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Angiogenic factors: potential to change clinical practice in pre-eclampsia?

ABSTRACT: Pre-eclampsia is a complex disease with significant maternal and fetal morbidity and mortality. Its syndromic nature makes diagnosis and management difficult. The field is rapidly evolving with the definition of pre-eclampsia being challenged by some organisations, with proteinuria no longer being essential in the presence of other features. In the last decade, angiogenic factors, in particular soluble fms-like tyrosine kinase 1 (sFlt-1), have emerged as important molecules in the pathogenesis of pre-eclampsia. Here we review the most recent evidence regarding the potential of these factors as biomarkers and therapeutic targets for pre-eclampsia. TWEETABLE ABSTRACT:A review of angiogenic factors, sFlt-1 and PlGF, in the diagnosis, prediction and management of pre-eclampsia.

SUBMITTER: Cerdeira AS

PROVIDER: S-EPMC6175139 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Angiogenic factors: potential to change clinical practice in pre-eclampsia?

Cerdeira A S AS Agrawal S S Staff A C AC Redman C W CW Vatish M M

BJOG : an international journal of obstetrics and gynaecology 20171228 11

Pre-eclampsia is a complex disease with significant maternal and fetal morbidity and mortality. Its syndromic nature makes diagnosis and management difficult. The field is rapidly evolving with the definition of pre-eclampsia being challenged by some organisations, with proteinuria no longer being essential in the presence of other features. In the last decade, angiogenic factors, in particular soluble fms-like tyrosine kinase 1 (sFlt-1), have emerged as important molecules in the pathogenesis o ...[more]

PMID: 29193681

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Project description:BackgroundThe pharmacokinetic basis of magnesium sulphate (MgSO4 ) dosing regimens for eclampsia prophylaxis and treatment is not clearly established.ObjectivesTo review available data on clinical pharmacokinetic properties of MgSO4 when used for women with pre-eclampsia and/or eclampsia.Search strategyMEDLINE, EMBASE, CINAHL, POPLINE, Global Health Library and reference lists of eligible studies.Selection criteriaAll study types investigating pharmacokinetic properties of MgSO4 in women with pre-eclampsia and/or eclampsia.Data collection and analysisTwo authors extracted data on basic pharmacokinetic parameters reflecting the different aspects of absorption, bioavailability, distribution and excretion of MgSO4 according to identified dosing regimens.Main resultsTwenty-eight studies investigating pharmacokinetic properties of 17 MgSO4 regimens met our inclusion criteria. Most women (91.5%) in the studies had pre-eclampsia. Baseline serum magnesium concentrations were consistently <1 mmol/l across studies. Intravenous loading dose between 4 and 6 g was associated with a doubling of this baseline concentration half an hour after injection. Maintenance infusion of 1 g/hour consistently produced concentrations well below 2 mmol/l, whereas maintenance infusion at 2 g/hour and the Pritchard intramuscular regimen had higher but inconsistent probability of producing concentrations between 2 and 3 mmol/l. Volume of distribution of magnesium varied (13.65-49.00 l) but the plasma clearance was fairly similar (4.28-5.00 l/hour) across populations.ConclusionThe profiles of Zuspan and Pritchard regimens indicate that the minimum effective serum magnesium concentration for eclampsia prophylaxis is lower than the generally accepted level. Exposure-response studies to identify effective alternative dosing regimens should target concentrations achievable by these standard regimens.Tweetable abstractMinimum effective serum magnesium concentration for eclampsia prophylaxis is lower than the generally accepted therapeutic level.

Project description:BackgroundHypertensive disorders account for 14% of global maternal deaths. Magnesium sulphate (MgSO4 ) is recommended for prevention and treatment of pre-eclampsia/eclampsia. However, MgSO4 remains underused, particularly in low- and middle-income countries (LMICs).ObjectiveThis qualitative evidence synthesis explores perceptions and experiences of healthcare providers, administrators and policy-makers regarding factors affecting use of MgSO4 to prevent or treat pre-eclampsia/eclampsia.Search strategyWe searched MEDLINE, EMBASE, Emcare, CINAHL, Global Health and Global Index Medicus, and grey literature for studies published between January 1995 and June 2021.Selection criteriaPrimary qualitative and mixed-methods studies on factors affecting use of MgSO4 in healthcare settings, from the perspectives of healthcare providers, administrators and policy-makers, were eligible for inclusion.Data collection and analysisWe applied a thematic synthesis approach to analysis, using COM-B behaviour change theory to map factors affecting appropriate use of MgSO4 .Main resultsWe included 22 studies, predominantly from LMICs. Key themes included provider competence and confidence administering MgSO4 (attitudes and beliefs, complexities of administering, knowledge and experience), capability of health systems to ensure MgSO4 availability at point of use (availability, resourcing and pathways to care) and knowledge translation (dissemination of research and recommendations). Within each COM-B domain, we mapped facilitators and barriers to physical and psychological capability, physical and social opportunity, and how the interplay between these domains influences motivation.ConclusionsThese findings can inform policy and guideline development and improve implementation of MgSO4 in clinical care. Such action is needed to ensure this life-saving treatment is widely available and appropriately used.Tweetable abstractGlobal qualitative review identifies factors affecting underutilisation of MgSO4 for pre-eclampsia and eclampsia.

Project description:BackgroundPre-eclampsia is the most common complication occurring during pregnancy. In the majority of cases, it is concurrent with other pathologies in a comorbid manner (frequent co-occurrences in patients), such as diabetes mellitus, gestational diabetes and obesity. Providing bronchial asthma, pulmonary tuberculosis, certain neurodegenerative diseases and cancers as examples, we have shown previously that pairs of inversely comorbid pathologies (rare co-occurrences in patients) are more closely related to each other at the molecular genetic level compared with randomly generated pairs of diseases. Data in the literature concerning the causes of pre-eclampsia are abundant. However, the key mechanisms triggering this disease that are initiated by other pathological processes are thus far unknown. The aim of this work was to analyse the characteristic features of genetic networks that describe interactions between comorbid diseases, using pre-eclampsia as a case in point.ResultsThe use of ANDSystem, Pathway Studio and STRING computer tools based on text-mining and database-mining approaches allowed us to reconstruct associative networks, representing molecular genetic interactions between genes, associated concurrently with comorbid disease pairs, including pre-eclampsia, diabetes mellitus, gestational diabetes and obesity. It was found that these associative networks statistically differed in the number of genes and interactions between them from those built for randomly chosen pairs of diseases. The associative network connecting all four diseases was composed of 16 genes (PLAT, ADIPOQ, ADRB3, LEPR, HP, TGFB1, TNFA, INS, CRP, CSRP1, IGFBP1, MBL2, ACE, ESR1, SHBG, ADA). Such an analysis allowed us to reveal differential gene risk factors for these diseases, and to propose certain, most probable, theoretical mechanisms of pre-eclampsia development in pregnant women. The mechanisms may include the following pathways: [TGFB1 or TNFA]-[IL1B]-[pre-eclampsia]; [TNFA or INS]-[NOS3]-[pre-eclampsia]; [INS]-[HSPA4 or CLU]-[pre-eclampsia]; [ACE]-[MTHFR]-[pre-eclampsia].ConclusionsFor pre-eclampsia, diabetes mellitus, gestational diabetes and obesity, we showed that the size and connectivity of the associative molecular genetic networks, which describe interactions between comorbid diseases, statistically exceeded the size and connectivity of those built for randomly chosen pairs of diseases. Recently, we have shown a similar result for inversely comorbid diseases. This suggests that comorbid and inversely comorbid diseases have common features concerning structural organization of associative molecular genetic networks.

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Angiogenic factors: potential to change clinical practice in pre-eclampsia?

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Angiogenic factors: potential to change clinical practice in pre-eclampsia?

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