Benefits of simulation on multidisciplinary management of severe pre-eclampsia/severe eclampsia in 15 health districts in eastern Democratic Republic of Congo: A randomized educational trial.

OBJECTIVE: The purpose of the present study was to assess the benefits of simulation for advancing knowledge and assisting healthcare staff in optimization of procedures when managing severe pre-eclampsia/eclampsia (sPE/E). METHODS: A randomized educational trial was conducted with two groups: Group I received theoretical training, while group II received the same training along with simulation scenarios based on the management of sPE/E. The study involved 199 healthcare providers, including physicians, midwives, skilled birth attendants, and nurses. The study analyzed the percentage of correct answers on both the multiple-choice questions (MCQ) and the objective structured clinical examinations (OSCE) to evaluate theoretical knowledge and clinical skills objectively. RESULTS: Statistically significant differences were found immediately after training between groups I and II, whose mean percentages were 65.0% (±11.2) versus 71.0% (±9.8) (P < 0.001). A statistically significant reduction in the percentage of correct answers was found in both groups and demonstrated a discrepancy between immediate post-training test and post-training test at 3 months scores of 11.6% (±1.3) in group I versus 7.2% (±0.6) in group II. OSCE1 and OSCE2 scores were significantly higher in group II than in group I (P < 0.001). CONCLUSION: Simulation combined with theoretical training would appear to be an interesting method of training for advancing knowledge and improving skills of healthcare providers in their management of sPE/E. Our goal is for this method to be used to reduce real-life maternal mortality in the South Kivu region of the Democratic Republic of Congo.

Thrombotic microangiopathy (TMA) associated with pregnancy: role of the clinical laboratory in differential diagnosis.

Objectives: Thrombotic microangiopathy (TMA) is characterized by thrombocytopenia, microangiopathic hemolytic anemia and target organ damage. Pregnancy is associated with several forms of TMA, including preeclampsia (PE), HELLP syndrome, thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS). When HUS is secondary to a deregulation of the alternative complement pathway, it is known as atypical HUS (aHUS). Differential diagnosis is challenging, as these forms share clinical characteristics. However, early diagnosis is crucial for a specific treatment to be established and improve prognosis. Case presentation: We present the case of a 43 year-old primiparous woman admitted to hospital for an urgent C-section at 33 gestational weeks due to a diagnosis of severe preeclampsia and fetal distress. In the immediate postpartum, the patient developed acute liver failure and anuric renal failure in the context of the HELLP syndrome, anemia, thrombocytopenia, arterial hypertension (HTN) and neurological deficit. TMA study and differential diagnosis confirmed pregnancy-associated aHUS. Treatment with eculizumab was initiated, with good response and progressive improvement of clinical and analytical parameters. Conclusions: aHUS is a rare multifactorial disease that used to be associated with high mortality rates before the advent of eculizumab. Due to challenging diagnosis, the clinical laboratory plays a major role in the differential diagnosis and management of the disease.

Cadmium Associated Preeclampsia: A Systematic Literature Review of Pregnancy and Birth Outcomes.

Preeclampsia (PE), caused by multiple factors, is one of the most serious complications of pregnancy. Cadmium (Cd) is a heavy metal environmental pollutant, reproductive toxicant, and endocrine disruptor, which can increase the risk of PE. Cd toxicity due to occupational, diet, and environmental factors has worsened the risk. Studies showed elevated Cd concentration in maternal blood and placenta of PE women. However, the implicit association between Cd associated PE is still not highlighted. We systematically reviewed Cd-associated PE and its effect on pregnancy and birth outcomes. Based on "Preferred reporting items for systematic reviews and meta-analyses (PRISMA)" guidelines, eighty-six studies were identified by PubMed, Web of Science (WOS), and Scopus databases. Publications were included until October 2023 and articles screened based on our inclusion criteria. Our study identified that the exposure of controlled and uncontrolled Cd induces PE, which negatively affects pregnancy and birth outcomes. Given the serious nature of this finding, Cd is a potential adverse agent that impacts pregnancy and future neonatal health. Further comprehensive studies covering the whole trimesters of pregnancy and neonatal developments are warranted. Data on the molecular mechanisms behind Cd-induced PE is also essential for potential preventive, diagnostic, or therapeutic targets.

STK40 inhibits trophoblast fusion by mediating COP1 ubiquitination to degrade P57Kip2.

BACKGROUND: The syncytiotrophoblast (SCT) layer in the placenta serves as a crucial physical barrier separating maternal-fetal circulation, facilitating essential signal and substance exchange between the mother and fetus. Any abnormalities in its formation or function can result in various maternal syndromes, such as preeclampsia. The transition of proliferative villous cytotrophoblasts (VCT) from the mitotic cell cycle to the G0 phase is a prerequisite for VCT differentiation and their fusion into SCT. The imprinting gene P57Kip2, specifically expressed in intermediate VCT capable of fusion, plays a pivotal role in driving this key event. Moreover, aberrant expression of P57Kip2 has been linked to pathological placental conditions and adverse fetal outcomes. METHODS: Validation of STK40 interaction with P57Kip2 using rigid molecular simulation docking and co-immunoprecipitation. STK40 expression was modulated by lentivirus in BeWo cells, and the effect of STK40 on trophoblast fusion was assessed by real-time quantitative PCR, western blot, immunofluorescence, and cell viability and proliferation assays. Co-immunoprecipitation, transcriptome sequencing, and western blot were used to determine the potential mechanisms by which STK40 regulates P57Kip2. RESULTS: In this study, STK40 has been identified as a novel interacting protein with P57Kip2, and its expression is down-regulated during the fusion process of trophoblast cells. Overexpressing STK40 inhibited cell fusion in BeWo cells while stimulating mitotic cell cycle activity. Further experiments indicated that this effect is attributed to its specific binding to the CDK-binding and the Cyclin-binding domains of P57Kip2, mediating the E3 ubiquitin ligase COP1-mediated ubiquitination and degradation of P57Kip2. Moreover, abnormally high expression of STK40 might significantly contribute to the occurrence of preeclampsia. CONCLUSIONS: This study offers new insights into the role of STK40 in regulating the protein-level homeostasis of P57Kip2 during placental development.

The effects of proton pump inhibitors during pregnancy on treatment of preeclampsia, and related outcomes: a systematic review and meta-analysis.

OBJECTIVE: This systematic review evaluated the available evidence of the effects of PPIs during pregnancy on preeclampsia and related maternal, fetal and neonatal outcomes. DATA SOURCES: Five electronic databases (MEDLINE, Embase, CINAHL, Cochrane CENTRAL, and Global Medicus Index) were searched on 17 November 2023. STUDY ELIGIBILITY CRITERIA: Randomized controlled trials involving pregnant women, using any class or dose of PPIs, were eligible. STUDY APPRAISAL AND SYNTHESIS METHODS: Meta-analysis was conducted for all outcomes of interest, with random-effects models. Results were presented as risk ratios or mean difference. Quality assessment was performed using the Risk of Bias 2 tool, and Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) assessment was completed to evaluate the certainty of the evidence. The study was registered on PROSPERO (CRD42023423673). RESULTS: Our search identified 3,879 records, which were screened by two authors independently. Nine reports (describing eight trials) met our eligibility criteria, however six trials were ultimately excluded from our analysis as women were only given PPIs immediately prior to Cesarean section for acid aspiration prevention. The two trials included in the meta-analysis evaluated the treatment of 177 women with diagnosed preeclampsia. For the primary outcomes, moderate-certainty evidence showed there is likely no effect of the use of PPIs on risk of HELLP syndrome (RR 1.21, 95% CI 0.37 - 3.99, I²â€¯= 0%) or perinatal mortality (RR 0.81, 95% CI 0.36 - 1.79, I²â€¯= 0%), while there were insufficient data to meta-analyse all other primary outcomes, including eclampsia and neonatal mortality. No trials investigated PPIs for preventing preeclampsia. CONCLUSIONS: Given the limited outcome data we are uncertain of the effect of PPIs in women with preeclampsia. Further trials are required to determine what (if any) effects PPIs might have for preeclampsia prevention or treatment.

Tandem mass tag-based proteomics analysis reveals the mechanism underlying the interleukin-6-mediated regulation of trophoblast function in preeclampsia.

OBJECTIVE: We investigated the mechanism whereby interleukin-6 (IL-6), an important inflammatory marker, influences trophoblast function during preeclampsia. METHODS: Quantitative PCR and enzyme-linked immunosorbent assay were used to determine the IL-6 mRNA and protein levels, respectively. CCK8 and transwell assays were used to detect how IL-6 affects the proliferation and invasion abilities of HTR-8/SVneo cells respectively; the tube-forming assay was conducted to explore how IL-6 affects the angiogenesis ability of human umbilical vein endothelial cells (HUVECs) after their co-culture with HTR-8/SVneo cells. Using tandem mass tag-based proteomics analysis, we screened for different proteins before and after IL-6 stimulation; Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed to investigate the functions and signal pathways associated with these proteins. RESULTS: The IL-6 levels were higher in the placenta of preeclampsia group than in the normal group. IL-6 suppressed the proliferation and invasion of HTR-8/SVneo cells, but promoted the angiogenesis of HUVECs. Seventy differentially expressed IL-6 downstream proteins were identified; these were enriched with various biological processes, molecular functions, cellular components, and biological pathways.Conclusions: IL-6 regulates trophoblast function by interacting with multiple proteins and pathways. Proteomics-based screening serves as a macroscopic approach to clarify the molecular mechanisms associated with preeclampsia.

Dietary patterns during pregnancy and maternal and birth outcomes in women with type 1 diabetes: the Environmental Determinants of Islet Autoimmunity (ENDIA) study.

AIMS/HYPOTHESIS: Dietary patterns characterised by high intakes of vegetables may lower the risk of pre-eclampsia and premature birth in the general population. The effect of dietary patterns in women with type 1 diabetes, who have an increased risk of complications in pregnancy, is not known. The aim of this study was to investigate the relationship between dietary patterns and physical activity during pregnancy and maternal complications and birth outcomes in women with type 1 diabetes. We also compared dietary patterns in women with and without type 1 diabetes. METHODS: Diet was assessed in the third trimester using a validated food frequency questionnaire in participants followed prospectively in the multi-centre Environmental Determinants of Islet Autoimmunity (ENDIA) study. Dietary patterns were characterised by principal component analysis. The Pregnancy Physical Activity Questionnaire was completed in each trimester. Data for maternal and birth outcomes were collected prospectively. RESULTS: Questionnaires were completed by 973 participants during 1124 pregnancies. Women with type 1 diabetes (n=615 pregnancies with dietary data) were more likely to have a 'fresh food' dietary pattern than women without type 1 diabetes (OR 1.19, 95% CI 1.07, 1.31; p=0.001). In women with type 1 diabetes, an increase equivalent to a change from quartile 1 to 3 in 'fresh food' dietary pattern score was associated with a lower risk of pre-eclampsia (OR 0.37, 95% CI 0.17, 0.78; p=0.01) and premature birth (OR 0.35, 95% CI 0.20, 0.62, p<0.001). These associations were mediated in part by BMI and HbA1c. The 'processed food' dietary pattern was associated with an increased birthweight (ß coefficient 56.8 g, 95% CI 2.8, 110.8; p=0.04). Physical activity did not relate to outcomes. CONCLUSIONS/INTERPRETATION: A dietary pattern higher in fresh foods during pregnancy was associated with sizeable reductions in risk of pre-eclampsia and premature birth in women with type 1 diabetes.

Coinciding Placental Abruption and Pulmonary Edema in a Patient With Preeclampsia.

Preeclampsia is a known complication of pregnancy. Patients meet diagnostic criteria when they have hypertension along with proteinuria and/or end-organ dysfunction. Preeclampsia can pose a serious threat to the lives of pregnant patients and their fetuses. A 35-year-old G4P0030 female was diagnosed with preeclampsia at 35 weeks gestation. She was scheduled for an induction of labor at 37 weeks. With further elevation in blood pressure during labor, she met the criteria for preeclampsia with severe features. Additionally, the presence of clinical signs concerning a placental abruption led to a cesarean delivery. Following her delivery, her respiratory distress prompted a computed tomography angiography, which showed evidence of pulmonary edema. The occurrence of both placental abruption and pulmonary edema can be related to the patient's preeclampsia. We urge that healthcare providers have a low threshold for diagnosing placental abruption and pulmonary edema in patients with preeclampsia.

Evaluation of placental bed uterine in L-NAME-induced early-onset preeclampsia (EO-PE) like the rat model.

Objective: Preeclampsia (PE) is the leading cause of maternal death worldwide and is associated with long-term morbidity in both mothers and newborns. Animal modeling is considered a functional source for understanding PE pathogenesis, diagnostic standards, and therapeutic approaches. Materials and Methods: This study aimed to demonstrate and evaluate the use of N-nitro-L-arginine methyl ester (L-NAME) in a Wistar rat model under conditions similar to PE. A total of 12 rats were divided into 4 groups, each consisting of 3 members, including the pregnant control group and treatment groups administered low-dose (PE 25 mg/kg L-NAME/day), medium-dose (PE 50 mg/kg L-NAME/day), and high-dose L-NAME (PE 75 mg/kg L-NAME/day) L-NAME from gestational day 4 to 19. Measurements included blood pressure, creatinine, and proteinuria levels, placental histological changes, and placental tissue hypoxia-inducible factor 1-alpha, and plasma endothelial nitric oxide synthase levels. Results: The results showed that intervention with L-NAME at 75 mg/kg body weight/day (PE3) induced PE earlier than that with 50 mg/kg body weight/day L-NAME. Conclusion: The model conditions also support further research into PE pathogenesis.

Cesarean Section in a Morbidly Obese Patient With Severe Preeclampsia and Pulmonary Edema: A Case Report.

Severe preeclampsia and pulmonary edema pose significant challenges for an anesthesiologist. Pregnancy is associated with major physiologic changes to meet the increased demands of the mother and fetus. Preeclampsia complicates this balance by adding additional stress to the mother and baby. Pulmonary edema is a rare complication of preeclampsia, and it is a potentially life-threatening condition. Meticulous care is needed in the anesthetic management of this condition, especially when the patient is morbidly obese and presents for an emergency cesarean section.

Maternal and neonatal outcomes in kidney transplant recipients: a single-center observational study.

OBJECTIVE: Pregnancy poses a high risk for adverse maternal and neonatal outcomes in kidney transplant recipients (KTRs), and data on long-term allograft functions compared to the healthy population are still limited. Therefore, we aimed to conduct a comparative analysis of maternal and neonatal outcomes in KTRs. SUBJECT AND METHODS: In this retrospective single-center study, KTRs who experienced pregnancy after transplantation were evaluated in comparison with an age-matched non-transplanted control group. Maternal outcomes included obstetric complications (preeclampsia, peripartum hemorrhage, duration of maternal hospitalization) and a composite kidney outcome for KTRs defined as progression to graft failure necessitating dialysis or retransplantation or doubling of serum creatinine at the end of follow-up. Neonatal outcomes were gestational age, preterm birth, newborn mortality, admittance to the neonatal intensive care unit (NICU), Apgar scores, and birth weight. RESULTS: In 53 KTRs, 68 pregnancies occurred. Preeclampsia (p < 0.001) and preterm birth (p = 0.003) were significantly higher in KTRs. The KTR pregnancies had lower mean birth weights (p = 0.001) and longer durations of maternal hospitalization (p = 0.001). Neonatal mortality, NICU admissions, peripartum hemorrhage rates, and Apgar scores were similar between groups. Follow-up for a median of 105 months after the index birth showed higher serum creatinine levels at postpartum visits (p < 0.001) and at the last follow-up (p = 0.001) compared to baseline. Of the KTRs 6 (11.3%) experienced composite kidney outcomes, including 5 patients with graft failure and 1 with a doubling of serum creatinine. CONCLUSION: The KTRs exhibit comparable neonatal mortality and NICU admission rates but have higher rates of preeclampsia and preterm birth. Importantly, graft functions worsen significantly during postpartum follow-up.

Preliminary study on the role of human defensins, interleukins and PCSK9 in early and late preeclampsia.

The lack of reliable methods for preeclampsia (PE) early diagnosis limits the opportunities for timely prevention, diagnosis and treatment. This study aims to identify the alterations of biochemical parameters and the immune system activity to build a panel of markers that can support preeclampsia diagnosis. For this study, we recruited 30 pregnant women: 10 healthy pregnant women (CTR); 10 pregnant women with early preeclampsia (EP); 10 pregnant women with late preeclampsia (LP). We evaluated lipid profile and, by gene expression, we assessed PCSK9, IL-2, IL-6, IL-8, IL-10, TNF-α and TGF-ß. Moreover, we evaluated both the serum and gene levels of the defensins HBD-1, HBD-2, HBD-4 and HNP-1. Our results showed an increase in gene expression levels of IL-6 and IL-8 in EP compared to LP (IL-6: median 11.7 vs 3.3, p = 0.005; IL-8: median 634.1 vs 214.1, p = 0.013) and to CTR (IL-6: median 11.7 vs 0.5, p < 0.001; IL-8: median 634.1 vs 225.6, p = 0.012), highlighting a massive activation of immune system in case of more severe preeclampsia. Furthermore, higher serum levels of HBD1 in LP compared to CTR (median: 278.8 vs 67.8, p = 0.005) and to EP (median: 278.8 vs 68.6, p = 0.001) might indicate that the same immune system puts in action protective actions to prevent adverse outcome in these cases. Finally, gene expression levels of PCSK9 decreased significantly in women with EP compared to controls and to LP (median: 0.2 vs 0.9, p = 0.010; median: 0.2 vs 1.2, p = 0.012), causing a decrease in circulating LDL-c necessary for the synthesis of placental hormones.

Cross-Species Insights into Trophoblast Invasion During Placentation Governed by Immune-Featured Trophoblast Cells.

Proper development of the placenta, the transient support organ forms after embryo implantation, is essential for a successful pregnancy. However, the regulation of trophoblast invasion, which is most important during placentation, remains largely unknown. Here, rats, mice, and pigs are used as biomedical models, used scRNA-seq to comparatively elucidate the regulatory mechanism of placental trophoblast invasion, and verified it using a human preeclampsia disease model combined with scStereo-seq. A dual-featured type of immune-featured trophoblast (iTrophoblast) is unexpectedly discovered. Interestingly, iTrophoblast only exists in invasive placentas and regulates trophoblast invasion during placentation. In a normally developing placenta, iTrophoblast gradually transforms from an immature state into a functional mature state as it develops. Whereas in the developmentally abnormal preeclamptic placenta, disordered iTrophoblast transformation leads to the accumulation of immature iTrophoblasts, thereby disrupting trophoblast invasion and ultimately leading to the progression of preeclampsia.

GPER Stimulation Attenuates Cardiac Dysfunction in a Rat Model of Preeclampsia.

BACKGROUND: Preeclampsia poses a substantial clinical challenge, characterized by maternal hypertension, cardiac dysfunction, and persistent cardiovascular risks for both the mother and offspring. Despite the known roles of the estrogen receptor (GPER [G protein-coupled estrogen receptor]) in placental development, its impact on cardiovascular aspects within a preeclampsia animal model remains unexplored. We propose that G-1, a GPER agonist, could have the potential to regulate not only hypertension but also cardiac dysfunction in rats with preeclampsia. METHODS: To explore the influence of G-1 on preeclampsia, we used the reduced uterine perfusion pressure (RUPP) model. RUPP rats were administered either G-1 (100 µg/kg per day) or hydralazine (25 mg/kg per day). We conducted echocardiography to probe the intricate cardiac effects of G-1. RESULTS: The RUPP rat model revealed signs of hypertension and cardiac dysfunction and alterations in gene and protein expression within placental and heart tissues. G-1 treatment reduced blood pressure and reversed cardiac dysfunction in rats with preeclampsia. In contrast, administration of the vasodilator hydralazine reduced blood pressure without an improvement in cardiac function. In addition, while G-1 treatment restored the levels of sFLT-1 (soluble fms-like tyrosine kinase-1) in RUPP rats, hydralazine did not normalize this antiangiogenic factor. CONCLUSIONS: The therapeutic intervention of G-1 significantly mitigated the cardiovascular dysfunction observed in the RUPP rat model of preeclampsia. This discovery underscores the broader significance of understanding GPER's role in the context of preeclampsia-related cardiovascular complications.

The Correlation Between Neutrophil Elastase and Neutrophil-Lymphocyte Ratio in Endothelial Dysfunction of Preeclampsia.

BACKGROUND: Preeclampsia (PE) is a serious inflammatory process that is unique to pregnancy, occurring at or after the 20th week of pregnancy, and leading to maternal and neonatal illness and systemic disruptions. Placental hypoxia leads to increased levels of cytokines and inflammatory syncytiotrophoblast microvillus membrane microparticles (STBM) which activates neutrophils leading to oxidative stress and endothelial dysfunction in preeclampsia. The mechanisms that cause PE in people remain unknown. To understand the pathophysiology of PE, numerous theories have been given. There is currently no proven treatment or early detecting marker for PE available so far. METHODS: The present study includes 40 patients (20 controls and 20 PE patients) aged 20-45 years hospitalized at the Department of Obstetrics and Gynecology, Hamdard Institute of Medical Sciences and Research (HIMSR) and Hakeem Abdul Hameed Centenary (HAHC) Hospital, Jamia Hamdard, New Delhi. Nitric oxide (NO), neutrophil elastase (NE), and the neutrophil-to-lymphocyte ratio were measured. The blood and biochemical parameters in PE patients were also analyzed. RESULTS: The neutrophil-to-lymphocyte ratio (NLR) was significantly increased in PE patients as compared to healthy pregnant. All the biochemical and hemodynamic parameters were assessed. The serum NO concentrations were lower in PE patients and endothelial dysfunction markers (NE and von Willebrand factor {vWF}) were markedly increased in PE patients. The difference was statistically significant with a p-value <0.05. CONCLUSIONS: NLR is greatly increased in PE patients. An increase in NLR in PE patients occurs due to an increase in inflammatory markers and endothelial damage. Hence, the NLR could act as a novel diagnostic biomarker for depicting PE progression.

Is the Transcription Factor NANOG Involved in Placental Aging?

PROBLEM: Accelerated placental aging is linked to abnormal fetal growth, preeclampsia (PE), and preterm birth (PTB). NANOG, a transcription factor, is known for its role in cellular reprogramming, self-renewal, and clonogenic growth. Its expression is regulated by Kruppel-like factor 4 (KLF4), which functions as both a transcriptional activator and repressor. This study evaluated the KLF4-NANOG pathway in placental samples from normal pregnancies (NP) as well as those with PE, fetal growth restriction (FGR), and PTB. METHOD OF STUDY: Placental samples from NP pregnancies and those with PE, FGR, and PTB were analyzed for NANOG and KLF4 expression using western blotting and immunohistochemistry. RESULTS: NANOG protein expression was significantly increased in placentas from PE, FGR, and PTB compared to NP (fold changes vs. NP: PE 2.48 ± 0.3, p = 0.002; FGR 1.64 ± 0.16, p = 0.03; PTB 6.03 ± 3.35, p = 0.01). Similarly, KLF4 protein expression was elevated in PE, FGR, and PTB placentas compared to NP (fold changes vs. NP: PE 5.78 ± 0.73, p = 0.001; FGR 2.61 ± 0.43, p = 0.02; PTB 11.42 ± 2.76, p = 0.0006). Immunohistochemistry revealed strong NANOG staining in the syncytiotrophoblast tissue of PE, FGR, and PTB samples, especially in extravillous trophoblasts, compared to NP placentas. CONCLUSIONS: The elevated expression of NANOG and KLF4 in abnormal placental tissues suggests their potential role as markers of enhanced placental aging and dysfunction. These findings underscore the importance of the KLF4-NANOG pathway in the pathology of PE, FGR, and PTB, providing a basis for future research into therapeutic targets for these conditions.

Magnesium sulfate improves blood flow of uterine, umbilical, and fetal middle cerebral arteries in women with severe preeclampsia at 30-34 gestational weeks.

OBJECTIVES: Magnesium sulfate (MgSO4) is one of the most commonly used agents for the treatment and prophylaxis of eclampsia in patients with severe preeclampsia. However, there is no international consensus regarding the optimal gestational age for MgSO4 treatment. The aim of this study was to assess the effect of MgSO4 on uterine (UtA), umbilical, and fetal middle cerebral arteries (MCA) by calculating the SD ratio (S/D), resistance index (RI), and pulsatility index (PI) at different gestational weeks. METHODS: In total, 66 pregnant women as participants with severe preeclampsia were divided into two groups based on gestational age: Group 1 (n = 28, 26-30 weeks) and Group 2 (n = 38, 30-34 weeks). Color Doppler (Philip HD11) measurements were taken and compared before and after the MgSO4 loading dose. RESULTS: Within-group analysis revealed significant differences in RI-UtA, PI-UtA, and S/D in UtA before and after MgSO4 administration in Group 1. Furthermore, the RI-UA and RI-MCA decreased statistically significantly after MgSO4 treatment, whereas the pulsatility index and S/D did not change in either the umbilical or middle cerebral arteries. After MgSO4 treatment, all Doppler parameters in the uterine and umbilical arteries in Group 2 showed significant changes when compared to before MgSO4 administration. CONCLUSION: MgSO4 can effectively improve umbilical and MCA blood flow at 30-34 gestational weeks but not at 26-30w. Meanwhile, using MgSO4 can improve uterine blood flow in severe preeclampsia, which may contribute to the management of reducing adverse events in pregnant women who have preeclampsia and fetal growth restriction.

Maternal and neonatal outcome among women with early-onset preeclampsia and late-onset preeclampsia.

OBJECTIVE: This study aimed to determine the differences in characteristics and outcomes of early-onset and late-onset Preeclampsia. METHODS: A retrospective cross-sectional study was conducted on female patients giving birth with preeclampsia admitted into the Department of Obstetrics and Gynecology of Dr. Hasan Sadikin Hospital Bandung from January 2020 to December 2022 who met the study criteria. A total of 435 subjects met the inclusion criteria were divided into two groups: early-onset preeclampsia and late-onset preeclampsia. Differences in outcomes were analyzed using the Chi-square or Fisher test for categorical data and the T-independent or Mann-Whitney test for numerical data. RESULTS: There were differences in the incidence of HELLP syndrome (9.0 vs. 2.7%; p = 0.009), prematurity (77.7 vs. 21.4%; p = 0.000), early neonatal death (10.4 vs. 2.7%; p = 0.002), asphyxia (22.7 vs. 8.0%; p = 0.000), SGA (41.7 vs 21.9%; p = 0.000), and LBW (78.7 vs 40.2%; p = 0.000) in early-onset preeclampsia with late-onset. Length of stay was longer in early-onset preeclampsia cases (4.0 vs 3.0 days; p = 0.000). Increased ureum and liver enzymes results were significantly higher in early-onset preeclampsia. CONCLUSION: There is a difference in the outcome of pregnant women with early-onset and late-onset preeclampsia. Women with early-onset preeclampsia tend to have more adverse maternal and neonatal outcomes. In terms of maternal outcome, they tend to have higher liver enzymes level and HELLP syndrome, while in terms of neonatal outcome they tend to have prematurity, early neonatal death, asphyxia, SGA, and LBW.

Association between iron status, preeclampsia and gestational hypertension: A bidirectional two-sample Mendelian randomization study.

BACKGROUND: Several recent observational studies have reported that iron overload during pregnancy is associated with preeclampsia (PE) and gestational hypertension (GH). However, the causal association between iron status, PE, and GH is still not clear. METHODS: We performed a two-sample Mendelian randomization (MR) study using the genome-wide association study (GWAS) summary statistics of iron status, included serum iron, ferritin, total iron-binding capacity (TIBC), and transferrin saturation (TSAT) from the largest available GWAS meta-analysis, and the summary statistics of PE and GH were obtained from the FinnGen consortium. Fixed-effect inverse variance weighted (IVW), random-effect IVW, maximum likelihood (ML), MR-Egger regression, weighted median, and MR-PRESSO methods were used. RESULTS: A total of 21, 58, 28, and 22 SNPs were used as IVs for serum iron, ferritin, TIBC, and TSAT, respectively. The F-statistics of IVs ranged from 95.23 to 421.36. The results of the fixed effects IVW method suggested that for per SD unit increase in serum iron, the risk of PE increases by 24 % (OR = 1.24, 95 % CI: 1.03-1.50, P = 0.02). No significant heterogeneity or horizontal pleiotropy was found. The association between ferritin, TIBC, TSAT and PE were statistically insignificant (P>0.05). Furthermore, the results of each MR methods do not support a causal association between iron status and GH, nor a reverse causal association between PE and GH and iron status. CONCLUSION: This two-sample MR study provides evidence supporting a causal association between serum iron level and PE.

Serum macrophage stimulating protein α-chain and uterine artery Doppler ultrasound in the first trimester for the prediction of preeclampsia.

To assess how effective macrophage stimulating protein α-chain (MSP-α) combined with uterine artery Doppler is in predicting preeclampsia in singleton pregnancies during 11-13+6 weeks of gestation. This prospective observational study included singleton pregnant women who attended antenatal care at King Chulalongkorn Memorial Hospital, Department of Obstetrics and Gynecology, Faculty of Medicine, Chulalongkorn University between December 2021 and April 2023, during 11-13+6 weeks of gestation. Serum MSP-α levels were collected and uterine artery Doppler ultrasound was performed. Pregnancy outcomes were recorded, and the predictive values of these tests were determined to predict preeclampsia. A total of 365 patients, with 21 cases of preeclampsia (5.8%), were analyzed. Serum MSP-α levels were higher in pregnant women who developed preeclampsia than those who did not (899.7 ± 550.1 ng/ml vs 642.5 ± 466.1 ng/ml, p = 0.016). The mean pulsatility index of the uterine artery and the presence of diastolic notching were not significantly different between the groups. As a cut-off value for predicting preeclampsia, using serum MSP-α levels higher than 1.0 multiple of median for gestational age, the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were 71.4%, 50.3%, 8.1%, and 96.7%, respectively. Additionally, when abnormal serum MSP-α levels were combined with a uterine artery Doppler pulsatility index above the 95th percentile and bilateral notching as predictive values for preeclampsia, the sensitivity was 85.7%, specificity was 18.3%, PPV was 6.0%, and NPV was 95.5%. Serum MSP-α alone at 11-13+6 weeks of gestation was effective in predicting preeclampsia. However, the use of serum MSP-α in combination with uterine artery Doppler increased sensitivity but reduced specificity for the prediction of preeclampsia.