Preeclampsia In Women Research Articles

Aspirin 162 mg vs 81 mg for preeclampsia prophylaxis in high-risk obese individuals: a comparative effectiveness open-label randomized trial (ASPREO)

In the United States, leading medical societies recommend 81 mg of aspirin daily for the prevention of preeclampsia in women at risk, whereas the NICE guidelines in the United Kingdom recommend a dose as high as 150 mg of aspirin. Recent data also suggest that in the obese population, inadequate dosing or aspirin resistance may impact the efficacy of aspirin at the currently recommended doses. We evaluated whether daily administration of 162 mg aspirinwould be more effective compared with 81 mg in decreasing the rate ofpreeclampsia with severe features in high-risk obese pregnant individuals. We performed a randomized trial between May 2019 and November 2022. Individuals at 12-20 weeks of gestational age with a body mass index ≥30 kg/m2 at the time of enrollment and at least 1 of 3 high-risk factors: history of preeclampsia in a prior pregnancy, at least stage I hypertension documented in the index pregnancy, pregestational diabetes or gestational diabetes diagnosed before 20 weeks of gestational age were randomized to either 162 mg or 81 mg of aspirin daily till delivery, participants were not blinded to treatment allocation. Exclusion criteria were multifetal gestation, known major fetal anomalies, seizure disorder, baseline proteinuria, on aspirin because of other indications, or contraindication to aspirin. The primary outcome was preeclampsia with severe features (preeclampsia or superimposed preeclampsia with severe features; eclampsia; or hemolysis, elevated liver enzymes, low platelet count syndrome). Secondary outcomes included rates of preterm birth because of preeclampsia, small for gestational age, postpartum hemorrhage, abruption, and medication side effects. A sample size of 220 was needed using a preplanned Bayesian analysis of the primary outcome to estimate the posterior probability of benefit or harm with a neutral informative prior. Approximately 220/343 (64.1%) individuals were randomized. The primary outcome was available for 209/220 (95%) individuals. Baseline characteristics were similar between groups, with the median gestational age at enrollment being 15.9 weeks in the 162 mg aspirin group and 15.6 weeks in the 81 mg aspirin group. Enrollment before 16 weeks occurred in 55 of 110of those assigned to 162 mg and 58 of 110 of those assigned to 81 mg ofaspirin. The primary outcome occurred in n of d individuals (35%) in the 162mg aspirin group and n of d individuals (40%) in the 81 mg aspirin group (posterior relative risk, 0.88; 95% credible interval, 0.64-1.22). Bayesian analysis indicated a 78% probability of a reduction in the primary outcome with 162 mg aspirin compared with 81 mg aspirin dose. Rates of indicated pretermbirth because of preeclampsia (21% vs 21%), small for gestational age (6.5% vs 2.9%), abruption (2.8% vs 3.0%), and postpartum hemorrhage (10.0% vs 8.8%) were similar between groups. Medication adverse effects were also similar. Among high-risk obese individuals, there was a 78% probability of benefit that 162 mg aspirin compared with 81 mg will decrease the rate of preeclampsia with severe features. With the best estimate of a 12% reduction when using 162 mg of aspirin compared with 81 mg of aspirin in this population. This trial supports doing a larger multicenter trial.

Decreased Extracellular Vesicle Vasorin in Severe Preeclampsia Plasma Mediates Endothelial Dysfunction.

Preeclampsia (PE) is a serious pregnancy complication affecting 5-8% of pregnancies globally. It is a leading cause of maternal and neonatal morbidity and mortality. Despite its prevalence, the underlying mechanisms of PE remain unclear. This study aimed to determine the potential role of vasorin (VASN) in PE pathogenesis by investigating its levels in extracellular vesicles (EV) and its effects on vascular function. We conducted unbiased proteomics on urine-derived EV from severe PE (sPE) and normotensive pregnant women (NTP), identifying differential protein abundances. Out of one hundred and twenty proteins with ≥ ±1.5-fold regulation at P<0.05 between sPE and NTP, we focused on Vasorin (VASN), which is downregulated in sPE in urinary EV, in plasma EV and in the placenta and is a known regulator of vascular function. We generated EV with high VASN content from both human and murine placenta explants (Plex EV), which recapitulated disease-state-dependent effects on vascular function observed when treating murine aorta rings (MAR) or human aortic endothelial cells (HAEC) with murine or human plasma-derived EV. In normal murine pregnancy, VASN increases with gestational age (GA), and VASN is decreased in plasma EV, in placenta tissue and in Plex EV after intravenous administration of adenovirus encoding short FMS-like tyrosine kinase 1 (sFLT-1), a murine model of PE (murine-PE). VASN is decreased in plasma EV, in placenta tissue and in EV isolated from conditioned media collected from placenta explants (Plex EV) in patients with sPE as compared to NTP. Human sPE and murine-PE plasma EV and Plex EV impair migration, tube formation, and induces apoptosis in human aortic endothelial cells (HAEC) and inhibit acetylcholine-induced vasorelaxation in murine vascular rings (MAR). VASN over-expression counteracts the effects of sPE EV treatment in HAEC and MAR. RNA sequencing revealed that over-expression or knock down of VASN in HAEC results in contrasting effects on transcript levels of hundreds of genes associated with vasculogenesis, endothelial cell proliferation, migration and apoptosis. The data suggest that VASN, delivered to the endothelium via EV, regulates vascular function and that the loss of EV VASN may be one of the mechanistic drivers of PE. What is NewVASN in circulating plasma EV in sPE is reduced compared with VASN content in plasma EV of gestational age-matched pregnant women.VASN is encapsulated and transported in EV and plays a pro-angiogenic role during pregnancy.VASN should be explored both for its pro-angiogenic mechanistic role and as a novel biomarker and potential predictive diagnostic marker for the onset and severity of PE.What Are the Clinical Implications?VASN plays a role in maintaining vascular health and the normal adaptive cardiovascular response in pregnancy. A decrease of VASN is observed in sPE patients contributing to cardiovascular maladaptation.Strategies to boost diminished VASN levels and/or to pharmacologically manipulate mechanisms downstream of VASN may be explored for potential therapeutic benefit in PE.The decrease in EV-associated VASN could potentially be used as a (predictive) biomarker for PE.

Placental neutrophil reverse trans-migration and maternal serum neutrophil extracellular trap expression in HIV infection co-morbid pre-eclampsia in women of African ancestry

Neutrophil extracellular traps (NETs) and placental neutrophil reverse transmigration (r-TM) are implicated in the pathogenesis of pre-eclampsia (PE). However, the role of the comorbidity of PE and human immunodeficiency virus (HIV) infection in placental neutrophil r-TM and serum NETs remains unknown. Human placental tissue (n = 160) and serum (n = 80) samples were obtained post-ethical approval and divided by pregnancy type and HIV status and across the study population. Immunohistochemistry and morphometry were performed to localize and quantify junctional adhesion molecule-C (JAM-C) expression as an inverse marker of neutrophil r-TM within placental villi. An enzyme-linked immunosorbent assay (ELISA) was performed to quantify the concentration of citrullinated histone H3 (cit-H3) as a marker of NETs. GraphPad Prism (version 8.0.2) was used to compare the results, and a p value of p < 0.05 was considered statistically significant. The localization of JAM-C was observed on the syncytiotrophoblasts (STBs) and endothelial cells of placental villi. The immunoexpression of JAM-C was elevated in PE vs. normotensive (N) placentae. In the exchange villi, JAM-C immunoexpression was higher in the N+ve vs. N-ve group. However, in PE comorbid HIV infection, JAM-C expression was lower in the PE+ve vs. PE-ve group. Citrullinated histone-H3 concentration was lower in the N+ve vs. N-ve group but elevated in early-onset PE (EOPE)+ve vs. late-onset PE (LOPE)+ve group. These results indicate that PE and HIV-infected placentae individually express elevated JAM-C, manifesting in less neutrophil r-TM. However, in exchange villi of PE comorbid with HIV infection reduced JAM-C enhances neutrophil r-TM, thus supporting the synergistic effect of PE comorbid with HIV.

CircPAPPA2 plays a role in preeclampsia pathogenesis via regulation of the miR-942/miR-5006-3p

CircRNAs are a class of endogenous non-coding RNAs implicated in the pathogenesis of many pregnancy related diseases, one of which is pre-eclampsia (PE). This study aims to investigate the role of CircPAPPA2 (circbase ID: hsa_circ_0015382) in regulating the migration and invasion of trophoblast cells. RNA sequencing was used to identify the differentially expressed circRNAs in placenta of PE and normal pregnant women. Quantitative polymerase chain reaction (qRT-PCR) was used to verify the expression of circPAPPA2 and two miRNAs (miR-942-5p, 5006-3p) in placenta of PE and normal pregnant women. CCK8 and transwell experiments were performed to assess the function of circPAPPA2 in PE development.The interaction between circPAPPA2 and miR-942-5p/miR-5006-3p was verified by dual-luciferase reporter assay. Finally, bioinformatics analyzed with gene ontology, Kyoto Encyclopedia of the target genes. The results showed that the expression of circPAPPA2 was increased in placenta of PE pregnant women. Also, circPAPPA2 impedes trophoblasts cell proliferation and invasion. Moreover, the expression of circPAPPA2 was positively correlated with systolic blood pressure and urine protein. In addition, circPAPPA2 serves as a sponge of miR-942-5p and miR-5006-3p. In conclusion, CircPAPPA2 regulates trophoblasts cell proliferation and invasion by mediating the miR-942/miR-5006-3p.

Preeclampsia in Multiples: A Comparative Case Study on Dichorionic-Diamniotic Twin Pregnancy

Multiple pregnancies have a 2-3 times greater risk of developing preeclampsia and have a significant long-term effect on both mothers and babies. The underlying cause of preeclampsia in women with multiple pregnancies is higher demand on the cardiovascular system, increased exposure of the chorionic villi, increased antiangiogenic substances compared to angiogenic substances and placental hypoperfusion. The condition of preeclampsia can worsen quickly, and without warning signs, it must be detected and managed appropriately; if the treatment is late, this condition can lead to eclampsia. The patient was referred with severe preeclampsia and multiple pregnancies with complaints of irregular contraction (+), a history of dizziness (-), nausea (-), vomiting (-), blurred vision (-), and breathlessness (-). Physical examination showed Blood pressure 188/125 mmHg with laboratory findings of proteinuria +3. Cesarean section and IUD insertion were performed. During and after surgery, there were no complications.

Longitudinal Assessment of Oxidative Stress Markers in Women with Preeclampsia.

Preeclampsia (PE) is a pregnancy-specific disorder and a major contributor to maternal and fetal morbidity and mortality. Role of oxidative stress in early pregnancy with the pathophysiology of the disorder is unclear. The current study aims to analyse maternal levels of oxidative stress markers (MDA and protein carbonyl) longitudinally across gestation and placental levels of oxidative stress markers (MDA, protein carbonyl and 8-oxo-2'-deoxyguanosine) in women with PE and compare them with non-PE women. 324 pregnant women (216 non-PE and 108 PE women) were longitudinally followed during pregnancy. Women with preeclampsia were stratified as early onset preeclampsia (EOP) and late onset preeclampsia (LOP) Maternal blood at four time points across gestation (11-14weeks, 18-22weeks, 26-28weeks, and at delivery) and placenta were collected. Maternal and placental levels of oxidative stress markers were assessed using commercially available kits. Maternal plasma MDA and protein carbonyl levels were comparable between the PE and non-PE group at all timepoints across gestation. Maternal plasma MDA were significantly higher levels at 26-28weeks in EOP women when compared to non-PE women (p < 0.05). Placental 8-oxo-dG levels were lower in the EOP group as compared to non-PE (p < 0.05). Elevated plasma MDA levels were positively associated with birth length at 18-22weeks and 26-28weeks in the PE group (p < 0.05 for both). Maternal plasma MDA levels were positively associated with systolic blood pressure at 18-22weeks. Oxidative stress in early pregnancy is not associated with risk of PE.

Evaluation of serum testosterone levels in pre-eclampsia

Background: Pre-eclampsia (PE) is a multi-system disorder that affects 3%–6% of human pregnancies and causes substantial maternal and foetal mortality and morbidity. Various studies have implicated testosterone as a causative factor in the pathogenesis of PE. The present study evaluated the association of serum testosterone levels with PE and maternal and foetal outcomes. Aim: The objectives of the study were to assess serum testosterone levels in PE compared to normotensive pregnant mothers, to look for its association with PE and to identify its utility as a biomarker for PE. Materials and Methods: A prospective cohort study was conducted in the 2nd trimester pregnant mothers (n = 110) attending the outpatient department at Vinayaka Mission’s Kirupananda Variyar Medical College Hospital, Salem. Serum testosterone, uric acid, high-sensitivity C-reactive protein (hsCRP) and creatinine were evaluated and compared amongst the pre-eclamptic and normal pregnant women. Results: The mean serum testosterone level was higher in PE women (2.625 ± 1.40 ng/dL) when compared to normal pregnant women (1.217 ± 0.258 ng/dL) (P &lt; 0.001). Serum testosterone was found to be positively correlated with uric acid (r = 0.517, P &lt; 0.001), hsCRP (r = 0.307, P &lt; 0.001), systolic blood pressure (BP) (r = 0.480, P &lt; 0.000) and diastolic BP (r = 0.544 P &lt; 0.001). Receiver operating characteristic curve analysis for serum testosterone levels was done (area under the curve = 0.815), with sensitivity and specificity of 78.18% and 78.18%, respectively. Conclusion: This study attempted to identify the association between serum testosterone levels, PE and pregnancy outcomes in a small South Indian population. Serum testosterone levels were found to be significantly elevated in pre-eclamptic women compared to normal pregnancies and could be used as a predictive biomarker. Serum uric acid and hsCRP also showed a significant positive association with PE.

AT1-AA Induced Placental Ischemia Contributes to Hypertension in Female Offspring

Objective: Preeclampsia (PE), new-onset hypertension during the third trimester of pregnancy alongside other organ dysfunction, is associated with chronic inflammation and fetal growth restriction. Agonistic autoantibodies against the angiotensin II type 1 receptor (AT1-AA) are produced in PE women and induce a PE-like phenotype when infused into pregnant rats. AT1-AA is still present in maternal circulation up to eight years postpartum. We have shown that AT1-AA exposure during pregnancy contributes to impairment of cerebral blood flow in the postpartum period. Moreover, PE offspring are at higher risk for cardiovascular disease and hypertension but AT1-AA’s role in this elevated risk is unknown. The objective of this study was to determine if AT1-AA contributes to the risk for hypertension in PE offspring. Therefore, we hypothesized that AT1-AA infusion during pregnancy would cause offspring to have low birth weight and hypertension in adulthood. Methods: We infused AT1-AA (1:40) starting on gestational day (GD) 14 and allowed the dams to give birth on GD21. Birth weight was measured within 12 hours. Offspring were aged to 4 months. At that time, one male and female per litter were randomly selected to undergo carotid catheterization. The following day mean arterial pressure (MAP) was measured and blood and tissues were collected. Immune cells were measured by flow cytometry. Sex hormones were measured by mass spectroscopy. AT1-AA was measured by cardiomyocyte bioassay. Renal endothelin was measured by ELISA and RT-PCR. A two-way ANOVA was used for statistical analysis. Results: AT1-AA male and female offspring (6.1±0.1g, n=19, p&lt;0.05; 5.8±0.1g, n=19, p&lt;0.05) were larger at birth than NP male and female offspring (5.8±0.1g, n=11; 5.5±0.1g, n=11). Female AT1-AA offspring had elevated MAP (124±2 mmHg, n=14, p&lt;0.05) compared to NP female offspring (110±5 mmHg, n=8) while male AT1-AA offspring had similar MAP to male NP offspring. Circulating cytolytic NK cells trended higher in female AT1-AA offspring (2.73±0.37 % gated, n=9, p=0.0949) compared to female NP offspring (1.66±0.31 % gated, n=6). Female AT1-AA offspring also had elevated progesterone (41.3±6.0 pg/μL, n=8, p=0.0556) compared to female NP offspring (26.9±4.9 pg/μL, n=7). Renal PPET expression was increased in female AT1-AA offspring (2.6±0.69 fold increase, n=4, p&lt;0.05) compared to female NP offspring. Renal endothelin-1 was increased in female AT1-AA offspring (1.02±0.23 pg/mg, n=7, p=0.062) compared to female NP offspring (0.59±0.06 pg/mg, n=6). Male and female AT1-AA offspring had increased circulating AT1-AA (9.5±2.2 ΔBPM, n=6, p&lt;0.0001; 7.9±0.9 ΔBPM, n=8, p&lt;0.001) compared to male and female NP offspring (-0.4±.4 ΔBPM, n=7; -0.8±0.4 ΔBPM, n=4). Conclusion: These data demonstrate that AT1-AA infusion during pregnancy can predispose female offspring to have elevated blood pressure in adulthood. This study was supported by NIH grants RO1HD067541 (BL), F31HD110230 (NC), P20GM121334 (BL, LMA), HL151407 (DCC) and American heart association (AHA) early career award 19CDA34670055 (LMA). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Vascular Endothelial Mitochondrial Oxidative Stress in Response to Placental Macrophages from Preeclamptic Pregnancies

Preeclampsia (PE), a hypertensive disorder of pregnancy characterized by maternal hypertension, fetal growth restriction (FGR), and chronic immune activation and inflammation, is a major cause of maternal and fetal morbidity and mortality worldwide. Prior clinical studies demonstrate that proinflammatory M1 macrophages are increased in women with PE. We do not understand the role that M1 macrophage polarization may play in PE pathophysiology. We set out to begin characterization of macrophages in patient samples obtained from the UMMC biobank and their ability to induce mitochondrial oxidative stress (ROS) in human umbilical vein endothelial cells (HUVECs). After obtaining informed consent, whole blood and placental tissues were collected from normal pregnant (n=5) and preeclamptic women (n=8) who delivered in the labor and delivery unit UMMC. Lymphocytes were isolated from blood on a Ficoll-Histopaque gradient and analyzed by flow cytometry for total and M1 macrophages. Total macrophages were isolated from digested placental tissue by magnetic bead separation using the Human Macrophage Isolation Kit (Miltenyi). Isolated macrophages were co-cultured with HUVECs overnight. After removal of culture inserts containing macrophages, HUVECs were serum-starved and incubated with MitoSox Red, collected, and analyzed on a flow cytometer. Total circulating macrophages were increased in placentas from PE women vs normal pregnant patients (10.8% PMBCs vs. 3.5% PMBCs, respectively, p&lt;0.05). Furthermore, macrophage polarization to M1 macrophages was significantly higher in women with PE (15.02% of total macrophages) compared to NP women (6.23% of total macrophages, p&lt;0.05 vs. PE). We also determined that mitochondrial ROS production was significantly elevated in HUVEC cells co-cultured with macrophages from PE pregnancies (15.37 A.U.) when compared to HUVECs co-cultured with normal pregnant control macrophages (7.788 A.U., p&lt;0.05 vs. PE). Future studies will include enrollment of additional participants and determination of endothelial activation by measurement of adhesion molecules, growth factors, extracellular matrix proteins, and cytokines in HUVECs and conditioned media via Western Blot, ELISA, and multiplex analysis. These data show that PE placental macrophages induce mitochondrial ROS production in endothelial cells and may play a role to directly induce vascular dysfunction contributing to hypertension during a preeclamptic pregnancy. This work was supported by National Institutes of Health Grants T32HL105324 to C. A. Shields, and R01HL151407 to D. C. Cornelius. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Elevated Renal Oxidative Stress and Na+ Transporters are Associated with Hypertension in Postpartum Preeclamptic Rats

Background: Approximately 5-10% of US pregnancies result in preeclampsia (PE). PE is characterized by new onset hypertension (HTN) during pregnancy and is usually accompanied by end-organ damage, especially in the kidneys. Postpartum (PP) women and dams that had PE have an increased risk of developing HTN and chronic kidney disease (CKD) later in life. However, mechanisms linking PE to the long-term development of HTN and CKD are unknown. One aspect that may contribute to renal injury in PP PE women and dams is oxidative stress. Elevated concentrations of oxidative stress have been shown to augment the abundance and activity of renal transporters to increase sodium (Na+) reabsorption and blood volume. These alterations in renal transporters can consequently increase Na+ and water to facilitate HTN. Thus, we hypothesize that at 6 weeks PP (~3 human years), PE dams will display increased oxidative stress, renal Na+ transporter abundance, and elevated blood pressure (BP). Methods: Pregnant Sprague Dawley rats were randomly assigned to two groups: normal (CON) and PE dams. On gestational day 14, the reduced uterine perfusion pressure surgery was performed to mimic placental ischemia and generate a model of PE. Dams gave birth naturally and weaned for 3 weeks. After 6 weeks PP, BP was measured via carotid catheterization, and kidneys were removed and sectioned. Western blots were used to quantify renal Na+ transporters: Na+ K+ 2Cl− transporter (NKCC2) in the kidney medulla (KM) and epithelial Na+ channel (ENaC) in both the kidney cortex (KC) and KM. Oxidative stress was evaluated by heat shock protein 1 (HSP-1), copper zinc superoxide dismutase (CuZnSOD), and manganese superoxide dismutase (MnSOD) via Western blots. Hydrogen peroxide (H2O2) and antioxidant capacity concentrations were assessed via colorimetric assays. Results: PP PE dams had increased BP (126.3±6.18vs105.7±3.74 mmHg, p&lt;0.05) at 6 weeks after birth. KC HSP-1, H2O2, MnSOD, and antioxidant capacity were unchanged between groups. However, KC CuZnSOD protein abundance was decreased in PP PE dams (69.51±11.64vs100±5.73 IU/Protein/Control%, p&lt;0.05). In the KM, HSP-1 abundance (113.7±3.3vs100±5.07 IU/Protein/Control%, p=0.06) and H2O2 concentrations (1.97±0.11vs1.31± 0.38 nM H2O2/mg Protein, p=0.08) were elevated in PP PE dams. MnSOD, CuZnSOD, and antioxidant capacity were unchanged between groups in the KM. No changes occurred in KC and KM ENaC protein abundance. However, NKCC2 protein abundance was elevated by ~50% in PP PE dams (151.71±22.17vs100±5.59 IU/Protein/Control%, p=0.06). Conclusion: In summary, BP, oxidative stress, and NKCC2 were elevated in PP PE dams at 6 weeks. Perhaps, the presence of oxidative stress in the KM may lead to increased NKCC2 abundance. However, more studies are warranted to make this conclusion. NKCC2 elevation may result in increased Na+ and water reabsorption, leading to an increase in BP. Future studies will assess the role of renal oxidative stress to regulate Na+ transporters in PP PE dams and determine the timeline after birth (PP) in which changes in oxidative stress, Na+ transporters, and BP occur. In summary, this study is clinically relevant because it indicates that both oxidative stress and NKCC2 in the KM, separately or together, may have a formative role in the pathogenesis of HTN and CKD in PP PE women later in life. This research was supported by the Neurobiology of Aging and Alzheimer’s Disease Training Program (funded by NIH training grant T32 AG020494). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

An Observational Study of Maternal and Perinatal Outcome in Preeclampsia Cases in a Tertiary Care Center.

Preeclampsia, a hypertensive disorder in pregnancy, is a multisystem disease of unknown etiology and is associated with an increased risk of maternal mortality and morbidity.Infants from preeclampsia mothers have significantly higher incidence of prematurity, somatic growth retardation, thrombocytopenia, low birth weight, respiratory distress syndrome, and long duration of admission to neonatal intensive care (NICU). This study was done to study the maternal mortality and morbidity and foetal outcome in pregnant women with severe preeclampsia. This observational study was done in the Department of Obstetrics and Gynaecology, of a tertiary care centre, from the period October 2015 to October 2017.Data was collected from all 130 women attending the antenatal clinic of tertiary care hospital and ward admission and all details such as demographic details, obstetrics examination, and all clinical findings were noted and from that made results. Result: After applying inclusion and exclusion criteria all 130 women were observed in this study.Among 130 women 47 were diagnosed with preeclampsia. Mainly primigravida women were diagnosed with preeclampsia in the 21-25 years group. Among 47 preeclampsia women, 39 women had a BMI of 19-25 kg/m2. Thirty-two of 47 (68.09%) women were diagnosed with preeclampsia around 36-39 weeks. Among all preeclampsia, 28 women out of 47 (59.5%) women delivered babies vaginally, 18 of 47 (38.3%) women delivered through cesarean section, and one of 47 (2.13%) underwent preterm vaginal delivery. In preeclampsia, women's babies were delivered mostly (25/47, 53.19%) ≤2.5 kg weight and only one baby was shifted to NICU because of low birth weight. Preeclampsia increases maternal mortality and morbidity but in this study mortality was not done because our hospital is a tertiary care center with all ICU (intensive care unit) and NICU setup. Preterm births and cesarean deliveries were the mild to severe outcomes that were noted. ICU and NICUhospitalizations as a result of severe complications place a heavy demand on medical facilities. There are firm guidelines for the management of pregnancy-induced hypertension and its complications. For appropriate management, there is careful consideration of various factors, and individual case studies are required.

Correlation between platelet indices and preeclampsia with severe features

Backgrounds: Pre-eclampsia is a pregnancy-related syndrome with a 2-8% prevalence worldwide. In Indonesia, its incidence was 128,273 (5.3%) cases that caused 30-40% of maternal deaths. In 2021, at Karawang General Public Hospital, there are 43% cases of pre-eclampsia with 3% of complication. The pathophysiology is related to the inflammatory and coagulation system that includes platelets. Thus, platelet indices as indicators for platelet changes could be potential laboratory markers for pre-eclampsia.Objective: To examine the relationship between the platelet indices and pre-eclampsia severe features at the Karawang General Public HospitalMethods: The six months cross-sectional study was conducted at the Karawang General Public Hospital for pre-eclampsia pregnant women with at least 28 weeks of gestational age. The pre-eclampsia criteria were blood pressure higher or equal to 140/90 mmHg and qualitative proteinuria dipstick +1. The subjects were divided into two groups: pre-eclampsia with severe features and without severe features. Severe features criteria were thrombocytopenia, impaired liver function, renal insufficiency, pulmonary edema, new onset headache, and visual disturbances. Pregnant women have their blood platelet indices checked in the form of platelet crit (PCT), mean platelet volume (MPV), platelet distribution width (PDW), and platelet large cell ratio (P-LCR). Data were analyzed with descriptive analysis (percentage), cut-off analysis, ROC curve, AUC analysis, bivariate Chi-square analysis, and multivariate logistic regression analysis.Results: There was a significant difference (p &lt; 0.05) in the value of PCT, MPV, PDW, and P-LCR between pregnant pre-eclampsia women with severe features and pregnant pre-eclampsia women without severe features. P-LCR has the best sensitivity (52.9%) and specificity (98.9%).Conclusions: There was a significant change in the value of the platelet indices (PCT, MPV, PDW, P-LCR) in pregnant pre-eclampsia women with severe features at the Karawang General Public Hospital.

Intrahepatic cholestasis of pregnancy and its association with preeclampsia and gestational diabetes: a retrospective analysis.

To evaluate maternal and neonatal outcomes in patients with intrahepatic cholestasis of pregnancy (ICP). Patients who gave birth in our hospital between January 2018 and March 2022 were retrospectively reviewed from the hospital database and patient file records. The study comprised 1686 patients, 54 in the ICP group and 1632 controls. Patients who had ICP after 20weeks of gestation and were monitored and delivered at our facility were enrolled. Maternal demographic and obstetric characteristics data were examined. Perinatal outcomes were also assessed. Logistic regression analysis was used to determine adverse maternal outcomes. The mean age was 29years. ART, GDM, and preeclampsia were significantly higher in the ICP group. The mean serum bile acid level was 19.3 ± 3μmol/L in the ICP group. There was a higher risk of GDM and pre-eclampsia in women with ICP compared with those without and a significant association between ICP and adverse perinatal outcomes. There was a statistically significant relation between the presence of ICP and spontaneous preterm delivery, iatrogenic preterm delivery, 5th-minute Apgar scores < 7, and NICU requirement. No significant relationship was found between the presence of ICP and SGA and meconium. There was a significant relationship between the presence of ICP, mode of delivery, and PPH (p < 0.05). Those with ICP had a lower gestational week and birth weight, and higher rates of cesarean delivery and PPH. ICP should prompt close monitoring and management to mitigate the potential exacerbation of adverse outcomes, including preeclampsia, GDM, and preterm birth.

The sFLT-1/PlGF Ratio for the Prediction of Preeclampsia-Related Adverse Fetal and Maternal Outcomes in Women with Preexisting Diabetes.

To evaluate the predictive value of the sFlt-1/PlGF ratio for the prediction of preeclampsia in women with preexisting diabetes mellitus. This is a monocentric retrospective observational study conducted between January 2018 and December 2020. All singleton pregnancies with preexisting diabetes mellitus, who had a dosage of the sFlt-1/PlGF ratio between 30 and 34 + 6 weeks of gestation were included. The principal outcome was preeclampsia. The secondary outcomes were preterm preeclampsia, gestational hypertension, placental abruption, intrauterine fetal death, IUGR, small for gestational age and a composite outcome named "hypertensive disorder of pregnancy" including gestational hypertension, preeclampsia and HELLP syndrome (hemolysis, elevated liver enzymes and low platelet count). Of 63 patients, 22% presented preeclampsia. The area under the curve of sFlt-1/PlGF ratio was 0.90 (95% CI: 0.79-0.96) for the prediction of preeclampsia. The receiver operator characteristic analysis suggested that the optimal sFlt-1/PlGF cutoff to predict preeclampsia was 29, with a sensitivity of 86% (95% CI: 60.1-96.0) and a specificity of 92% (95% CI: 80.8-96.8). A cut-off of 38 provided a sensitivity of 71% (95% CI: 45.4-88.3), a specificity of 92% (95% CI: 80.8-96.8). Further analysis using multivariable methods revealed nephropathy was significantly associated with PE (p = 0.014). The use of the sFlt-1/PlGF ratio during the third trimester of pregnancy seems to be of interest as a prognostic tool to improve multidisciplinary management of patients with preexisting diabetes mellitus.

The role of T cell stimulated agonistic autoantibodies to the angiotensin II type I receptor (AT1-AA) in mediating multiorgan dysfunction in IL-17 induced hypertension during pregnancy.

Preeclampsia (PE), new-onset hypertension during pregnancy accompanied by organ dysfunction, is associated with chronic inflammation including elevated IL-17, CD4+ T cells, B cells and natural killer (NK) cells. IL-17 can serve as a signal for either the adaptive or innate immune activation. We have previously shown that IL-17 contributes to increased blood pressure in association with elevated TH17 cells, NK cells and B cells secreting angiotensin II type 1 receptor agonistic autoantibodies (AT1-AA) during pregnancy. Moreover, we have shown an important role for CD4+T cells and AT1-AA in multiorgan dysfunction as measured by mitochondrial oxidative stress (mt ROS). However, we do not know the role of adaptive immune cells such as T cells or B cells secreting AT1-AA in mediating the PE phenotype in response to elevated IL-17. In order to answer this question, we infused IL-17 (150 pg/day i.p.) into either Sprague Dawley (SD) or athymic nude rats via mini-osmotic pump from gestational day (GD) 14-19 of pregnancy. On GD 19, blood pressure was determined and NK cells, mtROS and respiration and AT1-AA production from B cells were measured. Infusion of IL-17 increased blood pressure in the presence or absence of T cells. Mean arterial pressure (MAP) increased with IL-17 from 98±2mm Hg (n=12) to 114±2 (n=12) in SD rats and from 99±4mm Hg (n=7) versus 115±2mm Hg (n=7) in athymic nude rats. Similar trends were seen in NK cells and placental mt ROS. Knowing that IL-17 stimulates AT1-AA in SD pregnant rats, we included a group of SD and athymic nude pregnant rats infused with IL-17 and the AT1-AA inhibitor peptide ('n7AAc'). The inhibitor attenuated blood pressure (104.9±3.2, p=.0001) and normalized NK cells and mt function in SD pregnant rats. Importantly, the AT1-AA was not produced in pregnant nude IL-17 treated rats, nor did 'n7AAc' effect MAP, in nude athymic rats. These findings suggest two conclusions; one is that IL-17 causes hypertension and multiorgan dysfunction in the absence of T cells and AT1-AA, possibly through its activation of innate cells and secondly, in the presence of T cells, blockade of the AT1-AA attenuates the effect of IL-17. This study indicates the critical effects of elevated IL-17 during pregnancy and suggest treatment modalities to consider for PE women.

Biomarkers for Early Prediction and Management of Preeclampsia: A Comprehensive Review.

Preeclampsia is a common complication of pregnancy. It is a multi-organ disorder that remains one of the main causes of maternal morbidity and mortality. Additionally, preeclampsia leads to many complications that can occur in the fetus or newborn. Preeclampsia occurs in about 1 in 20 pregnant women. This review focuses on the prediction of preeclampsia in women, using various biomarkers, in particular, a factor combining the use of soluble FMS-like tyrosinokinase-1 (sFlt-1) and placental growth factor (PlGF). A low value of the sFlt-1/PlGF ratio rules out the occurrence of preeclampsia within 4 weeks of the test result, and its high value predicts the occurrence of preeclampsia within even 1 week. The review also highlights other factors, such as pregnancy-associated plasma protein A, placental protein 13, disintegrin and metalloprotease 12, ß-human chorionic gonadotropin, inhibin-A, soluble endoglin, nitric oxide, and growth differentiation factor 15. Biomarker testing offers reliable and cost-effective screening methods for early detection, prognosis, and monitoring of preeclampsia. Early diagnosis in groups of women at high risk for preeclampsia allows for quick intervention, preventing the undesirable effects of preeclampsia. However, further research is needed to validate and optimize the use of biomarkers for more accurate prediction and diagnosis. This article aims to review the role of biomarkers, including the sFlt1/PlGF ratio, in the prognosis and management of preeclampsia.

Reducing the Risk of Pre-Eclampsia in Women with Polycystic Ovary Syndrome Using a Combination of Pregnancy Screening, Lifestyle, and Medical Management Strategies.

Polycystic ovary syndrome (PCOS) is a multisystem disorder that presents with a variety of phenotypes involving metabolic, endocrine, reproductive, and psychological symptoms and signs. Women with PCOS are at increased risk of pregnancy complications including implantation failure, miscarriage, gestational diabetes, fetal growth restriction, preterm labor, and pre-eclampsia (PE). This may be attributed to the presence of specific susceptibility features associated with PCOS before and during pregnancy, such as chronic systemic inflammation, insulin resistance (IR), and hyperandrogenism, all of which have been associated with an increased risk of pregnancy complications. Many of the features of PCOS are reversible following lifestyle interventions such as diet and exercise, and pregnant women following a healthy lifestyle have been found to have a lower risk of complications, including PE. This narrative synthesis summarizes the evidence investigating the risk of PE and the role of nutritional factors in women with PCOS. The findings suggest that the beneficial aspects of lifestyle management of PCOS, as recommended in the evidence-based international guidelines, extend to improved pregnancy outcomes. Identifying high-risk women with PCOS will allow targeted interventions, early-pregnancy screening, and increased surveillance for PE. Women with PCOS should be included in risk assessment algorithms for PE.

Clinical study on the difference in intestinal microecology between patients with preeclampsia and pregnant women at different stages of pregnancy.

Objective: To explore the difference in intestinal microecology between patients with preeclampsia and pregnant women at different stages of pregnancy. Methods: From January 2020 to January 2022, clinical data, including blood routine, lipid profile, and renal function indicators, were gathered from a cohort consisting of 5 cases of preeclampsia and 34 cases of non-preeclampsia. The non-preeclampsia group was further categorized into 6 cases in the First trimester, 13 cases in the Second trimester, and 15 cases in the Third trimester. The data collection took place at the Obstetrics Department of the Maternal and Child Health Hospital of Hubei Province. Additionally, fecal samples were obtained from each subject for 16S rDNA gene sequencing and subsequent analysis. The clinical data and composition characteristics of the gut microbiota in each group were analyzed, and the correlation between gut microbiota and clinical data was analyzed by the Spearman correlation analysis method. Results: In comparison to pregnant women without preeclampsia, preeclampsia patients exhibited a statistically significant elevation in blood routine parameters (WBC, N, L, and PLT count), a rise in lipid-related indicators (TC, TG, and LDL-C levels), a reduction in HDL-C levels, and an increase in renal function-related indicators (Cr, BUN, UA and Pro levels). Compared with non-preeclampsia pregnant women, preeclampsia women exhibited an augmented diversity of gut microbiota. Differences in gut microbiota composition between the two groups were observed at the gate and genus levels. Moreover, there are significant differences in the composition of gut microbiota between the preeclampsia group and the third-trimester group in terms of genus and species, and this difference is mainly caused by Prevotella and s_ Bacteroides_ Uniformis and Ruminococcus_ bromii. In addition, actinobacteria, bifidobacterium at the genus level, and Ruminococcus_bromii at the species level are positively correlated with clinically relevant indicators (excluding HDL-C). Conclusion: There are significant differences in gut microbiota between preeclampsia pregnant women and late pregnancy pregnant without preeclampsia, including Prevotella and Bacteroides_ Uniformis, and Ruminococcus_ bromii. In addition, these differential bacteria are correlated with most clinical indicators. However, additional comprehensive analysis is required to ascertain the functional correlation between these bacteria and clinical indicators.

Impact of physical activity on preeclampsia and angiogenic markers in the Finnish Genetics of Pre-eclampsia Consortium (FINNPEC) cohort

Introduction Effect of physical activity in pregnancy on preeclampsia (PE) and angiogenic markers is not well understood. We studied the association of physical activity and PE in a case-control setting and assessed whether exercise in PE and non-PE women associate with maternal serum concentrations of soluble fms-like tyrosine kinase 1 (s-Flt-1), placental growth factor (PlGF) and soluble endoglin (sEng) and sFlt-1/PlGF ratio in the Finnish Genetics of Pre-eclampsia Consortium (FINNPEC) cohort. Materials and methods Participants completed a questionnaire on their background information and serum samples were collected from a subset. Questionnaire data on physical activity were available from 708 PE women and 724 non-PE women. Both first trimester serum samples and questionnaire data on physical activity were available from 160 PE women and 160 non-PE women, and second/third trimester serum samples and questionnaire data on physical activity were available from 139 PE women and 47 non-PE women. The PE and non-PE women were divided into categories of physically active (exercise 2 − 3 times/week or more) and physically inactive (exercise less than 2 − 3 times/week). Results A total of 43.4% of the PE women and 42.4% of the non-PE women were categorized as physically active. There were no differences in physical activity and exercise habits between the groups. The physically active women were more often nulliparous and non-smokers and had a lower body mass index. There were no differences in the concentrations of angiogenic markers (sFlt-1, PlGF and sEng and sFlt-1/PlGF ratio) between the groups who exercised more or less than 2 − 3 times/week. Conclusions In the FINNPEC study cohort, there was no association between physical activity and PE and no associations of physical activity in pregnant women with and without PE with maternal serum concentrations of sFlt-1, PlGF and sEng and sFlt-1/PlGF ratio.

Association of Pre-eclampsia in Women with Advanced Maternal Age

Background: Preeclampsia: Preeclampsia is a serious condition that typically occurs after the 20th week of pregnancy. Preeclampsia can occur in women of all ages, but the risk increases with certain factors. Objectives: This study aimed to find out the association of pre eclampsia in women with advanced maternal age. Material &amp; Methods: This cross-sectional study was carried out in high dependency unit (HDU) of the Obstetrics and Gynecology Department of the Fauji Foundation Hospital, Rawalpindi, from 30th November 2021 to 29th May 2022. Total of 260 pregnant patients were selected through non-probability, sequential sampling. After taking written informed consent, information on the mother's age (measured in categories) and parity for each patient was gathered on a pre-made Performa. SPSS version 20 software was used to analyze the data. With a p-value of 0.05 considered significant, the chi-square test was employed to compare the maternal age to pre-eclampsia.Results: The mean age of the participants was 27.9± 6.02 years. Pre-eclampsia in pregnant women was discovered in 32 (12.3%) individuals. It was found in 21% of patients having aged &lt;20 years, in 9.0% of patients having age 20-25 years, in 5.4% patients having age 26-30 years, in 14.2% patients having age 31-35 years and 27.5% % in patients having age &gt;35 years and the results were statistically significant.Conclusion: The current study's conclusions indicate that pre-eclampsia affects pregnant women quite frequently and that advance maternal age is a risk factor for the disease.Keywords: Advanced maternal age, Pre-eclampsia, Pregnancy.