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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.

Systemic lupus erythematosus (SLE) patients have more pregnancy complications than healthy patients. Data regarding pregnancy outcomes in women with undifferentiated connective tissue disease (UCTD) are more limited, and existing studies are concentrated in Italy and predominantly in patients with a new diagnosis. Our objective was to compare pregnancy outcomes for UCTD and SLE patients with established disease.Between 2008 and 2017, patients with UCTD and SLE at an academic medical center were recruited to a prospective pregnancy registry. UCTD was defined as a positive autoantibody plus connective tissue disease symptoms not meeting criteria for another rheumatic diagnosis. SLE was defined by American College of Rheumatology or Systemic Lupus International Collaborating Clinics classification criteria or by physician diagnosis. Data were collected throughout pregnancy and postpartum. Comparator groups included UCTD, low-activity SLE, and high-activity SLE.A total of 150 SLE and 51 UCTD pregnancies were analyzed. Disease activity was low in most patients, although more patients with SLE had severe activity during pregnancy (12% versus 2%; P = 0.05). The frequencies of prematurity and preeclampsia were significantly lower in UCTD than in high-activity SLE patients (preterm 17% versus 45% [P = 0.004] and preeclampsia 6% versus 34% [P = 0.0008]), although similar to low-activity SLE patients. More infants who were small for gestational age were born to SLE than UCTD patients (33% versus 7% [P = 0.0005]), regardless of disease activity level.Pregnancies in women with UCTD managed by a rheumatologist have a high rate of pregnancy success and fewer risks than those in women with active SLE.

Preeclampsia and eclampsia is a complication in the labor process whose incidence is always high. The purpose of this study was to study the relationship between Birth Weight and the incidence of preeclampsia in RSUD dr. M. Yunus, Bengkulu city in 2017. The type of research used in this study is Survey Analytic using the Cross Sectional method. The population in this study was overall in the hospital of Dr. M. Yunus City of Bengkulu in January to December in 2017 which is 362 babies. The sampling technique in this study was 78 proportional sampling. The data used is secondary data obtained from the patient register at Dr. M Yunus Hospital in Bengkulu. Data were analyzed using univariate and bivariate analysis with Chi-Square test (2) and Contingency Coefficient (C) test. The results obtained: Of the 78 newborns sampled there were 60 infants (76.9%) normal birth weight, 55 people (70.5%) did not experience preeclampsia, there was a significant relationship between preeclampsia and low infant weight in RSUD dr. M. Yunus Bengkulu in the tight category. It is expected that health workers can maintain and improve the quality of their abilities and skills to deal with babies with low birth weight born by preeclampsia patients or other patients.

OBJECTIVES: To determine whether the full spectrum of hypertensive disorders of pregnancy (HDP) -- comprising gestational hypertension; preeclampsia with or without severe features; eclampsia; and Hemolysis, Elevated Liver enzymes, and Low Platelets (HELLP) Syndrome -- is increased at high (≥2500 m, 8250 ft) compared with lower altitudes in Colorado independent of maternal background characteristics, and if so their relationship to neonatal well-being. METHODS: A retrospective cohort study was conducted using statewide birth-certificate data to compare the frequency of gestational hypertension, preeclampsia (with or without severe features), eclampsia, HELLP Syndrome, or all HDP combined in 617,958 Colorado women who lived at high vs. low altitude (2500 m)- vs. low (

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.

Contains fulltext : 249888.pdf (Publisher’s version ) (Open Access) BACKGROUND: In-depth insight into haemodynamic changes during normotensive pregnancy may help identify women at risk for gestational hypertensive complications. OBJECTIVES: To determine the magnitude of changes in cardiac output and its determinants stroke volume and heart rate, and total peripheral vascular resistance during singleton normotensive and hypertensive pregnancies. SEARCH STRATEGY: PubMed (NCBI) and Embase (Ovid) databases were searched from their inception up to November 2019. SELECTION CRITERIA: Studies reporting original measurements of haemodynamic parameters during pregnancy together with a non-pregnant reference measurement. Studies including women using antihypertensive medication were excluded. DATA COLLECTION AND ANALYSIS: Pooled mean differences between pregnant and non-pregnant women, and absolute values of haemodynamic parameters were calculated for predefined gestational intervals using a random-effects model in normotensive and hypertensive pregnancy. Meta-regression analysis was used to analyse group differences in adjustments and absolute values during pregnancy. MAIN RESULTS: In normotensive pregnancies, cardiac output increased from the first weeks on, reaching its highest level early in the third trimester (mean difference, 1.41 l·min(1) ; 95% CI 1.18-1.63 l·min). In parallel, vascular resistance decreased progressively until its nadir in the early third trimester (mean difference, -331 dyn·sec(-1) ·cm(-5) ; 95% CI -384 to -277 dyn·sec(-1) ·cm(-5) ) and then increased slightly at term. In hypertensive pregnancies, the initial cardiac output increase was higher and vascular resistance did not change throughout gestation compared with reference values. CONCLUSIONS: Hemodynamic changes in women who eventually develop hypertensive complications are substantially different. Serial monitoring and plotting against developed normograms can identify women at risk and may allow timely intervention. TWEETABLE ABSTRACT: Monitoring haemodynamic changes in pregnancy helps identify women at risk for hypertensive complications.

Pregnancy confers a substantially increased risk of stroke, especially during the third trimester and until 6 weeks postpartum. Hypertensive disorders of pregnancy and gestational hypercoagulability are important contributors to obstetric stroke. Preeclampsia and eclampsia confer risk for future cardiovascular disease. Hemorrhagic stroke is the most common type of obstetric stroke. Ischemic stroke can result from cardiomyopathy, paradoxical embolism, posterior reversible encephalopathy, reversible cerebral vasoconstriction syndrome, and dissections. Cerebral venous sinus thrombosis is a frequent complication of pregnancy.

Objective s : There is a need for markers to facilitate the diagnosis of preeclampsia, one of the most chief causes of maternal and infant mortality. Preeclampsia causes damage to the glomeruli and vascular endothelium in pregnant women. Podocalyxin is a sialoglycoprotein found in both glomeruli and vascular endothelium. In this study, we investigated the levels of podocalyxin in preeclampsia, and studied its potential to predict preeclampsia. Material and methods: Women admitted to the Health Sciences University Derince Training and Research Hospital, Department of Obstetrics and Gynecology between February–November 2018 due to high direct blood and diagnosed with preeclampsia according to the 2013 American College of Obstetricians and Gynecologists criteria were included in the study. The control group consisted of healthy volunteers having similar demographic features ‎(gestational week, gravida, parity, and age) with the preeclampsia group. The main outcome variable was serum podocalyxin levels. Results: ‎The mean (± SD) podocalyxin levels of the study and control groups were 124.15 ± ‎39.63 ng/mL and ‎71.47 ± ‎16.86 ng/mL, respectively (‎t = 7.845‎, ‎p < 0.001‎). Using a cut-off of 91.7123, podocalyxin could predict preeclampsia with 90% sensitivity and 98% specificity. Furthermore, podocalyxin levels were significantly higher than the normotensive participants in both early (‎14‎‎3.81‎ ± ‎5‎‎1.96 ng/mL‎ vs. ‎75.‎‎35 ± ‎1‎‎9.36 ng/mL‎) and late-onset (‎11‎‎0.22 ± ‎1‎‎9.11 ng/mL‎ vs ‎68.‎‎26 ± ‎1‎‎4.13 ng/mL‎) preeclampsia (p < 0.001). Conclusions: Serum podocalyxin levels increase in preeclampsia. We conclude that podocalyxin is a candidate for predicting preeclampsia.

Background: Hypertensive disorders of pregnancy (HDP) cause substantial preventable maternal morbidity and mortality. Postpartum hypertension that worsens after women are discharged is particularly...

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

Background: Preeclampsia (PE) is a pregnancy complication with serious maternal and neonatal consequences worldwide. Our understanding of PE pathophysiology has significantly evolved over the last decades by recognizing that endothelial dysfunction and systemic inflammation, with an associated angiogenic imbalance, are key pieces of this incomplete puzzle. In the present era, where no single treatment to cure or treat this obstetric condition has been developed so far, PE prevention and early prediction are the most useful clinical approach to reduce the PE burden. Introduction: Although most PE episodes occur in healthy nulliparous women, the identification of specific clinical conditions that increase the risk of PE dramatically provides a critical opportunity to improve outcomes by acting on potentially reversible factors, and also contributes to better understand this pathophysiologic enigma. Methods: Pertinent studies were searched in PubMed/Medline and Google Scholar (updated August 2020) using common keywords applied in the field of preeclampsia, inflammation and endothelial dysfunction. Given the design of this work as a narrative review, no formal criteria for study selection or appraisal were utilized. Conclusion: In this review, we highlight major clinical contributors of PE and shed light on their potential link with endothelial dysfunction and inflammation.

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.

Objectives: Fetal growth restriction is associated with chronic fetal hypoxia, poor perinatal outcome and increased perinatal mortality. There are no reliable methods to detect cell damage in the central nervous system (CNS) in these patients. The findings of increased an acidic calcium-binding protein (S100B) concentration in biological fluids of infants after brain injury have supported the use of S100B as a biochemical marker of CNS damage. The purpose of the study was to assess blood S100B concentrations in small for gestational age (SGA) and appropriate for gestational age (AGA) newborns and to evaluate the usefulness of S100B for early detection of hypoxia. Material and methods: The investigation was carried out between November 2011 and April 2014. Serum S100B protein level was assessed in cord blood collected from newborns after birth. Medical records of mothers of neonates studied were reviewed for pregnancy induced hypertension (PIH), preeclampsia, maternal smoking during pregnancy and abnormalities in umbilical artery (UA) Doppler ultrasound examination. Results: The study was carried out in 88 SGA neonates and 80 AGA neonates. The median value of S100B protein concentration in the SGA study group was significantly higher than in AGA controls (p < 0.001). Cord blood serum S100B concentration in SGA neonates with prenatal normal UA Doppler ultrasound findings (n = 32) did not differ from that SGA neonates with abnormal prenatal UA Doppler findings (n = 25) (p = 0.74), but was significantly higher than in AGA newborns (p < 0.001). Conclusions : Elevated S100B protein levels in cord blood collected from SGA newborns may be helpful in detecting infants at higher risk of postnatal neurologic disturbances at an early stage.

Women with hypertensive disorders of pregnancy (HDP) present with evidence of significant myocardial dysfunction on echocardiographic assessment at the time of diagnosis. Birth not only cures the syndrome of HDP, but is also associated with a reduction in cardiovascular (CV) volume and resistance load in the mother due to the delivery of the fetoplacental unit. The impact of this physiological change on maternal myocardial function in women with HDP has not been systematically evaluated. The aim of this study is to compare echocardiographic findings immediately before and after childbirth in women with HDP. In this prospective longitudinal study, 30 women with a diagnosis of HDP underwent two consecutive transthoracic echocardiography (TTE) examinations: the first prepartum and the second in the early postpartum period. Paired comparisons of these assessments were performed. Left ventricular (LV) concentric remodelling or hypertrophy were found in 21 (70%) patients and there were no significant differences in cardiac morphology indices: LV mass index (78.9±16.3 g/m vs 77.9 ±15.4 g/m , p=0.611) and relative wall thickness (0.45±0.1 vs 0.44±0.1, p=0.453). LV diastolic function did not demonstrate any peripartum variation: left atrial volume (52.40±15.3 vs 50.97±15.6, p=0.433); lateral E' (0.12±0.03 vs 0.12±0.03, p=0.307) and E/E' ratio (7.88±2.19 vs 7.91±1.74, p=0.934). Systolic function indices such as LV ejection fraction (57.5±4.4% vs 56.4±2.1%, p=0.295) and global longitudinal strain (-15.3±2.6% vs -15.1±3.1%, p=0.715) also remained unchanged. Maternal hemodynamic changes associated with birth did not significantly influence peripartum TTE indices in women with HDP. Suboptimal maternal echocardiographic findings in HDP are likely to be the consequence of chronic pregnancy CV load changes or pre-existing maternal CV impairment. Severity and persistence of myocardial dysfunction into the postpartum period may be related to the long-term maternal CV disease legacy of HDP. This article is protected by copyright. All rights reserved. [Abstract copyright: This article is protected by copyright. All rights reserved.]

Although the most recent guidance from the International Society for the Study of Hypertension in Pregnancy (ISSHP) has highlighted the role of angiogenic marker assessment in the diagnosis of pre-eclampsia (PE) in women with chronic hypertension, the ISSHP has withheld recommending its implementation due to the limited available evidence in this group of women. Therefore, we aimed to investigate the value of soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) assessment in women with chronic hypertension and suspected superimposed PE.This was a retrospective analysis of prospectively collected data recorded in an electronic database between January 2013 and October 2019. Women with chronic hypertension and singleton pregnancy who had suspected superimposed PE were included. Superimposed PE was suspected in women presenting with worsening hypertension, epigastric pain, new-onset edema, dyspnea or neurological symptoms. The exclusion criteria were delivery within 1 week after assessment for reasons other than PE, chronic kidney disease, history of cardiac disease, fetal aneuploidy, genetic syndrome or major structural anomaly and missing pregnancy outcome. Maternal serum angiogenic markers (sFlt-1, PlGF and sFlt-1/PlGF ratio) were measured. The primary outcome was the utility of angiogenic markers in the prediction of superimposed PE. Predictive accuracy was assessed for superimposed PE diagnosed at different timepoints, including within 1 week after assessment and any time before birth. The secondary outcome was comparison of adverse maternal and perinatal outcomes between women with superimposed PE diagnosed according to the traditional ISSHP criteria and those diagnosed according to extended criteria including angiogenic markers. The predictive accuracy of each angiogenic marker was assessed using receiver-operating-characteristics-curve analysis. Area under the curve (AUC) values were compared using De Long's test. A sensitivity analysis was planned for gestational age at assessment. The association of various variables with composite adverse maternal and perinatal outcomes was assessed using binomial regression.The study included 142 pregnant women with chronic hypertension and suspected superimposed PE, of whom 25 (17.6%) developed PE within 1 week after assessment, 52 (36.6%) developed PE at any timepoint before birth and 90 (63.4%) delivered without PE. Maternal serum angiogenic imbalance was associated significantly with superimposed PE diagnosed according to the ISSHP criteria within 1 week or at any time after assessment (P 0.001 for both). The predictive accuracy of maternal serum sFlt-1/PlGF ratio for superimposed PE diagnosed within 1 week after assessment was superior to that of maternal serum PlGF level (AUC, 0.91 vs 0.86; P = 0.032). The addition of angiogenic imbalance to the traditional ISSHP diagnostic criteria was associated with an increase in the detection rate (35.1% increase; 95% credible interval (CrI), 16.6-53.6%) and positive (9.6% increase; 95% CrI, 0.0-20.6%) and negative (3.1% increase; 95% CrI, 1.3-4.9%) predictive values for composite adverse maternal outcome, with high posterior probabilities of an increase in each predictive accuracy parameter ( 99.9%, 95.6% and 99.9%, respectively), without a meaningful decrease in specificity. The addition of angiogenic imbalance improved the detection rate for composite adverse perinatal outcome (20.6% increase; 95% CrI, 0.0-42.2%), with a high posterior probability (96.9%). There was a corresponding drop in specificity (5.7% decrease; 95% CrI, -2.3% to 13.6%), with a posterior probability of 91.8%.In women with chronic hypertension and suspected superimposed PE, addition of maternal serum angiogenic markers to the traditional diagnostic criteria for superimposed PE improved significantly the sensitivity for the prediction of both maternal and perinatal adverse outcomes. Implementation of angiogenic marker assessment in the evaluation of pregnant women with chronic hypertension should therefore be considered. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

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.

The study aimed to investigate whether serum sFlt-1 (soluble fms-like tyrosine kinase-1) at 11-13 weeks’ gestation in pregnancies that subsequently developed preeclampsia was different from those without preeclampsia and compare screening performance of the International Prediction of Pregnancy Complications (IPPIC) reported models, which include various combinations of maternal factors, systolic blood pressure, diastolic blood pressure, PlGF (placental growth factor) and sFlt-1 and the competing risk (CR) models, which include various combinations of maternal factors, mean arterial pressure (MAP) and PlGF for predicting any-onset, early-onset, and late-onset preeclampsia. This was a prospective multicenter study in 7877 singleton pregnancies. The differences of the predictive performance between the IPPIC and CR models were compared. There were 141 women (1.79%) who developed preeclampsia, including 13 cases (0.17%) of early-onset preeclampsia and 128 cases (1.62%) of late-onset preeclampsia. In pregnancies that developed preeclampsia compared to unaffected pregnancies, median serum sFlt-1 levels and its MoMs were not significantly different ( p >0.05). There was no significant association between gestational age at delivery and log 10 sFlt-1 and log 10 sFlt-1 MoM ( p >0.05). The areas under the curve of CR models were significantly higher than the IPPIC models for the prediction of any-onset and late-onset preeclampsia but not for early-onset preeclampsia. In conclusion, there are no significant differences in the maternal serum sFlt-1 levels at 11-13 weeks’ gestation between women who subsequently develop preeclampsia and those who do not. Moreover, the CR models for the prediction of any-onset and late-onset preeclampsia perform better than the IPPIC reported model.

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.

الملخص: أهداف البحث: تسمم الحمل هو عامل خطر رئيس لوفيات ومراضة الأمهات والجنين. كانت هناك جهود هائلة لتحديد المؤشرات الحيوية في المصل، والتي يمكن أن تتنبأ بشكل موثوق بتسمم الحمل. تهدف الدراسة إلى تقييم المؤشرات الحيوية التي لها أفضل فائدة في تشخيص تسمم الحمل. طرق البحث: تم إجراء بحث منهجي في قاعدة بيانات ''بب ميد'' وتم استرداد المراجع المتسلسلة. تم تضمين المقالات البحثية الأصلية التي تضم ضوابط الحالة، والأتراب، وتجارب التحكم العشوائية، والدراسات المقطعية. تضمنت المتغيرات المسجلة تصميم الدراسة ونوعها وسنة ومكان الدراسة وقيمة المتوسط ± الانحراف المعياري للعلامات في المرضى والضوابط والوحدة وحجم عينة مجتمع الدراسة. تم تفسير النتائج بناء على قيم فرق المتوسط المعيارية. النتائج: تم استرجاع ما مجموعه ٣٨٩ دراسة من قاعدة بيانات ''بب ميد''. وأدى التحليل الإضافي ٨٩ دراسة لهذه المراجعة. تم تضمين ٤٧ دراسة إضافية من سلسلة المراجع. في وقت لاحق، تمت مراجعة ١٣٦ مقالة ذات نص كامل بالتفصيل وتم إدخال البيانات. أخيرا، تم اختيار ٢٥ دراسة لهذا التحليل التلوي، وقيمت ١٣ واصما حيويا في مصل الدم. كانت الواسمات المولدة للأوعية والتيروزين كيناز، وعامل النمو المشيمي، والإندوغلين مرتفعة بشكل ملحوظ في المرضى الذين يعانون من تسمم الحمل مقارنة بالضوابط العادية للحوامل. وكان عامل النمو المشيمي والعلامات الحيوية الدهنية عالية الكثافة والأديبونكتين منخفضة بشكل ملحوظ. في حين أن الدهون الثلاثية، وصميم البروتين ب، واللبتين كانت مرتفعة في مرضى مقدمات الارتعاج مقارنة بالضوابط العادية للحوامل. الاستنتاجات: في دراستنا، أظهرت قيم المؤشرات الحيوية في المصل؛ الواسمات المولدة للأوعية وعامل النمو المشيمي والدهون عالية الكثافة والأديبونكتين واللبتين والدهون الثلاثية وصميم البروتين ب، اختلافات كبيرة بين المرضى والضوابط. تتطلب هذه النتائج تقييما متقدما للواسمات الحيوية من أجل الفحص التشخيصي لمقدمات الارتعاج. Abstract: Objective: Preeclampsia is a major risk factor for maternal and foetal mortality and morbidity. There have been tremendous efforts to identify serum biomarkers which can reliably predict the occurrence of preeclampsia. The study aims to assess the biomarkers that have the greatest utility in the diagnosis of preeclampsia. Methods: A systematic search was performed on the PubMed literature database, and chain references were retrieved. Original research articles composed of case controls, cohorts, randomised control trials, and cross-sectional studies were included. The recorded variables included each study's design, type, year, and location; the value (mean ± standard deviation) of the markers in the patients and the pregnant controls; and the p-value, unit of measurement, and the sample size of each study. The results were interpreted based on the standardised mean difference (SMD) values. Results: A total of 398 studies were retrieved from the PubMed database. After further analysis, 89 studies were selected for this review. An additional 47 studies were included based on chain referencing. Later, 136 full-text articles were reviewed in detail and their data were entered. Finally, 25 studies, in which 13 serum biomarkers were assessed, were selected for this meta-analysis. The levels of the angiogenic markers fms-like tyrosine kinase (sFlt), sFlt/placental growth factor (PlGF), and endoglin were significantly higher in patients with preeclampsia than in the pregnant controls. The levels of PlGF and the lipid biomarkers high density lipoprotein (HDL) and adiponectin were significantly lower, while the levels of triglycerides, apolipoprotein B (APO-B), and leptin were elevated in the preeclamptic patients compared to the pregnant controls (p

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.