors.

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