长期以来，子痫前期-子痫被看作妊娠期特发疾病，其实不然。在病因学方面的流行病学研究早已揭示其发病的多因素，此外，通过对早发子痫前期与晚发子痫前期的病因和发病机制的研究，进一步揭示了子痫前期不仅受多因素影响，还是多种成因致病、有不同发病机制和通路的妊娠期高血压相关综合征［1-4］。进而，对于综合征的认识，也提升了我们对于子痫前期多因素发病、多机制和多通路致病的认识［1，5-6］。由此看来，子痫前期是各种“变形虫”恶向孕育而来，如果要禁止各种“变形虫”恶性孕育-发育到高血压和蛋白尿等阶段，临床医生就要针对各种恶性孕育-发育“变形虫”的风险因素乃至生长环境（产前保健和营养等）及早识别、全方位监控和针对性干预，在临床上形成各路堵截，步步为营之势，创立良好环境，就能让早发子痫前期延缓发生，让早发或晚发子痫前期不发生或不发生重度。这种状况并不难见于获得了优质产前保健的妊娠人群［7］。知道了“变形虫”来由，认识到综合征性质，做到思辨，还要会辨识，从多元化和选择性逐一着手防范是关键。浏览更多请关注本刊微信公众号及当期杂志。

        妊娠期高血压疾病（hypertensive disorders in pregnancy）是严重威胁母儿健康和生命的产科常见病症，造成的孕产妇死亡约占妊娠相关死亡总数的10%～16%，不过有一半相关孕产妇死亡可以避免。孕产妇死亡事件和重症案例可以发生在各级医疗机构，而且存在的诊疗问题涉及各个环节并有其相似性。需解决的关键问题就是提高临床认知、临床思维和临床处置的实践能力。目前将妊娠期高血压疾病概括为妊娠期高血压、子痫前期-子痫综合征、慢性高血压伴子痫前期、慢性高血压4类。尤其是子痫前期-子痫是导致孕产妇及围产儿病死率升高主要原因。现今我们已经深刻认识到子痫前期-子痫更是存在多因素发病异源性、存在多发病机制和多通路致病的异质性，这个“多”字，就提升了临床要求的高度，要求产科医生在真实的临床世界实践中对复杂事物学会辨识、掌握辨析、把控诊疗，从而做好预防监控和处理，旨在获得最佳临床效果和避免可补偿的不良事件的发生。本文就妊娠期高血压疾病尤其是子痫前期-子痫综合征的“三多”发病特点阐释临床实践辨析要点。浏览更多请关注本刊微信公众号及当期杂志。

Hypertensive disorders of pregnancy constitute one of the leading causes of maternal and perinatal mortality worldwide. It has been estimated that preeclampsia complicates 2–8% of pregnancies globally (1). In Latin America and the Caribbean, hypertensive disorders are responsible for almost 26% of maternal deaths, whereas in Africa and Asia they contribute to 9% of deaths. Although maternal mortality is much lower in high-income countries than in developing countries, 16% of maternal deaths can be attributed to hypertensive disorders (1, 2). In the United States, the rate of preeclampsia increased by 25% between 1987 and 2004 (3). Moreover, in comparison with women giving birth in 1980, those giving birth in 2003 were at 6.7-fold increased risk of severe preeclampsia (4). This complication is costly: one study reported that in 2012 in the United States, the estimated cost of preeclampsia within the first 12 months of delivery was $2.18 billion ($1.03 billion for women and $1.15 billion for infants), which was disproportionately borne by premature births (5). This Practice Bulletin will provide guidelines for the diagnosis and management of gestational hypertension and preeclampsia.

目的 分析无严重并发症重度子痫前期（severe preeclampsia，sPE）的终止妊娠影响因素和现状。方法   分析2009年1月至2012年12月北京大学第三医院单个教学医院4年间入院即诊断为重度子痫前期但不伴有严重并发症的330例临床观察资料的终止妊娠指征，按终止妊娠孕周分组。结果   330例入院诊断为sPE且不伴有严重并发症病例占同期出院诊断为sPE的83.3%。终止妊娠的指征在＜26周终止者以孕周为考虑因素者占3/5。26~＜28周组中社会因素是独立影响因素(P<0.001)。在28~＜30周组的主要影响因素有单纯尿蛋白因素（>10g/24h）、发生严重并发症 ；独立影响因素顺位为社会因素、母体因素、胎儿因素、胎盘因素 (P<0.05)。在30~＜32周组影响终止妊娠的主要因素为出现严重并发症；独立影响因素顺位为母体因素、单纯尿蛋白因素、胎盘因素、胎儿因素(P<0.05)。32~＜34周组影响终止妊娠的主要因素为尿蛋白因素、难以控制的高血压及胎心监护异常；独立影响因素顺位为母体因素以及尿蛋白因素、胎儿因素、胎盘因素。34~＜36周组以孕周为考虑因素占44.3%；独立影响因素顺位为孕周因素、难以控制的高血压、脐血流值异常、胎心监护异常(P<0.05)。≥36周后终止妊娠指征以孕周为考虑因素占68.3%。结论   影响入院时无严重并发症sPE终止妊娠的指征性因素较多，但存在着单纯以尿蛋白定量或单纯孕周因素为终止指征者。单纯以尿蛋白定量或单纯孕周因素为终止妊娠指征是否适宜有待更深入研究。

To examine the role of preeclampsia and eclampsia in pregnancy-related mortality.We used data from the Centers for Disease Control and Prevention's Pregnancy Mortality Surveillance System to examine pregnancy-related deaths from preeclampsia and eclampsia from 1979 to 1992. The pregnancy-related mortality ratio for preeclampsia-eclampsia was defined as the number of deaths from preeclampsia and eclampsia per 100,000 live births. Case-fatality rates for 1988-1992 were calculated for preeclampsia and eclampsia deaths per 10,000 cases during the delivery hospitalization, using the National Hospital Discharge Survey.Of 4024 pregnancy-related deaths at 20 weeks' or more gestation in 1979-1992, 790 were due to preeclampsia or eclampsia (1.5 deaths/100,000 live births). Mortality from preeclampsia and eclampsia increased with increasing maternal age. The highest risk of death was at gestational age 20-28 weeks and after the first live birth. Black women were 3.1 times more likely to die from preeclampsia or eclampsia as white women. Women who had received no prenatal care had a higher risk of death from preeclampsia or eclampsia than women who had received any level of prenatal care. The overall preeclampsia-eclampsia case-fatality rate was 6.4 per 10,000 cases at delivery, and was twice as high for black women as for white women.The continuing racial disparity in mortality from preeclampsia and eclampsia emphasizes the need to identify those differences that contribute to excess mortality among black women, and to develop specific interventions to reduce mortality from preeclampsia and eclampsia among all women.

Clinical differences, maternal risk factors and pregnancy outcomes of deliveries complicated by early- (delivery<34 weeks) and late-onset (delivery≥34 weeks) preeclampsia were studied in a cohort of women in Reunion Island during 15 years (period 2001-2015; N=62,230 pregnancies). The overall preeclampsia rate in singleton pregnancies was 2.37%. Early- and late-onset preeclampsia rates were 0.75% and 1.5% respectively, and the trend for each type of disease was stable over time. In both form of preeclampsia, smoking during pregnancy was a protective factor and associated risk factors were: older age, primiparity, pre-existing diabetes, chronic hypertension, higher pre-pregnancy body mass index and obesity, infertility treatment, history of renal disease and hypercholesterolemia (all p<0.05). The rate of caesarean section, medically-induced delivery and impaired foetal and neonatal outcomes were significantly higher in preeclamptic women (all p<0.0001). When comparing early- versus late-onset preeclampsia, the only difference was the older maternal age in primiparae with early-onset preeclampsia (p=0.02), and the two groups of preeclamptic women were similar in terms of maternal risk factors, with the exception of higher rates of chronic hypertension in early-onset preeclampsia (p=0.02). Foetal and neonatal outcomes were evaluated after adjustment for gestational age at delivery and no difference was detected between early- and late-onset preeclamptic women. These analyses failed to identify a specific phenotype of preeclampsia in terms of predisposition or pre-existing risk factors for one form or another. Gestational age at delivery was the most important predictor for offspring outcome.Copyright © 2017 Elsevier B.V. All rights reserved.

Preeclampsia is a heterogeneous disorder, and as with other diseases (e.g., type I and type II diabetes), progress in the understanding of this disorder would be assisted greatly if subtypes could be characterized. We suggest that a first step would be to subdivide preeclampsia into early-onset disease (< 34 + 0 weeks') and late onset disease (> 34 + 0 weeks').

The importance of eosinophils in the pathogenesis of preeclampsia is an question of interest and there are recent studies in the literature indicating significantly lower eosinophil count values in pregnant women with preeclampsia. The present study aims to evaluate the utility of first-trimester eosinophil count and eosinophil-based complete blood cell count indices in the prediction of preeclampsia.Pregnant women diagnosed with preeclampsia (n = 281) were retrospectively compared with a control group (n = 307). The utility of first trimester eosinophil count, neutrophil to eosinophil ratio (NER) (neutrophil/eosinophil), leukocyte to eosinophil ratio (LER) (leukocyte/eosinophil), eosinophil to monocyte ratio (EMR) (eosinophil/monocyte) and, eosinophil to lymphocyte ratio (ELR) (eosinophil/lymphocyte) in the prediction of preeclampsia were evaluated.Optimal cut-off values for eosinophil count, NER, LER, EMR and, ELR in predicting preeclampsia were 0.07 (AUC: 0.62, 58.7% sensitivity, 56.4% specificity), 90.9 (AUC: 0.65, 61.1% sensitivity, 59.4% specificity), 125.7 (AUC: 0.64, 61.4% sensitivity, 58.4% specificity), 0.15 (AUC: 0.63, 60.1% sensitivity, 59.6% specificity) and, 0.03 (AUC: 0.62, 60.9% sensitivity, 57% specificity), respectively. Mentioned values in predicting early-onset preeclampsia were 0.07 (AUC: 0.64, 60.5% sensitivity, 50.8% specificity), 102.1 (AUC: 0.64, 62.4% sensitivity, 58.8% specificity), 140.2 (AUC: 0.65, 63.5% sensitivity, 59.1% soecificity), 0.14 (AUC: 0.66, 66.3% sensitivity, 59.2% specificity), and, 0.03 (AUC: 0.63, 60.5% sensitivity, 57.4% specificity), respectively. The optimal cut-off value for EMR in the prediction of preeclampsia with severe features was 0.16 (AUC: 0.56, 56.9% sensitivity, 53.2% specificity).Eosinophil-based complete blood count indices may be used to predict early-onset preeclampsia with relatively low sensitivity and specificity.Copyright © 2023 Elsevier Ltd. All rights reserved.

Soluble fms-like tyrosine kinase 1 (sFLT-1), a circulating anti-angiogenic factor that binds and antagonizes placental growth factor (PlGF), appears key to preeclamptic pathophysiology. Two main sFLT-1 splice variants exist: sFLT-1 e15a and sFLT-1 i13. Total sFLT-1/PlGF ratios are increasingly used clinically; we explore whether using placental-specific sFLT-1 e15a improves test performance compared with total sFLT-1 in preeclampsia diagnosis.Consent was obtained for serum sampling from 96 women with suspected preeclampsia. Total sFLT-1 and PlGF were quantified using the B.R.A.H.M.S Kryptor Compact Plus automated immunoassay platform, and sFLT-1 e15a by custom enzyme-linked immunosorbent assay. Test performance was then assessed by subsequent diagnosis.Of 96 participants, 32 did not develop preeclampsia, 32 had early-onset (<34 weeks') disease and 32 had late-onset (≥34 weeks') disease. In those with preeclampsia, median sFLT-1 and sFLT-1 e15a were significantly increased (7361.0 vs 2463.0 pg/mL, and 946.6 vs 305.4 ng/mL respectively; p < 0.001 for both), and PlGF significantly reduced (43.5 vs 154.4 pg/mL; p < 0.001) compared to those without preeclampsia. Those with early-onset, compared to late-onset, preeclampsia chiefly had lower median PlGF levels (16.0 vs 57.3; p < 0.001), which contributed to higher sFLT-1/PlGF and sFLT-1 e15a/PlGF ratios (830.1 vs 86.7, and 109258.9 vs 12608.7 respectively; p < 0.001 for both).sFLT-1 e15a performs comparably to total sFLT-1 in women with suspected preeclampsia, however with higher translational burden. Our results support the expanding clinical use of the sFLT-1/PlGF ratio in suspected preeclampsia, particularly early-onset, to assist with disease diagnosis.Copyright © 2022 Elsevier Ltd. All rights reserved.

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.Copyright © 2020 Elsevier Inc. All rights reserved.

To determine the prevalence of metabolic syndrome in formerly preeclamptic women according to three definitions of metabolic syndrome (World Health Organization [WHO], International Diabetes Federation [IDF], and Third Adult Treatment Panel updated [ATPIII]), to evaluate agreement amongst definitions and to compare the risk of recurrent preeclampsia. In 197 women with a history of preeclampsia, we determined presence of metabolic syndrome using WHO, IDF, and ATPIII criteria. We evaluated agreement amongst definitions by using Kappa statistics. The prevalence of recurrent preeclampsia was compared between women with and without inter-pregnancy metabolic syndrome, according to the three definitions. A total of 40 (20%), 46 (23%), and 31 (16%) of women with previous preeclampsia were classified as having metabolic syndrome postpartum according to WHO, IDF, and ATPIII criteria, respectively. Agreement among criteria was considered substantial between WHO and IDF (= 0.64, 95% CI 0.53-0.79), WHO and ATPIII (= 0.74, 95% CI 0.62-0.86), and IDF and ATPIII (= 0.66, 95% CI 0.51-0.77). The prevalence of recurrent preeclampsia was 45% versus 17% in women with and without inter-pregnancy metabolic syndrome according to the WHO definition ( < 0.001), 26% versus 21% according to the IDF criteria (P = 0.16), and 39% versus 20% according to the ATPIII definition (P = 0.02). Agreement among WHO, IDF, and ATPIII criteria of metabolic syndrome in women after preeclampsia is considered substantial. The risk of recurrent preeclampsia is almost one out of two in women with inter-pregnancy metabolic syndrome according to the WHO criteria.

Abnormal fatty acid oxidation (FAO) and lipid metabolism have been found related to preeclampsia (PE). Antiphospholipid syndrome (APS) as a clinical risk factor for PE has also been reported with abnormal lipid metabolism. However, the role of FAO in PE accompanied with APS is unknown. We aimed to investigate long-chain FAO changes in a PE-like rodent model induced by beta 2-glycoprotein I (β2GPI).The PE-like model was established by injection of β2GPI (β2GPI group) or normal saline (control group) into C57BL/6J mice which were sacrificed on day 14 or 18 of gestation. Serum levels of anti-cardiolipin antibodies (aCL), anti-β2GPI antibodies (aβ2GPI) and serum lipids were assayed. Lipid deposition in the placenta and maternal liver was detected by lipid staining. Long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) mRNA and protein expression in the placenta and maternal liver was analyzed.The β2GPI group showed PE-like symptoms including hypertension, proteinuria and adverse pregnancy outcomes. Serum aCL, aβ2GPI, free fatty acid (FFA) and triglyceride (TG) levels in the β2GPI group were significantly elevated compared with the corresponding control group (P < 0.05), while cholesterol showed no significant changes. Placenta and maternal liver fatty infiltration was found in the β2GPI group. LCHAD mRNA and protein expression in the placenta and maternal liver in the β2GPI group were significantly elevated compared with the corresponding control group (P < 0.05).β2GPI can induce PE-like symptoms, elevated serum FFA and TG, and abnormal LCHAD expression in pregnant mice. Changes in long-chain FAO could be a factor linking PE and APS.Copyright © 2014 Elsevier Ltd. All rights reserved.

Preeclampsia is a complex cardiovascular disorder of pregnancy with underlying multifactorial pathogeneses; however, its etiology is not fully understood. It is characterized by the new onset of maternal hypertension after 20 weeks of gestation, accompanied by proteinuria, maternal organ damage, and/or uteroplacental dysfunction. Preeclampsia can be subdivided into early- and late-onset phenotypes (EOPE and LOPE), diagnosed before 34 weeks or from 34 weeks of gestation, respectively. Impaired placental development in early pregnancy and subsequent growth restriction is often associated with EOPE, while LOPE is associated with maternal endothelial dysfunction. The innate immune system plays an essential role in normal progression of physiological pregnancy and fetal development. However, inappropriate or excessive activation of this system can lead to placental dysfunction or poor maternal vascular adaptation and contribute to the development of preeclampsia. This review aims to comprehensively outline the mechanisms of key innate immune cells including macrophages, neutrophils, natural killer (NK) cells, and innate B1 cells, in normal physiological pregnancy, EOPE and LOPE. The roles of the complement system, syncytiotrophoblast extracellular vesicles and mesenchymal stem cells (MSCs) are also discussed in the context of innate immune system regulation and preeclampsia. The outlined molecular mechanisms, which represent potential therapeutic targets, and associated emerging treatments, are evaluated as treatments for preeclampsia. Therefore, by addressing the current understanding of innate immunity in the pathogenesis of EOPE and LOPE, this review will contribute to the body of research that could lead to the development of better diagnosis, prevention, and treatment strategies. Importantly, it will delineate the differences in the mechanisms of the innate immune system in two different types of preeclampsia, which is necessary for a more personalized approach to the monitoring and treatment of affected women.Copyright © 2020 Aneman, Pienaar, Suvakov, Simic, Garovic and McClements.

A total of 125 women with severe preeclampsia that developed in the second trimester underwent follow-up for an average of 5.4 years. Seventeen women had no further pregnancies and 108 had 169 subsequent pregnancies: 59 (35%) were normotensive and 110 (65%) were complicated by preeclampsia (32% of these developing in the second trimester, 32% at 28 to 36 weeks, and 36% at 37 to 40 weeks). Overall, 21% of subsequent pregnancies were complicated by severe preeclampsia in the second trimester. Forty-four patients (35%) had chronic hypertension, the highest incidence being in those with recurrent severe preeclampsia in the second trimester and the lowest in those with only normotensive subsequent pregnancies (67% vs 4%, p less than 0.0001). Long-term maternal complications included two maternal deaths and two other patients with end-stage renal disease requiring dialysis. We conclude that these women are at increased risk for repeat preeclampsia, particularly in the second trimester, and are at increased risk for chronic hypertension and maternal mortality and morbidity.

ELABELA is a newly discovered peptide hormone that appears to be implicated in the mechanisms leading to preeclampsia, independently of angiogenic factors. The aim of the current study was to investigate whether women with early- or late-onset preeclampsia have altered ELABELA plasma concentrations compared to gestational-age-matched normal pregnant women. This retrospective cross-sectional study focused on the maternal plasma samples collected from 232 women with a singleton pregnancy who were allocated into the following groups: (1) early-onset preeclampsia (<34 weeks of gestation,  = 56); (2) late-onset preeclampsia (≥34 weeks of gestation,  = 57); and (3) gestational-age-matched controls with a normal pregnancy [(<34 weeks of gestation,  = 59); (≥34 weeks of gestation,  = 60)]. ELABELA plasma concentrations were determined using a validated enzyme immunoassay. (1) ELABELA plasma concentrations are higher in patients with late-onset preeclampsia compared with those from gestational-age-matched controls with a normal pregnancy [median: 7.99 ng/mL (IQR, 5.3-13.95 ng/mL) versus median: 4.17 ng/mL (IQR, 3-11.19 ng/mL), =.001]; (2) ELABELA plasma concentrations in patients with early-onset preeclampsia do not differ from those of normal pregnant women [median: 6.09 ng/mL (IQR, 2.8-10.66 ng/mL) versus median: 4.02 ng/mL (IQR, 3.26-7.49),  = .32]; and (3) ELABELA plasma concentrations are higher in patients with late-onset preeclampsia compared to those with early-onset preeclampsia [median: 7.99 ng/mL (IQR, 5.3-13.95 ng/mL) versus median: 6.09 ng/mL (IQR, 2.8-10.66 ng/mL),  = .01]. ELABELA plasma concentrations are higher in patients with late-onset preeclampsia than in those with a normal pregnancy. However, women with early-onset preeclampsia have similar ELABELA plasma concentrations to those with a normal pregnancy. These findings provide insight into the ELABELA axis during the human syndrome of preeclampsia. In addition, these data support the concept that different pathophysiologic mechanisms are implicated in early- and late-onset preeclampsia.

Placental growth factor (PlGF) is an increasingly important molecule in the prediction, diagnosis and treatment of pre-eclampsia. It has pro-angiogenic effects on the feto-placental circulation and supports trophoblast growth. Mechanisms by which PlGF expression is regulated continue to be investigated. Low circulating PlGF precedes the manifestation of clinical disease in pre-eclamptic pregnancies and intrauterine growth restriction. This suggests that low PlGF is a marker of abnormal placentation, but it remains uncertain whether this is a cause or consequence. Prediction of pre-eclampsia using PlGF is promising and may assist in the targeting of resources to women at highest risk of adverse pregnancy outcomes. Promisingly, experimental animal models of pre-eclampsia have been successfully treated with supplemental PlGF. Treatment of pre-eclampsia with PlGF is a potential therapeutic option requiring further exploration. This review focuses specifically on the role of PlGF in normal and pathological placental development and in the clinical management of pre-eclampsia.