158 research outputs found

    Keep on track:Monitoring growth and development in children born preterm and full-term

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    Environmental factors in early life influence early development and growth, and influence long-term health. In this thesis we showed that in premature infants, the length and growth of the cerebral cortex (corpus callosum) is a good marker of brain growth and a predictor of later neurological development. An eye-tracking test (watching a video) at the age of 1 year also appeared to be a predictive factor for overall cognitive and motor development 1 year later. We also found that weight gain after preterm birth is associated with body composition in childhood. We also compared 2 methods of measuring body composition in children (DXA and ADP) and found that the results of fat mass (percentage) and fat-free mass at 3-5 years of age differ significantly between both methods, and that these differences are greater in very preterm children compared to full-term children. We present improvements to the algorithm to improve results with ADP. We also investigated sleep and found that parent-reported sleep characteristics and problems are similar between very preterm and full-term children at the age of 3 years. In the general population, we have shown that low birth weight (<2500 grams) and growth retardation during fetal life and childhood are associated with longer sleep duration and higher sleep efficiency at 10-15 years of age. Furthermore, at the same school age, greater intraday variability (fragmentation of the 24-hour activity rhythm) was associated with a higher fat mass index and higher visceral fat mass in boys

    Using personalised cardiovascular models to identify new diagnostic predictors for pre-eclampsia

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    Haemodynamic adaptations play a crucial role in uteroplacental perfusion during pregnancy. In particular, modifications of the utero-ovarian arterial network cause a significant increase in blood volume distributed to the placenta and foetus. Failure to make these cardiovascular modifications results in complicated pregnancies caused by different disorders such as hypertension, pre-eclampsia, intrauterine growth restriction (IUGR), and placental insufficiency. In pre-eclampsia, the modifications of the utero-ovarian arterial network are unsuccessful and cause less blood volume to be distributed to the placenta and foetus. Pre-eclampsia is a hypertensive disorder that is still not fully understood, and clinicians still fail at identifying pre-eclamptic women during controls, especially at differentiating between hypertensive women and pre-eclamptic women. One reason for this is that clinicians rely heavily on blood pressure when diagnosing pre-eclampsia, and this biomarker has similar readings for both pre-eclampsia and hypertension. As part of the diagnosis of pre-eclampsia, proteinuria is used. In order to improve the diagnosis of pre-eclampsia, other biomarkers are being researched. A dataset of 21 patients was used to find novel biomarkers that can classify pre-eclampsia. The dataset is divided into two groups: uncomplicated pregnancies with hypertensive women and complicated pregnancies with pre-eclampsia. A computational model of the cardiovascular system is used to simulate blood and pressure solutions based on patient-specific observations in order to develop a new biomarker. The model employs 1D modelling which incorporates a wave intensity analysis that models forward and backward waves to provide more precise predictions of wave propagation across the artery system, particularly in the utero-ovarian system. The proposed biomarkers will include dimensionless terms formed by global maternal parameters such as systolic blood pressure, stroke volume, pulse wave velocity, etc., or local uterine parameters such as pressure and velocity in specific vessels of the uterine system. Afterwards, their ability as a classifier of pre-eclampsia will be investigated. Besides this, a case study of the prone position in pregnancy and its effects on cardiovascular changes will be carried out. To do this, the computational model will be used to study what happens when a pregnant woman is positioned in the prone position and how vital metrics like blood pressure and cardiac output are altered. It was found that the biomarkers based on the radial and arcuate arteries have a better classification ability for pre-eclampsia, even higher than the Doppler-measured Resistance Index (RI) and Pulsatility Index (PI). The novelty of this work is the introduction of new biomarkers through the use of a computational model, as well as the demonstration of the dependability and use of 1D modelling in pregnancy. The model demonstrated how biomarkers that could not be measured clinically may be easily calculated using 1D modelling and provide critical information about the utero-ovarian circulation. Future work should concentrate on changing the existing solver into a much faster and simpler solver, as well as validating the biomarkers in a larger dataset

    Deciphering the vascular disease mechanisms underlying hypertensive disorders of pregnancy

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    Summary. As the prevalence of hypertensive orders increases, particularly pre-eclampsia superimposed on a background of chronic hypertension (SPE), so too does the global disease burden they represent. Not only are these disorders detrimental to both mother and child during the course of pregnancy, they also have lasting longterm effects to future cardiovascular health for both. Despite this, relatively little is known about the generation and development of these multifactorial disorders. In combination with the effects of potential treatments to offspring health, the resultant scope for therapeutic interventions is severely limited. The stroke-prone spontaneously hypertensive (SHRSP) rat is an established model of chronic hypertension during pregnancy that can be further stressed by infusion of angiotensin II (ANGII) in mid-gestation to create a pre-eclamptic phenotype that closely mimics the clinical manifestation of SPE in humans. This thesis aimed to optimise and characterise a novel rodent model of SPE to provide a useful tool in understanding the underlying pathophysiology of the condition and in testing potential therapeutic strategies. The objectives were to assess the maternal, fetoplacental and neonatal response to SPE development in the SHRSP; evaluate the use of magnesium sulphate (MgSO4) as a preventative therapeutic in the context of SPE; investigate the underlying genetic mechanisms that may influence abnormal uterine artery remodelling due to maternal hypertension; and, finally, to validate these genetic mechanisms in vitro. A variety of in vivo and ex vivo techniques were employed in the generation and assessment of the optimised SPE rodent model. Pregnant SHRSP dams infused with 750ng/kg/min ANGII were found to exhibit signs of impaired maternal cardiovascular, renal and placental function alongside the abnormal uterine artery remodelling already characteristic of the SHRSP. Further, the offspring of these dams were more likely to be growth restricted and preliminary evidence suggested neonatal gene expression may be altered. When MgSO4 was administered in a preventative capacity in daily drinking water, it was shown to improve maternal blood pressure, proteinuria and weight. However, MgSO4 was ineffective at improving maternal cardiac function or uteroplacental flow and was observed to worsen fetal growth restriction. To better understand the maternally-derived factors in this impaired uterine artery remodelling associated with hypertensive pregnancy, RNA-sequencing was used to assess the genetic profiles of early pregnancy uterine arteries in SHRSP and normotensive WKY. Though the two strains shared a conserved response to pregnancy, there were striking differences in pathways related to vascular function, notably reactive oxygen species (ROS) production and calcium (Ca2+) signalling. Finally, using a combination of whole uterine arteries and vascular smooth muscle cells (UAVSMCs) derived from them, the gene expression patterns relating to ROS and Ca2+ were investigated to validate them. Though studies were preliminary and sample sizes small, there was evidence of altered ROS production, NOX subunit expression and UAVSMC Ca2+ release between WKY and SHRSP. This work has provided information on an optimised, novel rodent model of superimposed pre-eclampsia that may be used as a potential tool in investigating the pathophysiology of the condition or in assessing the long-term consequences of an adverse in utero environment. It has also deepened our understanding of the effects of prolonged MgSO4 exposure during pregnancy and highlighted the need for an optimised, standardised dosing regime in humans. Furthermore, this work has generated novel insights into the genetic factors that influence uterine artery remodelling and their functional consequences in early hypertensive pregnancy

    The Pathophysiology of Preeclampsia and Eclampsia

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    Preeclampsia is a hypertensive disorder of pregnancy, diagnosed after the 20th week of gestation in women experiencing new-onset hypertension along with symptoms affecting the liver, kidneys, or brain. In some cases, women with preeclampsia develop novel seizures or unexplained coma, at which time they are diagnosed with eclampsia. The mechanisms contributing to preeclampsia and eclampsia are not fully elucidated, although the placenta seems to play a critical role. Previous studies suggest that improper placentation stimulates mitochondrial dysfunction and the exaggerated release of placental-derived molecules including inflammatory cytokines, anti-angiogenic factors, reactive oxygen species, and cell-free nucleic acids into the maternal circulation that cause systemic vascular dysfunction. These, along with maternally derived molecules, act in concert, leading to hypertension and target organ damage during pregnancies complicated by preeclampsia and eclampsia.In this reprint, we present the original research articles and review papers published as part of the Special Issue: "The Pathophysiology of Preeclampsia and Eclampsia" in Cells

    Machine learning-based evaluation of application value of pulse wave parameter model in the diagnosis of hypertensive disorder in pregnancy

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    Hypertensive disorder in pregnancy (HDP) remains a major health burden, and it is associated with systemic cardiovascular adaptation. The pulse wave is an important basis for evaluating the status of the human cardiovascular system. This research aims to evaluate the application value of pulse waves in the diagnosis of hypertensive disorder in pregnancy.This research a retrospective study of pregnant women who attended prenatal care and labored at Beijing Haidian District Maternal and Child Health Hospital. We extracted maternal hemodynamic factors and measured the pulse wave of the pregnant women. We developed an HDP predictive model by using support vector machine algorithms at five-gestational-week stages.At five-gestational-week stages, the area under the receiver operating characteristic curve (AUC) of the predictive model with pulse wave parameters was higher than that of the predictive model with hemodynamic factors. The AUC values of the predictive model with pulse wave parameters were 0.77 (95% CI 0.64 to 0.9), 0.83 (95% CI 0.77 to 0.9), 0.85 (95% CI 0.81 to 0.9), 0.93 (95% CI 0.9 to 0.96) and 0.88 (95% CI 0.8 to 0.95) at five-gestational-week stages, respectively. Compared to the predictive models with hemodynamic factors, the predictive model with pulse wave parameters had better prediction effects on HDP.Pulse waves had good predictive effects for HDP and provided appropriate guidance and a basis for non-invasive detection of HDP

    Maternal cardiovascular adaptation to pregnancy in women with previous bariatric surgery and obese pregnant women

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    The prevalence of obesity in pregnancy is rising every year both in the UK and globally. Obese pregnant women are often of childbearing age and go on to have high risk pregnancies with increased risk of hypertensive disorders, gestational diabetes and large-for-gestational age neonates. Bariatric Surgery is a highly successful treatment for sustained weight loss and its use in the management of obesity is growing. Studies of individuals before and after bariatric surgery, outside of pregnancy, have shown a reduction or resolution in hypertension, cardiac remodelling with reduced left ventricular mass and improved function. Numerous retrospective studies have shown that pregnancy following bariatric surgery is associated with a reduced risk of developing hypertensive disorders, however, the mechanisms for this are largely unknown. In pathological pregnancy complicated by pre-eclampsia or growth restriction, studies have shown cardiovascular alterations in haemodynamic indices, cardiac geometry and function, highlighting the importance of the cardiovascular adaptation to pregnancy. This study is a prospective, observational study aiming to investigate the maternal cardiovascular adaptation to pregnancy in women with previous bariatric surgery compared to women with similar early pregnancy BMI and similar pre-surgery BMI. In addition, we investigated the cardiovascular adaptation to pregnancy in obese pregnant women compared to normal BMI pregnant women and the placental function in obese pregnant women and its association with cardiovascular parameters. Cardiovascular function was assessed at three time points during pregnancy by measuring blood pressure and using transthoracic echocardiography to assess haemodynamic function, cardiac geometry and systolic and diastolic function.Open Acces
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