Low dose aspirin in the prevention of recurrent spontaneous preterm labour - the APRIL study: A multicenter randomized placebo controlled trial

Background: Preterm birth (birth before 37 weeks of gestation) is a major problem in obstetrics and affects an estimated 15 million pregnancies worldwide annually. A history of previous preterm birth is the strongest risk factor for preterm birth, and recurrent spontaneous preterm birth affects more than 2.5 million pregnancies each year. A recent meta-analysis showed possible benefits of the use of low dose aspirin in the prevention of recurrent spontaneous preterm birth. We will assess the (cost-)effectiveness of low dose aspirin in comparison with placebo in the prevention of recurrent spontaneous preterm birth in a randomized clinical trial. Methods/design: Women with a singleton pregnancy and a history of spontaneous preterm birth in a singleton pregnancy (22-37 weeks of gestation) will be asked to participate in a multicenter, randomized, double blinded, placebo controlled trial. Women will be randomized to low dose aspirin (80 mg once daily) or placebo, initiated from 8 to 16 weeks up to maximal 36 weeks of gestation. The primary outcome measure will be preterm birth, defined as birth at a gestational age (GA) < 37 weeks. Secondary outcomes will be a composite of adverse neonatal outcome and maternal outcomes, including subgroups of prematurity, as well as intrauterine growth restriction (IUGR) and costs from a healthcare perspective. Preterm birth will be analyzed as a group, as well as separately for spontaneous or indicated onset. Analysis will be performed by intention to treat. In total, 406 pregnant women have to be randomized to show a reduction of 35% in preterm birth from 36 to 23%. If aspirin is effective in preventing preterm birth, we expect that there will be cost savings, because of the low costs of aspirin. To evaluate this, a cost-effectiveness analysis will be performed comparing preventive treatment with aspirin with placebo. Discussion: This trial will provide evidence as to whether or not low dose aspirin is (cost-) effective in reducing recurrence of spontaneous preterm birth. Trial registration: Clinical trial registration number of the Dutch Trial Register: NTR 5675. EudraCT-registration number: 2015-003220-31

Metabolic Syndrome After Preeclamptic Pregnancy: A Longitudinal Cohort Study

INTRODUCTION: History of preeclampsia increases the risk of cardiovascular disease in women. Most formerly, preeclamptic women have generally one or even more traditional cardiovascular and/or cardiometabolic risk factors consistent with metabolic syndrome in the first year after delivery. The objective of this study was to analyze the prevalence and persistence of risk factors contributing to metabolic syndrome for the course of years after preeclamptic pregnancy. METHODS: In a longitudinally cohort study, 107 formerly preeclamptic women were assessed for traditional risk factors (insulin resistance, obesity, dyslipidemia, hypertension, and microalbuminuria) of metabolic syndrome (World Health Organization criteria) at two time points: at 3-30 months postpartum (visit 1) and 24-65 months later (visit 2). RESULTS: At visit 1, 10 of 107 (9%) formerly preeclamptic women had metabolic syndrome, and at visit 2, 14 of 107 (13%) (p = 0.21) had metabolic syndrome. Most formerly, preeclamptic women (90%) did not change their metabolic syndrome status over the years, as 7 of 107 (7%) women had persistent metabolic syndrome and 90 of 107 (84%) women did not meet the criteria for metabolic syndrome on either visit. In 3 of 107 (3%) formerly preeclamptic women, metabolic syndrome disappeared over time, whereas 7 of 107 (7%) preeclamptic women developed it. CONCLUSION: The presence or absence of metabolic syndrome remains unchanged in 90% of formerly preeclamptic women for the first years after preeclampsia. Only in 10% of women, metabolic syndrome developed or recovered, indicating that early screening within the first year postpartum in these women effectively detects those with metabolic syndrome who are known to be at increased risk for cardiovascular disease later in life

Deformation and failure kinetics of polyvinylidene fluoride: Influence of crystallinity

The present study investigates the effect of processing conditions on the yield kinetics, such as rate dependence of the yield stress and creep rupture, of polyvinilidene fluoride. Samples were compression molded with cooling rates varying from 100°C/s to 0.5°C/min, or isothermally crystallized at temperatures varying from 20 to 120°C. Deformation kinetics were studied over a wide range of strain rates and temperatures. It is shown that for all conditions the yield response is well represented by the Ree–Eyring model. Moreover, the activation volumes and activation energies are independent from the processing conditions. The effect of processing is fully covered by a simple relationship between the rate factors and the degree of crystallinity. Subsequently, the versatility of this relationship is demonstrated by experimental validation

Modeling renal autoregulation in a hemodynamic, first-trimester gestational model

The maternal cardiovascular system, led by renal volume regulatory responses, changes during pregnancy to ensure an adequate circulation for fetal development and growth. Circulatory maladjustment predisposes to hypertensive complications during pregnancy. Mathematical models can be used to gain insight in the gestational cardiovascular physiology. In this study, we developed an accurate, robust, and transparent model for renal autoregulation implemented in an existing circulatory gestational model. This renal autoregulation model aims to maintain steady glomerular pressure by the myogenic response, and glomerular filtration rate by tubuloglomerular feedback, both by inducing a change in the radius, and thus resistance, of the afferent arteriole. The modeled response of renal blood flow and the afferent arteriole following blood pressure increase were compared to published observations in rats. With solely the myogenic response, our model had a maximum deviation of 7% in change in renal blood flow and 7% in renal vascular resistance. When both the myogenic response and tubuloglomerular feedback were concurrently activated, the maximum deviation was 7% in change in renal blood flow and 5% in renal vascular resistance. These results show that our model is able to represent renal autoregulatory behavior comparable to empirical data. Further studies should focus on extending the model with other regulatory mechanisms to understand the hemodynamic changes in healthy and complicated pregnancy

Modeling renal autoregulation in a hemodynamic, first-trimester gestational model

The maternal cardiovascular system, led by renal volume regulatory responses, changes during pregnancy to ensure an adequate circulation for fetal development and growth. Circulatory maladjustment predisposes to hypertensive complications during pregnancy. Mathematical models can be used to gain insight in the gestational cardiovascular physiology. In this study, we developed an accurate, robust, and transparent model for renal autoregulation implemented in an existing circulatory gestational model. This renal autoregulation model aims to maintain steady glomerular pressure by the myogenic response, and glomerular filtration rate by tubuloglomerular feedback, both by inducing a change in the radius, and thus resistance, of the afferent arteriole. The modeled response of renal blood flow and the afferent arteriole following blood pressure increase were compared to published observations in rats. With solely the myogenic response, our model had a maximum deviation of 7% in change in renal blood flow and 7% in renal vascular resistance. When both the myogenic response and tubuloglomerular feedback were concurrently activated, the maximum deviation was 7% in change in renal blood flow and 5% in renal vascular resistance. These results show that our model is able to represent renal autoregulatory behavior comparable to empirical data. Further studies should focus on extending the model with other regulatory mechanisms to understand the hemodynamic changes in healthy and complicated pregnancy

Adaptive changes of mesenteric arteries in pregnancy: a meta-analysis

van Drongelen J, Hooijmans CR, Lotgering FK, Smits P, Spaanderman ME. Adaptive changes of mesenteric arteries in pregnancy: a meta-analysis. Am J Physiol Heart Circ Physiol 303: H639-H657, 2012. First published July 20, 2012; doi:10.1152/ajpheart.00617.2011.-The vascular response to pregnancy has been frequently studied in mesenteric artery models by investigating endothelial cell (EC)- and smooth muscle cell (SMC)-dependent responses to mechanical (flow-mediated vasodilation, myogenic reactivity, and vascular compliance) and pharmacological stimuli (G protein-coupled receptor responses: Gq(EC), Gs(SMC), Gq(SMC)). It is unclear to what extent these pathways contribute to normal pregnancy-induced vasodilation across species, strains, and/or gestational age and at which receptor level pregnancy affects the pathways. We performed a meta-analysis on responses to mechanical and pharmacological stimuli associated with pregnancy-induced vasodilation of mesenteric arteries and included 55 (188 responses) out of 398 studies. Most included studies (84%) were performed in Wistar and Sprague-Dawley rats (SDRs) and compared late gestation versus nonpregnant controls (80%). Pregnancy promotes flow-mediated vasodilation in all investigated species. Only in SDRs, pregnancy additionally stimulates both vasodilator Gq(EC) sensitivity (EC50 reduced by -0.76 [-0.92, -0.60] log[M]) and Gs(SMC) sensitivity (EC50 reduced by -0.51 [-0.82, -0.20] log[M]), depresses vasopressor Gq(SMC) sensitivity (EC50 increase in SDRs by 0.23 [0.16, 0.31] log[M]), and enhances arterial compliance. We conclude that 1) pregnancy facilitates flow-mediated vasodilation at term among all investigated species, and the contribution of additional vascular responses is species and strain specific, and 2) late pregnancy mediates vasodilation through changes at the receptor level for the substances tested. The initial steps of vasodilation in early pregnancy remain to be elucidated

Effect of pregnancy at mid gestation on in vivo and whole organ perfusion# renal vascular resistance (RVR), renal flow and glomerular filtration rate (GFR) in absence and presence of NO and sympathetic blockade.

<p>The effect of pregnancy on RVR, renal flow (effects of renal plasma/blood/perfusion flow (RPF/RBF/RPPF) combined) and GFR is presented as percentage mean difference (MD) and its 95% CI. Studies and totals based on Long Evans rats (LER), Munich Wistar rats (MWR), Sprague Dawley rats (SDR) and Wistar Hannover rats (WHR). 1, 2, 3 represents first, second and third part of mid gestation. # Whole organ perfusion experiments, excluded in the “Overall in vivo“ analysis. * Experiments performed under anesthesia. I² represents the amount of heterogeneity. n.a.  =  not applicable.</p

Cervical intraepithelial neoplasia and the risk of spontaneous preterm birth

Background Excisional procedures of cervical intraepithelial neoplasia (CIN) may increase the risk of preterm birth. It is unknown whether this increased ri

Literature search-strategy for Embase.

<p>Literature search-strategy for Embase.</p