Human trophoblast invasion and migration are mediated by the YAP1-CCN1 pathway: defective signaling in trophoblasts during early-onset severe preeclampsia†.

The transcription coactivator YAP1 mediates the major effects of the Hippo signaling pathway. The CCN family is a small group of glycoproteins known to be downstream effectors of YAP1 in diverse tissues. However, whether CCN family members mediate the effects of YAP1 in human trophoblasts is unknown. In this study, placental expression of both YAP1 and CCN1 was found to be impaired in pregnancies complicated by early-onset severe preeclampsia. CCN1 was expressed not only in cytotrophoblasts, trophoblast columns, and mesenchymal cells, similar to active YAP1, but also in syncytiotrophoblasts of normal first-trimester placental villi; moreover, decidual staining of active YAP1 and CCN1 was found in both interstitial and endovascular extravillous trophoblasts. In cultured immortalized human trophoblastic HTR-8/SVneo cells, knockdown of YAP1 decreased CCN1 mRNA and protein expression and led to impaired cell invasion and migration. Also, CCN1 knockdown negatively affected HTR-8/SVneo cell invasion and migration but not viability. YAP1 knockdown was further found to impair HTR-8/SVneo cell viability via G0/G1 cell cycle arrest and apoptosis, while CCN1 knockdown had minimal effect on cell cycle arrest and no effect on apoptosis. Accordingly, treatment with recombinant CCN1 partially reversed the YAP1 knockdown-induced impairment in trophoblast invasion and migration but not in viability. Thus, CCN1 mediates the effects of YAP1 on human trophoblast invasion and migration but not apoptosis, and decreased placental expression of YAP1 and CCN1 in pregnancies complicated by early-onset severe preeclampsia might contribute to the pathogenesis of this disease.

Landscapes of gut bacterial and fecal metabolic signatures and their relationship in severe preeclampsia.

BACKGROUND: Preeclampsia is a pregnancy-specific disease leading to maternal and perinatal morbidity. Hypertension and inflammation are the main characteristics of preeclampsia. Many factors can lead to hypertension and inflammation, including gut microbiota which plays an important role in hypertension and inflammation in humans. However, alterations to the gut microbiome and fecal metabolome, and their relationships in severe preeclampsia are not well known. This study aims to identify biomarkers significantly associated with severe preeclampsia and provide a knowledge base for treatments regulating the gut microbiome. METHODS: In this study, fecal samples were collected from individuals with severe preeclampsia and healthy controls for shotgun metagenomic sequencing to evaluate changes in gut microbiota composition. Quantitative polymerase chain reaction analysis was used to validate the reliability of our shotgun metagenomic sequencing results. Additionally, untargeted metabolomics analysis was performed to measure fecal metabolome concentrations. RESULTS: We identified several Lactobacillaceae that were significantly enriched in the gut of healthy controls, including Limosilactobacillus fermentum, the key biomarker distinguishing severe preeclampsia from healthy controls. Limosilactobacillus fermentum was significantly associated with shifts in KEGG Orthology (KO) genes and KEGG pathways of the gut microbiome in severe preeclampsia, such as flagellar assembly. Untargeted fecal metabolome analysis found that severe preeclampsia had higher concentrations of Phenylpropanoate and Agmatine. Increased concentrations of Phenylpropanoate and Agmatine were associated with the abundance of Limosilactobacillus fermentum. Furthermore, all metabolites with higher abundances in healthy controls were enriched in the arginine and proline metabolism pathway. CONCLUSION: Our research indicates that changes in metabolites, possibly due to the gut microbe Limosilactobacillus fermentum, can contribute to the development of severe preeclampsia. This study provides insights into the interaction between gut microbiome and fecal metabolites and offers a basis for improving severe preeclampsia by modulating the gut microbiome.

Effect of low-molecular-weight heparin calcium combined with magnesium sulfate and labetalol on coagulation, vascular endothelial function and pregnancy outcome in early-onset severe preeclampsia.

OBJECTIVE: This paper was aimed at unveiling the effect of low-molecular-weight heparin calcium (LMWH) combined with magnesium sulfate and labetalol on coagulation, vascular endothelial function, and pregnancy outcome in early-onset severe preeclampsia (EOSP). METHODS: Pregnant women with EOSP were divided into the control group and the study group, each with 62 cases. Patients in the control group were treated with labetalol and magnesium sulfate, and those in the study group were treated with LMWH in combination with the control grou Blood pressure (systolic blood pressure [SBP] and diastolic blood pressure [DBP]), 24-h urine protein, coagulation indices [D-dimer (D-D), plasma fibrinogen (Fg), prothrombin time (PT), activated partial thromboplastin time (APTT), and prothrombin time (TT)], endothelial function [endothelin (ET-1) and nitric oxide (NO)], oxidative stress indices [oxidized low-density lipoproteins (ox-LDL), lipid peroxidation (LPO), superoxide dismutase (SOD), and malondialdehyde (MDA)], pregnancy outcome, and adverse effects occurred in the two groups were compared. RESULTS: After treatment, lower SBP, DBP, and 24-h urine protein levels; lower Fg and D-D levels; higher PT, APPT, and TT levels; higher NO levels; lower ET-1 levels; lower ox-LDL, MDA, and LPO levels; higher SOD levels; and lower incidence of adverse pregnancy and adverse reactions were noted in the study group in contrast to the control group. CONCLUSION: EOSP patients given with LMWH combined with magnesium sulfate and labetalol can effectively reduce the patient's blood pressure and urinary protein level; improve coagulation function, oxidative stress, and vascular endothelial function indices; reduce the adverse pregnancy outcomes; and improve the safety of treatment.

Enoxaparin sodium combined with magnesium sulfate in the treatment of severe preeclampsia.

Objective: To observe the treatment of severe preeclampsia in newborns with enoxaparin sodium combined with magnesium sulfate. Methods: A retrospective analysis was conducted on the clinical data of 80 patients with severe preeclampsia admitted to Hefei Second People's Hospital, China from January 2019 to December 2020. Treatment records showed that 40 cases received magnesium sulfate treatment (single group), and 40 cases received enoxaparin sodium combined with magnesium sulfate treatment (combination group). Levels of D-dimer, soluble fms-like tyrosine kinase 1 (sFlt-1), placental growth factor (PLGF), Apgar scores of newborns delivered before and after treatment were compared. Gestation weeks and incidence of adverse reactions were analyzed. Results: After treatment, levels of D-dimer, sfit-1 and adverse reactions in the combination group were significantly lower than those in the single group (P<0.05), and the level of PLGF, newborn Apgar score and length of gestation were significantly higher than those in the single group (P<0.05). Conclusion: Compared to magnesium sulfate alone, the combination of enoxaparin sodium and magnesium sulfate in the treatment of pregnant women with severe preeclampsia can more effectively regulate the cytokine level of patients, improve pregnancy outcome, and improve neonatal Apgar score. The incidence of adverse reactions is low, making it a safe and efficient treatment modality.

HELLP syndrome, intracerebral hemorrhage, and hemophagocytic syndrome after cesarean section in a pregnant patient with severe preeclampsia: a case report.

BACKGROUND: Pregnancy-related intracranial hemorrhage (ICH) is a rare but potentially life-threatening event with complex and varied cause, such as HELLP syndrome and hemophagocytic syndrome. CASE PRESENTATION: A 33-year-old patient underwent a cesarean section with a preliminary diagnosis of "severe preeclampsia and class3 HELLP syndrome ". The patient had poor response to language before surgery, and the catheter drainage fluid was hematuria. Later, the surgeon reported severe bleeding in the operation. Following thromboelastography (TEG) result and postoperative laboratory tests confirmed class1 HELLP syndrome and ICH occurred on the second day after the surgery, and hemophagocytic syndrome was diagnosed during subsequent treatments. CONCLUSION: For patients with HELLP syndrome, we should pay attention to their coagulation condition. The coagulation tests and platelet counts should be repeated if their clinical presentation changed. Those with neurological alarm signs should receive CT or MRI scan. If a pregnant woman had prolonged hemocytopenia and thrombocytopenia, not only the HELLP but also the hemophagocytic syndrome should be considered.

Pregnancy outcomes and disease phenotype of hypertensive disorders of pregnancy in singleton pregnancies after in vitro fertilization: a retrospective analysis of 1130 cases.

BACKGROUND: Although in vitro fertilization (IVF) can increase the incidence of hypertensive disorders of pregnancy (HDP), the pregnancy outcomes and disease phenotype of HDP in singleton pregnancies conceived via IVF remain unclear. METHODS: This retrospective cohort study enrolled 1130 singleton pregnancies with HDP from 2016 to 2020. According to the mode of conception, they were allocated into IVF (n = 102) and natural conception (NC) groups (n = 1028). All IVF pregnancies were subdivided into frozen embryo transfer (FET) group (n = 42) and fresh embryo transfer (ET) group (n = 60). Demographic data, pregnancy outcomes and disease phenotypes of HDP among the groups were compared. The risk factors for severe preeclampsia (PE) and early-onset PE were analyzed. RESULTS: The incidences of early-onset PE (P<0.001), severe PE (P = 0.016), cesarean section (P<0.001) and preterm births (P = 0.003) in the IVF-HDP group were significantly higher than those in the NC-HDP group, and gestational age at diagnosis of HDP (P = 0.027) and gestational age at delivery (P = 0.004) were earlier and birthweight of the neonates (P = 0.033) were lower in the IVF group. In singleton pregnancies with HDP, IVF was associated with increased risks for both severe PE and early-onset PE (aOR 1.945, 95% CI 1.256, 3.014; and aOR 2.373, 95% CI 1.537, 3.663, respectively), as well as FET, family history of preeclampsia, intrahepatic cholestasis of pregnancy, gestational hypothyroidism and multiparity were associated with increased risks of severe PE and early-onset PE. CONCLUSIONS: In singleton pregnancies with HDP, IVF was associated with an increased incidence of the disease phenotype (severe or early-onset PE), as well as an increased incidence of pregnancy outcomes related to severe PE and early-onset PE.

The transversus abdominis plane block in conjunction with intrathecal morphine use after cesarean section in women with severe pre-eclampsia: a randomized controlled trial.

BACKGROUND: The transversus abdominis plane (TAP) block in conjunction with intrathecal morphine has been demonstrated to provide more superior postcesarean analgesia to intrathecal morphine alone. However, the analgesia efficacy of their conjunction has not been demonstrated in patients with severe pre-eclampsia. The study aimed to compare the postcesarean analgesia of TAP block in conjunction with intrathecal morphine versus intrathecal morphine alone in women with severe pre-eclampsia. METHODS: Pregnant women with severe pre-eclampsia undergoing planned cesarean section were randomly allocated into 2 groups to receive TAP block with 20 ml of 0.35% Ropivacaine (TAP group) or with the same volume of 0.9% saline (Sham group) after undergoing elective cesarean section under spinal anaesthesia with 15 mg of 0.5% Ropivacaine plus 0.1 mg of morphine. The outcomes for this analysis include the visual analog scale (VAS) pain score at rest and with movement at 4,8,12,24 h after TAP block was performed, times of use of intravenous patient-controlled analgesia (PCA) within 12 h after anesthesia, the occurrence of maternal side effects, maternal satisfaction, and Apgar score at 1 and 5 min of newborns. RESULTS: 119 subjects receive TAP block with 0.35% Ropivacaine (n = 59)or 0.9% saline (n = 60). At 4,8, 12 h after TAP block, the TAP group reported lower VAS score at rest [at 4 h: 1(0,1) vs. 1(1,2), P < 0.001; at 8 h:1(1,1) vs. 1(1.5,2),P < 0.001; at 12 h:1(1,2) vs. 2(1,2),P = 0.001] and higher satisfaction [53(89.9%) vs.45(75.0%), P < 0.05]. There were no differences between groups in VAS score at 24 h at rest and at all time points above with movement, times of use of PCA within 12 h after anesthesia, maternal side-effect, and Apgar score at 1 and 5 min of newborns. CONCLUSIONS: In conclusion, The TAP block performed in conjunction with intrathecal morphine may not reduce opioid consumption, but it could reduce VAS scores at rest in the first 12 h after cesarean section in women with severe pre-eclampsia, and improve maternal satisfaction, which is worthy of clinical promotion. TRIAL REGISTRATION: Registered at Chinese Clinical Trial Registry( http://www.chictr.org.cn ) on 13/12/2021: ChiCTR2100054293.

The evaluation of serum bisphenol A in patients with preeclampsia.

AIMS: High bisphenol A (BPA) concentration may compromise normal placental development. The aim of this study was to determine maternal serum BPA concentrations in pregnant women with complicated preeclampsia (PE) and normal pregnant women, to compare BPA concentrations, and to examine pregnancy outcomes. METHODS: This prospective case-control study was conducted between March 2021 and October 2021. Serum BPA levels of preeclamptic pregnancy and normal pregnancy were statistically evaluated. In addition, the PE group was divided into three subgroups according to the course of pregnancy. Group 1: patients with non-severe PE who delivered at 37 weeks or later, Group 2: patients with severe PE who delivered at less than 34 weeks, Group 3: patients with severe PE who delivered between 34 and 37 weeks. The association between BPA levels and pregnancy outcome was investigated. RESULTS: Forty-six cases in the PE group were compared with 46 cases of normal pregnancies. The median BPA level was 19.46 ng/mL in the PE group and 16.36 ng/mL in the control group. The median BPA levels in the PE group were significantly higher than those in the control group (p = 0.007). Serum BPA levels were significantly lower in women who delivered at 37 weeks or later than in women who delivered at less than 34 weeks due to severe PE (p ≤ 0.018). CONCLUSION: Our study highlights the association between elevated maternal serum levels of BPA and PE. Moreover, knowledge of BPA levels in women with PE may provide information about the prognosis of pregnancy.

Evaluation of intravenous infusion of labetalol versus magnesium sulfate on cerebral hemodynamics of preeclampsia patients with severe features using transcranial doppler.

PURPOSE: It is essential to understand the underlying pathophysiological mechanisms of preeclampsia cerebral complications. This study aimed to compare the cerebral hemodynamic effects of magnesium sulfate (MgSO4) and labetalol in pre-eclampsia patients with severe features. METHODS: Singleton pregnant women who suffered from late onset preeclampsia with severe features were enrolled and subjected to baseline Transcranial doppler (TCD) evaluation and then randomly assigned to either the magnesium sulfate group or labetalol group. TCD to measure middle cerebral artery (MCA) blood flow indices including mean flow velocity (cm/s), mean end-diastolic velocity (DIAS), and pulsatility index (PI) and to estimate CPP and MCA velocity were performed as basal measurements before study drug administration and at post-treatment one and six hours after administration. The occurrence of seizures and any adverse effects were recorded for each group. RESULTS: Sixty preeclampsia patients with severe features were included and randomly allocated into two equal groups. In group M the PI was 0.77 ± 0.04 at baseline versus 0.66 ± 0.05 at 1hour and 0.66 ± 0.05 at 6 hours after MgSO4 administration (p value < 0.001) also the calculated CPP was significantly decreased from 103.3 ± 12.7mmHg to 87.8 ± 10.6mmHg and 89.8 ± 10.9mmHg (p value < 0.001) at 1 and 6 hours respectively. Similarly, in group L the PI was significantly decreased from 0.77 ± 0.05 at baseline to 0.67 ± 0.05 and 0.67 ± 0.06 at 1 and 6 hours (p value < 0.001) after labetalol administration. Moreover, the calculated CPP was significantly decreased from 103.6 ± 12.6 mmHg to 86.2 ± 13.02mmHg at 1 hour and to 83.7 ± 14.6mmHg at 6 hours (p value < 0.001). In terms of changes in blood pressure and the heart rate, they were significantly lower in the labetalol group. CONCLUSION: Both magnesium sulfate and labetalol reduce CPP while maintaining cerebral blood flow (CBF) in preeclampsia patients with severe features. TRIAL REGISTRATION: The institutional review board of the Faculty of Medicine, Zagazig University approved this study with the reference number (ZU-IRB#: 6353-23-3-2020) and it was registered at clinicaltrials.gov (NCT04539379).

The combined use of ultrasound examination of hemodynamics in the umbilical artery and urine microalbumin levels can predict adverse pregnancy outcomes in patients with severe preeclampsia.

The aim of this study was to elucidate the application of ultrasound examination of umbilical artery (UA) hemodynamics with urine microalbumin (UmA) determination in evaluating the outcomes of sPE patients. Altogether 80 sPE patients and 75 healthy pregnant women were recruited. UmA, RI (resistance index) and PI (pulsatility index) were separately measured by ELISA and the ultrasonic Doppler flow detector. The correlation between parameters was analysed using Pearson's coefficient method. The independent risk factors of sPE were identified using the Logistic regression model. sPE patients had increased UmA, RI and PI (all p < 0.05). UmA level was positively correlated with RI and PI in sPE patients. RI, PI and UmA were independent risk factors of sPE (all p < 0.05). sPE can predict adverse pregnancy outcomes. High UmA levels may increase the risk of poor prognosis. Overall, ultrasound examination of UA hemodynamics with UmA determination can predict the adverse pregnancy outcomes of sPE patients.IMPACT STATEMENTWhat is already known on this subject? Doppler ultrasound and urine microalbumin (UmA) measurement are important tools in assessing the clinical severity of severe preeclampsia (sPE).What do the results of this study add? This study aims to unravel the application of ultrasound examination of hemodynamics in the umbilical artery (UA) combined with the determination of UmA in evaluating the outcomes of sPE patients.What are the implications of these findings for clinical practice and/or further research? Ultrasound examination of hemodynamics in UA combined with the determination of UmA can predict the adverse pregnancy outcomes of sPE patients.

Decidualization resistance in the origin of preeclampsia.

Preeclampsia is a major obstetrical complication with short- and long-term life-threatening consequences for both mother and child. Shallow cytotrophoblast invasion through the uterine decidua into the spiral arteries is implicated in the pathogenesis of preeclampsia, although the cause of deficient arterial invasion remains unknown. Research that is focused on the "soil"-the maternal decidua-highlights the importance of this poorly understood but influential uterine layer. Decidualization of endometrial cells regulates embryo invasion, which is essential for spiral artery remodeling and establishing the maternal-fetal interface. Exploration of the association between impaired decidualization and preeclampsia revealed suboptimal endometrial maturation and uterine natural killer cells present in the decidua before preeclampsia development. Furthermore, decidualization defects in the endometrium of women with severe preeclampsia, characterized by impaired cytotrophoblast invasion, were detected at the time of delivery and persisted 5 years after the affected pregnancy. Recently, a maternal deficiency of annexin A2 expression was found to influence aberrant decidualization and shallow cytotrophoblast invasion, suggesting that decidualization resistance, which is a defective endometrial cell differentiation during the menstrual cycle, could underlie shallow trophoblast invasion and the poor establishment of the maternal-fetal interface. Based on these findings, the transcriptional signature in the endometrium that promotes decidualization deficiency could be detected before (or after) conception. This would serve to identify women at risk of developing severe preeclampsia and aid the development of therapies focused on improving decidualization, perhaps also preventing severe preeclampsia. Here, we discuss decidualization deficiency as a contributor to the pathogenesis of pregnancy disorders with particular attention to severe preeclampsia. We also review current diagnostic strategies and discuss future directions in diagnostic methods based on decidualization.

Preeclampsia and eclampsia: the conceptual evolution of a syndrome.

Preeclampsia, one of the most enigmatic complications of pregnancy, is considered a pregnancy-specific disorder caused by the placenta and cured only by delivery. This article traces the condition from its origins-once thought to be a disease of the central nervous system, recognized by the occurrence of seizures (ie, eclampsia)-to the present time when preeclampsia is conceptualized primarily as a vascular disorder. We review the epidemiologic data that led to the recommendation to use diastolic hypertension and proteinuria as diagnostic criteria, as their combined presence was associated with an increased risk of fetal death and the birth of small-for-gestational-age neonates. However, preeclampsia is a multisystemic disorder with protean manifestations, and the condition can be present even in the absence of hypertension and proteinuria. Toxins gaining access to the maternal circulation have been proposed to mediate the clinical manifestations-hence, the term "toxemia of pregnancy," which was used for several decades. The search for putative toxins has challenged investigators for more than a century, and a growing body of evidence suggests that products of an ischemic or a stressed placenta are responsible for the vascular changes that characterize this syndrome. The discovery that the placenta can produce antiangiogenic factors, which regulate endothelial cell function and induce intravascular inflammation, has been a major step forward in the understanding of preeclampsia. We view the release of antiangiogenic factors by the placenta as an adaptive response to improve uterine perfusion by modulating endothelial function and maternal cardiovascular performance. However, this homeostatic response can become maladaptive and lead to damage of target organs during pregnancy or the postpartum period. Early-onset preeclampsia has many features in common with atherosclerosis, whereas late-onset preeclampsia seems to result from a mismatch of fetal demands and maternal supply, that is, a metabolic crisis. Preeclampsia, as it is understood today, is essentially vascular dysfunction unmasked or caused by pregnancy. A subset of patients diagnosed with preeclampsia are at greater risk of the subsequent development of hypertension, ischemic heart disease, heart failure, vascular dementia, and end-stage renal disease. However, these adverse events may be the result of a preexisting vascular pathologic process; it is not known if the occurrence of preeclampsia increases the baseline risk. Therefore, the understanding, prediction, prevention, and treatment of preeclampsia are healthcare priorities.

Reduced left ventricular function and sustained hypertension in women seven years after severe preeclampsia.

Objective. To study left ventricular (LV) function and blood pressure (BP) at a long-term follow-up in women after severe pre-eclampsia. Design. In this single-centre, cross-sectional study, 96 patients were eligible for inclusion. LV function was examined by transthoracic echocardiography including tissue Doppler echocardiography and speckle tracking. BP was measured at rest using repeated non-invasive techniques. Results. We compared 36 patients with early-onset and 33 patients with late-onset pre-eclampsia with 28 healthy controls. Mean age (40 ± 3 years) and median time since delivery (7 ± 2 years) were similar across the study groups. The patients had 18% higher systolic BP (139 ± 15 mmHg) and 24% higher diastolic BP (87 ± 19 mmHg) than controls (p < .01). Hypertension was present in 23 patients (33%), where the estimated LV mass was 16% higher (p = .05) than in controls. The LV ejection fraction was 19% lower in the early-onset group (51 ± 4%; p = .01) and 14% lower in the late-onset group (54 ± 6; p = .04) compared with controls. LV global longitudinal strain was 18% lower in the patient group (-17.7 ± 2.1%) compared with controls (p = .01). Indicative of a more restrictive filling pattern, the diastolic indices showed a lower e' mean (p < .01) and subsequently higher E/e' ratio (p < .01). There were no significant differences in BP, systolic or diastolic function indices between the patient groups. Conclusion. We found sustained hypertension, higher LV mass and reduced LV systolic and diastolic function 7 y after severe pre-eclampsia. Our findings emphasize the importance of early risk stratification and clinical counselling, and follow-up for such cases.

High miR-200a-3p expression has high diagnostic values for hypertensive disorders complicating pregnancy and predicts adverse pregnancy outcomes.

BACKGROUND: Hypertensive disorders complicating pregnancy (HDCP) are various heterogeneous conditions. microRNA (miR)-200a-3p is involved in HDCP diagnosis. This study explored the effects of miR-200a-3p on HDCP patients. METHODS: A total of 126 singleton HDCP patients including 50 cases of gestation hypertension (GH), 42 cases of mild preeclampsia (MP) and 34 cases of severe preeclampsia (SP), were enrolled as study subjects, and 50 normal pregnant women were selected as the control. Serum miR-200a-3p expression was detected and its efficacy in HDCP diagnosis and grading was evaluated. GH, MP and SP patients were allocated to high/low miR-200a-3p expression groups. The correlation between miR-200a-3p expression and general clinical indexes was analyzed. HDCP patients were allocated to high/low miR-200a-3p expression group and maternal and fetal outcomes were followed up. Effects of miR-200a-3p expression on adverse pregnancy outcome incidence were analyzed. RESULTS: miR-200a-3p expression in the serum of HDCP patients was upregulated. The sensitivity and specificity of serum miR-200a-3p level > 1.201 were 87.3% and 96.0%, respectively. Serum miR-200a-3p level in GH, MP and SP patients was increased with the aggravation of the disease. The cut-off value and area under the curve (AUC) of miR-200a-3p for GH, MP and SP diagnosis were 1.145 and 0.9094 (82.0% sensitivity and 88.0% specificity), 1.541 and 0.8126 (73.8% sensitivity and 76.0% specificity), and 1.866 and 0.7367 (64.7% sensitivity and 76.2% specificity), respectively. Serum miR-200a-3p level was correlated with general clinical indexes, fetal birth weight, systolic to diastolic ratio, and fetal growth restriction incidence. High serum miR-200a-3p expression in HDCP patients was associated with increased adverse pregnancy outcomes. CONCLUSION: High miR-200a-3p expression could help to diagnose HDCP, judge severity and was associated with increased adverse pregnancy outcomes.

Incidence and predictors of acute kidney injury among women with severe pre-eclampsia at Mbarara Regional Referral Hospital.

BACKGROUND: The presence of acute kidney injury (AKI) in pre-eclampsia complicates treatment including; increasing length of hospital stay and a need to access services like dialysis which are largely expensive in resource-limited settings. We aimed to determine incidence and predictors of acute kidney injury among women with severe pre-eclampsia at Mbarara Regional Referral Hospital in southwestern Uganda. METHODS: We carried out a hospital-based prospective cohort study from 16 November  2018 to 18 April 2019, among pregnant women with severe pre-eclampsia followed up in the hospital. We enrolled 70 mothers with severe pre-eclampsia and eclampsia; we excluded patients with a history of chronic kidney disease, chronic hypertension, and gestational hypertension. Data on socio-demographics, laboratory parameters, health system, obstetric and medical factors were collected. Baseline serum creatinine, complete blood count, and CD4 T-cell count were all done at admission (0-hour). A second serum creatinine was done at 48-hours to determine the presence of AKI and AKI was defined as a relative change of serum creatinine value at least 1.5 times the baseline (i.e., at admission) within 48 h. The proportion of women diagnosed with acute kidney injury among the total number of women with severe pre-eclampsia was reported as incidence proportion. Univariate and multivariate logistic regression was used to establish the association between acute kidney injury and severe pre-eclampsia. RESULTS: Incidence of acute kidney injury was high (42.86%) among women with severe pre-eclampsia. Antenatal care attendance was protective with an odds ratio of 0.14 (0.03, 0.73), p-value 0.020 at bivariate analysis but had no statistical significance at multivariate analysis. Eclampsia was an independent risk factor for acute kidney injury. (aOR 5.89 (1.51, 38.88), p-value 0.014. CONCLUSION: The incidence of acute kidney injury in patients with severe pre-eclampsia is high. Eclampsia is an independent risk factor of acute kidney injury. The findings of this study highlight the urgent need for more research and better perinatal care for these women.

A retrospective review of the risk factors affecting the therapeutic serum concentrations of magnesium sulfate in pre-eclamptic patients.

WHAT IS KNOWN AND OBJECTIVE: To identify factors that may affect the therapeutic serum magnesium levels after intravenous administration for seizure prophylaxis in pre-eclamptic patients. METHODS: One hundred and two women with PE with severe features were identified categorized into two groups: subtherapeutic and therapeutic group. Multivariate logistic regression analysis and receiver operation characteristic curve analysis were conducted for the risk factors influencing the serum magnesium concentration. RESULTS: Among 102 eligible patients, 63 (62%) patients did not attain ideal therapeutic serum magnesium levels. Those patients had elevated albumin levels (p < 0.05), higher creatinine clearance (Ccr) (p < 0.001), and higher body mass index (BMI) (p < 0.001). Logistic regression analysis identified BMI and Ccr as independent risk factors for subtherapeutic serum magnesium concentration (p < 0.05). Receiver operating characteristic (ROC) curve analysis revealed a greater area under the curve for BMI than for Ccr in predicting subtherapeutic serum magnesium levels (0.787 vs. 0.774). WHAT IS NEW AND CONCLUSION: Maternal body weight and renal function were independent risk factors for subtherapeutic serum magnesium concentration in the early stage after administration.

Diagnostic value of miR-101 levels in blood and urine of patients with hypertensive disorder complicating pregnancy.

OBJECTIVES: This study explored the miR-101 clinical significance in hypertensive disorder complicating pregnancy (HDCP). METHODS: Pregnant women with gestational hypertension (GH)/mild preeclampsia (mPE)/severe preeclampsia (sPE) were included. The miR-101 levels were measured. Correlation between miR-101 and soluble fmslike tyrosine kinase-1 (sFlt-1), miR-101 predictive value, and factors influencing HDCP grade were evaluated. RESULTS: Serum miR-101 was down-regulated and negatively correlated with sFlt-1. miR-101 was an independent risk factor for HDCP and decreased with HDCP severity. The area under the curve of miR-101 in differentiating GH from mPE and mPE from sPE was 0.7764 and 0.8529. CONCLUSION: Serum miR-101 level may be a biomarker for grading HDCP.

Diagnostic value of serum miR-25-3p in hypertensive disorders in pregnancy.

Hypertensive disorders in pregnancy (HDIP) represent one of the leading causes of maternal and perinatal mortality. microRNA (miR)-25-3p plays roles in HDIP diagnosis. We explored miR-25-3p clinical roles in HDIP. HDIP patients [gestation hypertension (GH), mild preeclampsia (mPE), and severe preeclampsia (sPEz)], and normal pregnant women serving as the control were enrolled. Serum miR-25-3p expression patterns were detected by RT-qPCR. The diagnostic efficacy of miR-25-3p on HDIP was analyzed with a ROC curve. Patients were assigned to the high/low miR-25-3p expression groups according to the median value of miR-25-3p expression. All patients were followed up until delivery, and gestational weeks and pregnancy outcomes were recorded at delivery. The effects of miR-25-3p expression on pregnancy outcomes of GH, mPE, and sPEz patients were analyzed by Kaplan-Meier. miR-25-3p expression in GH, mPE, and sPEz patients was up-regulated. In sPEz patients, systolic and diastolic blood pressure, 24-h urine protein, AST, ALT, GGT, and SCr were increased, and PLT was decreased in the high expression group. High miR-25-3p expression was associated with an increased risk of adverse pregnancy outcomes in PE patients. Collectively, high miR-25-3p expression could aid HDIP diagnosis, and associated with an increased risk of adverse pregnancy outcomes in PE patients.

Serum catestatin level is increased in women with preeclampsia.

Catestatin can inhibit catecholamine release from chromaffin cells and adrenergic neurons. Catestatin can also have a strong vasodilator effect. This may be useful in understanding the pathophysiology of preeclampsia and its treatment. In this study, we investigated the serum catestatin levels in pregnant women with and without preeclampsia. Fifty consecutive women with mild preeclampsia, 50 consecutive women with severe preeclampsia, and 100 consecutive pregnant women with a gestational age-matched (±1 week) uncomplicated pregnancy were evaluated in a cross-sectional study. Mean serum catestatin was significantly increased in the preeclampsia group compared to the control group (290.7 ± 95.5 pg/mL vs. 182.8 ± 72.0 pg/mL). Mean serum catestatin was comparable in mild and severe preeclampsia groups (282.7 ± 97.9 pg/mL vs. 298.7 ± 93.4 pg/mL, p = .431). Serum catestatin levels had positive correlations with systolic and diastolic blood pressure, urea, uric acid, and creatinine. In conclusion, serum catestatin levels are increased in preeclamptic pregnancies compared to gestational age-matched controls.IMPACT STATEMENTWhat is already known on this subject? The role of autonomic nervous system dysregulation in the pathophysiology of preeclampsia is known. The most obvious part of this dysregulation is the sympathetic nervous system activation. The adrenal medulla is one of the locations of the sympathetic nervous system in the body.What do the results of this study add? Serum catestatin levels were found to be correlated with clinical and laboratory data of preeclampsia. This highlights the importance of chromaffin cell secretions in the adrenal medulla in preeclampsia.What are the implications of these findings for clinical practice and/or further research? This study will help understand the role of the adrenal medulla in the autonomic nervous system dysregulation in preeclampsia. Also, control of serum catestatin levels may support the treatment of hypertension in preeclampsia.

Incidence and risk factors for severe preeclampsia, hemolysis, elevated liver enzymes, and low platelet count syndrome, and eclampsia at preterm and term gestation: a population-based study.

BACKGROUND: The majority of previous studies on severe preeclampsia, eclampsia, and hemolysis, elevated liver enzymes, and low platelet count syndrome were hospital-based or included a relatively small number of women. Large, population-based studies examining gestational age-specific incidence patterns and risk factors for these severe pregnancy complications are lacking. OBJECTIVE: This study aimed to assess the gestational age-specific incidence rates and risk factors for severe preeclampsia, hemolysis, elevated liver enzymes, and low platelet count syndrome, and eclampsia. STUDY DESIGN: We carried out a retrospective, population-based cohort study that included all women with a singleton hospital birth in Canada (excluding Quebec) from 2012 to 2016 (N=1,078,323). Data on the primary outcomes (ie, severe preeclampsia, hemolysis, elevated liver enzymes, and low platelet count syndrome, and eclampsia) were obtained from delivery hospitalization records abstracted by the Canadian Institute for Health Information. A Cox regression was used to assess independent risk factors (eg, maternal age and chronic comorbidity) for each primary outcome and to assess differences in the effects at preterm vs term gestation (<37 vs ≥37 weeks). RESULTS: The rates of severe preeclampsia (n=2533), hemolysis, elevated liver enzymes, and low platelet count syndrome (n=2663), and eclampsia (n=465) were 2.35, 2.47, and 0.43 per 1000 singleton pregnancies, respectively. The cumulative incidence of term-onset severe preeclampsia was lower than that of preterm-onset severe preeclampsia (0.87 vs 1.54 per 1000; rate ratio, 0.57; 95% confidence intervals, 0.53-0.62), the rates of hemolysis, elevated liver enzymes, and low platelet count syndrome were similar (1.32 vs 1.23 per 1000; rate ratio, 0.93; 95% confidence interval, 0.86-1.00), and the preterm-onset eclampsia rate was lower than the term-onset rate (0.12 vs 0.33 per 1000; rate ratio, 2.64; 95% confidence interval, 2.16-3.23). For each primary outcome, chronic comorbidity and congenital anomalies were stronger risk factors for preterm- vs term-onset disease. Younger mothers (aged <25 years) were at higher risk for severe preeclampsia at term and for eclampsia at all gestational ages, whereas older mothers (aged ≥35 years) had elevated risks for severe preeclampsia and hemolysis, elevated liver enzymes, and low platelet count syndrome. Regardless of gestational age, nulliparity was a risk factor for all outcomes, whereas socioeconomic status was inversely associated with severe preeclampsia. CONCLUSION: The risk for severe preeclampsia declined at term, eclampsia risk increased at term, and hemolysis, elevated liver enzymes, and low platelet count syndrome risk was similar for preterm and term gestation. Young maternal age was associated with an increased risk for eclampsia and term-onset severe preeclampsia. Prepregnancy comorbidity and fetal congenital anomalies were more strongly associated with severe preeclampsia, hemolysis, elevated liver enzymes, and low platelet count syndrome, and eclampsia at preterm gestation.