Reduced Risk Of Preeclampsia Research Articles

Factors Associated with Guideline Concordant Clinician Counseling about Low-Dose Aspirin to Prevent Preeclampsia in Nulliparous Patients.

The primary aim of this study was to examine the United States Preventative Services Task Force (USPSTF) guidelines concordant low-dose aspirin (LDA) counseling and factors associated with counseling in nulliparous birthing individuals. We conducted a retrospective cohort study of nulliparous birthing individuals who delivered between January 1, 2019 and June 30, 2020 and received prenatal care at the Duke High Risk Obstetrical Clinics (HROB). All nulliparous patients over 18 years old who established or transferred care to HROB by 16 weeks, 6 days were included in the analysis. We excluded patients with more than two previous first-trimester pregnancy losses, multiple gestation, a known contraindication to LDA, initiation of LDA prior to their prenatal care, or documented medical history of coagulation disorder. Bivariate associations between demographic/medical characteristics and our primary outcome, receipt of counseling (yes/no), were assessed using two-sample t-tests for continuous variables and chi-square or Fisher's exact test for categorical variables. Factors significantly associated with the primary outcome (p < 0.05) were entered into the multivariable logistic regression model. Among 391 birthing individuals included in the final analysis cohort, 51.7% of eligible patients received guideline consistent LDA counseling. Factors associated with increased odds of LDA counseling were advanced maternal age (adjusted odds ratio [aOR]: 1.05, 95% confidence interval [CI]: 1.01-1.09), Black race compared with White race (aOR:1.75, 95% CI: 1.03-2.98), chronic hypertension (aOR: 4.17, 95% CI: 1.82-9.55), and obesity (aOR: 5.02, 95% CI: 3.12-8.08). Approximately half of all nulliparous birthing individuals had appropriately documented LDA counseling. The USPSTF guidelines on LDA for preeclampsia risk reduction are complex, which may lead to ineffective provider adherence. Efforts to simplify guidelines and improve LDA counseling are vital to ensuring this low-cost, evidence-based preeclampsia prevention is used in a consistent and equitable manner. · A total of 51.7% of eligible patients received guideline consistent LDA counseling.. · Advanced maternal age , body mass index > 30, Black race, and chronic hypertension associated with increased odds of counseling.. · Among patients most likely to be counseled, high numbers did not receive LDA counseling..

Increased Risk of Preeclampsia with Assisted Reproductive Technologies.

We summarized recent available data to assess the association between assisted reproductive technology (ART) and risk for preeclampsia. The majority of clinical studies supporting the association of preeclampsia and ART are retrospective. Published data from both clinical and pre-clinical studies suggest specific ART procedures may contribute to the increased risk, including in vitro embryo handling and development, hormone stimulation, transfer cycle types, and use of donor oocytes/embryos. Potential mechanisms include epigenetic aberrations leading to abnormal placentation, absence of factors secreted by the corpus luteum, and immunologic responses to allogenic gametes. There is an increased risk of preeclampsia following ART. Treatment plans that favor reduced preeclampsia risk should be considered for ART pregnancies. To make ART pregnancies safer, additional clinical and animal model studies are needed to elucidate the underpinnings of this risk association.

Low-Dose Aspirin after ASPRE—More Questions Than Answers? Current International Approach after PE Screening in the First Trimester

Preeclampsia (PE) is a multi-factorial disorder of pregnancy, and it continues to be one of the leading causes of fetal and maternal morbidity and mortality worldwide. Aspirin is universally recommended for high-risk women to reduce preeclampsia risk. The purpose of this review is to summarize the recommendations of various scientific societies on predicting preeclampsia and their indications for the inclusion of acetylsalicylic acid (ASA) prophylaxis. Fourteen guidelines were compared. The recommended dose, screening method, and gestational age at the start of the test vary depending on the recommendation. The societies are inclined to recommend using increasingly higher doses (&gt;75 mg) of ASA, with many encouraging doses from 100 mg upward. Most societies indicate that the optimal time for implementing aspirin is prior to 16 weeks’ gestation. Following the publication of the Aspirin for Evidence-Based Preeclampsia Prevention (ASPRE) trial results and other papers evaluating the Fetal Medicine Foundation (FMF) screening model, a large number of societies have changed their recommendations from those based on risk factors alone to the ones based on the risk assessment proposed by the FMF. This allows for the detection of a high-risk pregnancy population in whom aspirin will be remarkably effective in preventing preterm PE, thereby decreasing maternal and fetal morbidity.

Physician's Knowledge and Practices Surrounding Low-Dose Aspirin for Preeclampsia Risk Reduction.

Preeclampsia is a leading cause of pregnancy-related deaths. Up to 60% of maternal deaths associated with preeclampsia may be prevented. Clinical trials have shown that low-dose aspirin reduces preeclampsia up to 30% among women at increased risk. Since 2014, multiple professional societies and the U.S. Preventive Services Task Force have released guidelines on the use of low-dose aspirin to reduce the risk of preeclampsia. We aimed to evaluate physician's knowledge and practices surrounding low-dose aspirin for preeclampsia risk reduction. We distributed an anonymous electronic survey to licensed physicians in the Rio Grande Valley of Texas who provide prenatal care, including general obstetrician-gynecologists, maternal fetal medicine subspecialists, and family medicine physicians. The survey consisted of 20 items assessing demographics, provider practices, and knowledge on the use of low-dose aspirin for preeclampsia risk reduction. We received 48 surveys with a response rate of 55%. More than 90% of physicians reported recommending low-dose aspirin for preeclampsia risk reduction, of which 98% correctly identified the dose. Of the physicians recommending aspirin, 83% initiate dosing between 12 and 16 weeks, but only 52% continue it until the day of delivery. Nearly 80% of respondents identified that one high-risk factor for preeclampsia is an indication for prophylaxis, but only 56% identified that two or more moderate risk factors should prompt aspirin recommendation. Despite clear professional guidelines, physicians demonstrated gaps in knowledge and differences in practices. Enhancing screening tools to assess patient's risk of developing preeclampsia and tailored medical education on moderate risk factors are needed to identify patients who may benefit from this intervention. Increasing the use of aspirin in patients at risk is critical given the benefits of low-dose aspirin in the reduction of poor maternal and neonatal outcomes related to preeclampsia. · Low-dose aspirin reduces preeclampsia in patients up to 30%.. · Physicians have gaps in knowledge despite guidelines.. · Following guidelines reduces poor outcomes associated with preeclampsia..

Racial/ethnic differences in low-dose aspirin use for preeclampsia risk reduction

There are significant racial/ethnic disparities in development of preeclampsia and perinatal morbidity and mortality due to preeclampsia. Low-dose aspirin (LDA) is the only strategy proven effective for preeclampsia risk reduction among high-risk patients. This study aims to determine if there are racial/ethnic differences in use of LDA for preeclampsia risk reduction among patients who meet criteria based on ACOG/SMFM recommendations.

Relationship between risk factor profile and prescription of low-dose aspirin for preeclampsia prevention.

The purpose of this study was to assess obstetrician-gynecologist utilization of low-dose aspirin for women at increased risk for hypertensive disorders of pregnancy using guidelines developed by the American College of Obstetricians and Gynecologists and supported by the United States Preventive Services Task Force. Further, the study evaluated prescribing practices in relation to specific risk factor profiles to identify which women are at highest risk of not receiving recommended therapy. This was a retrospective cohort study reviewed and approved by the local Institutional Review Board. Electronic health records of women with singleton pregnancies who delivered between February and August 2020 were reviewed to identify risk factors for preeclampsia. Women were eligible for aspirin prophylaxis if they had at least one "high" risk factor or multiple "moderate" risk factors, as defined by the United States Preventive Services Task Force guidelines. Associations of interest were addressed using Pearson Chi-squared tests and multinomial logistic regression. 970 patients were included and 301 pregnant persons(31%) met criteria for low-dose aspirin prophylaxis; of these, 92 (31%) were given this recommendation. Those eligible for prophylaxis by presence of multiple "moderate" risk factors alone are least likely (0-6%) to receive indicated aspirin prophylaxis. Low-dose aspirin is an underutilized tool for preventing preeclampsia. Women with a combination of "moderate" risk factors are most likely to not receive indicated aspirin prophylaxis. Efforts should be made to encourage broader uptake of the recommendations for aspirin prophylaxis among obstetrician-gynecologists. What is already known on this subject? Low-dose aspirin has been shown to reduce preeclampsia risk in pregnant persons. This preventive measure has been recommended by most national and international organizations including the American College of Obstetricians and Gynecologists and the United States Preventive Services Task Force. Yet despite widespread support of this recommendation, uptake is not universal among obstetric care providers. What this study adds? This study identifies those who are most likely to experience a missed opportunity for aspirin prophylaxis, thus providing a suggestion for where provider education or other efforts to increase adherence to this guideline may be most impactful.

Short-term effects of ambient temperature on the risk of preeclampsia in Nanjing, China: a time-series analysis

ObjectivesPrevious studies on the association between temperature and preeclampsia mainly considered temperature on a monthly or seasonal time scale. The objective of this study was to assess the preeclampsia risk associated with short-term temperature exposure using daily data.Study designDaily preeclampsia hospitalization data, daily meteorological data and daily air pollutant data from Nanjing were collected from 2016 to 2017. Both the T test and distributed lag nonlinear model (DLNM) were applied to assess the short-term effect of temperature on preeclampsia risk. Three kinds of daily temperature, including the daily mean temperature, daily minimum temperature and daily maximum temperature, were analysed.ResultsWhen the daily number of preeclampsia hospital admissions was divided into two subgroups based on temperature, it was significantly larger on cold days than on hot days. Regarding the mean temperature, a very low level of mean temperature (4.5 °C, lag = 0–20) and a low level of mean temperature (9.1 °C, lag = 0–20) increased the cumulative relative risk of preeclampsia by more than 60%. At the same time, a very high level of mean temperature (28.7 °C, lags = 0–10, 0–15, 0–20) and a high level of mean temperature (24.1 °C, lags = 0–10, 0–15) decreased the cumulative relative risk of preeclampsia by more than 35%. At a minimum temperature, a very low level of minimum temperature (0.9 °C, lag 0–5) and a low level of minimum temperature (5.6 °C, lag 0–5) increased the cumulative relative risk of preeclampsia by more than 55%. At the same time, a high level of mean temperature (20.9 °C, lags = 0, 0–5) decreased the cumulative relative risk of preeclampsia by more than 20%. The maximum temperature result was similar to the mean temperature result.ConclusionsBoth direct and lag effects of low temperature on preeclampsia were demonstrated to be significant risk factors. These results could be used to help pregnant women and the government reduce preeclampsia risk.

Assessment of adherence to aspirin for preeclampsia prophylaxis and reasons for nonadherence

Preeclampsia is a hypertensive disease unique to pregnancy and has a significant impact on maternal and neonatal morbidity and mortality. Daily aspirin has been demonstrated to reduce the risk of preeclampsia. The American College of Obstetricians and Gynecologists recommends daily low-dose aspirin, ideally before 16 weeks' gestation, in at-risk patients for preeclampsia risk reduction. This study examined whether patients at-risk for preeclampsia by the American College of Obstetricians and Gynecologists criteria recalled aspirin recommendation and factors associated with treatment adherence. This study examined whether patients at-risk for preeclampsia by the American College of Obstetricians and Gynecologists criteria recalled aspirin recommendation and factors associated with treatment adherence. This study used an anonymous written survey. Pregnant patients were asked to record self-reported risk factors and to recall recommendation to take aspirin for preeclampsia prophylaxis. Participants were then determined to be high-, moderate-, or low-risk on the basis of the American College of Obstetricians and Gynecologists guidelines. Self-reported adherence to recommendations and factors contributing to the patients' decisions to take or decline aspirin were assessed. Secondary outcomes included demographic characteristics of adherent patients and patients who did not recall aspirin recommendation. A total of 544 surveys were distributed and 500 were returned (91.9% response rate). Of the 104 high-risk pregnancies identified, aspirin was recommended in 60 (57.7%; 95% confidence interval, 0.48-0.67). Of the 269 patients with 2 or more moderate-risk factors, aspirin was recommended for 13 (4.8%; 95% confidence interval, 0.03-0.08). Among the participants who recalled aspirin recommendation, adherence was similar between high-risk (81.7%) and moderate-risk (76.9%) groups (P=.69). Patients with chronic hypertension, a history of preeclampsia or gestational hypertension in a previous pregnancy, and pregestational diabetes mellitus were most likely to report receiving aspirin recommendation (78.8%, 76.5%, 63.8%, and 53.3%, respectively). No high-risk factor was associated with a decreased likelihood of adherence. Nonadherent patients rarely discussed their decision with their medical provider (5.9%). In the 42.3% of high-risk participants who did not recall aspirin recommendation, autoimmune disease, multiple gestation, and kidney disease were the most prevalent risk factors (42.9%, 35.7%, and 25.0%, respectively). In the population studied, many at-risk patients, as defined by the American College of Obstetricians and Gynecologists criteria, did not recall recommendations to take aspirin for preeclampsia prophylaxis. This raises concerns for absent or ineffective counseling. Of the patients who recalled aspirin recommendation, most reported adherence, and a history of hypertensive disorders or preeclampsia, autoimmune disease, and pregestational diabetes mellitus were most often associated with adherence. There was no single factor most strongly associated with intentional nonadherence.

Operationalizing Aspirin to Reduce Preeclampsia Risk and Related Morbidity and Mortality [A302

INTRODUCTION: Low-dose aspirin (ASA) reduces the incidence of preeclampsia and related morbidity and mortality when given to pregnant patients at moderate to high risk of disease. The United States Preventive Services Task Force (USPSTF) provides clear guidelines for identifying patients who warrant a prescription for ASA; however, complexity of the algorithm may inhibit comprehensive screening and implementation. We aimed to implement a standardized approach to ASA screening and prescription in an academic obstetrics and gynecology practice. METHODS: Using a quality improvement framework, we implemented universal prenatal screening according to the USPSTF recommendations for ASA to prevent preeclampsia. Pre-intervention, we analyzed prescription adherence at 201 new obstetric (NOB) visits. A multistep intervention was then implemented. Nurses utilized a checklist created from USPSTF guidelines to identify high-risk patients, defined as having 1 or more high-risk factors or 2 or more moderate-risk factors. ASA orders were signed by physicians. Three months after implementation, 199 NOB visits were reviewed. The primary outcome was the percent of patients screened (goal=90%). The secondary outcome was the percent of patients who screened positive that received the ASA recommendation (goal=90%). RESULTS: Pre-intervention, 47% of patients met criteria for ASA, and 28% of those patients received a recommendation for ASA. Post-intervention, 99% were screened. Half (48%) met criteria for an ASA recommendation and 78% of those patients received a recommendation for ASA. CONCLUSION: It is feasible to standardize screening and implementation of ASA to patients at elevated risk for preeclampsia. Providers can easily reproduce our processes to improve delivery of reliable preventative obstetric care.

Leveraging Quality Improvement to Promote Health Equity: Prenatal Aspirin Recommendations by Race [A303

INTRODUCTION: Black patients are disproportionately affected by preeclampsia and associated morbidity and mortality. Aspirin (ASA) reduces these risks and the United States Preventative Services Task Force (USPSTF) recommends ASA for pregnant patients at moderate to high risk for preeclampsia. We aimed to assess whether a quality-improvement intervention to standardize ASA screening and prescription resulted in similar rates of indicated ASA recommendations for patients who self-identified as Black versus non-Black. METHODS: Using a quality-improvement framework, we implemented universal prenatal screening according to the USPSTF recommendations for ASA to prevent preeclampsia. We analyzed 201 new OB (NOB) visits pre-intervention and 199 NOB visits 3 months post-intervention. Nurses utilized a checklist created from USPSTF guidelines to identify high-risk patients, defined as having 1 or more high-risk factor or 2 or more moderate-risk factors. ASA orders were signed by physicians. Results were stratified by self-identified Black versus non-Black race. RESULTS: Pre-intervention, 88% of Black patients met criteria, and 29% of those patients correctly received a recommendation for ASA. Among non-Black patients, 41% met criteria for ASA, and 27% of those patients a recommendation. Post-intervention, 93% and 41% of Black and non-Black patients met criteria, respectively, with 80% and 79% of those patients, respectively, receiving the recommendation. CONCLUSION: A strikingly high percentage of Black patients warrant a recommendation for ASA to reduce preeclampsia risk, as per USPSTF guidelines. Our standardized approach to prenatal screening and prescribing of ASA resulted in similar rates of correct prescriptions for ASA in Black and non-Black patients, suggesting a mechanism for delivering equitable preventative obstetric care.

Assessment of compliance with aspirin for preeclampsia prophylaxis and reasons for non-compliance

The American College of Obstetricians and Gynecologists (ACOG) recommends daily aspirin (ASA) initiation by 16 weeks gestation in at-risk patients for preeclampsia risk reduction. This study examined whether patients at high-risk for preeclampsia recalled ASA counseling and treatment compliance.

Aspirin for the prevention of pre-eclampsia in women with pre-existing diabetes: Systematic review.

There is a lack of evidence for pre-eclampsia prophylaxis with aspirin in women with pre-existing diabetes mellitus (DM). To examine the evidence for aspirin in pre-eclampsia prophylaxis in women with pre-existing DM. An electronic search using Ovid MEDLINE, Embase, CinicalTrials.gov and the Cochrane CENTRAL register of controlled trials through to February 2021 was performed. Reference lists of identified studies, previous review articles, clinical practice guidelines and government reports were manually searched. Randomised controlled trials (RCTs) of aspirin vs placebo for pre-eclampsia prophylaxis were included. Articles were manually reviewed to determine if cohorts included women with DM. The systematic review was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Data from included trials were extracted independently by two authors who also independently assessed risk of bias as per the Cochrane Handbook criteria version 5.1.0. Data were analysed using Rev-Man 5.4. Forty RCTs were identified, of which 11 included a confirmed subset of women with DM; however, data were insufficient for meta-analysis. Meta-analysis of 930 women with DM, from individual patient data included in a systematic review and unpublished data from one of the 11 RCTs, showed a non-significant difference in the outcome of pre-eclampsia in participants treated with aspirin compared to placebo (odds ratio 0.58; 95% CI 0.20-1.71; P=0.33). Pre-eclampsia risk reduction with aspirin prophylaxis in women with pre-existing DM may be similar to women without pre-existing DM. However, randomised data within this meta-analysis were insufficient, warranting the need for further studies within this high-risk group of women.

Prevention, Diagnosis, and Management of Hypertensive Disorders of Pregnancy: a Comparison of International Guidelines

Hypertensive disorders of pregnancy (HDP)-gestational hypertension, preeclampsia, and eclampsia-are a leading cause of adverse maternal and perinatal outcomes internationally. Prevention, timely diagnosis, and prompt management can reduce associated morbidity. The purpose of this review is to compare international guidelines pertaining to HDP. Fourteen HDP guidelines were compared relative to guidelines for the United States (US) where the authors practice. Aspirin is universally recommended for high-risk women to reduce preeclampsia risk. Recommended dose and gestational age at initiation vary. Diagnoses of chronic hypertension, gestational hypertension, and preeclampsia in pregnant women are similar, although blood pressure (BP) thresholds for antihypertensive medication initiation and treatment targets vary due to the limitations in high-quality evidence. There are differences among international HDP guidelines related to dose and timing of aspirin initiation, thresholds for antihypertensive medication initiation, and BP targets. However, all guidelines acknowledge the significant morbidity associated with HDP and advocate for timely diagnosis and management to reduce associated morbidity and mortality. More research is needed to understand optimal BP thresholds at which to initiate antihypertensive medication regimens and BP targets in pregnancy.

O impacto do uso da metformina para gestantes obesas na prevenção da pré-eclâmpsia

Objetivos: o artigo objetiva avaliar o uso de metformina em gestantes obesas na prevenção da pré-eclâmpsia.Métodos: trata-se de um ensaio clínico randomizado com mulheres grávidas obesas com índice de massa corporal superior ou igual a 30 kg/m2 divididos em dois grupos – um grupo de estudo, que utilizou metformina, e um grupo controle, que seguiu a rotina de pré-natal. As gestantes entraram no estudo com idade gestacional menor que 20 semanas e foram acompanhadas durante todo o período pré-natal. O diagnóstico de pré-eclâmpsia foi feito de acordo com os critérios da Organização Mundial de Saúde.Resultados: verificou-se a redução de risco absoluto e o número necessário para tratar em um intervalo de confiança de 95% para o resultado pré-eclâmpsia. Nos resultados, 272 gestantes foram avaliadas. No grupo de estudo (n = 127), oito (6,3%) desenvolveram pré-eclâmpsia. No grupo controle (n = 145), 31 (21,4%) tiveram a doença (p &lt;0,01).Conclusão: o estudo apontou uma redução de risco absoluto de 15,1 vezes (IC95%: 7,1-22,9) e número necessário para tratar de sete (IC95%: 4,4-13,9). O uso de 1000 miligramas diárias de metformina indicou uma redução de 15,1 vezes no risco absoluto de pré-eclâmpsia na população estudada, com a necessidade de tratar sete gestantes para evitar um desfecho.

Socioeconomic Status, Preeclampsia Risk and Gestational Length in Black and White Women.

Higher socioeconomic status (SES) has less impact on cardio-metabolic disease and preterm birth risk among Black women compared to White women, an effect called "diminishing returns." No studies have tested whether this also occurs for pregnancy cardio-metabolic disease, specifically preeclampsia, or whether preeclampsia risk could account for race-by-SES disparities in birth timing. A sample of 718,604 Black and White women was drawn from a population-based California cohort of singleton births. Education, public health insurance status, gestational length, and preeclampsia diagnosis were extracted from a State-maintained birth cohort database. Age, prenatal care, diabetes diagnosis, smoking during pregnancy, and pre-pregnancy body mass index were covariates. In logistic regression models predicting preeclampsia risk, the race-by-SES interaction (for both education and insurance status) was significant. White women were at lower risk for preeclampsia, and higher SES further reduced risk. Black women were at higher risk for preeclampsia, and SES did not attenuate risk. In pathway analyses predicting gestational length, an indirect effect of the race-by-SES interaction was observed. Among White women, higher SES predicted lower preeclampsia risk, which in turn predicted longer gestation. The same was not observed for Black women. Compared to White women, Black women had increased preeclampsia risk. Higher SES attenuated risk for preeclampsia among White women, but not for Black women. Similarly, higher SES indirectly predicted longer gestational length via reduced preeclampsia risk among White women, but not for Black women. These findings are consistent with diminishing returns of higher SES for Black womenwith respect to preeclampsia.

Use of antidepressants and anxiolytics in early pregnancy and the risk of preeclampsia and gestational hypertension: a prospective study

BackgroundWe investigated the association between antidepressant and anxiolytic exposure during the first and early second trimester of pregnancy (< 16 weeks), and hypertensive disorders of pregnancy (including preeclampsia and gestational hypertension) in women with singleton pregnancy.MethodsThis study is based on a large prospective cohort of 7866 pregnant women. We included pregnant women aged 18 years or older without chronic hepatic or renal disease at the time of recruitment. Participants lost to the follow-up, with multiple pregnancies and pregnancy terminations, miscarriages or fetal deaths before 20 weeks of gestation were excluded from the study, as well as women with no data on the antidepressant/anxiolytic medication use during pregnancy. Information concerning antidepressant or anxiolytic medication use was extracted from hospital records after delivery. The associations between their use and the risk of gestational hypertension or preeclampsia were calculated.ResultsThe final sample for analysis included 6761 participants including 218 (3.2%) women who were exposed to antidepressant and/or anxiolytic medication before the 16th week of gestation. Forty-one women had a non-medicated depression or anxiety during the pregnancy. Moreover, 195 (2.9%) and 122 (1.8%) women developed gestational hypertension and preeclampsia respectively. When compared to women unexposed to antidepressant/anxiolytic medication, depression and anxiety, those using antidepressant and/or anxiolytic drugs before the 16th week of gestation were at increased risk of preeclampsia (adjusted odd ratio (aOR) 3.09 [CI95% 1.56–6.12]), especially if they continued their medication after the 16th week (aOR 3.41 [CI95% 1.66–7.02]) compared to those who did not (1.60 [CI95% 0.21–12.34]).ConclusionsWomen exposed to antidepressant and/or anxiolytic medication before the 16th week of pregnancy have a 3-fold increased risk for preeclampsia when compared to women unexposed to antidepressant/anxiolytic medication, depression and anxiety. Also, our results suggested that women who stopped their medication before the 16th week of pregnancy could be benefit from reduced preeclampsia risk.

Metformin for prevention of hypertensive disorders of pregnancy in women with gestational diabetes or obesity: systematic review and meta-analysis of randomized trials.

Metformin has been reported to reduce the risk of pre-eclampsia. It is also known to influence soluble fms-like tyrosine kinase-1 level, which correlates significantly with the gestational age at onset and severity of pre-eclampsia. The main aim of this systematic review and meta-analysis of randomized trials was to determine whether metformin use is associated with the incidence of hypertensive disorders of pregnancy (HDP). MEDLINE (1947 to September 2017), Scopus (1970 to September 2017) and the Cochrane Library (inception to September 2017) were searched for relevant citations in the English language. Only randomized controlled trials on metformin use, reporting the incidence of pre-eclampsia or pregnancy-induced hypertension, were included. Studies on populations with a high probability of metformin use prior to randomization (those with type II diabetes or polycystic ovary syndrome) were excluded. Random-effects models with the Mantel-Haenszel method were used for subgroup analyses. Bayesian random-effects meta-regression was used to summarize the evidence. In total, 3337 citations matched the search criteria. After evaluating 2536 abstracts and performing full-text review of 52 studies, 15 were included in the review. In women with gestational diabetes, metformin use was associated with a reduced risk of pregnancy-induced hypertension when compared with insulin (relative risk (RR), 0.56; 95% CI, 0.37-0.85; I2 = 0%; 1260 women) and a non-significantly reduced risk of pre-eclampsia (RR, 0.83; 95% CI, 0.60-1.14; I2 = 0%; 1724 women). In obese women, when compared with placebo, metformin use was associated with a non-significant reduction in risk of pre-eclampsia (RR, 0.74; 95% CI, 0.09-6.28; I2 = 86%; 840 women). In women with gestational diabetes, metformin use was also associated with a non-significant reduction in risk of any HDP (RR, 0.71; 95% CI, 0.41-1.25; I2 = 0%; 556 women) when compared with glyburide. When studies were combined using Bayesian random-effects meta-regression, with treatment type as a covariate, the posterior probabilities of metformin having a beneficial effect on the prevention of pre-eclampsia, pregnancy-induced hypertension and any HDP were 92.7%, 92.8% and 99.2%, respectively, when compared with any other treatment or placebo. There is a high probability that metformin use is associated with reduced HDP incidence when compared with other treatments or placebo. The small number of studies included in the analysis, the low quality of evidence and the clinical heterogeneity preclude generalization of these results to broader populations. Given the clinical importance of this topic and the magnitude of effect observed in this meta-analysis, further prospective trials are urgently needed. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

92. Does maternal folic acid supplementation reduce the risk of preeclampsia? A systematic review and meta-analysis of observational studies

Introduction Preeclampsia contributes significantly to maternal and neonatal morbidity and mortality worldwide. Maternal folic acid supplementation is recommended peri-conceptionally for the prevention of neural tube defects. Research suggests an association between folic acid supplementation during pregnancy and a reduced risk of preeclampsia. Objective A systematic review and meta-analysis was conducted to review the evidence of an association between maternal folic acid supplementation during pregnancy and preeclampsia risk. Methods The protocol for this review was prospectively registered with PROSPERO (CRD42015029310). Multiple scientific databases and unpublished literature were searched for relevant studies. Two reviewers independently reviewed studies against a priori inclusion and exclusion criteria. Study data was extracted and quality of each included study assessed. Meta-analysis was conducted to examine the effect of maternal folic acid supplementation on preeclampsia risk. Sub-group analysis was used to explore any sub-group differences between folic acid taken alone or in/alongside a multivitamin, on preeclampsia risk. Results Meta-analysis of eight cohort studies showed a significantly lower risk of preeclampsia with folic acid supplementation in comparison to no folic acid (Odds Ratio = 0.78 [95% CI = 0.63–0.98]). Heterogeneity between studies was moderately high (I-squared = 67%). No significant subgroup difference was found between folic acid taken alone vs folic acid taken in or with a multivitamin on the risk of preeclampsia (Chi-squared = 0.34 (p = 0.56); I-squared = 0%). Discussion This systematic review and meta-analysis found a modest association between maternal folic acid supplementation and reduction in preeclampsia risk, however the overall level of available evidence for the association is low. Further, well-designed prospective studies investigating this relationship are required. These should clearly define the duration and regularity of supplementation, control for the presence of multivitamins, measure folate biomarkers to validate maternal self-report of supplementation, and differentiate between preeclampsia sub-types in their outcomes.

Maternal folic acid supplementation for the prevention of preeclampsia: A systematic review and meta-analysis.

Preeclampsia is a significant contributor to maternal and neonatal morbidity and mortality. Folic acid supplementation is recommended periconceptionally for the prevention of neural tube defects. Epidemiological evidence suggests that maternal folic acid supplementation may play a role in preventing other adverse birth outcomes. This systematic review aimed to investigate the effect of maternal folic acid supplementation during pregnancy on risk of preeclampsia and gestational hypertension. Multiple scientific databases and grey literature were searched for relevant studies. Studies were reviewed according to pre-specified inclusion and exclusion criteria. Study characteristics were summarised and study quality was assessed. A meta-analysis of observational studies was conducted to examine the effect of maternal folic acid supplementation on preeclampsia risk. Meta-analysis of eight observational studies showed significantly lower odds of preeclampsia with folic acid supplementation in comparison to no folic acid supplementation: OR=0.78 (95% CI 0.63, 0.98), with moderately high heterogeneity between studies. Subgroup analysis showed no significant subgroup difference between folic acid supplementation taken by itself, in comparison to folic acid taken in or alongside a multivitamin. Low level evidence is available for a modest association between maternal folic acid supplementation and reduction in preeclampsia risk. Future studies should differentiate between early and late onset and mild vs severe preeclampsia, and should control for relevant confounders including the presence of multivitamin supplements. The protocol for this systematic review was prospectively registered with PROSPERO (CRD42015029310).

Nutritional approach to preeclampsia prevention.

Although not fully understood, the physiopathology of preeclampsia is thought to involve an abnormal placentation, diffuse endothelial cell dysfunction and increased systemic inflammation. As micronutrients play a key role in placental endothelial function, oxidative stress and expression of angiogenic factors, periconceptional micronutrient supplementation has been proposed to reduce the risk of preeclampsia. However, recent studies reported conflicting results. Calcium intake (>1 g/day) may reduce the risk of preeclampsia in women with low-calcium diet. Data from recently updated Cochrane reviews did not support routine supplementation of vitamins C, E or D for either the prevention or treatment of preeclampsia. Evidences are also poor to support zinc or folic acid supplementation for preeclampsia prevention. Dark chocolate, flavonoid-rich food, and long-chain polyunsaturated fatty acids might also be candidates for prevention of preeclampsia. Through antioxidant, anti-inflammatory or vasoactive proprieties, micronutrients are good candidates for preeclampsia prevention. Calcium supplementation is recommended to prevent preeclampsia in women with low-calcium intake. Despite positive clinical and in-vitro data, strong evidence to support periconceptional supplementation of other micronutrients for preeclampsia risk-reduction is still lacking. Further studies are also needed to evaluate the benefit of nutritional supplementation such as chocolate and long-chain polyunsaturated fatty acids.