Occurrence Of Preeclampsia In Women Research Articles

Chloroquine is a safe autophagy inhibitor for sustaining the expression of antioxidant enzymes in trophoblasts

Inhibition of autophagy contributes to the pathophysiology of preeclampsia. Although chloroquine (CHQ) is an autophagy inhibitor, it can reduce the occurrence of preeclampsia in women with systemic lupus erythematosus. To clarify this important clinical question, this study aimed to address the safety of CHQ in trophoblast cells from the viewpoint of homeostasis, in which the anti-oxidative stress (OS) response and autophagy are involved. We used Western blotting to evaluate the protein levels in the trophoblast cells. The expression levels of heme oxygenase-1 (HO-1), an anti-OS enzyme, mediate resistance to OS induced by hydrogen peroxide (H2O2) in trophoblast cell lines. Among the autophagy modulators, bafilomycin A1 (BAF), an autophagy inhibitor, but not autophagy activators, suppressed HO-1 expression in BeWo cells; CHQ did not suppress HO-1 expression in BeWo cells. To clarify the role of autophagy in HO-1 induction, we observed no difference in HO-1 induction by H2O2 between autophagy-normal and autophagy-deficient cells. As for the mechanism of HO-1 induction by OS, BAF suppressed HO-1 induction by downregulating the expression of neighbor of BRCA1 gene 1 (NBR1) in the selective p62-NBR1-nuclear factor erythroid 2-related factor 2 (Nrf2) autophagy pathway. CHQ did not inhibit HO-1 expression by sustaining NBR1 expression in human villous tissues compared to BAF treatment. In conclusion, CHQ is a safer medicine than BAF for sustaining NBR1, which resist against OS in trophoblasts by connecting selective autophagy and the anti-OS response.

An open-label randomized-controlled trial of low dose aspirin with an early screening test for pre-eclampsia and growth restriction (TEST): Trial protocol

ObjectivePre-eclampsia remains a worldwide cause of maternal and perinatal morbidity and mortality. Low dose aspirin (LDA) can reduce the occurrence of pre-eclampsia in women with identifiable risk factors. Emerging screening tests can determine the maternal risk of developing placental disease, such as pre-eclampsia from the first trimester of pregnancy. The aim of this study is to determine if it is more beneficial in terms of efficacy and acceptability to routinely prescribe LDA to nulliparous low-risk women compared to test indicated LDA on the basis of a positive screening test for placental disease. MethodsWe propose a three armed multi-center open-labeled randomized control trial of; (i) routine LDA, (ii) no aspirin, and (iii) LDA on the basis of a positive first trimester pre-eclampsia screening test. LDA (75mg once daily) shall be given from the first trimester until 36-week gestation. The primary outcome measures include; (i) the proportion of eligible women that agree to participate (acceptability), (ii) compliance with study protocol (acceptability and feasibility), (iii) the proportion of women in whom it is possible to obtain first trimester trans-abdominal uterine artery Doppler examination (feasibility) and (iv) the proportion of women with a completed screening test that are issued the screening result within one week of having the test performed (feasibility). ConclusionThis will be the first clinical trial to determine the efficacy and acceptability in low-risk women of taking routine LDA versus no aspirin versus LDA based on a positive first trimester screening test for the prevention of placental disease.

تأثير مضادات الأكسدة على حدوث مقدمات الارتعاج عند النساء المعرضات لخطر متزايد

الهدف من هذا العمل هو: تقييم الفائدة المحتملة لمكملات مضادات الأكسدة على حدوث تسمم الحمل عند النساء المعرضات لخطر كبير. المرضى والطرق: كان عدد النساء الحوامل "294" وتراوحت أعمار الحمل بين 18-22 أسبوعًا. من (294) حالة حمولة أولية ، تم تحديد (25) امرأة على أنهن معرضات لخطر متزايد للإصابة بمقدمات الارتعاج عن طريق شكل موجة دوبلر غير طبيعية في أي من الشريان الرحمي عند 18-22 أسبوعًا من الحمل (يُعرَّف على أنه مؤشر مقاومة أقل من الشريحة المئوية 95 من أجل الحمل أو وجود درجة انبساطية مبكرة) ، (25) امرأة أخرى لديهن تاريخ في الحمل السابق من تسمم الحمل أو تسمم الحمل أو HELLP (انحلال الدم ، ارتفاع إنزيمات الكبد ، انخفاض الصفائح الدموية). - اجمالي عدد المشاركين المؤهلين (50) حالة. التصميم والاجراء: الحالات مقسمة عشوائيا الى مجموعتين كل 25 حالة تلقت مجموعة واحدة أقراص 1000 مجم فيتامين ج (سيفيتيل efferecent. EPICO) + 400 وحدة دولية من فيتامين E (E-Viton 400 pharco). الدم الوريدي قياس PAI-1 و PAI-2 ، كان قياس النتيجة الأولية هو نسبة PAI-1 / PAI-2 والنتيجة الثانوية مستقبليًا وفقًا لإرشادات المجتمع الدولي لدراسة ارتفاع ضغط الدم أثناء الحمل. النتائج: تم إجراء فحص دوبلر على 294 حمولة أولية تتراوح أعمارهم بين 18-22 أسبوعًا. أظهر 42 امرأة فقط دراسة دوبلر غير طبيعية ، لذا طُلب منهن المجيء لإعادة المسح في الأسبوع 24 من الحمل. 31 من أصل 42 مريضًا (75٪) لديهم دراسات غير طبيعية مستمرة. تم سحب ما تبقى من 42 امرأة (25 ٪) من الدراسة في 24 أسبوعًا. الحمل لأن لديهم مسحًا طبيعيًا للشريان الرحمي. كان تطور تسمم الحمل الخفيف أقل إحصائيًا (P <0.5) في الدراسة منه في المجموعة الضابطة. ومع ذلك ، فإن تطور تسمم الحمل الحاد أو تسمم الحمل المتراكب كان غير مهم إحصائيًا بين المجموعتين. تمت زيادة PAI-1 بشكل ملحوظ في النساء المصابات بمقدمات الارتعاج أكثر من العادي (167 ± 71.2 ، 113.8 ± 35.6 نانوغرام / مل على التوالي) مع P = 0.03 في المقابل انخفض PAI-2 بشكل كبير في النساء المصابات بمقدمات الارتعاج أقل من الضغط الطبيعي (105 ± 34.9 ، 181.1 ± 67.9ng / ml على التوالي) مع P = 0.018. الخلاصة: كانت تجارب العلاج والوقاية من تسمم الحمل مخيبة للآمال حتى الآن. ومع ذلك ، فقد اقترحت هذه الدراسة وجود روابط سببية بين الإجهاد التأكسدي وتطور تسمم الحمل تشير إلى أنه قد يكون دورًا للفيتامينات المضادة للأكسدة في الوقاية من تسمم الحمل. يمكن تحديد مجموعة سكانية عالية الخطورة بنجاح على أساس فحص دوبلر الشريان الرحمي والتاريخ السابق للمرض.

Circulating levels of the antiangiogenic marker sFLT-1 are increased in first versus second pregnancies

Preeclampsia is far more common in women's first pregnancy but the mechanism of this association is unknown. Altered angiogenesis, marked by increased levels of circulating soluble fms-like tyrosine kinase (sFlt-1), an inhibitor of placental growth factor (PlGF) and vascular endothelial growth factor, has been implicated in the pathogenesis of preeclampsia. We tested the hypothesis that nulliparous women demonstrate increased sFlt-1 levels compared with multiparous women, suggesting an overall increase in relative antiangiogenesis during first pregnancies. We measured sFlt-1 and PlGF levels in early pregnancy serum samples from the first 2 completed pregnancies of 97 women who participated in the MOMS cohort study. Repeated measures analyses demonstrated that sFlt-1 levels were significantly increased in first compared with second pregnancies (877+/-598 pg/mL vs 728+/-399 pg/mL; P=.01) but there was no significant difference in PlGF levels (45.3+/-40.7 pg/mL vs 40.1+/-31.9 pg/mL; P=.14). After adjusting for age, gestational age, blood pressure, body mass index, smoking, and the interpregnancy time interval, the residual decrease in sFlt-1 levels from the first to the second pregnancy remained significant at 107 pg/mL (P=.04). Significant interaction between ethnicity and pregnancy order on sFlt-1 levels was observed such that Hispanic women demonstrated greater sFlt-1 levels than white women during their first pregnancy but lower levels in their second pregnancies. Increased sFlt-1 secretion in first versus second pregnancies may account in part for the increased risk of preeclampsia among nulliparous women. Additional studies are needed to verify these findings and to further examine ethnic differences in angiogenesis factors and their potential impact on the incidence of preeclampsia.

Effect of Antioxidants on the Occurrence of Pre-Eclampsia in Women at Increased Risk: A Randomised Trial

Summary Background Oxidative stress has been implicated in the pathophysiology of pre-eclampsia. This randomised controlled trial investigated the effect of supplementation with vitamins C and E in women at increased risk of the disorder on plasma markers of vascular endothelial activation and placental insufficiency and the occurrence of pre-eclampsia. Methods 283 women were identified as being at increased risk of pre-eclampsia by abnormal two-stage uterine-artery doppler analysis or a previous history of the disorder and were randomly assigned vitamin C (1000 mg/day) and vitamin E (400 IU/day) or placebo at 16–22 weeks' gestation. Plasma markers of endothelial activation (plasminogen-activator inhibitor 1 [PAI-1]) and placental dysfunction (PAI-2) were measured every month until delivery. Pre-eclampsia was assessed by the development of proteinuric hypertension. Analyses were done by intention to treat, and in the cohort who completed the study. Findings Supplementation with vitamins C and E was associated with a 21% decrease in the PAI-1/PAI-2 ratio during gestation (95% CI 4–35, p=0·015). In the intention-to-treat cohort, pre-eclampsia occurred in 24 (17%) of 142 women in the placebo group and 11 (8%) of 141 in the vitamin group (adjusted odds ratio 0·39 [0·17–0·90], p=0·02). In the cohort who completed the study (81 placebo group, 79 vitamin group), the odds ratio for pre-eclampsia was 0·24 (0·08–0·70, p=0·002). Interpretation Supplementation with vitamins C and E may be beneficial in the prevention of pre-eclampsia in women at increased risk of the disease. Multicentre trials are needed to show whether vitamin supplementation affects the occurrence of pre-eclampsia in low-risk women and to confirm our results in larger groups of high-risk women from different populations.

Effect of antioxidants on the occurrence of pre-eclampsia in women at increased risk: a randomised trial

Effect of antioxidants on the occurrence of pre-eclampsia in women at increased risk: a randomised trial

Effect of antioxidants on the occurrence of pre-eclampsia in women at increased risk: a randomised trial

Oxidative stress has been implicated in the pathophysiology of pre-eclampsia. This randomised controlled trial investigated the effect of supplementation with vitamins C and E in women at increased risk of the disorder on plasma markers of vascular endothelial activation and placental insufficiency and the occurrence of pre-eclampsia. 283 women were identified as being at increased risk of pre-eclampsia by abnormal two-stage uterine-artery doppler analysis or a previous history of the disorder and were randomly assigned vitamin C (1000 mg/day) and vitamin E (400 IU/day) or placebo at 16-22 weeks' gestation. Plasma markers of endothelial activation (plasminogen-activator inhibitor 1 [PAI-1]) and placental dysfunction (PAI-2) were measured every month until delivery. Pre-eclampsia was assessed by the development of proteinuric hypertension. Analyses were done by intention to treat, and in the cohort who completed the study. Supplementation with vitamins C and E was associated with a 21% decrease in the PAI-1/PAI-2 ratio during gestation (95% CI 4-35, p=0.015). In the intention-to-treat cohort, pre-eclampsia occurred in 24 (17%) of 142 women in the placebo group and 11 (8%) of 141 in the vitamin group (adjusted odds ratio 0.39 [0.17-0.90], p=0.02). In the cohort who completed the study (81 placebo group, 79 vitamin group), the odds ratio for pre-eclampsia was 0.24 (0.08-0.70, p=0.002). Supplementation with vitamins C and E may be beneficial in the prevention of pre-eclampsia in women at increased risk of the disease. Multicentre trials are needed to show whether vitamin supplementation affects the occurrence of pre-eclampsia in low-risk women and to confirm our results in larger groups of high-risk women from different populations.