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BMC Medicine Nov 2022Several recent observational studies have reported that gut microbiota composition is associated with preeclampsia. However, the causal effect of gut microbiota on... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Several recent observational studies have reported that gut microbiota composition is associated with preeclampsia. However, the causal effect of gut microbiota on preeclampsia-eclampsia is unknown.
METHODS
A two-sample Mendelian randomization study was performed using the summary statistics of gut microbiota from the largest available genome-wide association study meta-analysis (n=13,266) conducted by the MiBioGen consortium. The summary statistics of preeclampsia-eclampsia were obtained from the FinnGen consortium R7 release data (5731 cases and 160,670 controls). Inverse variance weighted, maximum likelihood, MR-Egger, weighted median, weighted model, MR-PRESSO, and cML-MA were used to examine the causal association between gut microbiota and preeclampsia-eclampsia. Reverse Mendelian randomization analysis was performed on the bacteria that were found to be causally associated with preeclampsia-eclampsia in forward Mendelian randomization analysis. Cochran's Q statistics were used to quantify the heterogeneity of instrumental variables.
RESULTS
Inverse variance weighted estimates suggested that Bifidobacterium had a protective effect on preeclampsia-eclampsia (odds ratio = 0.76, 95% confidence interval: 0.64-0.89, P = 8.03 × 10). In addition, Collinsella (odds ratio = 0.77, 95% confidence interval: 0.60-0.98, P = 0.03), Enterorhabdus (odds ratio = 0.76, 95% confidence interval: 0.62-0.93, P = 8.76 × 10), Eubacterium (ventriosum group) (odds ratio = 0.76, 95% confidence interval: 0.63-0.91, P = 2.43 × 10), Lachnospiraceae (NK4A136 group) (odds ratio = 0.77, 95% confidence interval: 0.65-0.92, P = 3.77 × 10), and Tyzzerella 3 (odds ratio = 0.85, 95% confidence interval: 0.74-0.97, P = 0.01) presented a suggestive association with preeclampsia-eclampsia. According to the results of reverse MR analysis, no significant causal effect of preeclampsia-eclampsia was found on gut microbiota. No significant heterogeneity of instrumental variables or horizontal pleiotropy was found.
CONCLUSIONS
This two-sample Mendelian randomization study found that Bifidobacterium was causally associated with preeclampsia-eclampsia. Further randomized controlled trials are needed to clarify the protective effect of probiotics on preeclampsia-eclampsia and their specific protective mechanisms.
Topics: Female; Humans; Mendelian Randomization Analysis; Genome-Wide Association Study; Polymorphism, Single Nucleotide; Eclampsia; Pre-Eclampsia; Gastrointestinal Microbiome
PubMed: 36380372
DOI: 10.1186/s12916-022-02657-x -
American Journal of Obstetrics and... Feb 2022Preeclampsia is one of the "great obstetrical syndromes" in which multiple and sometimes overlapping pathologic processes activate a common pathway consisting of... (Review)
Review
Preeclampsia is one of the "great obstetrical syndromes" in which multiple and sometimes overlapping pathologic processes activate a common pathway consisting of endothelial cell activation, intravascular inflammation, and syncytiotrophoblast stress. This article reviews the potential etiologies of preeclampsia. The role of uteroplacental ischemia is well-established on the basis of a solid body of clinical and experimental evidence. A causal role for microorganisms has gained recognition through the realization that periodontal disease and maternal gut dysbiosis are linked to atherosclerosis, thus possibly to a subset of patients with preeclampsia. The recent reports indicating that SARS-CoV-2 infection might be causally linked to preeclampsia are reviewed along with the potential mechanisms involved. Particular etiologic factors, such as the breakdown of maternal-fetal immune tolerance (thought to account for the excess of preeclampsia in primipaternity and egg donation), may operate, in part, through uteroplacental ischemia, whereas other factors such as placental aging may operate largely through syncytiotrophoblast stress. This article also examines the association between gestational diabetes mellitus and maternal obesity with preeclampsia. The role of autoimmunity, fetal diseases, and endocrine disorders is discussed. A greater understanding of the etiologic factors of preeclampsia is essential to improve treatment and prevention.
Topics: Female; Humans; Pre-Eclampsia; Pregnancy
PubMed: 35177222
DOI: 10.1016/j.ajog.2021.11.1356 -
Journal of the American College of... Oct 2020Preeclampsia is a hypertensive disorder of pregnancy. It affects 2% to 8% of pregnancies worldwide and causes significant maternal and perinatal morbidity and mortality.... (Review)
Review
Preeclampsia is a hypertensive disorder of pregnancy. It affects 2% to 8% of pregnancies worldwide and causes significant maternal and perinatal morbidity and mortality. Hypertension and proteinuria are the cornerstone of the disease, though systemic organ dysfunction may ensue. The clinical syndrome begins with abnormal placentation with subsequent release of antiangiogenic markers, mediated primarily by soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin (sEng). High levels of sFlt-1 and sEng result in endothelial dysfunction, vasoconstriction, and immune dysregulation, which can negatively impact every maternal organ system and the fetus. This review comprehensively examines the pathogenesis of preeclampsia with a specific focus on the mechanisms underlying the clinical features. Delivery is the only definitive treatment. Low-dose aspirin is recommended for prophylaxis in high-risk populations. Other treatment options are limited. Additional research is needed to clarify the pathophysiology, and thus, identify potential therapeutic targets for improved treatment and, ultimately, outcomes of this prevalent disease.
Topics: Female; Humans; Hypertension; Nervous System Diseases; Pre-Eclampsia; Pregnancy; Review Literature as Topic
PubMed: 33004135
DOI: 10.1016/j.jacc.2020.08.014 -
Seminars in Fetal & Neonatal Medicine Oct 2020Preeclampsia is an obstetric disorder that affects 3-8% of pregnant women and remains a leading cause of short- and long-term neonatal and maternal morbidity and... (Review)
Review
Preeclampsia is an obstetric disorder that affects 3-8% of pregnant women and remains a leading cause of short- and long-term neonatal and maternal morbidity and mortality. Professional societies recommend the use of low dose aspirin to prevent preeclampsia in high-risk women. However, interest in prevention of this disease and better understanding of its pathophysiology have led to growing research on other agents. This review focuses on the main therapeutic agents evaluated or in use for preeclampsia prevention.
Topics: Aspirin; Female; Fibrinolytic Agents; Humans; Hypertension; Pre-Eclampsia; Pregnancy
PubMed: 32513597
DOI: 10.1016/j.siny.2020.101123 -
American Journal of Obstetrics and... Feb 2022High blood pressure in the postpartum period is most commonly seen in women with antenatal hypertensive disorders, but it can develop de novo in the postpartum time... (Review)
Review
High blood pressure in the postpartum period is most commonly seen in women with antenatal hypertensive disorders, but it can develop de novo in the postpartum time frame. Whether postpartum preeclampsia or eclampsia represents a separate entity from preeclampsia or eclampsia with antepartum onset is unclear. Although definitions vary, the diagnosis of postpartum preeclampsia should be considered in women with new-onset hypertension 48 hours to 6 weeks after delivery. New-onset postpartum preeclampsia is an understudied disease entity with few evidence-based guidelines to guide diagnosis and management. We propose that new-onset hypertension with the presence of any severe features (including severely elevated blood pressure in women with no history of hypertension) be referred to as postpartum preeclampsia after exclusion of other etiologies to facilitate recognition and timely management. Older maternal age, black race, maternal obesity, and cesarean delivery are all associated with a higher risk of postpartum preeclampsia. Most women with delayed-onset postpartum preeclampsia present within the first 7 to 10 days after delivery, most frequently with neurologic symptoms, typically headache. The cornerstones of treatment include the use of antihypertensive agents, magnesium, and diuresis. Postpartum preeclampsia may be associated with a higher risk of maternal morbidity than preeclampsia with antepartum onset, yet it remains an understudied disease process. Future research should focus on the pathophysiology and specific risk factors. A better understanding is imperative for patient care and counseling and anticipatory guidance before hospital discharge and is important for the reduction of maternal morbidity and mortality in the postpartum period.
Topics: Anticonvulsants; Antihypertensive Agents; Blood Pressure Monitoring, Ambulatory; Diuresis; Eclampsia; Female; Humans; Magnesium Sulfate; Pre-Eclampsia; Pregnancy; Puerperal Disorders; Risk Factors
PubMed: 35177218
DOI: 10.1016/j.ajog.2020.10.027 -
EBioMedicine Jan 2022Preeclampsia is pregnancy-specific, and significantly contributes to maternal, and perinatal morbidity and mortality worldwide. An effective predictive test for... (Review)
Review
Preeclampsia is pregnancy-specific, and significantly contributes to maternal, and perinatal morbidity and mortality worldwide. An effective predictive test for preeclampsia would facilitate early diagnosis, targeted surveillance and timely delivery; however limited options currently exist. A first-trimester screening algorithm has been developed and validated to predict preterm preeclampsia, with poor utility for term disease, where the greatest burden lies. Biomarkers such as sFlt-1 and placental growth factor are also now being used clinically in cases of suspected preterm preeclampsia; their high negative predictive value enables confident exclusion of disease in women with normal results, but sensitivity is modest. There has been a concerted effort to identify potential novel biomarkers that might improve prediction. These largely originate from organs involved in preeclampsia's pathogenesis, including placental, cardiovascular and urinary biomarkers. This review outlines the clinical imperative for an effective test and those already in use and summarises current preeclampsia biomarker research.
Topics: Biomarkers; Female; Humans; Infant, Newborn; Placenta; Placenta Growth Factor; Pre-Eclampsia; Predictive Value of Tests; Pregnancy; Pregnancy Trimester, First; Vascular Endothelial Growth Factor Receptor-1
PubMed: 34954654
DOI: 10.1016/j.ebiom.2021.103780 -
Cardiology Clinics Feb 2021Hypertension is the most common medical disorder occurring during pregnancy and a leading cause of maternal and perinatal morbidity and mortality. Accurate blood... (Review)
Review
Hypertension is the most common medical disorder occurring during pregnancy and a leading cause of maternal and perinatal morbidity and mortality. Accurate blood pressure measurement and the diagnosis and treatment of hypertensive disorders during pregnancy and in the postpartum period are pivotal to improve outcomes. This article details hemodynamic adaptations to pregnancy and provides an approach to the prevention, diagnosis, and management of hypertensive disorders of pregnancy (HDP) and hypertensive emergencies. In addition, it reviews optimal strategies for the care of women with hypertension during the fourth trimester and beyond to minimize future cardiovascular risk.
Topics: Antihypertensive Agents; Female; Heart Disease Risk Factors; Humans; Hypertension, Pregnancy-Induced; Pre-Eclampsia; Pregnancy; Preventive Health Services; Prognosis; Risk Assessment
PubMed: 33222817
DOI: 10.1016/j.ccl.2020.09.005 -
Ultrasound in Obstetrics & Gynecology :... Feb 2023Pre-eclampsia (PE) is characterized by placental and maternal endothelial dysfunction, and associated with fetal growth restriction (FGR), placental abruption, preterm... (Review)
Review
Pre-eclampsia (PE) is characterized by placental and maternal endothelial dysfunction, and associated with fetal growth restriction (FGR), placental abruption, preterm delivery and stillbirth. The angiogenic factors soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) are altered in pregnancies complicated by placenta-related disorders. In this Review, we summarize the existing knowledge, examining the performance of maternal PlGF, sFlt-1 and the sFlt-1/PlGF ratio for screening PE, predicting development of PE in the short term, diagnosing PE, monitoring established PE and predicting other placenta-related disorders in singleton pregnancy. We also discuss the performance of PlGF and the sFlt-1/PlGF ratio for predicting PE in twin pregnancy. For first-trimester screening in singleton pregnancy, a more accurate way of identifying high-risk women than current practice is to combine maternal PlGF levels with clinical risk factors and ultrasound markers. Later in pregnancy, the sFlt-1/PlGF ratio has advantages over PlGF because it has a higher pooled sensitivity and specificity for diagnosing and monitoring PE. It has clinical value because it can rule out the development of PE in the 1-4-week period after the test. Once a diagnosis of PE is established, repeat measurement of sFlt-1 and PlGF can help monitor progression of the condition and may inform clinical decision-making regarding the optimal time for delivery. The sFlt-1/PlGF ratio is useful for predicting FGR and preterm delivery, but the association between stillbirth and the angiogenic factors is unclear. The sFlt-1/PlGF ratio can be used to predict PE in twin pregnancy, although different sFlt-1/PlGF ratio cut-offs from those for singleton pregnancy should be applied for optimal performance. In summary, PlGF, sFlt-1 and the sFlt-1/PlGF ratio are useful for screening, diagnosing, predicting and monitoring placenta-related disorders in singleton and twin pregnancy. We propose that tests for these angiogenic factors are integrated more fully into clinical practice.© 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.
Topics: Infant, Newborn; Pregnancy; Female; Humans; Placenta Growth Factor; Pre-Eclampsia; Fetal Growth Retardation; Premature Birth; Stillbirth; Predictive Value of Tests; Biomarkers; Vascular Endothelial Growth Factor Receptor-1; Placenta; Vascular Endothelial Growth Factor A
PubMed: 35816445
DOI: 10.1002/uog.26032 -
Acta Obstetricia Et Gynecologica... May 2023There has been increasing recognition of the association between various pregnancy complications and development of chronic disease in later life. Pregnancy has come to... (Review)
Review
There has been increasing recognition of the association between various pregnancy complications and development of chronic disease in later life. Pregnancy has come to be regarded as a physiological stress test, as the strain it places on a woman's body may reveal underlying predispositions to disease that would otherwise remain hidden for many years. Despite the increasing body of data, there is a lack of awareness among healthcare providers surrounding these risks. We performed a narrative literature review and have summarized the associations between the common pregnancy complications including gestational hypertension, pre-eclampsia, gestational diabetes, placental abruption, spontaneous preterm birth, stillbirth and miscarriage and subsequent development of chronic disease. Hypertensive disorders of pregnancy, spontaneous preterm birth, gestational diabetes, pregnancy loss and placental abruption are all associated with increased risk of various forms of cardiovascular disease. Gestational diabetes, pre-eclampsia, early miscarriage and recurrent miscarriage are associated with increased risk of diabetes mellitus. Pre-eclampsia, stillbirth and recurrent miscarriage are associated with increased risk of venous thromboembolism. Pre-eclampsia, gestational diabetes and stillbirth are associated with increased risk of chronic kidney disease. Gestational diabetes is associated with postnatal depression, and also with increased risk of thyroid and stomach cancers. Stillbirth, miscarriage and recurrent miscarriage are associated with increased risk of mental health disorders including depression, anxiety and post-traumatic stress disorders. Counseling in the postnatal period following a complicated pregnancy, and advice regarding risk reduction should be available for all women. Further studies are required to establish optimal screening intervals for cardiovascular disease and diabetes following complicated pregnancy.
Topics: Pregnancy; Female; Infant, Newborn; Humans; Pre-Eclampsia; Stillbirth; Abruptio Placentae; Diabetes, Gestational; Premature Birth; Cardiovascular Diseases; Placenta; Pregnancy Complications; Women's Health; Abortion, Habitual; Risk Factors
PubMed: 36799269
DOI: 10.1111/aogs.14523 -
Current Hypertension Reports Aug 2020Hypertensive disorders of pregnancy (HDP)-gestational hypertension, preeclampsia, and eclampsia-are a leading cause of adverse maternal and perinatal outcomes... (Review)
Review
PURPOSE OF REVIEW
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.
RECENT FINDINGS
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.
Topics: Antihypertensive Agents; Blood Pressure; Eclampsia; Female; Humans; Hypertension, Pregnancy-Induced; Pre-Eclampsia; Pregnancy
PubMed: 32852691
DOI: 10.1007/s11906-020-01082-w