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1.
Blood pressure postpartum (BP2) RCT protocol: Follow-up and lifestyle behaviour change strategies in the first 12 months after hypertensive pregnancy.
Henry, A, Arnott, C, Makris, A, Davis, G, Hennessy, A, Beech, A, Pettit, F, Se Homer, C, Craig, ME, Roberts, L, et al
Pregnancy hypertension. 2020;:1-6
Abstract
OBJECTIVES Women who had hypertensive disorders of pregnancy (HDP) are twice as likely to experience maternal cardiovascular disease later in life. The primary aim of this study (BP2) is to compare outcomes of 3 different management strategies, including lifestyle behaviour change (LBC), in the first 12 months postpartum in women who had HDP in their preceding pregnancy. Secondary aims include assessing the effects on other cardiometabolic parameters. STUDY DESIGN Three-arm multicentre randomised trial in metropolitan Australian hospitals, (registration: ACTRN12618002004246) target sample size 480. Participants are randomised to one of three groups: 1) Optimised usual care: information package and family doctor follow-up 6 months postpartum 2) Brief intervention: information package as per group 1, plus assessment and brief LBC counselling at a specialised clinic with an obstetric physician and dietitian 6 months postpartum 3) Extended intervention: as per group 2 plus enrolment into a 6 month telephone-based LBC program from 6 to 12 months postpartum. All women have an outcome assessment at 12 months. MAIN OUTCOME MEASURES Primary outcomes: (a) BP change or (b) weight change and/or waist circumference change. SECONDARY OUTCOMES maternal health-related quality of life, engagement and retention in LBC program, biochemical markers, vascular function testing, infant weight trajectory, incremental cost-effectiveness ratios. The study is powered to detect a 4 mmHg difference in systolic BP between groups, or a 4 kg weight loss difference/2cm waist circumference change. CONCLUSIONS BP2 will provide evidence regarding the feasibility and effectiveness of postpartum LBC interventions and structured clinical follow-up in improving cardiovascular health markers after HDP.
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2.
Maternal prepregnancy overweight and obesity and the risk of preeclampsia: A meta-analysis of cohort studies.
He, XJ, Dai, RX, Hu, CL
Obesity research & clinical practice. 2020;(1):27-33
Abstract
OBJECTIVE The aim of our meta-analysis was to explore whether overweight and obesity was associated with preeclampsia or not. DESIGN Three databases were systematically reviewed and reference lists of relevant articles were checked. Meta-analysis of published cohort studies comparing whether overweight and obesity was associated with preeclampsia and adjusting for potential confounding factors. Calculations of pooled estimates were conducted in random-effects models. Heterogeneity was tested by using Chi-square test with Cochrane and heterogeneity was explored with meta-regression. Publication bias was estimated from Egger's test (linear regression method) and Begg's test (rank correlation method). RESULTS Nineteen studies met the inclusion criteria. The meta-analysis showed that overweight and obesity was associated with an increased risk of preeclampsia. The aOR calculated for 13 studies (compared overweight to normal weight) was 1.71, 95% CI (1.52, 1.91) for random-effects models and 19 studies (compared obesity to normal weight) was 2.48, 95% CI (2.05, 2.90) for random-effects models, stratified analyses showed no differences regarding quality grade, location of study and period of anthropometric measurement. There was no indication of a publication bias either from the result of Egger's test or Begg's test. CONCLUSIONS Our results suggested that prepregnancy maternal overweight and obesity are significantly associated with an increased risk of preeclampsia.
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3.
Environmental risk factors, protective factors, and peripheral biomarkers for ADHD: an umbrella review.
Kim, JH, Kim, JY, Lee, J, Jeong, GH, Lee, E, Lee, S, Lee, KH, Kronbichler, A, Stubbs, B, Solmi, M, et al
The lancet. Psychiatry. 2020;(11):955-970
Abstract
BACKGROUND Many potential environmental risk factors, environmental protective factors, and peripheral biomarkers for ADHD have been investigated, but the consistency and magnitude of their effects are unclear. We aimed to systematically appraise the published evidence of association between potential risk factors, protective factors, or peripheral biomarkers, and ADHD. METHODS In this umbrella review of meta-analyses, we searched PubMed including MEDLINE, Embase, and the Cochrane Database of Systematic Reviews, from database inception to Oct 31, 2019, and screened the references of relevant articles. We included systematic reviews that provided meta-analyses of observational studies that examined associations of potential environmental risk factors, environmental protective factors, or peripheral biomarkers with diagnosis of ADHD. We included meta-analyses that used categorical ADHD diagnosis criteria according to DSM, hyperkinetic disorder according to ICD, or criteria that were less rigorous than DSM or ICD, such as self-report. We excluded articles that did not examine environmental risk factors, environmental protective factors, or peripheral biomarkers of ADHD; articles that did not include a meta-analysis; and articles that did not present enough data for re-analysis. We excluded non-human studies, primary studies, genetic studies, and conference abstracts. We calculated summary effect estimates (odds ratio [OR], relative risk [RR], weighted mean difference [WMD], Cohen's d, and Hedges' g), 95% CI, heterogeneity I2 statistic, 95% prediction interval, small study effects, and excess significance biases. We did analyses under credibility ceilings, and assessed the quality of the meta-analyses with AMSTAR 2 (A Measurement Tool to Assess Systematic Reviews 2). This study is registered with PROSPERO, number CRD42019145032. FINDINGS We identified 1839 articles, of which 35 were eligible for inclusion. These 35 articles yielded 63 meta-analyses encompassing 40 environmental risk factors and environmental protective factors (median cases 16 850, median population 91 954) and 23 peripheral biomarkers (median cases 175, median controls 187). Evidence of association was convincing (class I) for maternal pre-pregnancy obesity (OR 1·63, 95% CI 1·49 to 1·77), childhood eczema (1·31, 1·20 to 1·44), hypertensive disorders during pregnancy (1·29, 1·22 to 1·36), pre-eclampsia (1·28, 1·21 to 1·35), and maternal acetaminophen exposure during pregnancy (RR 1·25, 95% CI 1·17 to 1·34). Evidence of association was highly suggestive (class II) for maternal smoking during pregnancy (OR 1·6, 95% CI 1·45 to 1·76), childhood asthma (1·51, 1·4 to 1·63), maternal pre-pregnancy overweight (1·28, 1·21 to 1·35), and serum vitamin D (WMD -6·93, 95% CI -9·34 to -4·51). INTERPRETATION Maternal pre-pregnancy obesity and overweight; pre-eclampsia, hypertension, acetaminophen exposure, and smoking during pregnancy; and childhood atopic diseases were strongly associated with ADHD. Previous familial studies suggest that maternal pre-pregnancy obesity, overweight, and smoking during pregnancy are confounded by familial or genetic factors, and further high-quality studies are therefore required to establish causality. FUNDING None.
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4.
Prophylactic aspirin for preventing pre-eclampsia and its complications: An overview of meta-analyses.
Ghazanfarpour, M, Sathyapalan, T, Banach, M, Jamialahmadi, T, Sahebkar, A
Drug discovery today. 2020;(8):1487-1501
Abstract
Benefits of aspirin administration on pre-eclampsia and IUGR depend on the gestational age and dose of aspirin administration. Meta-analyses show that, to prevent preterm labor, aspirin could be administrated even after 16 weeks of gestational age.
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5.
Study protocol for the randomized controlled EVA (early vascular adjustments) trial: tailored treatment of mild hypertension in pregnancy to prevent severe hypertension and preeclampsia.
Mulder, E, Ghossein-Doha, C, Appelman, E, van Kuijk, S, Smits, L, van der Zanden, R, van Drongelen, J, Spaanderman, M
BMC pregnancy and childbirth. 2020;(1):775
Abstract
BACKGROUND In contrast to severe gestational hypertension, it is questioned whether antihypertensive medication for mild to moderate gestational hypertension prevents adverse maternal and offspring outcomes. Hypertensive drugs halve the risk of severe hypertension, but do not seem to prevent progression to preeclampsia or reduce the risk of complications in offspring. In fact, beta-blockers, a first line therapy option, are suspected to impair foetal growth. Disappointing effects of antihypertensive medication can be anticipated when the pharmacological mode of action does not match the underlying haemodynamic imbalance. Hypertension may result from 1) high cardiac output, low vascular resistance state, in which beta blockade is expected to be most effective, or 2) low cardiac output, high vascular resistance state where dihydropyridine calcium channel blockers or central-acting alpha agonists might be the best corrective medication. In the latter, beta-blockade might be maternally ineffective and even contribute to impaired foetal growth by keeping cardiac output low. We propose a randomized controlled trial to determine whether correcting the haemodynamic imbalance in women with mild to moderate hypertension reduces the development of severe hypertension and/or preeclampsia more than non-pharmacological treatment does, without alleged negative effects on foetal growth. METHODS Women diagnosed with mild to moderate hypertension without proteinuria or signs of other organ damage before 37 weeks of pregnancy are invited to participate in this randomized controlled trial. Women randomized to the intervention group will be prescribed tailored antihypertensive medication, using a simple diagnostic and treatment algorithm based on the mean arterial pressure/heart rate ratio, which serves as an easy-to-determine proxy for maternal circulatory state. Women randomized to the control group will receive non-pharmacological standard care according to national and international guidelines. In total, 208 women will be randomized in a 1:1 ratio. The primary outcome is progression to severe hypertension and preeclampsia and the secondary outcomes are adverse maternal and neonatal outcomes. DISCUSSION This trial will provide evidence of whether tailoring treatment of mild to moderate gestational hypertension to the individual haemodynamic profile prevents maternal disease progression. TRIAL REGISTRATION NCT02531490 , registered on 24 August 2015.
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6.
Oxidative stress markers in preeclamptic placentas: A systematic review with meta-analysis.
Ferreira, RC, Fragoso, MBT, Bueno, NB, Goulart, MOF, de Oliveira, ACM
Placenta. 2020;:89-100
Abstract
INTRODUCTION Oxidative stress (OS) is the basis of several diseases. Preeclampsia (PE) is a multisystemic syndrome, considered one of the major causes of maternal and fetal mortality. The placenta is considered the main anatomical pathogenetic substrate for the disease, being the placental OS a likely critical pathway in the pathogenesis of PE. This meta-analysis aimed to verify whether there is OS in the preeclamptic placenta and which markers are altered in this condition. METHODS The search was conducted in the following databases: MEDLINE (via PubMed), Lilacs and Scopus. Relevant studies were identified until May 2020. The quality of the studies was evaluated according to the Newcastle-Ottawa scale. RESULTS From the 3998 screened records, 43 were finally included in the systematic review, and 23 in the meta-analysis. The biomarkers evaluated were related to cell and macromolecules' damage, such as malondialdehyde (MDA), 8-hydroxy-2'-deoxyguanosine (8-OH-dG), lipid peroxides, isoprostane, total oxidant status (TOS), carbonylated proteins and some of the reactive oxygen and nitrogen species (RONS), like hydrogen peroxide and nitric oxide. It was also related to antioxidant activity, both enzymatic, including superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), glutathione S-transferase and total antioxidant status, and non-enzymatic, through quantification of reduced glutathione, vitamin C and E, zinc and copper. CONCLUSION It was observed that there was OS in the preeclamptic placentas, based on results, like lower activity of some of the enzymes of the antioxidant system (SOD and GPx) as well as the increase in oxidative damage markers (MDA and lipid peroxide), corroborating literature data.
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7.
Preeclampsia and low sodium (PALS): A case and systematic review.
Powel, JE, Rosenthal, E, Roman, A, Chasen, ST, Berghella, V
European journal of obstetrics, gynecology, and reproductive biology. 2020;:14-20
Abstract
Normal physiologic changes in pregnancy include mild hyponatremia. In some cases of preeclampsia, more significant hyponatremia has been associated with syndrome of inappropriate antidiuretic hormone secretion and hypervolemic hyponatremia. A 45-year-old gravida 2, para 0010 with a dichorionic twin gestation was diagnosed with preeclampsia at 30 weeks 6 days and noted to have concomitant hyponatremia of 125 mEq/L at our institution. Her hyponatremia was initially managed with furosemide and water restriction. She was delivered at 33 weeks 5 days due to worsening preeclampsia and continued significant hyponatremia despite treatment. Her hyponatremia resolved within 48 h after delivery. Our objectives were to discuss trends, treatment, and outcomes of cases with hyponatremia in preeclampsia. We performed a systematic review of the literature using Ovid Medline (1963-2017), Scopus (1962-2017), and PubMed (1963-2017, including Cochrane database). Relevant articles describing any case report of hyponatremia in preeclampsia were identified from the above databases without any time, language, or study limitations. Studies were deemed eligible for inclusion if they described a case of hyponatremia in the setting of preeclampsia. 18 manuscripts detailing 55 cases were identified. Pertinent demographic data and laboratory values were extracted. Maternal management strategy, diagnosis, delivery, and neonatal outcome data were also collected. Mean, range, standard deviation, and percentage calculations were used as applicable. Advanced maternal age (46 %), nulliparity (79 %), and multifetal gestation (34 %) were noted in patients with preeclampsia and low sodium. Hyponatremia was detected on average at 34 weeks gestation. 64 % were diagnosed with preeclampsia with severe features. When reported, diagnoses related to hyponatremia were syndrome of inappropriate antidiuretic hormone secretion (41 %) or hypervolemic hyponatremia (59 %). Indications for delivery included severe hyponatremia unresponsive to conservative measures in addition to other known obstetric or preeclamptic indications. Hyponatremia resolved within 48 h on average in cases where postpartum resolution was reported. It may be prudent to screen women with preeclampsia for electrolyte disturbances as part of their evaluation, especially in the setting of severe features. Initially, hyponatremia may be treated with medical management. In addition to established obstetric or preeclamptic indications, delivery may be considered if severe hyponatremia no longer responds to conservative measures.
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8.
The bivariate NRIP1/ZEB2 RNA marker permits non-invasive presymptomatic screening of pre-eclampsia.
Manders, V, Visser, A, Keijser, R, Min, N, Poutsma, A, Mulders, J, van den Berkmortel, T, Hortensius, M, Jongejan, A, Pajkrt, E, et al
Scientific reports. 2020;(1):21857
Abstract
Using genome-wide transcriptome analysis by RNA sequencing of first trimester plasma RNA, we tested whether the identification of pregnancies at risk of developing pre-eclampsia with or without preterm birth or growth restriction is possible between weeks 9-14, prior to the appearance of clinical symptoms. We implemented a metaheuristic approach in the self-learning SVM algorithm for differential gene expression analysis of normal pregnancies (n = 108), affected pregnancies (n = 34) and non-pregnant controls (n = 19). Presymptomatic candidate markers for affected pregnancies were validated by RT-qPCR in first trimester samples (n = 34) from an independent cohort. PRKG1 was significantly downregulated in a subset of pregnancies with birth weights below the 10thpercentile as shared symptom. The NRIP1/ZEB2 ratio was found to be upregulated in pregnancies with pre-eclampsia or trisomy 21. Complementary quantitative analysis of both the linear and circular forms of NRIP1 permitted discrimination between pre-eclampsia and trisomy 21. Pre-eclamptic pregnancies showed an increase in linear NRIP1 compared to circular NRIP1, while trisomy 21 pregnancies did not.
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9.
Tracking placental development in health and disease.
Aplin, JD, Myers, JE, Timms, K, Westwood, M
Nature reviews. Endocrinology. 2020;(9):479-494
Abstract
Pre-eclampsia and fetal growth restriction arise from disorders of placental development and have some shared mechanistic features. Initiation is often rooted in the maldevelopment of a maternal-placental blood supply capable of providing for the growth requirements of the fetus in later pregnancy, without exerting undue stress on maternal body systems. Here, we review normal development of a placental bed with a safe and adequate blood supply and a villous placenta-blood interface from which nutrients and oxygen can be extracted for the growing fetus. We consider disease mechanisms that are intrinsic to the maternal environment, the placenta or the interaction between the two. Systemic signalling from the endocrine placenta targets the maternal endothelium and multiple organs to adjust metabolism for an optimal pregnancy and later lactation. This signalling capacity is skewed when placental damage occurs and can deliver a dangerous pathogenic stimulus. We discuss the placental secretome including glycoproteins, microRNAs and extracellular vesicles as potential biomarkers of disease. Angiomodulatory mediators, currently the only effective biomarkers, are discussed alongside non-invasive imaging approaches to the prediction of disease risk. Identifying the signs of impending pathology early enough to intervene and ameliorate disease in later pregnancy remains a complex and challenging objective.
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10.
Clinical Procedures for the Prevention of Preeclampsia in Pregnant Women: A Systematic Review.
Moura, NS, Gomes, MLS, Rodrigues, IR, Rolnik, DL, Costa, FS, Oriá, MOB
Revista brasileira de ginecologia e obstetricia : revista da Federacao Brasileira das Sociedades de Ginecologia e Obstetricia. 2020;(10):659-668
Abstract
OBJECTIVE To identify the most effective procedures recommended for the prevention of preeclampsia. DATA SOURCES A systematic review was performed in the following databases: Pubmed/MEDLINE, CINAHL, Web of Science, Cochrane and LILACS via the Virtual Health Library (VHL). A manual search was also performed to find additional references. The risk of bias, the quality of the evidence, and the classification of the strength of the recommendations were evaluated using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. SELECTION OF STUDIES In the initial search in the databases, the total number of articles retrieved was 351, and 2 were retrieved through the manual search; after duplicate articles were removed, 333 citations remained. After a thorough review of the titles and abstracts, 315 references were excluded. Accordingly, 18 articles were maintained for selection of the complete text (phase 2). This process led to the exclusion of 6 studies. In total, 12 articles were selected for data extraction and qualitative synthesis. DATA COLLECTION The articles selected for the study were analyzed, and we inserted the synthesis of the evidence in the online software GRADEpro Guideline Development Tool (GDT) (McMaster University and Evidence Prime Inc. All right reserved. McMaster University, Hamilton, Ontário, Canada); thus, it was possible to develop a table of evidence, with the quality of the evidence and the classification of the strength of the recommendations. DATA SYNTHESIS In total, seven studies recommended the individual use of aspirin, or aspirin combined with calcium, heparin or dipyridamole. The use of calcium alone or in combination with phytonutrients was also highlighted. All of the studies were with women at a high risk of developing preeclampsia. CONCLUSION According to the studies evaluated, the administration of aspirin is still the best procedure to be used in the clinical practice to prevent preeclampsia.