Prevention of preeclampsia.

Preeclampsia is a relatively common pregnancy complication and constitutes a major cause of morbidity and mortality for mothers and children worldwide. It disproportionally affects low-resource countries. Appropriate identification of individuals at increased risk and prevention of the disease and its complications remain healthcare and research priorities, and the investigation of potential interventions to prevent preeclampsia has driven much of the obstetric research in recent decades. In this article, we review the scientific literature on the topic, highlighting established benefits and remaining questions regarding different non-pharmacological and pharmacological strategies, including exercise, the timing of birth, aspirin and calcium use, among others, as well as potential novel therapies under investigation.

Inpatient versus outpatient management of prenatally diagnosed vasa praevia: A systematic review and meta-analysis.

OBJECTIVE: Vasa praevia is a serious pregnancy complication that is potentially life-threatening for the fetus. The possible benefits of prophylactic hospital admission of asymptomatic women diagnosed with vasa praevia antenatally remain unclear. This study aims to compare the pregnancy outcomes of inpatient versus outpatient management in women with a prenatal diagnosis of vasa praevia. METHODS: A systematic search of four electronic databases was conducted and two reviewers independently screened studies for eligibility. The inclusion criteria incorporated studies with prenatally diagnosed vasa praevia, a distinction on whether women were managed as inpatients and/or outpatients and where perinatal mortality was recorded as an outcome. The primary outcome of the study was perinatal mortality with additional outcomes of perinatal morbidity, need for emergency caesarean and antenatal steroid administration. Reporting of the results followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. RESULTS: The search produced 2,300 studies with ten of these studies included in the qualitative synthesis and four included in the quantitative analysis. There was no significant difference in perinatal mortality (OR 1.12, 95 % CI 0.10-12.07, p = 0.93, I2 = 0 %) or morbidity between women managed as inpatients or outpatients. The prophylactic inpatient group had higher rates of earlier gestational delivery and antenatal corticosteroid administration (OR 10.78, 95 % CI 1.07-108.74, p = 0.04, I2 = 82 %), but lower rates of emergency caesareans (OR 0.35, 95 % CI 0.17-0.72, p = 0.004, I2 = 0 %). CONCLUSION: There were no significant differences in perinatal mortality or morbidity rates observed between inpatient and outpatient management of asymptomatic women with antenatally diagnosed vasa praevia. However, outpatient management is associated with prolonged gestation, a decrease in antenatal corticosteroid administration, and higher odds of emergency caesarean. Outpatient management of prenatally diagnosed vasa praevia seems appropriate for carefully selected asymptomatic women.

Preterm Birth: Screening and Prediction.

Preterm birth (PTB) affects approximately 10% of births globally each year and is the most significant direct cause of neonatal death and of long-term disability worldwide. Early identification of women at high risk of PTB is important, given the availability of evidence-based, effective screening modalities, which facilitate decision-making on preventative strategies, particularly transvaginal sonographic cervical length (CL) measurement. There is growing evidence that combining CL with quantitative fetal fibronectin (qfFN) and maternal risk factors in the extensively peer-reviewed and validated QUanititative Innovation in Predicting Preterm birth (QUiPP) application can aid both the triage of patients who present as emergencies with symptoms of preterm labor and high-risk asymptomatic women attending PTB surveillance clinics. The QUiPP app risk of delivery thus supports shared decision-making with patients on the need for increased outpatient surveillance, in-patient treatment for preterm labor or simply reassurance for those unlikely to deliver preterm. Effective triage of patients at preterm gestations is an obstetric clinical priority as correctly timed administration of antenatal corticosteroids will maximise their neonatal benefits. This review explores the predictive capacity of existing predictive tests for PTB in both singleton and multiple pregnancies, including the QUiPP app v.2. and discusses promising new research areas, which aim to predict PTB through cervical stiffness and elastography measurements, metabolomics, extracellular vesicles and artificial intelligence.

Ophthalmic artery Doppler in the complementary diagnosis of preeclampsia: a systematic review and meta-analysis.

OBJECTIVE: To evaluate the accuracy of different parameters of the ophthalmic artery Doppler (OAD) in the complementary diagnosis of preeclampsia (PE). METHODS: This meta-analysis adhered to the PRISMA guidelines. To investigate the mean difference in OAD values, peak systolic velocity (PSV), end-diastolic velocity (EDV), second systolic velocity peak (P2), resistance index (RI), pulsatility index (PI), and peak ratio (PR), between PE cases (overall and according to severity) and controls, random-effects meta-analyses were conducted for each Doppler parameter, with overall PE and mild and severe PE subgroups. Diagnostic performance and heterogeneity were evaluated with summary receiver operating characteristic (sROC) curves and 95% confidence intervals obtained with bivariate models. RESULTS: Eight studies stratified the results into mild and severe or late and early PE, involving 1,425 pregnant women. PR and P2 had better diagnostic performance than the other indexes, with the PR of AUsROC at 0.885, the sensitivity of 84%, and specificity of 92%, with a low false-positive rate of 0.08 and the P2 with AUsROC of 0.926, the sensitivity of 85% and specificity of 88%. RI, PI, and EDV showed good performance and consistency across studies but lower AUsROC values of 0.833, 0.794, and 0.772, respectively. CONCLUSION: Ophthalmic artery Doppler is a complementary tool with good performance for the diagnosis of overall and severe preeclampsia, with high and best sensitivity and specificity when using PR and P2 parameters.

Perspectives on the Use of Placental Growth Factor (PlGF) in the Prediction and Diagnosis of Pre-Eclampsia: Recent Insights and Future Steps.

Pre-eclampsia (PE) is a complex multisystem disease of pregnancy that is becoming increasingly recognized as a state of angiogenic imbalance characterized by low concentrations of placental growth factor (PlGF) and elevated soluble fms-like tyrosine kinase (sFlt-1). PlGF is a protein highly expressed by the placenta with vasculogenic and angiogenic properties, which has a central role in spiral artery remodeling and the development of a low-resistance placental capillary network. PlGF concentrations are significantly lower in women with preterm PE, and these reduced levels have been shown to precede the clinical onset of disease. Subsequently, the clinical utility of maternal serum PlGF has been extensively studied in singleton gestations from as early as 11 to 13 weeks' gestation, utilizing a validated multimarker prediction model, which performs superiorly to the National Institute for Health and Care Excellence (NICE) and American College of Obstetricians and Gynecologists (ACOG) guidelines in the detection of preterm PE. There is extensive research highlighting the role of PlGF-based testing utilizing commercially available assays in accelerating the diagnosis of PE in symptomatic women over 20 weeks' gestation and predicting time-to-delivery, allowing individualized risk stratification and appropriate antenatal surveillance to be determined. "Real-world" data has shown that interpretation of PlGF-based test results can aid clinicians in improving maternal outcomes and a growing body of evidence has implied a role for sFlt-1/PlGF in the prognostication of adverse pregnancy and perinatal events. Subsequently, PlGF-based testing is increasingly being implemented into obstetric practice and is advocated by NICE. This literature review aims to provide healthcare professionals with an understanding of the role of angiogenic biomarkers in PE and discuss the evidence for PlGF-based screening and triage. Prospective studies are warranted to explore if its implementation significantly improves perinatal outcomes, explore the value of repeat PlGF testing, and its use in multiple pregnancies.

The accuracy of cell-free DNA screening for fetal segmental copy number variants: A systematic review and meta-analysis.

BACKGROUND: The performance of cell-free DNA (cfDNA) screening for microscopic copy number variants (CNVs) is unclear. OBJECTIVES: This was a systematic review and meta-analysis to investigate the sensitivity, specificity and positive predictive value (PPV) of cfDNA screening for CNVs. SEARCH STRATEGY: Articles published in EMBASE, PubMed or Web of Science before November 2022 were screened for inclusion. This protocol was registered with PROSPERO (23 March 2021, CRD42021250849) prior to initiation. SELECTION CRITERIA: Articles published in English, detailing diagnostic outcomes for at least 10 high-risk CNV results with cfDNA were considered for inclusion. DATA COLLECTION AND ANALYSIS: The PPV was calculated and pooled with random-effects models for double-arcsine transformed proportions, using cases with diagnostic confirmation. Overall sensitivity, specificity and a summary receiver-operating characteristics (ROC) curve were calculated using bivariate models. The risk of bias was assessed using QUADAS-2. MAIN RESULTS: In all, 63 articles were included in the final analysis, detailing 1 591 459 cfDNA results. The pooled PPV was 37.5% (95% confidence interval [CI] 30.6-44.8), with substantial statistical heterogeneity (I2  = 93.9%). Bivariate meta-analysis estimated sensitivity and specificity to be 77.4% (95% CI 65.7-86.0) and 99.4% (95% CI 98.0-99.8), respectively, with an area under the summary ROC curve of 0.947 (95% CI 0.776-0.984). CONCLUSIONS: Approximately one-third of women who screen high-risk for CNVs with cfDNA will have an affected fetus. This value is of importance for screening counselling.

Performance of a risk factor-based approach in the detection of small for gestational age neonates: A cohort study.

BACKGROUND: Antenatal detection of fetal growth restriction allows the opportunity to increase surveillance and initiate intervention to prevent adverse outcomes. Detection of small for gestational age (SGA) fetuses with risk factor screening and selective ultrasonography is the standard of care in Australia, but evidence regarding performance is lacking. AIMS: To evaluate the diagnostic performance of a risk factor-based screening approach in detection of SGA neonates. MATERIALS AND METHODS: Retrospective cohort study conducted in a metropolitan maternity service, including all consecutive singleton deliveries over 20 weeks gestation from July 2016 to December 2017, and excluding terminations of pregnancy. An SGA neonate was defined by birthweight below the tenth percentile according to Australian reference ranges. Antenatally detected SGA cases were defined by estimated fetal weight or abdominal circumference below the tenth percentile for gestational age, or abnormal symphysio-fundal height. The diagnostic accuracy of the screening protocol was calculated using detection rates and false-positive rates. RESULTS: There were 13 384 singleton pregnancies included. There were 1330 infants (10.0%) who were SGA at birth. Antenatal detection rate of SGA neonates was 39.6% (95% confidence interval (CI) 37.0-42.3%), with a false-positive rate of 10.2% (95% CI 9.6-10.7%). There were 10 266 pregnancies (77.0%) which had at least one risk factor for an SGA infant. Of these, 6650 (64.8%) underwent at least one fetal growth ultrasound after 24 weeks gestation. CONCLUSIONS: Antenatal recognition of poor fetal growth is suboptimal using our current screening protocol. Three-quarters of pregnancies demonstrated risk factors for delivering an SGA infant, but growth ultrasonography may be underutilised.

Cell-free DNA screening for rare autosomal trisomies and segmental chromosome imbalances.

OBJECTIVE: To assess the outcomes of pregnancies at high-risk for rare autosomal trisomies (RATs) and segmental imbalances (SIs) on cell-free DNA (cfDNA) screening. METHOD: A retrospective study of women who underwent cfDNA screening between September 2019 and July 2021 at three ultrasound services in Australia. Positive predictive values (PPVs) were calculated using fetal chromosomal analysis. RESULTS: Among 23,857 women screened, there were 93 high-risk results for RATs (0.39%) and 82 for SIs (0.34%). The PPVs were 3.8% (3/78, 95% CI 0.8%-10.8%) for RATs and 19.1% (13/68, 95% CI 10.6%-30.5%) for SIs. If fetuses with structural anomalies were also counted as true-positive cases, the PPV for RATS increased to 8.5% (7/82, 95% CI 3.5%-16.8%). Among 85 discordant cases with birth outcomes available (65.4%), discordant positive RATs had a significantly higher proportion of infants born below the 10th and 3rd birthweight percentiles than expected (19.6% (p = 0.022) and 9.8% (p = 0.004), respectively), which was not observed in the SI group (2.9% < 10th (p = 0.168) and 0.0% <3rd (p = 0.305)). CONCLUSION: The PPVs for SI and RAT results are low, except when a structural abnormality is also present. Discordant positive RATs are associated with growth restriction.

Predictors for insulin use in gestational diabetes mellitus.

OBJECTIVES: Gestational diabetes mellitus (GDM) affects about 15% of pregnancies in Australia, with approximately 30% of those diagnosed with GDM requiring insulin therapy. There are several established risk factors for developing GDM, however limited studies show how these can be used to predict need for insulin treatment. The aim of this study is to identify predictors of insulin therapy in women diagnosed with GDM once an oral glucose tolerance test (OGTT) is performed during pregnancy. STUDY DESIGN: This is a retrospective cohort study of women with singleton pregnancies complicated by GDM between 2016 and 2017 at a single, large health network in Melbourne, Australia. Data were obtained from hospital record and pathology result systems. Univariable and multivariable logistic regression models were fit to the data to obtain crude and adjusted odds ratios. RESULTS: Of 2,048 women diagnosed with GDM, 647 (31.6%) required insulin therapy. Positive predictors included in the final multivariable model after backwards, stepwise elimination were an elevated fasting result on an OGTT (adjusted odds ratio (AOR) 2.93 [95% CI 2.34-3.66]), previous birth weight greater than 90th% (AOR 2.04 [95% CI 1.412.94]), previous diagnosis of GDM (AOR 1.68 [95% CI 1.28-2.21]), being born in the South Asian region (AOR 1.58 [95% CI 1.27-1.98]), the 2hr OGTT result (AOR 1.14 [95% CI 1.05-1.24]), body mass index (BMI; AOR 1.13 [95% CI 1.04-1.23]) and age (AOR 1.03 [95% CI 1.00-1.05]) The final predictive model had an area under the receiver-operating characteristics (ROC) curve of 0.744 (95% CI 0.720-0.767). CONCLUSIONS: This study highlights the possible predictors of insulin use, informing counselling for women who are newly diagnosed with gestational diabetes.

Business as usual during the COVID-19 pandemic? Reflections on state-wide trends in maternity telehealth consultations during lockdown in Victoria and New South Wales.

COVID-19 has resulted in unprecedented changes to maternity care across Australia. This study aims to analyse trends in maternity consultations and the uptake of telehealth in Victoria and New South Wales (NSW) since the first restrictions to reduce COVID-19 transmission were implemented. From March 2020 to April 2021, a higher proportion of antenatal care consultations was delivered via telehealth in Victoria compared to NSW (13.8% vs 7.4%, P < 0.0001). Uptake of telehealth and a shift from in-person care has been a major contributor to maintaining pregnancy care during pandemic restrictions. However, further research is required to understand women's perspectives and health outcomes.

Ultrasound findings and detection of fetal abnormalities before 11 weeks of gestation.

OBJECTIVE: To determine the proportion of major fetal structural abnormalities that can be detected before 11 gestational weeks. METHODS: We conducted a retrospective study of individual patient files at a tertiary provider of obstetric and gynecological ultrasound in Melbourne, Australia. All women who had a pre-cell-free DNA ultrasound with a crown-rump length of less than 45 mm and had one or more ultrasounds at a later gestation were included in the analysis. The primary outcome was the incidence of a fetal structural abnormality. RESULTS: A total of 3333 cases were included in the final analysis. Overall, 316 fetuses (9.5%) had a structural abnormality detected at any point throughout gestation, of which 86 were major structural abnormalities (2.6%). Sixteen fetal abnormalities were detected before 11 weeks of gestation, including 15 major abnormalities (17.4% of the major anomalies). All major fetal abnormalities detected before 11 gestational weeks were confirmed at later ultrasound examinations or the pregnancy did not continue (in four cases due to termination of pregnancy and in one case spontaneous miscarriage before first trimester morphology ultrasound). CONCLUSION: Detection of fetal abnormalities is possible before 11 weeks of gestation. Early suspicion is more likely in cases of major structural abnormalities.

Perspectives on administration of COVID-19 vaccine to pregnant and lactating women: a challenge for low- and middle-income countries.

Women who are in the pregnancy-puerperal cycle or are lactating have been deliberately excluded from participating in COVID-19 vaccine clinical trials that aimed to evaluate either the efficacy of the vaccines in inducing the formation of neutralizing antibodies or the investigational products' safety profile. The exclusion of pregnant and lactating women from such studies certainly and inequitably denies these women access to COVID-19 vaccines, since these products have become increasingly available to nonpregnant people and even to those who are pregnant and are in high-income settings. In this clinical opinion article, we discuss some aspects of the prolonged pandemic, the emergence of viral variants, the risks of severe complications of COVID-19 in pregnant women, and the disproportionate impact of the above on low- and middle-income countries. We argue that the decision to receive the COVID-19 vaccine should be a joint decision between the pregnant or lactating women and the healthcare providers, while considering the available data on vaccine efficacy, safety, the risks of SARS-CoV-2 infection in pregnant women, and the women's individual risks for infection and serious illness. The various types of vaccines that are already in use and their safety, effectiveness, and the potential risks and benefits of their administration to pregnant or lactating women are also reviewed.

The impact of the definition of preeclampsia on disease diagnosis and outcomes: a retrospective cohort study.

BACKGROUND: The diagnostic criteria for preeclampsia have evolved from the traditional definition of de novo hypertension and proteinuria to a broader definition of hypertension with evidence of end-organ dysfunction. Although this change is endorsed by various societies such as the International Society for the Study of Hypertension in Pregnancy and the American College of Obstetricians and Gynecologists, there remains controversy with regard to the implementation of broader definitions and the most appropriate definition of end-organ dysfunction. OBJECTIVE: This study aimed to assess the impact of different diagnostic criteria for preeclampsia on rates of disease diagnosis, disease severity, and adverse outcomes and to identify associations between each component of the different diagnostic criteria and adverse pregnancy outcomes. STUDY DESIGN: We performed a retrospective cohort study of singleton pregnancies at Monash Health between January 1, 2016 and July 31, 2018. Within this population, all cases of gestational hypertension and preeclampsia were reclassified according to the International Society for the Study of Hypertension in Pregnancy 2001, American College of Obstetricians and Gynecologists 2018, and International Society for the Study of Hypertension in Pregnancy 2018 criteria. Differences in incidence of preeclampsia and maternal and perinatal outcomes were compared between the International Society for the Study of Hypertension in Pregnancy 2001 group and the extra cases identified by American College of Obstetricians and Gynecologists 2018 and International Society for the Study of Hypertension in Pregnancy 2018. Outcomes assessed included biochemical markers of preeclampsia, a composite of adverse maternal outcomes, and a composite of adverse perinatal outcomes. Multiple logistic regression analysis was also performed to assess each component of the American College of Obstetricians and Gynecologists 2018 and International Society for the Study of Hypertension in Pregnancy 2018 criteria and their associations with adverse maternal and perinatal outcomes. RESULTS: Of 22,094 pregnancies, 751 (3.4%) women had preeclampsia as defined by any of the 3 criteria. Compared with International Society for the Study of Hypertension in Pregnancy 2001, the American College of Obstetricians and Gynecologists 2018 criteria identified an extra 42 women (n=654 vs n=696, 6.4% relative increase) with preeclampsia, and International Society for the Study of Hypertension in Pregnancy 2018 identified an extra 97 women (n=654 vs n=751, 14.8% relative increase). The additional women identified by International Society for the Study of Hypertension in Pregnancy 2018 exhibited a milder form of disease with lower rates of severe hypertension (62.4% vs 44.3%; P<.01) and magnesium sulfate use (11.9% vs 4.1%; P<.05) and a trend toward lower rates of adverse maternal outcomes (9.8% vs 4.1%). These women also delivered at a later gestation, and their babies had a lower number of neonatal intensive care unit admissions and adverse perinatal outcomes. Objective features such as fetal growth restriction, thrombocytopenia, renal and liver impairment, and proteinuria were associated with an increased risk of adverse maternal and perinatal outcomes, whereas subjective neurologic features demonstrated poorer associations. CONCLUSION: Implementation of broader definitions of preeclampsia will result in an increased incidence of disease diagnosis. However, because women who exclusively fulfill the new criteria have a milder phenotype of the disease, it remains uncertain whether this will translate to improved outcomes.

Clinical Procedures for the Prevention of Preeclampsia in Pregnant Women: A Systematic Review.

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.

OBJETIVO: Identificar quais são as condutas recomendadas para a prevenção de pré-eclâmpsia em gestantes. FONTES DE DADOS: Foi feita uma revisão sistemática da literatura, e foram desenvolvidas estratégias detalhadas de busca individual nas bases de dados PubMed/MEDLINE, CINAHL, Web of Science, Cochrane e LILACS pela Biblioteca Virtual em Saúde (BVS). Uma pesquisa manual também foi realizada para encontrar referências adicionais. O risco de viés, a qualidade da evidência, e a classificação da força das recomendações foram avaliadas usando a abordagem Classificação de Recomendações, Avaliação, Desenvolvimento e Análises (Gradings of Recommendations, Assessment, Development and Evaluations, GRADE). SELEçãO DOS ESTUDOS: No total, foram encontrados 351 artigos na busca inicial nas bases de dados consultadas e 2 na busca manual; após exclusões por duplicidade, 333 artigos permaneceram. Após a leitura de títulos e resumos, 315 referências foram excluídas. Portanto, 18 artigos foram mantidos para a seleção do texto completo (fase 2); esse processo levou à exclusão de 6 artigos. Após as exclusões por incompatibilidade com os critérios de inclusão, 12 artigos compuseram a amostra. COLETA DE DADOS: Os artigos selecionados para o estudo foram analisados, e a digitação da síntese das evidências foi realizada no software online GRADEpro Guideline Development Tool (GDT) (McMaster University and Evidence Prime Inc. Todos os direitos reservados. McMaster University, Hamilton, Ontário, Canadá), o que possibilitou a elaboração de uma tabela de evidências, com a qualidade das evidências e a classificação da força das recomendações. SíNTESE DOS DADOS: No total, sete estudos recomendaram o uso individual de aspirina, ou aspirina combinada com cálcio, heparina ou dipiridamol. O uso de cálcio isolado ou em combinação com fitonutrientes também foi destacado. Todos os estudos foram realizados com mulheres com alto risco de desenvolver pré-eclâmpsia. CONCLUSãO: De acordo com os estudos avaliados, a administração de aspirina ainda é a melhor conduta a ser utilizada na prática clínica para prevenir a pré-eclâmpsia.

Clinical procedures for the prevention of preeclampsia in pregnant women: a systematic peview / Procedimentos clínicos para a prevenção de pré-eclâmpsia em gestantes: Uma revisão sistemática

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.

Resumo Objetivo Identificar quais são as condutas recomendadas para a prevenção de pré-eclâmpsia em gestantes. Fontes de Dados Foi feita uma revisão sistemática da literatura, e foram desenvolvidas estratégias detalhadas de busca individual nas bases de dados PubMed/MEDLINE, CINAHL, Web of Science, Cochrane e LILACS pela Biblioteca Virtual em Saúde (BVS). Uma pesquisa manual também foi realizada para encontrar referências adicionais. O risco de viés, a qualidade da evidência, e a classificação da força das recomendações foram avaliadas usando a abordagem Classificação de Recomendações, Avaliação, Desenvolvimento e Análises (Gradings of Recommendations, Assessment, Development and Evaluations, GRADE). Seleção dos Estudos No total, foram encontrados 351 artigos na busca inicial nas bases de dados consultadas e 2 na busca manual; após exclusões por duplicidade, 333 artigos permaneceram. Após a leitura de títulos e resumos, 315 referências foram excluídas. Portanto, 18 artigos foram mantidos para a seleção do texto completo (fase 2); esse processo levou à exclusão de 6 artigos. Após as exclusões por incompatibilidade com os critérios de inclusão, 12 artigos compuseram a amostra. Coleta de Dados Os artigos selecionados para o estudo foram analisados, e a digitação da síntese das evidências foi realizada no software online GRADEpro Guideline Development Tool (GDT) (McMaster University and Evidence Prime Inc. Todos os direitos reservados. McMaster University, Hamilton, Ontário, Canadá), o que possibilitou a elaboração de uma tabela de evidências, com a qualidade das evidências e a classificação da força das recomendações. Síntese dos Dados No total, sete estudos recomendaram o uso individual de aspirina, ou aspirina combinada com cálcio, heparina ou dipiridamol. O uso de cálcio isolado ou em combinação com fitonutrientes também foi destacado. Todos os estudos foram realizados com mulheres com alto risco de desenvolver pré-eclâmpsia. Conclusão De acordo com os estudos avaliados, a administração de aspirina ainda é a melhor conduta a ser utilizada na prática clínica para prevenir a pré-eclâmpsia.

Prediction of preterm pre-eclampsia at midpregnancy using a multivariable screening algorithm.

BACKGROUND: Competing risk models used for midpregnancy prediction of preterm pre-eclampsia have shown detection rates (DR) of 85%, at fixed false-positive rate (FPR) of 10%. The full algorithm used between 19+0 and 24+6  weeks includes maternal factors, mean arterial pressure (MAP), mean uterine artery pulsatility index (UtAPI), serum placental growth factor (PlGF) level in multiples of the median (MoM), and soluble Fms-like tyrosine kinase-1 (sFlt-1) level in MoM. AIMS: To assess performance of the Fetal Medicine Foundation (FMF) algorithm at midpregnancy to screen for preterm (<37 weeks) pre-eclampsia. The outcome measured was preterm pre-eclampsia. MATERIALS AND METHODS: This is a prospective study including singleton pregnancies at 19-22 weeks gestation. Maternal bloods were collected and analysed using three different immunoassay platforms. Maternal characteristics, medical history, MAP, mean UtAPI, serum PlGF MoM and serum sFlt-1 MoM were used for risk assessment. DR and FPR were calculated, and receiver operating characteristic curves produced. RESULTS: Five hundred and twelve patients were included. Incidence of preterm pre-eclampsia was 1.6%. Using predicted risk of pre-eclampsia of one in 60 or more and one in 100 or higher, as given by the FMF predictive algorithm, the combination with the best predictive performance for preterm pre-eclampsia included maternal factors, MAP, UtAPI and PlGF MoM, giving DRs of 100% and 100%, respectively, and FPRs of 9.3 for all platforms and 12.9-13.5, respectively. Addition of sFlt-1 to the algorithm did not appear to improve performance. sFlt-1 MoM and PlGF MoM values obtained on the different platforms performed very similarly. CONCLUSIONS: Second trimester combined screening for preterm pre-eclampsia by maternal history, MAP, mean UtAPI and PlGF MoM using the FMF algorithm performed very well in this patient population.

Challenging the definition of hypertension in pregnancy: a retrospective cohort study.

BACKGROUND: In routine antenatal care, blood pressure is used as a screening tool for preeclampsia and its associated adverse outcomes. As such women with a blood pressure greater than 140/90 mm Hg undergo further investigation and closer follow-up, whereas those with lower blood pressures receive no additional care. In the nonpregnant setting, the American College of Cardiology now endorses lower hypertensive thresholds and it remains unclear whether these lower thresholds should also be considered in pregnancy. OBJECTIVE: (1) To examine the association between lower blood pressure thresholds (as per the American College of Cardiology guidelines) and pregnancy outcomes and (2) to determine whether there is a continuous relationship between blood pressure and pregnancy outcomes and identify the point of a change at which blood pressure is associated with an increased risk of such outcomes. STUDY DESIGN: This was a retrospective study of singleton pregnancies at Monash Health, Australia. Data were obtained with regards to maternal characteristics and blood pressure measurements at varying gestational ages. Blood pressures were then categorized as (1) mean arterial pressure and (2) normal, elevated, stage 1 and stage 2 hypertension, as per the American College of Cardiology guidelines. Multivariable regression analysis was performed to identify associations between blood pressure categories and pregnancy outcomes. RESULTS: This study included 18,243 singleton pregnancies. We demonstrated a positive dose-response relationship between mean arterial pressure and the development of preeclampsia in later pregnancy. Across all gestational ages, the risk of preeclampsia was greater in those with "elevated blood pressure" and "stage 1 hypertension" in comparison with the normotensive group (adjusted risk ratio; 2.45, 95% confidence interval, 1.74-3.44 and adjusted risk ratio, 6.60; 95% confidence interval, 4.98-8.73 respectively, at 34-36 weeks' gestation). There was also an association between stage 1 hypertension, preterm birth, and adverse perinatal outcomes. CONCLUSION: This study demonstrated that preeclampsia and the associated adverse outcomes are not exclusive to those with blood pressures greater than 140/90 mm Hg. As such, those with prehypertensive blood pressures may also benefit from closer monitoring. Further research is essential to determine whether lowering the blood pressure threshold in pregnancy would improve detection and outcomes.

Evaluation of Cardiac Function in Women With a History of Preeclampsia: A Systematic Review and Meta-Analysis.

Background Women with a history of preeclampsia are at increased risk of cardiovascular morbidity and mortality. However, the underlying mechanisms of disease association, and the ideal method of monitoring this high-risk group, remains unclear. This review aims to determine whether women with a history of preeclampsia show clinical or subclinical cardiac changes when evaluated with an echocardiogram. Methods and Results A systematic search of MEDLINE, EMBASE, and CINAHL databases was performed to identify studies that examined cardiac function in women with a history of preeclampsia, in comparison with those with normotensive pregnancies. In the 27 included studies, we found no significant differences between preeclampsia and nonpreeclampsia women with regard to left ventricular ejection fraction, isovolumetric relaxation time, or deceleration time. Women with a history of preeclampsia demonstrated a higher left ventricular mass index and relative wall thickness with a mean difference of 4.25 g/m2 (95% CI, 2.08, 6.42) and 0.03 (95% CI, 0.01, 0.05), respectively. In comparison with the nonpreeclampsia population, they also demonstrated a lower E/A and a higher E/e' ratio with a mean difference of -0.08 (95% CI, -0.15, -0.01) and 0.84 (95% CI, 0.41, 1.27), respectively. Conclusions In comparison with women who had a normotensive pregnancy, women with a history of preeclampsia demonstrated a trend toward altered cardiac structure and function. Further studies with larger sample sizes and consistent echocardiogram reporting with the use of sensitive preclinical markers are required to assess the role of echocardiography in monitoring this high-risk population group.