Thromboembolic complications remain a major public health burden, making antithrombotic agents one of the most widely prescribed groups of medication, but the treatment is often challenging as it... Show moreThromboembolic complications remain a major public health burden, making antithrombotic agents one of the most widely prescribed groups of medication, but the treatment is often challenging as it at the same time increases risk of bleeding. With nationwide data from Statistics Netherlands, antithrombotic therapy and relevant clinical outcomes were comprehensively examined in the patient population of atrial fibrillation, overall or among those with comorbid cancer. The results suggest the patient population was increasingly receiving anticoagulants, driven by the newly introduced medication- direct oral anticoagulant and guided by the CHA2DS2-VASc score, and meanwhile the patient population experienced fewer ischemic stroke and major bleeding. In spite of these promising changes, suboptimal medication adherence and potential underuse of anticoagulants remain directions for further improvement. Antithrombotic agent use during pregnancy was also examined in the general Dutch pregnant population, which featured a surge in antiplatelet prescriptions, and risk of preeclampsia/eclampsia decreased and several newborn outcomes improved simultaneously. Together, the studies presented in this thesis provide an overview of antithrombotic therapy in the Netherlands in recent years, providing insights for further improving this treatment and relevant patient outcomes. Show less
Pulmonary embolism (PE) is a serious and sometimes life-threatening condition that refers to a blood clot that occludes the arteries of the lung. Despite all improvements over the past decades,... Show morePulmonary embolism (PE) is a serious and sometimes life-threatening condition that refers to a blood clot that occludes the arteries of the lung. Despite all improvements over the past decades, diagnosing PE is still a difficult process due to the non-specific symptoms, which can frequently overlap with symptoms of other cardiopulmonary diseases. Currently recommended diagnostic strategies for suspected acute PE consist of standardized assessment of the clinical pre-test probability (CPTP) using validated clinical decision rules (CDRs) and D-dimer testing. PE is considered safely ruled out in patients with a non-high CPTP and a normal D-dimer test. Imaging tests as computed tomography pulmonary angiography (CTPA) are required in the case of a high CPTP and/or abnormal D-dimer test to confirm the diagnosis. The first part of this thesis describes the challenges of diagnosing PE in general and in specific clinically relevant patient subgroups. Moreover, this part evaluates the diagnostic performance of non-invasive diagnostic strategies for suspected PE in specific relevant patient subgroups. The second part of this thesis focuses on venous thrombotic complications in hospitalized patients with COVID-19. Show less
In this thesis the aim was to study immune cell interactions at the maternal-fetal interface to understand the role for immune cells during healthy pregnancy development an pregnancy complications.... Show moreIn this thesis the aim was to study immune cell interactions at the maternal-fetal interface to understand the role for immune cells during healthy pregnancy development an pregnancy complications. Specifically in cases of recurrent pregnancy loss and chronic histiocytic intervillositis. Show less
Heemelaar, J.C.; Heemelaar, S.; Hertel, S.N.; Jukema, J.W.; Sueters, M.; Louwerens, M.; Antoni, M.L. 2023
Background: Childhood cancer survivors (CCS) are at increased risk of cardiomyopathy during pregnancy if they have prior cardiotoxic exposure. Currently, there is no consensus on the necessity,... Show moreBackground: Childhood cancer survivors (CCS) are at increased risk of cardiomyopathy during pregnancy if they have prior cardiotoxic exposure. Currently, there is no consensus on the necessity, timing and modality of cardiac monitoring during and after pregnancy. Therefore, we examined cardiac function using contemporary echocardiographic parameters during pregnancy in CCS with cardiotoxic treatment exposure, and we observed obstetric outcomes in CCS, including in women without previous cardiotoxic treatment exposure. Method: A single-center retrospective cohort study was conducted among 39 women enrolled in our institution's cancer survivorship outpatient clinic. Information on potential cardiotoxic exposure in childhood, cancer diagnosis and outcomes of all pregnancies were collected through interviews and review of health records. Echocardiographic exams before and during pregnancy were retrospectively analyzed for left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS) if available. The primary outcomes were (i) left ventricular dysfunction (LVD) during pregnancy, defined as LVEF < 50% or a decline of >= 10% in LVEF below normal (< 54%), and (ii) symptomatic heart failure (HF). Rate of obstetric and fetal complications was compared to the general population through the national perinatal registry (PERINED). Results: All pregnancies (91) of 39 women were included in this study. The most common malignancy was leukemia (N = 17, 43.6%). In 22 patients, echocardiograms were retrospectively analyzed. LVEFbaseline was 55.4 +/- 1.2% and pre-existing subnormal LVEF was common (7/22, 31.8/%). The minimum value of LVEF during pregnancy was 3.8% lower than baseline (p = 0.002). LVD occurred in 9/22 (40.9%) patients and HF was not observed. When GLS was normal at baseline (< -18.0%; N = 12), none of the women developed LVD. Nine of out ten women with abnormal GLS at baseline developed LVD later in pregnancy. In our cohort, the obstetric outcomes seemed comparable with the general population unless patients underwent abdominal irradiation (N = 5), where high rates of preterm birth (only 5/18 born at term) and miscarriage (6/18 pregnancies) were observed. Conclusion: Our study suggests that women with prior cardiotoxic treatment have a low risk of LVD during pregnancy if GLS at baseline was normal. Pregnancy outcomes are similar to the healthy population except when patients underwent abdominal irradiation. Show less
Recurrent pregnancy loss (RPL) is a poorly understood condition that comes with many uncertainties, both for affected couples and healthcare providers. Important goals are to provide answers to... Show moreRecurrent pregnancy loss (RPL) is a poorly understood condition that comes with many uncertainties, both for affected couples and healthcare providers. Important goals are to provide answers to these couples and to improve their pregnancy outcomes. To achieve this, we need a better understanding of contributing and predictive factors. Until now, the male role in RPL has been underexposed. In this thesis, we aimed to expand our knowledge regarding the ‘forgotten father’ in RPL. We have found strong clues that in RPL, male contribution really matters.The main conclusions are that advanced paternal age and paternal smoking are associated with an increased risk of pregnancy loss, that inclusion of paternal factors into a prediction model improves the accuracy of predicting ongoing pregnancy after RPL, and that impaired immunomodulatory effects of seminal plasma may play a role in RPL. At the same time, our studies have led to new questions and uncovered new challenges, which are excellent opportunities for further research. Show less
Aim: To examine whether maternal angiogenic factors in the first half of pregnancy are associated with offspring left and right cardiac development. Methods: In a population-based prospective... Show moreAim: To examine whether maternal angiogenic factors in the first half of pregnancy are associated with offspring left and right cardiac development. Methods: In a population-based prospective cohort among 2,415 women and their offspring, maternal first and second trimester plasma PlGF and sFlt-1 concentrations were measured. Cardiac MRI was performed in their offspring at 10 years. Results: Maternal angiogenic factors were not associated with childhood cardiac outcomes in the total population. In children born small-for-their-gestational-age, higher maternal first trimester PlGF concentrations were associated with a lower childhood left ventricular mass (-0.24 SDS [95a/aCI-0.42,-0.05 per SDS increase in maternal PlGF]), whereas higher sFlt-1 concentrations were associated with higher childhood left ventricular mass (0.22 SDS [95a/aCI 0.09, 0.34 per SDS increase in maternal sFlt-1]). Higher second trimester maternal sFlt-1 concentrations were also associated with higher childhood left ventricular mass (P-value > .05). In preterm born children, higher maternal first and second trimester sFlt-1/PlGF ratio were associated with higher childhood left ventricular mass (0.30 SDS [95a/aCI 0.01, 0.60], 0.22 SDS [95a/aCI-0.03, 0.40]) per SDS increase in maternal sFlt-1/PlGF ratio in first and second trimester respectively). No effects on other childhood cardiac outcomes were present within these higher-risk children. Conclusions: In a low-risk population, maternal angiogenic factors are not associated with childhood cardiac ventricular structure, and function within the normal range. In children born small for their gestational age or preterm, an imbalance in maternal angiogenic factors in the first half of pregnancy was associated with higher childhood left ventricular mass only. Show less
BackgroundSchistosoma antigen detection in urine is a valuable diagnostic approach for schistosomiasis control programmes because of the higher sensitivity compared to parasitological methods and... Show moreBackgroundSchistosoma antigen detection in urine is a valuable diagnostic approach for schistosomiasis control programmes because of the higher sensitivity compared to parasitological methods and preferred sampling of urine over stool. Highly accurate diagnostics are important in low Schistosoma transmission areas. Pregnant women and young children could particularly benefit from antigen testing as praziquantel (PZQ) can be given to only confirmed Schistosoma cases. This prevents the unborn baby from unnecessary exposure to PZQ. We present here the protocol of a diagnostic study that forms part of the freeBILy project. The aim is to evaluate the accuracy of circulating anodic antigen (CAA) detection for diagnosis of Schistosoma haematobium infections in pregnant women and to validate CAA as an endpoint measure for anti-Schistosoma drug efficacy. The study will also investigate Schistosoma infections in infants.MethodsA set of three interlinked prospective, observational studies is conducted in Gabon. The upconverting phosphor lateral flow (UCP-LF) CAA test is the index diagnostic test that will be evaluated. The core trial, sub-study A, comprehensively evaluates the accuracy of the UCP-LF CAA urine test against a set of other Schistosoma diagnostics in a cross-sectional trial design. Women positive for S. haematobium will proceed with sub-study B and will be randomised to receive PZQ treatment immediately or after delivery followed by weekly sample collection. This approach includes comparative monitoring of CAA levels following PZQ intake and will also contribute further data for safety of PZQ administration during pregnancy. Sub-study C is a longitudinal study to determine the incidence of S. haematobium infection as well as the age for first infection in life-time.DiscussionThe freeBILy trial in Gabon will generate a comprehensive set of data on the accuracy of the UCP-LF CAA test for the detection of S. haematobium infection in pregnant women and newborn babies and for the use of CAA as a marker to determine PZQ efficacy. Furthermore, incidence of Schistosoma infection in infants will be reported. Using the ultrasensitive diagnostics, this information will be highly relevant for Schistosoma prevalence monitoring by national control programs as well as for the development of medicaments and vaccines.Trial registrationThe registration number of this study is NCT03779347 (clinicaltrials.gov, date of registration: 19 December 2018). Show less
Background Maternal right ventricular (RV) dysfunction (measured by echocardiography) is associated with impaired uteroplacental circulation, however echocardiography has important limitations in... Show moreBackground Maternal right ventricular (RV) dysfunction (measured by echocardiography) is associated with impaired uteroplacental circulation, however echocardiography has important limitations in the assessment of RV function. We therefore aimed to investigate the association of pre-pregnancy RV and left ventricular (LV) function measured by cardiovascular magnetic resonance with uteroplacental Doppler flow parameters in pregnant women with repaired Tetralogy of Fallot (ToF). Methods Women with repaired ToF were examined, who had been enrolled in a prospective multicenter study of pregnant women with congenital heart disease. Clinical data and CMR evaluation before pregnancy were compared with uteroplacental Doppler parameters at 20 and 32 weeks gestation. In particular, pulsatility index (PI) of uterine and umbilical artery were studied. Results We studied 31 women; mean age 30 years, operated at early age. Univariable analyses showed that reduced RV ejection fraction (RVEF;P = 0.037 andP = 0.001), higher RV end-systolic volume (P = 0.004) and higher LV end-diastolic and end-systolic volume (P = 0.001 andP = 0.003, respectively) were associated with higher uterine or umbilical artery PI. With multivariable analyses (corrected for maternal age and body mass index), reduced RVEF before pregnancy remained associated with higher umbilical artery PI at 32 weeks (P = 0.002). RVEF was lower in women with high PI compared to women with normal PI during pregnancy (44% vs. 53%,p = 0.022). LV ejection fraction was not associated with uterine or umbilical artery PI. Conclusions Reduced RV function before pregnancy is associated with abnormal uteroplacental Doppler flow parameters. It could be postulated that reduced RV function on pre-pregnancy CMR (<= 2 years) is a predisposing factor for impaired placental function in women with repaired ToF. Show less
Aims Data on the early course and use of systemic thrombolysis in pregnant women with pulmonary embolism associated or not with haemodynamic failure are scarce. We investigated these aspects using... Show moreAims Data on the early course and use of systemic thrombolysis in pregnant women with pulmonary embolism associated or not with haemodynamic failure are scarce. We investigated these aspects using the information from the German Nationwide Inpatient Registry (years 2005-2016). Methods and results In Germany, all diagnoses referring to hospitalized patients are coded according to the International Classification of Diseases and Related Health Problems, 10th Revision with German Modification. We analysed data of pregnant women aged 18-50 years for whom the following diagnoses were recorded during hospitalization: (i) pulmonary embolism (I26) during pregnancy or peripartum (O09) or (ii) obstetric thromboembolism (O88.2). Haemodynamic failure at any time during the in-hospital stay was defined as need for cardiopulmonary resuscitation (OPS code 8-77) or the presence of shock (International Classification of Diseases and Related Health Problems, 10th Revision with German Modification code R57). The primary study outcome was in-hospital death. A total of 8 271 327 births were registered in Germany from 2005 to 2016. During this 12 year time period, there were 1846 hospitalizations for pregnancy-associated pulmonary embolism in patients aged 18-50, corresponding to 2.2 [95% confidence interval (CI): 2.1-2.3] cases every 10 000 births and 0.2% of all hospitalizations for pulmonary embolism in Germany. The median age was 31 years, and the median length of hospitalization was 8 days. A total of 63 deaths were reported, corresponding to an overall in-hospital fatality rate of 3.4% (95% CI: 2.7-4.4) and a pulmonary embolism-related mortality rate of 0.8 (95% CI: 0.6-1.0) per 100 000 (live) births per year. Pulmonary embolism-related deaths in hospitalized pregnant women represented 14% of all maternal deaths recorded in Germany between 2005 and 2016. A total of 135 (7.3%) women had haemodynamic failure, of whom 51 (37.8%) received systemic thrombolysis and 50 (37.0%) died. Conclusions Pulmonary embolism-related fatality remains substantial in pregnant women with pulmonary embolism and represents a frequent cause of maternal mortality. The use of systemic thrombolysis was reported in one third of pregnant women with pulmonary embolism and haemodynamic failure. Better preventive and management strategies should be urgently implemented in this vulnerable patient group. Show less
Pregnancy can be seen as an immunologic paradox. Even though the fetus expresses paternally inherited alloantigens it is protected from rejection by a proper regulation of the maternal immune... Show morePregnancy can be seen as an immunologic paradox. Even though the fetus expresses paternally inherited alloantigens it is protected from rejection by a proper regulation of the maternal immune system. With the studies described in this thesis, we want to get more insight in the immunologic mechanisms that play a role in pregnancy. The results of this research can help to identify underlying etiologies in patients with unexplained pregnancy complications, such as recurrent miscarriage. Identifying these causes is important for providing answers and taking away anxiety in these couples, and eventually for the development of effective therapies. Furthermore, elucidating the mechanism leading to survival or rejection of the fetal allograft is not only essential for our understanding of processes leading to normal and abnormal pregnancies, but may also result in important concepts in the field of transplantation and autoimmunity. Show less
Petrus, A.H.J.; Jongert, B.L.; Kies, P.; Sueters, M.; Jongbloed, M.R.M.; Vliegen, H.W.; ... ; Akker, T. van den 2020
Objective: Maternal heart disease (HD) complicates 1-4 % of pregnancies and is associated with adverse maternal and fetal outcomes. Although vaginal birth is generally recommended in the guidelines... Show moreObjective: Maternal heart disease (HD) complicates 1-4 % of pregnancies and is associated with adverse maternal and fetal outcomes. Although vaginal birth is generally recommended in the guidelines, cesarean section (CS) rates in women with HD are often high. Aim of the present study was to evaluate mode of birth and pregnancy outcomes in women with HD in a tertiary care hospital in the Netherlands.Study design: The study population consisted of 128 consecutive pregnancies in 99 women with HD, managed by a pregnancy heart team between 2012-2017 and ending in births after 24 weeks' gestation. Pregnancy risk was assessed per modified World Health Organization class. Mode of birth (planned and performed) and maternal and fetal complications (cardiovascular events, postpartum hemorrhage, prematurity, small for gestational age and death) were assessed for each pregnancy.Results: Pregnancy risk was classified as modified World Health Organization class I in 23 %, class II in 50 %, class III in 21 % and class IV in 6% of pregnancies. Planned mode of birth was vaginal in 114 pregnancies (89 %) and CS in 14 (11 %; nine for obstetric and five for cardiac indication). An unplanned CS was performed in 18 pregnancies (16 %; 16 for obstetric and two for cardiac indications). Overall mode of birth was vaginal in 75 % and CS in 25 %. Twelve cardiovascular events occurred in eight pregnancies (6 %), postpartum hemorrhage in nine (7 %) and small for gestational age in 14 (11 %). No maternal or fetal deaths occurred.Conclusions: Findings of this study indicate that - given that pregnancies are managed and mode of birth is meticulously planned by a multidisciplinary pregnancy heart team - vaginal birth is a suitable option for women with HD. (C) 2020 Elsevier B.V. All rights reserved. Show less
Galbally, M.; Watson, S.J.; IJzendoorn, M. van; Saffery, R.; Ryan, J.; Kloet, E.R. de; ... ; Lewis, A.J. 2020
Understanding fetal programming pathways that underpin the relationship between maternal and offspring mental health necessitates an exploration of potential role of epigenetic variation in early... Show moreUnderstanding fetal programming pathways that underpin the relationship between maternal and offspring mental health necessitates an exploration of potential role of epigenetic variation in early development. Two genes involved in stress response regulation, the glucocorticoid and mineralocorticoid receptors (NR3C1 and NR3C2) have been a focus in understanding stressful exposures and mental health outcomes. Data were obtained from 236 pregnant women from the Mercy Pregnancy Emotional Wellbeing Study (MPEWS), a selected pregnancy cohort, recruited in early pregnancy. Depression was measured using the Structured Clinical Interview for DSM-IV (SCID-IV) and repeated measures of the Edinburgh Postnatal Depression Scale (EPDS). Antidepressant use, stressful events and anxiety symptoms were measured. NR3C1 and NR3C2 DNA methylation was measured in placental and infant buccal samples. Infant cortisol was measured in repeat saliva samples across a task. This study found maternal early pregnancy depressive disorder and symptoms were associated with lower DNA methylation at NR3C2 CpG_24 in placental tissue. There were no significant differences for depression or antidepressant use for DNA methylation of NR3C1. Antenatal depression was associated with lower infant cortisol reactivity at 12 months. DNA methylation in CpG_24 site in NR3C2 in placental samples suppressed the relationship between early maternal depressive symptoms and infant cortisol reactivity. These findings show a relationship between antenatal depression, NR3C2 DNA methylation and infant cortisol response providing support for a specific fetal programming pathway. Further research is required to examine the stability of this epigenetic mark across childhood and long-term mental health outcomes. Show less
Objective: Little is known about the course of echocardiographic parameters used for the evaluation of valvular heart disease (VHD) during pregnancy, hampering interpretation of possible changes ... Show moreObjective: Little is known about the course of echocardiographic parameters used for the evaluation of valvular heart disease (VHD) during pregnancy, hampering interpretation of possible changes (physiological vs. pathophysiological). Therefore we studied the course of these parameters and ventricular function in pregnant women with aortic and pulmonary VHD.Methods: The cohort comprised 66 pregnant women enrolled in the prospective ZAHARA studies or evaluated by an identical protocol who had pulmonary VHD or aortic VHD (stenosis/prosthetic valve). The control group comprised 46 healthy pregnant women. Echocardiography was performed preconception, during pregnancy and 1 year postpartum. Peak gradient, mean gradient, aortic valve area (AVA)/effective orifice area (EOA), left ventricular ejection fraction (LVEF) and right ventricular function (RVF; TAPSE) were assessed.Results: Peak and mean gradients increased during pregnancy compared to preconception inwomen with aortic VHD and controls (p < 0.0125), but not in women with pulmonary VHD. AVA/EOA remained unchanged. Preconception and postpartum gradients were comparable in all groups. Mean LVEF was normal in pregnant women with VHD and controls. Mean TAPSE was lower (p < 0.001) in women with pulmonary VHD compared to women with aortic VHD and controls (<20 mm vs. >= 23 mm; p < 0.001). In women with pulmonary VHD a decrease of TAPSE was observed during pregnancy (p = 0.005).Conclusion: Physiological changes during pregnancy lead to increased Doppler gradients in women with aortic VHD. This increase was not found inwomen with pulmonary VHD, probably caused by impaired RVF. Therefore, evaluation of RVF during pregnancy might be important to prevent underestimation of the degree of stenosis. (c) 2019 Elsevier B.V. All rights reserved. Show less
During pregnancy a unique situation arises in which the mother's immune system accepts the fetus, which carries both maternal and paternal genes, and does not reject it as can occur in solid organ... Show moreDuring pregnancy a unique situation arises in which the mother's immune system accepts the fetus, which carries both maternal and paternal genes, and does not reject it as can occur in solid organ transplantation. The aim of this dissertation was to unravel the immunological mechanisms that ensure tolerance during a healthy pregnancy and uncover how alterations could contribute to the development of pregnancy complications, such as pre-eclampsia and preterm birth.We applied the new technique mass cytometry and the associated computational analyzes to map all immune cells of the mother during a healthy pregnancy. Furthermore, we demonstrated the presence of three types of functional regulatory CD4+ T cells, identified a phenotype of CD8+ T cells that can offer both tolerance and immunity against infections, and demonstrated potential cross-reactivity of T cells against fetal allo-antigens. The results described in this thesis have contributed to a better understanding of healthy pregnancies and form a basis on which further research can be built. Show less
Women with Von Willebrand disease (VWD) have an increased risk of developing postpartum hemorrhage (PPH). Our aim is to evaluate peripartum management strategies in relation to maternal and... Show moreWomen with Von Willebrand disease (VWD) have an increased risk of developing postpartum hemorrhage (PPH). Our aim is to evaluate peripartum management strategies in relation to maternal and neonatal bleeding complications in VWD. Electronic databases were searched up to January 2019. Seventy-one case-reports and series and 16 cohort studies were selected, including 811 deliveries. Cohort studies reported primary PPH in 32% and secondary PPH in 13% of the women. The overall primary PPH incidence in the individual patient data was 34%, similar between women who received prophylactic treatment to prevent PPH and those who didn't. Neonatal bleeding events were reported in 4.6% of deliveries. Overall, the available evidence on peripartum management in women with VWD was of low quality. The ongoing high risk for PPH is evident, despite prophylactic treatment, as well as the need for higher quality evidence from larger prospective cohort studies to improve management strategies. Show less
Understanding maternal mental health and cortisol regulation across pregnancy and the relationship to the development of the offspring's stress regulation Is critical to a range of health outcomes.... Show moreUnderstanding maternal mental health and cortisol regulation across pregnancy and the relationship to the development of the offspring's stress regulation Is critical to a range of health outcomes. The aim of this study was to investigate infant and maternal cortisol in women with depression. Data were obtained from 241 pregnant women within the Mercy Pregnancy and Emotional Wellbeing Study (MPEWS), a selected pregnancy cohort study. Depression was measured using the Structured Clinical Interview for DSM-IV (SCID-IV) and repeat Edinburgh Postnatal Depression Scale (EPDS). Repeated measures of antidepressant use, stressful events, anxiety symptoms and maternal hair cortisol concentrations (HCC) and infant cortisol at 12 months postpartum in saliva and hair. Socio-emotional outcomes were measured at 12 months by maternal report on the Brief Infant and Toddler Socio-emotional Assessment (BITSEA). This study found that maternal depression was not associated with maternal HCC. Anxiety, stress and antidepressant use were not associated with maternal HCC. Independently, higher maternal 3rd trimester maternal depressive and anxiety symptoms were associated with lower infant cortisol response at 12 months of age. A higher number of postpartum stressful events was associated with lower infant cortisol response. Lower infant stress reactivity was associated with higher externalizing symptoms at 12 months of age. Future studies are required to understand implications for later mental health. Show less
Pulmonary embolism (PE) refers to a blood clot in the pulmonary artery or one of its branches, which is most commonly originating from deep venous thrombosis (DVT) of the legs or pelvis. Venous... Show morePulmonary embolism (PE) refers to a blood clot in the pulmonary artery or one of its branches, which is most commonly originating from deep venous thrombosis (DVT) of the legs or pelvis. Venous thrombo-embolism (VTE) encompasses both pulmonary embolism (PE) and deep venous thrombosis (DVT). VTE is the third most frequent cardiovascular disease and it is a major cause of mortality, morbidity and chronic disease and disability. In Europe, it affects 430,000 patients each year and worldwide the overall annual incidence is 100-200 per 100,000 inhabitants. The diagnostic process of patients with suspected PE is challenging due to the non-specific symptoms and clinical presentation. Integrated diagnostic algorithms including validated clinical decision rules, high sensitive D-dimer tests and imaging tests such as computed tomography pulmonary angiography (CTPA) may guide the clinician, and close adherence to the diagnostic algorithm is of crucial importance for the clinical outcome of patients with suspected PE. The focus of this thesis is the diagnostic management of patients with suspected PE. Show less
Craenmehr, M.H.C.; Egmond, A. van; Haasnoot, G.W.; Eikmans, M.; Roelen, D.L.; Heidt, S.; ... ; Claas, F.H.J. 2019
Background: A considerable body of evidence accumulated especially during the last decade, demonstrating that early nutrition and lifestyle have long-term effects on later health and disease (... Show moreBackground: A considerable body of evidence accumulated especially during the last decade, demonstrating that early nutrition and lifestyle have long-term effects on later health and disease ("developmental or metabolic programming"). Methods: Researchers involved in the European Union funded international EarlyNutrition research project consolidated the scientific evidence base and existing recommendations to formulate consensus recommendations on nutrition and lifestyle before and during pregnancy, during infancy and early childhood that take long-term health impact into account. Systematic reviews were performed on published dietary guidelines, standards and recommendations, with special attention to long-term health consequences. In addition, systematic reviews of published systematic reviews on nutritional interventions or exposures in pregnancy and in infants and young children aged up to 3 years that describe effects on subsequent overweight, obesity and body composition were performed. Experts developed consensus recommendations incorporating the wide-ranging expertise from additional 33 stakeholders. Findings: Most current recommendations for pregnant women, particularly obese women, and for young children do not take long-term health consequences of early nutrition into account, although the available evidence for relevant consequences of lifestyle, diet and growth patterns in early life on later health and disease risk is strong. Interpretation: We present updated recommendations for optimized nutrition before and during pregnancy, during lactation, infancy and toddlerhood, with special reference to later health outcomes. These recommendations are developed for affluent populations, such as women and children in Europe, and should contribute to the primary prevention of obesity and associated non-communicable diseases. (c) 2019 S. Karger AG, Basel Show less
