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Understanding and communicating the risk of pregnancy complications post-living kidney donation is imperative as the majority of living kidney donors (LKD) are women of childbearing age. We aimed to identify all original research articles examining complications in post-donation pregnancies and compared the quality and consistency of related guidelines. We searched Embase, MEDLINE, PubMed, society webpages, and guideline registries for English-language publications published up until December 18, 2020. Ninety-three articles were screened from which 16 studies were identified, with a total of 1399 post-donation pregnancies. The outcome of interest, post-donation pregnancy complications, was not calculable, and only a narrative synthesis of the evidence was possible. The absolute risk of pre-eclampsia increased from similar to 1%-3% pre-donation (lower than the general population) to similar to 4%-10% post-donation (comparable to the general population). The risks of adverse fetal and neonatal outcomes were no different between post-donation and pre-donation pregnancies. Guidelines and consensus statements were consistent in stating the need to inform LKDs of their post-donation pregnancy risk, however, the depth and scope of this guidance were variable. While the absolute risk of pregnancy complications remains low post-donation, a concerted effort is required to better identify and individualize risk in these women, such that consent to donation is truly informed.

Background Pregnancy in women with systemic lupus erythematosus (SLE) and nephritis (LN) is at risk of foetal and maternal complications. Objective To evaluate the effect of LN on pregnancy with respect to foetal and maternal outcome. Methods We retrospectively studied all pregnant SLE patients with and without diagnosis of LN, who attended the Materno Neonatal Hospital in Cordoba city, Argentina, from January 2015 to April 2017. Demographic, clinical, and laboratory data were collected. The presence of antiphospholipid syndrome (APS) and antiphospholipid antibodies (AAF), and maternal and foetal outcome were evaluated. Results 121 pregnancies in 79 patients were included. Pregnancies were divided into those with LN (69) and those without LN (52). The presence of APS and AAF was more frequent in the LN group as well as higher basal SLEDAI. The LN group received more immunosuppressive therapy and increased steroid dose treatment. Of the patients, 47.5% had Class IV LN. Lupus flares occurred more frequently in the LN group 25.8% vs 10.9% in the group without LN (P = .041), mainly renal flares in the LN group. No patients developed end-stage renal failure. Preeclampsia was more frequent in the LN group, 18.8% vs 6.3% in the group without LN (P = .047). There was only one maternal death. A caesarean section was required in 68.5% of the LN group vs 31.5 in the group without LN, and urgent caesarean section was also performed in the LN group. There were no differences in foetal outcomes in either group: live birth, gestational age, weight birth, perinatal death, foetal distress. Conclusions Patients with LN experienced more maternal complications such as lupus flares and preeclampsia. However, LN does not lead to a worse pregnancy and foetal outcome. Patients should be strictly monitored before and after conception.

Only a few studies have explored the role of microbiota-dependent metabolite trimethylamine N-oxide (TMAO) in non-complicated pregnancy and in pre-eclampsia (PE). We enrolled 139 PE and 29 healthy pregnant women in a nested case control study. We hypothesized that elevated levels of circulating TMAO and its precursors choline and glycine betaine in the late second or in third trimester might contribute to the PE and are associated with the onset of the disease and clinical features such as elevated blood pressure. The association with a few available lifestyle factors (use of fish and physical activity) was also evaluated. In contrast with the previous findings, there was no difference in TMAO concentration between PE and healthy women. In addition, TMAO concentration was not associated with any of the PE related clinical features, angiogenic or inflammatory markers. In future, it is crucial to obtain longitudinal data on TMAO in both non-complicated and in PE pregnancies before we could have more detailed understanding of TMAO. publishedVersion

Objective To identify the prevalence of pre-pregnancy overweight/obesity in pregnant women and its relationship with socio-demographic factors and to describe the maternal and perinatal outcomes in a Barcelona hospital (Spain). Method A descriptive cross-association study, with retrospective data collection, was performed Barcelona Hospital. The data of 5447 pregnant women who delivered at >=23 weeks of gestation were included. Body Mass Index (BMI) data were categorised into World Health Organization classifications. p values Results The prevalence of pre-pregnancy obesity was 8.4% and 18.9% for overweight. Gestational diabetes was more frequent in pre-pregnancy overweight/obesity (OR 1.92: 95% CI 1.54–2.40 and OR 3.34: 95% CI 2.57–4.33), as were preeclampsia (OR 2.08: 95% CI 1.55–2.79 and OR 3.35: 95% CI 2.38–4.71), induction of labour (OR 1.19: 95% CI 1.02–1.38 and OR 1.94: 95% CI 1.57–2.10), caesarean section (OR 1.41: 95% CI 1.21–1.65 and OR 2.68: 95% CI 2.18–3.29), prematurity (OR 1.28: 95% CI 1–1.65 and OR 1.79: 95% CI 1.32–2.44) and macrosomia (OR 1.87: 95% CI 1.43–2.46 and OR 2.03: 95% CI 1.40–2.93). Conclusions One in four pregnant women had pre-pregnancy overweight or obesity. This study shows the relationship between pre-pregnancy overweight or obesity with adverse maternal and perinatal outcomes.

Standardized combined Doppler-electrocardiogram assessment was performed longitudinally at three different locations of internal jugular veins between 12 wk of gestation and 6 wk postnatally in 24 uncomplicated pregnancies. All images were classified as typical or non-typical based on the presence of the physiologic deflections A, X, H and C. Linear mixed models with random intercepts of typical images were used to investigate gestational changes in venous pulse transit time and venous impedance index. Unequivocal identification of venous pulse transit time and venous impedance index was possible in 2617 of 3798 (69%) and 2234 of 3798 (59%) images, respectively. The best identification rate (80%, 1018/1266) was at the right distal internal jugular vein. Venous pulse transit time increased with gestational age at all locations; venous impedance index decreased at the right sided internal jugular vein. Maternal jugular venous pulse waveform by combined Doppler-electrocardiogram allows unequivocal identification of A-deflection and calculation of venous pulse transit time and venous impedance index in around two-thirds of assessments, with the highest success rate at the right distal internal jugular vein. Gestational evolutions of venous pulse transit time and venous impedance index are similar to those reported at the level of renal interlobar and hepatic veins.

Background and aims: Preeclampsia (PE) is associated with life-long increased risk of cardiovascular disease. One of the main protective functions of high-density lipoprotein (HDL) is its role in reverse cholesterol transport. HDL-mediated cholesterol efflux capacity (CEC) is decreased during pregnancy in women with PE. Whether this persists postpartum is unknown. Methods: Basal and transporter-specific CEC were determined 6 months postpartum in women who had a normotensive (n = 44) or a PE (n = 42) pregnancy. CEC was also measured in 23 normotensive and 20 PE women for whom samples were collected 24 months postpartum. Basal, ATP-binding cassette transporter-A1 (ABCA1)- and -G1 (ABCG1)-specific CEC were primarily determined using Chinese hamster ovary cells stably expressing human ABCA1 or ABCG1, and were also assessed using a J774 mouse macrophage cell line. Results: ABCA1-specific CEC was significantly lower in women who had PE 6 months postpartum (0.57 ± 0.1 vs 0.53 ± 0.08; p

OBJECTIVE This study evaluated urinary angiotensinogen in preeclampsia. METHODS Normal pregnant (n = 57) and preeclamptic patients (n = 31); Normal pregnant (n = 10) and preeclamptic rats (n = 10) were studied. Urinary angiotensinogen and plasma angiotensin II were assayed by enzyme-linked immunosorbent assay (ELISA). RESULTS Urinary angiotensinogen in preeclampsia patients (2.0 ± 1.1 ng/mg creatinine) was suppressed (*p

Objective In this brief review, the authors focus on the effects of gestational exposures to urban air pollution on fetal development and neonatal outcomes. Source of data In this review the authors used PubMed, Web of Science and SciELO research platforms, analyzing papers from the last 30 years. Summary of the findings Epidemiological and experimental evidence agree that gestational exposure to air pollution in urban increases the risks for low birth weight, preterm birth, congenital malformation, intrauterine growth restriction, and neonatal mortality. Furthermore, exposures are associated with increased risks for preeclampsia, hypertension, gestational diabetes. Conclusions Therefore, it is time for greater involvement and engagement of the health sector in the discussion of public policies that may affect the quality of the environment, and that directly or indirectly impact the health of those who were not yet born.

The reported incidence of eclampsia is 1.6 to 10 per 10,000 deliveries in developed countries, whereas it is 50 to 151 per 10,000 deliveries in developing countries. In addition, low-resource countries have substantially higher rates of maternal and perinatal mortalities and morbidities. This disparity in incidence and pregnancy outcomes may be related to universal access to prenatal care, early detection of preeclampsia, timely delivery, and availability of healthcare resources in developed countries compared to developing countries. Because of its infrequency in developed countries, many obstetrical providers and maternity units have minimal to no experience in the acute management of eclampsia and its complications. Therefore, clear protocols for prevention of eclampsia in those with severe preeclampsia and acute treatment of eclamptic seizures at all levels of healthcare are required for better maternal and neonatal outcomes. Eclamptic seizure will occur in 2% of women with preeclampsia with severe features who are not receiving magnesium sulfate and in

The opinion on the mechanisms underlying the pathogenesis of preeclampsia still divides scientists and clinicians. This common complication of pregnancy has long been viewed as a disorder linked primarily to placental dysfunction, which is caused by abnormal trophoblast invasion, however, evidence from the previous two decades has triggered and supported a major shift in viewing preeclampsia as a condition that is caused by inherent maternal cardiovascular dysfunction, perhaps entirely independent of the placenta. In fact, abnormalities in the arterial and cardiac functions are evident from the early subclinical stages of preeclampsia and even before conception. Moving away from simply observing the peripheral blood pressure changes, studies on the central hemodynamics reveal two different mechanisms of cardiovascular dysfunction thought to be reflective of the early-onset and late-onset phenotypes of preeclampsia. More recent evidence identified that the underlying cardiovascular dysfunction in these phenotypes can be categorized according to the presence of coexisting fetal growth restriction instead of according to the gestational period at onset, the former being far more common at early gestational ages. The purpose of this review is to summarize the hemodynamic research observations for the two phenotypes of preeclampsia. We delineate the physiological hemodynamic changes that occur in normal pregnancy and those that are observed with the pathologic processes associated with preeclampsia. From this, we propose how the two phenotypes of preeclampsia could be managed to mitigate or redress the hemodynamic dysfunction, and we consider the implications for future research based on the current evidence. Maternal hemodynamic modifications throughout pregnancy can be recorded with simple-to-use, noninvasive devices in obstetrical settings, which require only basic training. This review includes a brief overview of the methodologies and techniques used to study hemodynamics and arterial function, specifically the noninvasive techniques that have been utilized in preeclampsia research.

The definition of preeclampsia is changing. However, with the addition of organ symptoms to the presence of hypertension in pregnancy instead of relying only on proteinuria, a more precise detection of women at risk of preeclampsia-associated adverse events has not been achieved. Instead, under the new definitions of the American College of Obstetricians and Gynecologists and of the International Society for the Study of Hypertension in Pregnancy, more women are classified as preeclamptic, with a tendency to milder disease. Furthermore, angiogenic and antiangiogenic factors have emerged as essential tools for predicting and diagnosing preeclampsia at high accuracies. Next to being rooted in the pathophysiology of the disease, they have been proven to be reliable tools for predicting and diagnosing the disease. In addition, 2 cutoffs have been evaluated for the clinical setting. As shown in the Prediction of Short-Term Outcome in Pregnant Women With Suspected Preeclampsia Study, at the soluble fms-like tyrosine kinase-1-to-placental growth factor ratio cutoff of 38, a preeclampsia can be ruled out for 1 week with a negative predictive value of 99.3% (95% confidence interval, 97.9-99.9) and ruled in with a positive predictive value of 36.7% (95% confidence interval, 28.4-45.7). The diagnostic cutoff of 85 has been shown to accurately identify women with preeclampsia, with a sensitivity of up to 88% and a specificity of 99.5%. In this review, we highlight the central role of angiogenic and antiangiogenic factors in the differential diagnosis of women presenting at high risk of the disease, such as patients with chronic hypertension or chronic kidney disease. We will focus on their ability to predict preeclampsia-associated adverse fetal and maternal outcomes. This is only possible when critically reviewing the evolution of the definition of "preeclampsia." We show how changes in this definition shape our clinical picture of the condition and how angiogenic and antiangiogenic biomarkers might be included to better identify women destined to develop preeclampsia-related adverse outcomes.

International audience; Objective: To explore the regulatory role of soluble CD146 (sCD146) and its interaction with galectin-1 (Gal1) in placenta-mediated complications of pregnancy.Design: Prospective pilot and experimental studies.Setting: University-affiliated hospital and academic research laboratory.Patient(s): One hundred fifteen women divided into three groups: 30 healthy, nonpregnant women, 50 women with normal pregnancies, and 35 with placenta-mediated pregnancy complications.Intervention(s): Wound-healing experiments were conducted to study trophoblast migration.Main outcome measure(s): Quantification of sCD146 and Gal1 by enzyme-linked immunosorbent assay. Analysis of trophoblast migration by wound closure.Result(s): Concomitant detection of sCD146 and Gal1 showed lower sCD146 and higher Gal1 concentrations in women with normal pregnancies compared with nonpregnant women. In addition, follow-up of these women revealed a decrease in sCD146 associated with an increase in Gal1 throughout pregnancy. In contrast, in women with preeclampsia, we found significantly higher sCD146 concentrations compared with women with normal pregnancies and no modification of Gal1. We emphasize the opposing effects of sCD146 and Gal, since, unlike Gal1, sCD146 inhibits trophoblast migration. Moreover, the migratory effect of Gal1 was abrogated with the use of an anti-CD146 blocking antibody or the use of small interfering RNA to silence VEGFR2 expression. This suggests that trophoblast migration is mediated though the interaction of Gal1 with CD146, further activating the VEGFR2 signaling pathway. Significantly, sCD146 blocked the migratory effects of Gal1 on trophoblasts and inhibited its secretion, suggesting that sCD146 acts as a ligand trap.Conclusion(s): Soluble CD146 could be proposed as a biomarker in preeclampsia and a potential therapeutic target. Clinical trial registration number: NCT 01736826.Trial registration: ClinicalTrials.gov NCT01736826.

Preeclampsia is a devastating medical complication of pregnancy that can lead to significant maternal and fetal morbidity and mortality. It is currently believed that there is abnormal placentation in as early as the first trimester in women destined to develop preeclampsia. Although the etiology of the abnormal placentation is being debated, numerous epidemiologic and experimental studies suggest that imbalances in circulating angiogenic factors released from the placenta are responsible for the maternal signs and symptoms of preeclampsia. In particular, circulating levels of soluble fms-like tyrosine kinase 1, an antiangiogenic factor, are markedly increased in women with preeclampsia, whereas free levels of its ligand, placental, growth factor are markedly diminished. Alterations in these angiogenic factors precede the onset of clinical signs of preeclampsia and correlate with disease severity. Recently, the availability of automated assays for the measurement of angiogenic biomarkers in the plasma, serum, and urine has helped investigators worldwide to demonstrate a key role for these factors in the clinical diagnosis and prediction of preeclampsia. Numerous studies have reported that circulating angiogenic biomarkers have a very high negative predictive value to rule out clinical disease among women with suspected preeclampsia. These blood-based biomarkers have provided a valuable tool to clinicians to accelerate the time to clinical diagnosis and minimize maternal adverse outcomes in women with preeclampsia. Angiogenic biomarkers have also been useful to elucidate the pathogenesis of related disorders of abnormal placentation such as intrauterine growth restriction, intrauterine fetal death, twin-to-twin transfusion syndrome, and fetal hydrops. In summary, the discovery and characterization of angiogenic proteins of placental origin have provided clinicians a noninvasive blood-based tool to monitor placental function and health and for early detection of disorders of placentation. Uncovering the mechanisms of altered angiogenic factors in preeclampsia and related disorders of placentation may provide insights into novel preventive and therapeutic options.

Physiologic, mechanical and immunologic alterations in pregnancy could potentially affect susceptibility to and severity of COVID-19 during pregnancy. Due to lack of comparable incidence data and challenges with disentangling differences in susceptibility from different exposure risks, data are insufficient to determine whether pregnancy increases susceptibility to SARS-CoV-2 infection. Data support pregnancy as a risk factor for severe disease associated with COVID-19; some of the best evidence comes from the Centers for Disease Control and Prevention’s (CDC’s) COVID-19 surveillance system, which reported that pregnant persons were more likely to be admitted to an intensive care unit (ICU), require invasive ventilation, require extracorporeal membrane oxygenation, and die compared with nonpregnant women of reproductive age. Although intrauterine transmission of SARS-CoV-2 has been documented, it appears to be rare, possibly related to low levels of SARS-CoV-2 viremia and decreased co-expression of angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) needed for SARS-CoV-2 entry into cells in the placenta. Evidence is accumulating that SARS-CoV-2 infection during pregnancy is associated with a number of adverse pregnancy outcomes including preeclampsia, preterm birth, and stillbirth, especially among pregnant persons with severe COVID-19 disease. In addition to the direct impact of COVID-19 on pregnancy outcomes, there is evidence that the pandemic and its effects on healthcare systems have had adverse effects on pregnancy outcomes, such as increased stillbirths and maternal deaths. These trends may represent widening disparities and an alarming reversal of recent improvements in maternal and infant health. All three COVID-19 vaccines currently available under an Emergency Use Authorization by the United States Food and Drug Administration can be administered to pregnant or lactating persons, with no preference for vaccine type. Although safety data in pregnancy are rapidly accumulating and no safety signals in pregnancy have been detected, additional information about birth outcomes, particularly among persons vaccinated earlier in pregnancy, are needed.

Objective To estimate the annual cost associated with obstetric events in women of reproductive age with immune-mediated inflammatory diseases, from the perspective of the National Healthcare System. Methods A cost-analysis was developed to estimate the impact associated with obstetric events in women of reproductive age with psoriasis (PSO), psoriatic arthritis (PsA), rheumatoid arthritis (RA) and axial spondyloarthritis (axSpA). The analysis considered complications during fertility and conception, in pregnancy and in the postpartum. All parameters were validated and agreed by a multidisciplinary expert panel. Unitary costs (€, 2019) were obtained from national, local databases. Results During fertility and conception, an annual cost per patient of €229 was estimated for a preconception consultation in a patient with PSO, of €3,642 for a preconception consultation in patients with PsA, RA and axSpA and €4,339 for assisted reproduction. Women with complications in pregnancy had an annual cost per patient of €1,214 for a miscarriage in the first trimester, €4,419 for a late miscarriage in the second trimester, €11,260 for preeclampsia €3,188 for restricted intrauterine growth and €12,131 for threat of premature delivery. In the postpartum, an annual cost per patient of €120,364, €44,709, and €5,507 were estimated associated with admissions to neonatology of premature infants of Conclusions This analysis provides insight on the economic burden of complications associated with women of reproductive age for immune-mediated diseases (PSO, PsA, RA, axSpA). Individualization of treatment, additional and close monitoring may reduce the risk and burden of these complications.

Qualitative and quantitative measurement of urine protein excretion is one of the most common tests performed during pregnancy. For more than 100 years, proteinuria was necessary for the diagnosis of preeclampsia, but recent guidelines recommend that proteinuria is sufficient but not necessary for the diagnosis. Still, in clinical practice, most patients with gestational hypertension will be diagnosed as having preeclampsia based on the presence of proteinuria. Although the reference standard for measuring urinary protein excretion is a 24-hour urine collection, spot urine protein-to-creatinine ratio is a reasonable "rule-out" test for proteinuria. Urine dipstick screening for proteinuria does not provide any clinical benefit and should not be used to diagnose proteinuria. The classic cutoff cited to define proteinuria during pregnancy is a value of >300 mg/24 hours or a urine protein-to-creatinine ratio of at least 0.3. Using this cutoff, the rate of isolated proteinuria in pregnancy may reach 8%, whereas preeclampsia occurs among 3% to 8% of pregnancies. Although this threshold is widely accepted, its origin is not based on evidence on adverse pregnancy outcomes but rather on expert opinion and results of small studies. After reviewing the available data, the most important factor that influences maternal and neonatal outcome is the severity of blood pressures and presence of end organ damage, rather than the excess protein excretion. Because the management of gestational hypertension and preeclampsia without severe features is almost identical in frequency of surveillance and timing of delivery, the separation into 2 disorders is unnecessary. If the management of women with gestational hypertension with a positive assessment of proteinuria will not change, we believe that urine assessment for proteinuria is unnecessary in women who develop new-onset blood pressure at or after 20 weeks' gestation. Furthermore, we do not recommend repeated measurement of proteinuria for women with preeclampsia, the amount of proteinuria does not seem to be related to poor maternal and neonatal outcomes, and monitoring proteinuria may lead to unindicated preterm deliveries and related neonatal complications. Our current diagnosis of preeclampsia in women with chronic kidney disease may be based on a change in protein excretion, a baseline protein excretion evaluation is critical in certain conditions such as chronic hypertension, diabetes, and autoimmune or other renal disorders. The current definition of superimposed preeclampsia possesses a diagnostic dilemma, and it is unclear whether a change in the baseline proteinuria reflects another systemic disease such as preeclampsia or whether women with chronic disease such as chronic hypertension or diabetes will experience a different "normal" pattern of protein excretion during pregnancy. Finally, limited data are available regarding angiogenic and other biomarkers in women with chronic kidney disease as a potential aid in distinguishing the worsening of baseline chronic kidney disease and chronic hypertension from superimposed preeclampsia.

Maternal tolerance of the semiallogenic fetus necessitates conciliation of competing interests. Viviparity evolved with a placenta to mediate the needs of the fetus and maternal adaptation to the demands of pregnancy and to ensure optimal survival for both entities. The maternal-fetal interface is imagined as a 2-dimensional porous barrier between the mother and fetus, when in fact it is an intricate multidimensional array of tissues and resident and circulating factors at play, encompassing the developing fetus, the growing placenta, the changing decidua, and the dynamic maternal cardiovascular system. Pregnancy triggers dramatic changes to maternal hemodynamics to meet the growing demands of the developing fetus. Nearly a century of extensive research into the development and function of the placenta has revealed the role of placental dysfunction in the great obstetrical syndromes, among them preeclampsia. Recently, a debate has arisen questioning the primacy of the placenta in the etiology of preeclampsia, asserting that the maternal cardiovascular system is the instigator of the disorder. It was the clinical observation of the high rate of preeclampsia in hydatidiform mole that initiated the focus on the placenta in the etiology of the disease. Over many years of research, shallow trophoblast invasion with deficient remodeling of the maternal spiral arteries into vessels of higher capacitance and lower resistance has been recognized as hallmarks of the preeclamptic milieu. The lack of the normal decrease in uterine artery resistance is likewise predictive of preeclampsia. In abdominal pregnancies, however, an extrauterine pregnancy develops without remodeling of the spiral arteries, yet there is reduced resistance in the uterine arteries and distant vessels, such as the maternal ophthalmic arteries. Proponents of the maternal cardiovascular model of preeclampsia point to the observed maternal hemodynamic adaptations to pregnancy and maladaptation in gestational hypertension and preeclampsia and how the latter resembles the changes associated with cardiac disease states. Recognition of the importance of the angiogenic-antiangiogenic balance between placental-derived growth factor and its receptor soluble fms-like tyrosine kinase-1 and disturbance in this balance by an excess of a circulating isoform, soluble fms-like tyrosine kinase-1, which competes for and disrupts the proangiogenic receptor binding of the vascular endothelial growth factor and placental-derived growth factor, opened new avenues of research into the pathways to normal adaptation of the maternal cardiovascular and other systems to pregnancy and maladaptation in preeclampsia. The significance of the "placenta vs heart" debate goes beyond the academic: understanding the mutuality of placental and maternal cardiac etiologies of preeclampsia has far-reaching clinical implications for designing prevention strategies, such as aspirin therapy, prediction and surveillance through maternal hemodynamic studies or serum placental-derived growth factor and soluble fms-like tyrosine kinase-1 testing, and possible treatments to attenuate the effects of insipient preeclampsia on women and their fetuses, such as RNAi therapy to counteract excess soluble fms-like tyrosine kinase-1 produced by the placenta. In this review, we will present an integrated model of the maternal-placental-fetal array that delineates the commensality among the constituent parts, showing how a disruption in any component or nexus may lead to the multifaceted syndrome of preeclampsia.

Preeclampsia is a common hypertensive disorder of pregnancy associated with considerable neonatal and maternal morbidities and mortalities. However, the exact cause of preeclampsia remains unknown; it is generally accepted that abnormal placentation resulting in the release of soluble antiangiogenic factors, coupled with increased oxidative stress and inflammation, leads to systemic endothelial dysfunction and the clinical manifestations of the disease. Statins have been found to correct similar pathophysiological pathways that underlie the development of preeclampsia. Pravastatin, specifically, has been reported in various preclinical and clinical studies to reverse the pregnancy-specific angiogenic imbalance associated with preeclampsia, to restore global endothelial health, and to prevent oxidative and inflammatory injury. Human studies have found a favorable safety profile for pravastatin, and more recent evidence does not support the previous teratogenic concerns surrounding statins in pregnancy. With reassuring and positive findings from pilot studies and strong biological plausibility, statins should be investigated in large clinical randomized-controlled trials for the prevention of preeclampsia.

Preeclampsia evolves in 2 stages: a placental problem that generates signals to the mother to cause a range of responses that comprise the second stage (preeclampsia syndrome). The first stage of early-onset preeclampsia is poor placentation, which we here call malplacentation. The spiral arteries are incompletely remodeled, leading to later placental malperfusion, relatively early in the second half of pregnancy. The long duration of the first stage (several months) is unsurprisingly associated with fetal growth restriction. The first stage of late-onset preeclampsia, approximately 80% of total cases, is shorter (several weeks) and part of a process that is common to all pregnancies. Placental function declines as it outgrows uterine capacity, with increasing chorionic villous packing, compression of the intervillous space, and fetal hypoxia, and causes late-onset clinical presentations such as "unexplained" stillbirths, late-onset fetal growth restriction, or preeclampsia. The second stages of early- and late-onset preeclampsia share syncytiotrophoblast stress as the most relevant feature that causes the maternal syndrome. Syncytiotrophoblast stress signals in the maternal circulation are probably the most specific biomarkers for preeclampsia. In addition, soluble fms-like tyrosine kinase-1 (mainly produced by syncytiotrophoblast) is the best-known biomarker and is routinely used in clinical practice in many locations. How the stress signals change over time in normal pregnancies indicates that syncytiotrophoblast stress begins on average at 30 to 32 weeks' gestation and progresses to term. At term, syncytiotrophoblast shows increasing markers of stress, including apoptosis, pyroptosis, autophagy, syncytial knots, and necrosis. We label this phenotype the "twilight placenta" and argue that it accounts for the clinical problems of postmature pregnancies. Senescence as a stress response differs in multinuclear syncytiotrophoblast from that of mononuclear cells. Syncytiotrophoblast irreversibly acquires part of the senescence phenotype (cell cycle arrest) when it is formed by cell fusion. The 2 pathways converge on the common pathologic endpoint, syncytiotrophoblast stress, and contribute to preeclampsia subtypes. We highlight that the well-known heterogeneity of the preeclampsia syndrome arises from different pathways to this common endpoint, influenced by maternal genetics, epigenetics, lifestyle, and environmental factors with different fetal and maternal responses to the ensuing insults. This complexity mandates a reassessment of our approach to predicting and preventing preeclampsia, and we summarize research priorities to maximize what we can learn about these important issues.

Objective This study aimed to review pregnancy hypertension clinical practice guidelines to inform international clinical practice and research priorities. Study Eligibility Criteria Relevant national and international clinical practice guidelines, 2009-19, published in English, French, Dutch or German. Study Appraisal and Synthesis Methods Following published methods and prospective registration (CRD42019123787), a literature search was updated. CPGs were identified by 2 authors independently who scored quality and usefulness for practice (Appraisal of Guidelines for Research and Evaluation II instrument), abstracted data, and resolved any disagreement by consensus. Results Of note, 15 of 17 identified clinical practice guidelines (4 international) were deemed “clinically useful” and had recommendations abstracted. The highest Appraisal of Guidelines for Research and Evaluation II scores were from government organizations, and scores have improved over time. The following were consistently recommended: (1) automated blood pressure measurement with devices validated for pregnancy and preeclampsia, reflecting increasing recognition of the prevalence of white-coat hypertension and the potential usefulness of home blood pressure monitoring; (2) use of dipstick proteinuria testing for screening followed by quantitative testing by urinary protein-to-creatinine ratio or 24-hour urine collection; (3) key definitions and most aspects of classification, including a broad definition of preeclampsia (which includes proteinuria and maternal end-organ dysfunction, including headache and visual symptoms and laboratory abnormalities of platelets, creatinine, or liver enzymes) and a recognition that it can worsen after delivery; (4) preeclampsia prevention with aspirin; (5) treatment of severe hypertension, most commonly with intravenous labetalol, oral nifedipine, or intravenous hydralazine; (6) treatment for nonsevere hypertension when undertaken, with oral labetalol (in particular), methyldopa, or nifedipine, with recommendations against the use of renin-angiotensin-aldosterone inhibitors; (7) magnesium sulfate for eclampsia treatment and prevention among women with “severe” preeclampsia; (8) antenatal corticosteroids for preterm birth but not hemolysis, elevated liver enzymes, and low platelet count syndrome; (9) delivery at term for preeclampsia; (10) a focus on usual labor and delivery care but avoidance of ergometrine; and (11) an appreciation that long-term health complications are increased in incidence, mandating lifestyle change and risk factor modification. Lack of uniformity was seen in the following areas: (1) the components of a broad preeclampsia definition (specifically respiratory and gastrointestinal symptoms, fetal manifestations, and biomarkers), what constitutes severe preeclampsia, and whether the definition has utility because at present what constitutes severe preeclampsia by some guidelines that mandate proteinuria now defines any preeclampsia for most other clinical practice guidelines; (2) how preeclampsia risk should be identified early in pregnancy, and aspirin administered for preeclampsia prevention, because multivariable models (with biomarkers and ultrasonography added to clinical risk markers) used in this way to guide aspirin therapy can substantially reduce the incidence of preterm preeclampsia; (3) the value of calcium added to aspirin for preeclampsia prevention, particularly for women with low intake and at increased risk of preeclampsia; (4) emerging recommendations to normalize blood pressure with antihypertensive agents even in the absence of comorbidities; (5) fetal neuroprotection as an indication for magnesium sulfate in the absence of “severe” preeclampsia; and (6) timing of birth for chronic and gestational hypertension and preterm preeclampsia. Conclusion Consistent recommendations should be implemented and audited. Inconsistencies should be the focus of research.

The placenta is a highly metabolically active organ fulfilling the bioenergetic and biosynthetic needs to support its own rapid growth and that of the fetus. Placental metabolic dysfunction is a common occurrence in preeclampsia although its causal relationship to the pathophysiology is unclear. At the outset, this may simply be seen as an "engine out of fuel." However, placental metabolism plays a vital role beyond energy production and is linked to physiological and developmental processes. In this review, we discuss the metabolic basis for placental dysfunction and propose that the alterations in energy metabolism may explain many of the placental phenotypes of preeclampsia such as reduced placental and fetal growth, redox imbalance, oxidative stress, altered epigenetic and gene expression profiles, and the functional consequences of these aberrations. We propose that placental metabolic reprogramming reflects the dynamic physiological state allowing the tissue to adapt to developmental changes and respond to preeclampsia stress, whereas the inability to reprogram placental metabolism may result in severe preeclampsia phenotypes. Finally, we discuss common tested and novel therapeutic strategies for treating placental dysfunction in preeclampsia and their impact on placental energy metabolism as possible explanations into their potential benefits or harm.

Exudative retinal detachment (ERD) is a rare complication that occurring in 1% of patients with preeclampsia, its incidence is increased when it is associated with HELLP syndrome. Preeclampsia is defined by the development of arterial hypertension and proteinuira occurs after 20 weeks of gestation until postpartum. HELLP syndrome (low platelets, hemolysis and elevated liver enzymes) is a severe form of preeclampsia. ERD in preeclampsia is related to choroidal ischaemia, in the vast majority of the cases associated with hypertensive retinopathy. However, it has been proposed that the combination of hypertension with a microangiopathic hemolysis, hipercoagulability and hypoalbuminemia are the main factors contributing to the development of ERD. Its treatment includes a rapid resolution of labor to reverse ocular manifestations and prevent visual sequels. We describe the case of a pregnant woman with atypical preeclampsia who, in the postpartum of a cesarean, presented an ERD concomitantly with a HELLP syndrome.

Accurate assessment of blood pressure is fundamental to the provision of safe obstetrical care. It is simple, cost effective, and life-saving. Treatments for preeclampsia, including antihypertensive drugs, magnesium sulfate, and delivery, are available in many settings. However, the instigation of appropriate treatment relies on prompt and accurate recognition of hypertension. There are a number of different techniques for blood pressure assessment, including the auscultatory method, automated oscillometric devices, home blood pressure monitoring, ambulatory monitoring, and invasive monitoring. The auscultatory method with a mercury sphygmomanometer and the use of Korotkoff sounds was previously recommended as the gold standard technique. Mercury sphygmomanometers have been withdrawn owing to safety concerns and replaced with aneroid devices, but these are particularly prone to calibration errors and regular calibration is imperative to ensure accuracy. Automated oscillometric devices are straightforward to use, but the physiological changes in healthy pregnancy and pathologic changes in preeclampsia may affect the accuracy of a device and monitors must be validated. Validation protocols classify pregnant women as a "special population," and protocols must include 15 women in each category of normotensive pregnancy, hypertensive pregnancy, and preeclampsia. In addition to a scarcity of devices validated for pregnancy and preeclampsia, other pitfalls that cause inaccuracy include the lack of training and poor technique. Blood pressure assessment can be affected by maternal position, inappropriate cuff size, conversation, caffeine, smoking, and irregular heart rate. For home blood pressure monitoring, appropriate instruction should be given on how to use the device. The classification of hypertension and hypertensive disorders of pregnancy has recently been revised. These are classified as preeclampsia, transient gestational hypertension, gestational hypertension, white-coat hypertension, masked hypertension, chronic hypertension, and chronic hypertension with superimposed preeclampsia. Blood pressure varies across gestation and by ethnicity, but gestation-specific thresholds have not been adopted. Hypertension is defined as a sustained systolic blood pressure of ≥140 mm Hg or a sustained diastolic blood pressure of ≥90 mm Hg. In some guidelines, the threshold of diagnosis depends on the setting in which blood pressure measurement is taken, with a threshold of 140/90 mm Hg in a healthcare setting, 135/85 mm Hg at home, or a 24-hour average blood pressure on ambulatory monitoring of >126/76 mm Hg. Some differences exist among organizations with respect to the criteria for the diagnosis of preeclampsia and the correct threshold for intervention and target blood pressure once treatment has been instigated. Home blood pressure monitoring is currently a focus for research. Novel technologies, including early warning devices (such as the CRADLE Vital Signs Alert device) and telemedicine, may provide strategies that prompt earlier recognition of abnormal blood pressure and therefore improve management. The purpose of this review is to provide an update on methods to assess blood pressure in pregnancy and appropriate technique to optimize accuracy. The importance of accurate blood pressure assessment is emphasized with a discussion of preeclampsia prediction and treatment of severe hypertension. Classification of hypertensive disorders and thresholds for treatment will be discussed, including novel developments in the field.

Preeclampsia is defined as hypertension arising after 20 weeks of gestational age with proteinuria or other signs of end-organ damage and is an important cause of maternal and perinatal morbidity and mortality, particularly when of early onset. Although a significant amount of research has been dedicated in identifying preventive measures for preeclampsia, the incidence of the condition has been relatively unchanged in the last decades. This could be attributed to the fact that the underlying pathophysiology of preeclampsia is not entirely understood. There is increasing evidence suggesting that suboptimal trophoblastic invasion leads to an imbalance of angiogenic and antiangiogenic proteins, ultimately causing widespread inflammation and endothelial damage, increased platelet aggregation, and thrombotic events with placental infarcts. Aspirin at doses below 300 mg selectively and irreversibly inactivates the cyclooxygenase-1 enzyme, suppressing the production of prostaglandins and thromboxane and inhibiting inflammation and platelet aggregation. Such an effect has led to the hypothesis that aspirin could be useful for preventing preeclampsia. The first possible link between the use of aspirin and the prevention of preeclampsia was suggested by a case report published in 1978, followed by the first randomized controlled trial published in 1985. Since then, numerous randomized trials have been published, reporting the safety of the use of aspirin in pregnancy and the inconsistent effects of aspirin on the rates of preeclampsia. These inconsistencies, however, can be largely explained by a high degree of heterogeneity regarding the selection of trial participants, baseline risk of the included women, dosage of aspirin, gestational age of prophylaxis initiation, and preeclampsia definition. An individual patient data meta-analysis has indicated a modest 10% reduction in preeclampsia rates with the use of aspirin, but later meta-analyses of aggregate data have revealed a dose-response effect of aspirin on preeclampsia rates, which is maximized when the medication is initiated before 16 weeks of gestational age. Recently, the Aspirin for Evidence-Based Preeclampsia Prevention trial has revealed that aspirin at a daily dosage of 150 mg, initiated before 16 weeks of gestational age, and given at night to a high-risk population, identified by a combined first trimester screening test, reduces the incidence of preterm preeclampsia by 62%. A secondary analysis of the Aspirin for Evidence-Based Preeclampsia Prevention trial data also indicated a reduction in the length of stay in the neonatal intensive care unit by 68% compared with placebo, mainly because of a reduction in births before 32 weeks of gestational age with preeclampsia. The beneficial effect of aspirin has been found to be similar in subgroups according to different maternal characteristics, except for the presence of chronic hypertension, where no beneficial effect is evident. In addition, the effect size of aspirin has been found to be more pronounced in women with good compliance to treatment. In general, randomized trials are underpowered to investigate the treatment effect of aspirin on the rates of other placental-associated adverse outcomes such as fetal growth restriction and stillbirth. This article summarizes the evidence around aspirin for the prevention of preeclampsia and its complications.

Physiological transformation with remodeling of the uteroplacental spiral arteries is key to a successful placentation and normal placental function. It is an intricate process that involves, but is not restricted to, complex interactions between maternal decidual immune cells and invasive trophoblasts in the uterine wall. In normal pregnancy, the smooth muscle cells of the arterial tunica media of uteroplacental spiral arteries are replaced by invading trophoblasts and fibrinoid, and the arterial diameter increases 5- to 10-fold. Poor remodeling of the uteroplacental spiral arteries is linked to early-onset preeclampsia and several other major obstetrical syndromes, including fetal growth restriction, placental abruption, and spontaneous preterm premature rupture of membranes. Extravillous endoglandular and endovenous trophoblast invasions have recently been put forth as potential contributors to these syndromes as well. The well-acknowledged disturbed extravillous invasion of maternal spiral arteries in preeclampsia is summarized, as are briefly novel concepts of disturbed extravillous endoglandular and endovenous trophoblast invasions. Acute atherosis is a foam cell lesion of the uteroplacental spiral arteries associated with poor remodeling. It shares some morphologic features with early stages of atherosclerosis, but several molecular differences between these lesions have also recently been revealed. Acute atherosis is most prevalent at the maternal-fetal interface, at the tip of the spiral arteries. The localization of acute atherosis downstream of poorly remodeled arteries suggests that alterations in blood flow may trigger inflammation and foam cell development. Acute atherosis within the decidua basalis is not, however, confined to unremodeled areas of spiral arteries or to hypertensive disorders of pregnancy and may even be present in some clinically uneventful pregnancies. Given that foam cells of atherosclerotic lesions are known to arise from smooth muscle cells or macrophages activated by multiple types of inflammatory stimulation, we have proposed that multiple forms of decidual vascular inflammation may cause acute atherosis, with or without poor remodeling and/or preeclampsia. Furthermore, we propose that acute atherosis may develop at different gestational ages, depending on the type and degree of the inflammatory insult. This review summarizes the current knowledge of spiral artery remodeling defects and acute atherosis in preeclampsia. Some controversies will be presented, including endovascular and interstitial trophoblast invasion depths, the concept of 2-stage trophoblast invasion, and whether the replacement of maternal spiral artery endothelium by fetal endovascular trophoblasts is permanent. We will discuss the role of acute atherosis in the pathophysiology of preeclampsia and short- and long-term health correlates. Finally, we suggest future opportunities for research on this intriguing uteroplacental interface between the mother and fetus.

Made available in DSpace on 2022-05-01T09:47:28Z (GMT). No. of bitstreams: 0 Previous issue date: 2022-01-01 This study aimed to evaluate the immunomodulatory effect of vitamin D (VD) on the NLRP1 and NLRP3 inflammasomes in placental explants from preeclamptic (PE) and normotensive (NT) pregnant women. Placental explants from eight PE and eight NT pregnant women were cultured with or without hydrogen peroxide (H2O2), VD or H2O2 + VD. Gene and protein expression of NLRP1, NLRP3, HMGB1, caspase-1, IL-1β, TNF-α and IL-18 were determined by qPCR and Western blotting/ELISA. Compared to NT pregnant women, the endogenous gene expression of NLRP1, NLRP3, HMGB1, IL-1β, TNF-α and IL-18 was significantly higher in explants from PE and became decreased after VD treatment. Similarly, VD decreased the protein expression of NLRP1, NLRP3, caspase-1, HMGB1, IL-1β, TNF-α and IL-18 in PE. Placental explants from NT cultured with H2O2 showed increased gene and protein expression of NLRP1, NLRP3, caspase-1, IL-1β, TNF-α and HMGB1, while H2O2 was also able to increase TNF-α and caspase-1 gene expression in PE. Treatment with H2O2 + VD decreased gene/protein expression of NLRP1, NLRP3, caspase-1, HMGB1, IL-1β, TNF-α and IL-18 in PE and NT explants with H2O2. NLRP1 and NLRP3 are upregulated in the PE. VD may play an immunomodulatory role in the placental inflammation and downregulates oxidative stress induced in vitro by H2O2. Botucatu Medical School Sao Paulo State University (Unesp) Institute of Biosciences Sao Paulo State University (Unesp) Botucatu Medical School Sao Paulo State University (Unesp) Institute of Biosciences Sao Paulo State University (Unesp)

Background Hypertensive disorders are important causes of maternal and perinatal morbidity and death. Considering the role of both physical and psychological factors in pregnancies complicated by hypertension, the aim of this study is to examine psychological factors and coping strategies in pregnancies complicated by hypertension. Methods Cross-sectional study. A sample of 552 pregnant women, 343 with pregnancies complicated by hypertension, were assessed in terms of depression, anxiety, stress and coping. Results The hypertensive group had higher scores of depression, stress and anxiety than the control one. Coping strategies were different between hypertensive and control groups (except for confrontive and self-reliant coping styles). When splitting up the hypertensive group into gestational hypertension, chronic hypertension and preeclampsia syndrome, differences between this new classification reached the statistical level. Our data suggests that women with preeclampsia have more symptoms of depression and worse coping strategies – they are less optimistic and more fatalistic. However, after a cluster analysis, two different subgroups of hypertensive women were found: one with worst coping strategies and more vulnerability to negative affective states and another with better coping and more resilient to mental health problems. Limitations Data were cross-sectional. We excluded women with some comorbidities, such as a diagnosis of kidney disease, diabetes or fetal malformation. Conclusions It is important to consider distinct profiles of pregnant women, in order to be able to better understand the peculiarities of mental health and coping during the gestation, especially in pregnancies complicated by hypertension.

First trimester circulating ADAM12 is reduced in fetal growth restriction (FGR) and preeclampsia. We measured plasma ADAM12 at 36 weeks' gestation preceding diagnosis of term preeclampsia or delivery of a small for gestational age (SGA; birthweight10th centile) infant in two independent cohorts (Cohort 1 90 SGA, 41 preeclampsia, 862 controls; Cohort 2121 SGA 23 preeclampsia; 190 controls). ADAM12 was reduced with SGA in both cohorts (p = 0.0015 and 0.011 respectively), and further reduced with birthweight5th centile (p = 0.0013 and 0.0058 respectively). This validates ADAM12 as an SGA biomarker near term. Circulating ADAM12 preceding preeclampsia was not consistently altered.

Objective To analyse a cohort of pregnant patients with systemic lupus erythematosus and compare the outcomes of both the disease and pregnancy with the results of previous studies conducted in the same geographical area. Patients and methods Retrospective cohort study of 37 women with systemic lupus erythematosus (64 pregnancies) followed in a multidisciplinary unit. Comparative study with similar Spanish studies identified after literature search. Results Our cohort was characterized by an older age and by the presence of non-Caucasian patients. Although we found no clinical differences, from the serological point of view our cohort presented a higher frequency of antiphospholipid antibodies. Patients included in this study were treated more frequently with antimalarials and low-dose aspirin. Systemic lupus erythematosus flare frequency was very similar between the different studies, and we did not identify clear predictors for them. Although the rate of live births was similar among studies, the obstetric outcome of our series was better with a very low rate of preeclampsia, preterm birth and low birth weight newborn. The only predictor of adverse obstetric event was age. Conclusions Although changes in the therapeutic attitude and planning of pregnancy in recent years have not had a direct impact on the rate of systemic lupus erythematosus flares during pregnancy, they have meant an improvement in the obstetric results. The introduction of new variables independent of the disease such as age at conception, socio-cultural origin, or the availability of multidisciplinary units should be considered in the results of future studies.

Background LDA triggers biosynthesis of endogenous anti-inflammatory molecules, aspirin-triggered 15-epi-lipoxin A4 (15-epi-LXA4), which may counteract inflammatory process of preeclampsia (PE), and play role in LDA’s mechanism of action in PE prevention in high-risk patients. Objective Investigate the effects of daily LDA on levels of 15-epi-LXA4 in pregnancies at high-risk for developing PE. Materials and methods Secondary analysis of multi-centered randomized controlled trial investigating effects of daily LDA (60 mg) in high-risk pregnancies. Maternal samples were drawn at three points: before LDA initiation (13–26 weeks’ gestation), 24–28 weeks’ gestation (at least two weeks after LDA) and 34–36 weeks’ gestation. 15-epi-LXA4 levels were measured by ELISA. Results Analysis included 82 patients: 63 receiving daily LDA and 29 receiving daily placebo starting between 13 and 25 weeks gestation. Prior to randomization, baseline 15-epi-LXA4 levels were similar between both groups (75.9 pg/mL [IQR; 63.8–114.0] vs 136.2 pg/mL [52.4–476.2]; p = 0.10). Patients receiving daily LDA were noted to have significantly increased levels of 15-epi-LXA4 after LDA administration (136.2 pg/mL [IQR; 52.4–476.2] vs 1758.2 pg/mL [905.4–6638.5]; p Conclusion Daily LDA administration increases 15-epi-LXA4 levels in high-risk pregnancies for PE. In LDA group, pregnancies complicated by PE have lower levels of 15-epi-LXA4 compared to pregnancies without PE.

Background Preeclampsia is associated with increased risk of future heart failure (HF), but the relationship between preeclampsia and HF subtypes are not well-established. Objectives The objective of this analysis was to identify the risk of HF with preserved ejection fraction (HFpEF) following a delivery complicated by preeclampsia/eclampsia. Methods A retrospective cohort study using the New York and Florida state Healthcare Cost and Utilization Project State Inpatient Databases identified delivery hospitalizations between 2006 and 2014 for women with and without preeclampsia/eclampsia. The authors identified women admitted for HF after discharge from index delivery hospitalization until September 30, 2015, using International Classification of Diseases-9th Revision-Clinical Modification diagnosis codes. Patients were followed from discharge to the first instance of primary outcome (HFpEF hospitalization), death, or end of study period. Secondary outcomes included hospitalization for any HF and HF with reduced ejection fraction, separately. The association between preeclampsia/eclampsia and HFpEF was analyzed using Cox proportional hazards models. Results There were 2,532,515 women included in the study: 2,404,486 without and 128,029 with preeclampsia/eclampsia. HFpEF hospitalization was significantly more likely among women with preeclampsia/eclampsia, after adjusting for baseline hypertension and other covariates (aHR: 2.09; 95% CI: 1.80-2.44). Median time to onset of HFpEF was 32.2 months (interquartile range: 0.3-65.0 months), and median age at HFpEF onset was 34.0 years (interquartile range: 29.0-39.0 years). Both traditional (hypertension, diabetes mellitus) and sociodemographic (Black race, rurality, low income) risk factors were also associated with HFpEF and secondary outcomes. Conclusions Preeclampsia/eclampsia is an independent risk factor for future hospitalizations for HFpEF.

Background In women, preeclampsia has a known association with increased long-term cardiovascular morbidity and mortality. However, it is unknown whether it is associated with increased postoperative cardiovascular morbidity and mortality in women. We aimed to determine if preeclampsia is an independent risk factor for myocardial injury after noncardiac surgery (MINS) and postoperative 30-day mortality. Methods This study was a large international multicentre cohort study of a representative sample of 40,004 patients recruited from August 2007 to November 2013. Participants were ≥ 45 years of age and underwent inpatient noncardiac surgery. Within this cohort, our study examined women with a history of pregnancy. Using multivariable models, we explored the association between a history of pregnancy affected by preeclampsia and our primary outcome of MINS and secondary outcome of postoperative mortality within 30 days. MINS was defined as prognostically relevant myocardial injury due to ischemia that occurred during or within 30 days after noncardiac surgery. Results Analyses were restricted to the 13,902 participants with a history of pregnancy. Among these women, 976 (7.0%) had a history of preeclampsia. A history of preeclampsia was associated with an increased risk of MINS, with an adjusted hazard ratio of 1.26 (95% confidence interval 1.03-1.53; P = 0.02). Preeclampsia was not significantly associated with 30-day mortality. Conclusions Preeclampsia is a risk factor for MINS and should be considered in the preoperative cardiovascular risk assessment of women.

Preeclampsia (PE) threatens the safety of mothers and fetuses, and its pathogenesis is still unclear. Our previous study has found the relationship between PE and serum Clusterin (CLU). This study aimed to investigate the role of CLU on PE. Firstly, levels of CLU in serum and placental tissue from PE patients and healthy pregnancies were compared. Then, RNA sequencing, cell counting kit-8, matrigel invasion, cell apoptosis, and angiogenesis assay were performed to evaluate the role of CLU on primary isolation trophoblast cells. We found the expression of CLU was increased before the clinical syndrome occurred, whereas its level was positively related to the severity of PE. CLU significantly inhibited the expression of matrix metalloproteinase-9 and Vimentin and enhanced E-cadherin to inhibit epithelial-mesenchymal transition of trophoblast cells, further reducing its migration and invasion. Our results suggested that CLU may play a role in regulating trophoblast invasion and migration during placental development, which may be one of the risk factors for PE.

Objectives Studies suggest preeclampsia as a risk factor for long term cardiovascular diseases (CVD), while evidence is limited regarding the risk of high blood pressures (BP) in early pregnancy. Study design A register-based follow-up of 2434 mothers in the Helsingborg Birth Cohort. Associations of high BP in early pregnancy (>95th percentile systolic [SBP], diastolic [BDP], or mean arterial BP [MAP]) during the first antenatal visit and/or preeclampsia with an incident CVD event (ischemic heart disease or stroke) were assessed. To model risks and adjust for co-variables, Cox proportional hazard regression was used. Results Of the included women, 120 (4.9%) had high SBP, 49 (2%) high DBP, 104 (4.3%) high MAP in early pregnancy; and 115 (4.7%) developed preeclampsia. During 52 years of follow-up, totalling 121,457 person-years, 534 (21.9%) women experienced a CVD event. Women with preeclampsia had a higher risk of developing CVD compared to women without preeclampsia (HR 1.5, 95%CI: 1.1–2.2), while risks among women with high BPs were slightly higher. In adjusted analysis, risk estimates were approximately 50% higher than that of the reference groups for all four studied exposures. Of women with later CVD, 35 (6.6%) had preeclampsia, and another 31 (5,8%) women high SBP or high MAP. Without later preeclampsia, high SBP constituted a significant risk factor (HR 1.6, 95%CI: 1.1–2.4) for CVD. Conclusions Women with SBP > 95th percentile in early pregnancy, but without later preeclampsia, have a higher risk of developing CVD that is comparable to women with history of preeclampsia.

OBJECTIVE To validate a combined algorithm for early prediction of pre-eclampsia (PE) in the Brazilian population. STUDY DESIGN This is an unplanned secondary analysis of a cohort study. Consecutive singleton pregnancies undergoing first-trimester screening for PE involving examination of maternal characteristics, medical history, and biophysical markers were considered eligible. Women were classified as low-or high-risk using a cutoff of 1/200, but the individual risk was not used to dictate management, as aspirin prophylaxis was given to women based solely on clinical risk factors. Receiver-operating characteristics (ROC) curves for PE, preterm PE(PE

OBJECTIVE The immunological factors have role in the development of preeclampsia. The thymus is one of the main organs of the fetal immune system. The aim of this prospective clinical study was to investigate the association between fetal thymus volume and preeclampsia by adding the 3-dimensional measurement of thymus volume to the routine fetal ultrasound scan at 11-14 week of gestation. STUDY DESIGN Totally 72 pregnant women in their first trimester of pregnancy were included and 3-D fetal thymus volume was measured with sonographic VOCAL programme. All women gestational period was followed. The data of women with preeclampsia (n = 10, study group) and without preeclampsia (n = 62, control group) were compared. MAIN OUTCOME MEASURES Fetal thymus volume, preeclampsia development. RESULTS Fetal thymus volume, mean gestational age at birth and newborn birthweight were found to be statistically lower in cases with preeclampsia compared with those without any complications. When the fetal thymus volume measured by the VOCAL programme in the study group was used as a marker for preeclampsia development, the limit value was 0.0375 cm3; sensitivity was 87.1% and specificity was 50% (AUC 85.3%, P

Pregnancy risk assessment for patients with adult congenital heart disease (ACHD) must include physiologic and anatomic impacts. We aimed to determine whether maternal cardiac and pregnancy outcomes vary by disease severity defined according to the following 3 different classifications: ACHD anatomic severity, ACHD physiologic class, and modified World Health Organization (mWHO) class. Cardiac outcomes included a composite of arrhythmia, heart failure, stroke, and thromboembolism. Pregnancy outcomes included a composite of intrauterine growth restriction, preterm birth, preeclampsia, or postpartum hemorrhage. We employed generalized estimating equations to account for multiple pregnancies. Of the 245 pregnancies, 17.1% were preterm and 45.7% were cesarean deliveries. Cardiac hospitalizations occurred in 22.0% and arrhythmias in 12.7%. Cardiac outcomes tended to be more prevalent in people with more severe heart disease. Pregnancy outcomes were U-shaped or less prevalent in people with more severe disease. There was a 2.9-fold increased risk for the composite cardiac outcome for complex anatomy (adjusted incidence rate ratio 2.90, 95% confidence interval 1.08 to 7.81, p = 0.04), a 9.4-fold increased risk for physiologic class C or D (9.37, 1.28 to 68.79, p = 0.03), and a fourfold increased risk for mWHO class III or IV (3.99, 1.53 to 10.40, p = 0.005). There was a lower risk for the composite pregnancy outcome for mWHO class II or II to III (0.54, 0.36 to 0.79, p = 0.002) but no association with anatomy or physiology. In conclusion, physiologic class may be most accurately associated with adverse outcomes and therefore efforts to optimize hemodynamics before pregnancy may help to mitigate the risk.

Objectives To investigate the prevalence and risk factors of labor-onset hypertension (LOH), defined as hypertension first detected during labor among women without hypertension prior to admission for labor. Study design In this multicenter retrospective study, clinical data of women who delivered vaginally at term between 2012 and 2018 were collected from 12 primary maternity care units. Blood pressure was measured at five time points from admission to 2 h postpartum in a total of 30,129 normotensive women at the last prenatal check-up. LOH was defined as systolic blood pressure (SBP) of ≥ 140 mmHg or diastolic blood pressure (DBP) of ≥ 90 mmHg during the first to fourth stages of labor. Main outcome measures Multivariate regression analyses were conducted to evaluate the risk factors of LOH and severe LOH (SBP of ≥ 160 mmHg or DBP of ≥ 110 mmHg). Results Among the 30,129 women, 8,565 (28.4%) presented with LOH and 734 (2.4%) with severe LOH. The prevalence of LOH was the highest at the second stage of labor (21.7%) and decreased rapidly after delivery. The independent risk factors of LOH were maternal age of ≥ 35 years, pre-pregnancy body mass index of ≥ 25 kg/m2, and pregnancy weight gain of ≥ 15 kg. Conclusion LOH is common, with approximately one in four women experiencing LOH during labor and early postpartum. Meanwhile, severe LOH occurred in 2.4% of the pregnancies. Closer blood pressure monitoring during labor may enable obstetric caregivers to recognize LOH in a timely manner and reduce maternal adverse outcomes, such as eclampsia and stroke.

Objectives To evaluate, in pregnancies complicated by hypertensive disorders of pregnancy (HDP), the predictive role of uterine artery (UtA) Doppler for pregnancy outcome compared to the definition of preeclampsia (PE) established by ISSHP recommendations. Study design Retrospective cohort study including singleton pregnancies diagnosed with HDP, who underwent UtA Doppler assessment at admission in 2011–2017. The study population was classified considering the presence or absence of PE and according to the presence or absence of abnormal UtA Doppler (mean pulsatility index > 95th percentile). Main outcome measures Pregnancy outcome, maternal and fetal complications, evaluated as composite outcomes (CO), and duration of pregnancy (from admission to delivery). Results A total of 311 mother-infant couples was included. The diagnostic ability of the two classifications was analysed comparing the relative likelihood ratio in the Biggerstaff graph. ISSHP definition turned out to be more efficient in detecting maternal adverse CO in comparison to UtA Doppler, relative positive likelihood ratio 1.50 (1.35–1.66) and 1.31 (1.07–1.60). UtA Doppler classification resulted more efficient in predicting adverse neonatal CO than PE definition, relative positive likelihood ratio 2.21 (1.77–2.75) and 1.61 (1.37–1.90). UtA Doppler was significantly associated with delivery at earlier gestational ages both for patients affected by PE and for women affected by HDP without superimposed PE (respectively p = 0.009 and p = 0.037). Conclusions UtA Doppler at HDP diagnosis is a useful bedside marker of fetal/neonatal complications, and is associated with pregnancy duration.

Induction of labor may be indicated to minimize maternal and fetal risks. The rate of induction is likely to increase as recent evidence supports elective induction at 39 weeks gestation. We review methods of induction and then analgesic options as they relate to indications and methods to induce labor. We specifically focus on parturients at high risk for anesthetic complications including those requiring anticoagulation, and those with cardiac disease, obesity, chorioamnionitis, prior spinal instrumentation, elevated intracranial pressure, known or anticipated difficult airway, thrombocytopenia, and preeclampsia. Guidelines regarding timing of anticoagulation dosing with neuraxial anesthetic techniques have been defined through consensus statements. Early epidural placement may be beneficial in patients with cardiac disease, obesity, anticipated difficult airway, and HELLP syndrome. Questions remain regarding how early is too early for epidural placement, what options are safest for patients with bacteremia, and what pain relief should be offered to those unable to tolerate cervical exams in early labor.

Women with valvular heart disease may be more likely to have adverse obstetric and cardiovascular complications during pregnancy. Most current recommendations focus on stenotic lesions with less guidance regarding regurgitant lesions. We aimed to compare adverse events at delivery for women with various stenotic and regurgitant valvular diseases. We used the 2016 to 2018 National Inpatient Sample data to compare demographics, comorbidities, and obstetric and cardiovascular complications during delivery hospitalizations. After adjusting for clinical and socioeconomic factors, logistic regression was performed to investigate associations between valvular disease and outcomes. Among >11.2 million deliveries, 20,349 were in women with valvular disease. Women with valvular disease were older, had longer length of stays, and higher costs associated with delivery. They had higher prevalence of underlying cardiovascular comorbidities compared with women without valvular disease (hypertension: 5.1 vs 0.25%; pulmonary hypertension: 7.0 vs

INTRODUCTION Preeclampsia is a hypertensive disorder affecting both mother and the fetus and is a major cause of maternal and neonatal morbidity and mortality. Abnormal placentation is a common feature in preeclampsia that contributes to placental dysfunction. It is likely that increased homocysteine and oxidative stress influence apoptosis in preeclampsia. Increased placental apoptosis may aggravate the symptoms of preeclampsia through disruption of the placental structure. The current study aims to examine the association between various placental apoptotic markers with placental dimensions and maternal and neonatal characteristics in women with preeclampsia. METHODS A total of 80 pregnant women [preeclampsia (n = 40); normotensive control (n = 40)] were included in the study. Placental characteristics such as its major axis, minor axis, breadth, thickness (at centre, cord insertion and periphery) and trimmed placental weight were recorded.Placental protein levels of caspase-3, caspase-8, BAX and Bcl-2 were estimated by ELISA and gene expression were examined by real time quantitative PCR. RESULT Protein levels of proapoptotic markers such as caspase-8 and 3 were higher (p

Chronic hypoxia is a common cause of pulmonary hypertension, preeclampsia, and intrauterine growth restriction (IUGR). The molecular mechanisms underlying these diseases are not completely understood. Chronic hypoxia may induce the generation of reactive oxygen species (ROS) in mitochondria, promote endoplasmic reticulum (ER) stress, and result in the integrated stress response (ISR) in the pulmonary artery and uteroplacental tissues. Numerous studies have implicated hypoxia-inducible factors (HIFs), oxidative stress, and ER stress/unfolded protein response (UPR) in the development of pulmonary hypertension, preeclampsia and IUGR. This review highlights the roles of HIFs, mitochondria-derived ROS and UPR, as well as their interplay, in the pathogenesis of pulmonary hypertension and preeclampsia, and their implications in drug development.

Background and aims Information regarding inflammation and cardiovascular disease (CVD) risk in type 1 diabetes (T1D) or preeclampsia (PE) is scarce. We assessed differences in inflammation markers according to the presence of both conditions and their association with atherosclerosis. Methods and results We recruited 112 women without CVD and last pregnancy ≥5 years previously (n = 28 per group): a)T1D and PE; b)T1D without PE; c)PE without T1D; and d)Controls (without T1D or PE). Groups were matched by several CVD risk factors, and diabetes duration and retinopathy in T1D. Carotid intima-media thickness (IMT) and plaque presence (IMT ≥1.5 mm) were assessed by ultrasonography. Inflammatory markers included classical variables (leucocytes and high-sensitivity C-reactive protein [hsCRP]) and glycoproteins by nuclear magnetic resonance (1H-NMR) spectroscopy (GlycA, GlycB, GlycF and the height/width [H/W] ratios of GlycA and GlycB). The age of the participants was 44.9 ± 7.8 years, and 20.5% harbored plaque. There were no differences in inflammatory markers among the four study groups. Overall, in multivariate-adjusted models, all 1H-NMR-glycoproteins (except GlycB) were positively associated with IMT measures (IMT of bulb and maximum-IMT of any carotid segment; p Conclusions High 1H-NMR-glycoprotein concentrations have a negative impact on carotid atherosclerosis among women with preeclampsia, regardless of T1D status.

Introduction Maternal immune system tolerance to the semi-allogeneic fetus is critical to a successful pregnancy. We previously reported that myeloid-derived suppressor cells (MDSC) was associated with maternal immune imbalance. T cell immunoglobulin and mucin-containing protein 3 (Tim-3)/Galectin-9 (Gal-9) pathway modulates function of various immune cells in maternal-fetal interface. However, the regulatory effects of Tim-3/Gal-9 signaling on MDSCs and its role in preeclampsia (PE) remain unclear. Methods : In the current study we investigated the expression of Tim-3 on MDSC in preeclampsia (PE) patients to further explore the pathogenesis of PE. Results : The proportion of Tim-3+ M-MDSC (monocytic MDSC) cells was higher in PE patients than in healthy control. Meanwhile, the protein expression of Gal-9, as the ligand of Tim-3, was increased in placenta of PE patients. M-MDSC also expressed a higher level of interferon-γ (IFN-γ) and a lower level of transforming growth factor-β (TGF-β) in PE. Furthermore, our study suggested that blocking Tim-3 could attenuate the inhibitory function of MDSC. Discussion : The abnormal expression of Tim-3 on MDSC might be involved in the pathogenesis of PE, and could be a marker to evaluate the immune function in PE.

Introduction Advanced oxidation protein products (AOPPs), which are novel markers of oxidant-mediated protein damage, are prevalent in numerous diseases. We previously demonstrated that AOPPs act as a new class of pathogenic mediators in preeclampsia by causing trophoblast damage and dysfunction. Herein, we explored whether AOPPs could regulate the Nrf-2/ARE/HO-1 anti-oxidative pathway to facilitate the progression of preeclampsia. Methods To investigate the pathophysiology of preeclampsia, we evaluated the effects of AOPPs on trophoblast damage, apoptotic proteins, and Nrf-2/ARE/HO-1 anti-oxidative pathway expression, as well as their underlying mechanisms. Results AOPPs directly increased the expression of apoptotic proteins and significantly inhibited the expression of Nrf-2/ARE/HO-1 pathway in trophoblasts. Nrf-2 silencing aggravated the AOPPs-induced cell apoptosis in vitro by activating p53 and caspase cascade, whereas Nrf-2 overexpression had the opposite effect. Moreover, Nrf-2 exerted cytoprotective effects by increasing HO-1. Discussion These findings suggest that AOPPs induce trophoblast apoptosis by triggering p53 and caspase activation via inhibition of the Nrf-2/ARE/HO-1 anti-oxidative pathway. Hence, Nrf-2/ARE/HO-1 pathway activation plays a protective role in AOPPs-induced cell apoptosis; thus, holding potential as a therapeutic target against preeclampsia.

Objective: To evaluate the possible associations between serum Neprilysin (NEP) levels and preeclampsia and mild and severe preeclampsia subgroups. Materials and methods: Fifty -five consecutive women with mild preeclampsia and fifty -five consecutive women with severe preeclampsia were compared with 110 approximately gestational age-matched (+/- 1 week) women with an uncomplicated pregnancy. Results: Mean serum NEP was significantly higher in women with preeclampsia compared to that of the gestational age-matched-controls (231.62 +/- 65.30 pg/mL vs. 187.75 +/- 84.38 pg/mL, p < 0.001). Mean serum NEP was significantly higher in the mild preeclampsia group compared to its gestational age -matched control group (228.84 +/- 67.26 pg/mL vs. 186.14 +/- 85.09 pg/mL, p = 0.008); and in the severe preeclampsia group compared to its gestational age-matched control group (234.45 +/- 63.85 pg/mL vs. 189.29 +/- 84.59 pg/mL, p = 0.004). Serum NEP was positively correlated with systolic and diastolic blood pressure, BUN, uric acid, and creatinine. Conclusion: Mean serum NEP was significantly higher in women with preeclampsia than women with an uncomplicated pregnancy. Further studies are needed to elucidate the possible therapeutic role of NEP inhibitors to treat preeclampsia. (c) 2021 Taiwan Association of Obstetrics & Gynecology. Publishing services by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Istanbul Cerrahpasa University, Istanbul, Turkey; Carl von Ossietzky University Oldenburg, University Hospital for Obstetrics and Gynecology in Klinikum Oldenburg AoEuroR, Oldenburg, Germany This study was financed by Istanbul Cerrahpasa University, Istanbul, Turkey, and Carl von Ossietzky University Oldenburg, University Hospital for Obstetrics and Gynecology in Klinikum Oldenburg AoEuroR, Oldenburg, Germany.