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1.
Harefuah ; 159(11): 804-808, 2020 Nov.
Artigo em Hebraico | MEDLINE | ID: mdl-33210850

RESUMO

BACKGROUND: The use of magnesium sulphate (MgSO4) in combination with antihypertensive drugs such as Labetalol is common in preeclampsia. OBJECTIVES: We aimed to examine the effects of MgSO4 and Labetalol on placental blood vessel reactivity in response to angiotensin II (ATII). METHODS: A dual-perfused single cotyledon model was used. Placentas from normal pregnancies were obtained. Selected cotyledons were cannulated and dually perfused. The intervillous space was infused for 60 minutes with three perfusion protocols: MgSO4 [7 mg%], MgSO4 [7 mg%], with Labetalol [1×10-4 mmol/L] and controls. After 60 minutes, ATII was injected as a bolus into the chorionic artery causing contraction/relaxation response in the fetal compartment. Perfusion pressure was measured continuously during contraction and relaxation phases. RESULTS: Twenty complete experiments were performed (9 controls, 7 with MgSO4 (7mg%) and 4 with MgSO4 [7mg%] and Labetalol [1×10-4 mmol/L]). Basal perfusion pressure did not differ between the treatment groups. Mean area under the pressure curve (AUC), the amplitude of the contraction response and the relaxation factor did not differ significantly between the groups in response to ATII administration. CONCLUSIONS: Magnesium sulphate and Labetalol did not have any effect on feto-placental vasculature reactivity.


Assuntos
Labetalol , Pré-Eclâmpsia , Feminino , Feto , Humanos , Sulfato de Magnésio/farmacologia , Placenta , Pré-Eclâmpsia/tratamento farmacológico , Gravidez
2.
Pan Afr Med J ; 36: 216, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32963682

RESUMO

Introduction: there is variance in both the types and combinations of antihypertensive drugs used for managing pre-eclampsia in the postpartum period. Knowledge of the most common and suitable single or combination antihypertensive drug therapies in the postpartum period will minimize harmful effects, promote adherence to medications, overcome any fears that lactating mothers may have about these drugs and will assist in healthcare planning. Objective: to determine the types of antihypertensive drug therapies used in managing pre-eclampsia with severe features (sPE) in the postpartum period in a regional hospital in South Africa. Methods: fifty consecutively presenting pregnant women with sPE were followed up prospectively from the pre-delivery period (within 48 hours before delivery) until day 3 postpartum. The antihypertensive drug therapies administered to the participants were observed. Their blood pressures were measured daily at 04: 00, 08: 00, 14: 00 and 22: 00 hours. Results: nifedipine was the commonest rapid-acting agent used for severe hypertension. Prepartum, 9 different combinations of antihypertensive drugs were prescribed; alpha-methyldopa was the commonest single long-acting agent used. Postpartum, the number of different drug combinations administered were 15, 18, 22 and 16 on days 0, 1, 2 and 3 respectively. Alpha-methyldopa was the commonest single agent used on postpartum days 0 - 2 while hydrochlorothiazide was the most frequently used single agent on postpartum day 3. Postpartum, the commonest combination therapy was alpha-methyldopa and amlodipine on day 0; alpha-methyldopa and amlodipine as a regimen as well as alpha-methyldopa, amlodipine and hydrochlorothiazide as another regimen on day 1; alpha-methyldopa and amlodipine on day 2; and many amlodipine-based regimens on day 3. Conclusion: a variety of antihypertensive drug combinations were used in the postpartum period indicating the need for standardised guidelines; however, detailed studies are required to evaluate their efficacies completely.


Assuntos
Anti-Hipertensivos/administração & dosagem , Pressão Sanguínea/efeitos dos fármacos , Adesão à Medicação , Pré-Eclâmpsia/tratamento farmacológico , Adulto , Quimioterapia Combinada , Feminino , Humanos , Período Pós-Parto , Gravidez , Estudos Prospectivos , Adulto Jovem
3.
Am J Obstet Gynecol ; 223(5): 739.e1-739.e13, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32780999

RESUMO

BACKGROUND: Despite expectant management, preeclampsia remote from term usually results in preterm delivery. Antithrombin, which displays antiinflammatory and anticoagulant properties, may have a therapeutic role in treating preterm preeclampsia, a disorder characterized by endothelial dysfunction, inflammation, and activation of the coagulation system. OBJECTIVE: This randomized, placebo-controlled clinical trial aimed to evaluate whether intravenous recombinant human antithrombin could prolong gestation and therefore improve maternal and fetal outcomes. STUDY DESIGN: We performed a double-blind, placebo-controlled trial at 23 hospitals. Women were eligible if they had a singleton pregnancy, early-onset or superimposed preeclampsia at 23 0/7 to 30 0/7 weeks' gestation, and planned expectant management. In addition to standard therapy, patients were randomized to receive either recombinant human antithrombin 250 mg loading dose followed by a continuous infusion of 2000 mg per 24 hours or an identical saline infusion until delivery. The primary outcome was days gained from randomization until delivery. The secondary outcome was composite neonatal morbidity score. A total of 120 women were randomized. RESULTS: There was no difference in median gestational age at enrollment (27.3 weeks' gestation for the recombinant human antithrombin group [range, 23.1-30.0] and 27.6 weeks' gestation for the placebo group [range, 23.0-30.0]; P=.67). There were no differences in median increase in days gained (5.0 in the recombinant human antithrombin group [range, 0-75] and 6.0 for the placebo group [range, 0-85]; P=.95). There were no differences between groups in composite neonatal morbidity scores or in maternal complications. No safety issues related to recombinant human antithrombin were noted in this study, despite the achievement of supraphysiological antithrombin concentrations. CONCLUSION: The administration of recombinant human antithrombin in preterm preeclampsia neither prolonged pregnancy nor improved neonatal or maternal outcomes.


Assuntos
Proteínas Antitrombina/uso terapêutico , Cesárea/estatística & dados numéricos , Idade Gestacional , Pré-Eclâmpsia/tratamento farmacológico , Administração Intravenosa , Adolescente , Adulto , Parto Obstétrico/estatística & dados numéricos , Método Duplo-Cego , Feminino , Sofrimento Fetal/epidemiologia , Humanos , Doenças do Prematuro/epidemiologia , Recém-Nascido Pequeno para a Idade Gestacional , Pessoa de Meia-Idade , Sepse Neonatal/epidemiologia , Mortalidade Perinatal , Pré-Eclâmpsia/sangue , Pré-Eclâmpsia/fisiopatologia , Gravidez , Segundo Trimestre da Gravidez , Terceiro Trimestre da Gravidez , Estudos Prospectivos , Proteínas Recombinantes , Adulto Jovem
4.
Reprod Sci ; 27(12): 2158-2169, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32557282

RESUMO

Low-dose aspirin, which selectively inhibits thromboxane synthesis, is now standard of care for the prevention of preeclampsia in at risk women, but some women still develop preeclampsia despite an aspirin regimen. To explore the "aspirin failures," we undertook a comprehensive evaluation of placental lipids to determine if abnormalities in non-aspirin sensitive lipids might help explain why some women on low-dose aspirin develop preeclampsia. We studied placentas from women with normal pregnancies and women with preeclampsia. Placental villous explants were cultured and media analyzed by mass spectrometry for aspirin-sensitive and non-aspirin-sensitive lipids. In women who developed severe preeclampsia and delivered preterm, there were significant elevations in non-aspirin-sensitive lipids with biologic actions that could cause preeclampsia. There were significant increases in 15- and 20-hydroxyeicosatetraenoic acids and sphingolipids: D-e-C18:0 ceramide, D-e-C18:0 sphingomyelin, D-e-sphingosine-1-phosphate, and D-e-sphinganine-1-phosphate. With regard to lipids sensitive to aspirin, there was no difference in placental production of thromboxane or prostacyclin, but prostaglandins were lower. There was no difference for isoprostanes, but surprisingly, anti-inflammatory omega 3 and 6 PUFAs were increased. In total, 10 of 30 eicosanoids and 5 of 42 sphingolipids were abnormal in women with severe early onset preeclampsia. Lipid changes in women with mild preeclampsia who delivered at term were of lesser magnitude with few significant differences. The placenta produces many aspirin-sensitive and non-aspirin-sensitive lipids. Abnormalities in eicosanoids and sphingolipids not sensitive to aspirin might explain why some aspirin-treated women develop preeclampsia.


Assuntos
Aspirina/uso terapêutico , Eicosanoides/biossíntese , Placenta/metabolismo , Pré-Eclâmpsia/tratamento farmacológico , Pré-Eclâmpsia/metabolismo , Esfingolipídeos/biossíntese , Adulto , Feminino , Humanos , Espectrometria de Massas , Gravidez , Resultado do Tratamento
8.
Int J Mol Sci ; 21(7)2020 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-32260307

RESUMO

In preeclampsia, widespread maternal endothelial dysfunction is often secondary to excessive generation of placental-derived anti-angiogenic factors, including soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin (sEng), along with proinflammatory cytokines such as tumour necrosis factor-α (TNF-α) and activin A, understanding of which offers potential opportunities for the development of novel therapies. The antimalarial hydroxychloroquine is an anti-inflammatory drug improving endothelial homeostasis in lupus. It has not been explored as to whether it can improve placental and endothelial function in preeclampsia. In this in vitro study, term placental explants were used to assess the effects of hydroxychloroquine on placental production of sFlt-1, sEng, TNF-α, activin A, and 8-isoprostane after exposure to hypoxic injury or oxidative stress. Similarly, human umbilical vein endothelial cells (HUVECs) were used to assess the effects of hydroxychloroquine on in vitro markers of endothelial dysfunction. Hydroxychloroquine had no effect on the release of sFlt-1, sEng, TNF-α, activin A, or 8-isoprostane from placental explants exposed to hypoxic injury or oxidative stress. However, hydroxychloroquine mitigated TNF-α-induced HUVEC production of 8-isoprostane and Nicotinanamide adenine dinucleotide phosphate (NADPH) oxidase expression. Hydroxychloroquine also mitigated TNF-α and preeclamptic serum-induced HUVEC monolayer permeability and rescued the loss of zona occludens protein zona occludens 1 (ZO-1). Although hydroxychloroquine had no apparent effects on trophoblast function, it may be a useful endothelial protectant in women presenting with preeclampsia.


Assuntos
Dinoprosta/análogos & derivados , Células Endoteliais da Veia Umbilical Humana/citologia , Hidroxicloroquina/farmacologia , Placenta/efeitos dos fármacos , Pré-Eclâmpsia/metabolismo , Hipóxia Celular , Sobrevivência Celular/efeitos dos fármacos , Dinoprosta/metabolismo , Endoglina/metabolismo , Feminino , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Subunidades beta de Inibinas/metabolismo , Modelos Biológicos , Placenta/metabolismo , Pré-Eclâmpsia/tratamento farmacológico , Gravidez , Fator de Necrose Tumoral alfa/metabolismo , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/metabolismo
9.
BMC Pregnancy Childbirth ; 20(1): 205, 2020 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-32272909

RESUMO

BACKGROUND: Hypertensive disorders of pregnancy are among the most common causes of perinatal death. The disorders are highly linked to multiple factors that make prediction and prevention challenging. Early diagnosis and proper management play a crucial role in the wellbeing and life of the women and her baby. In this study, we aimed to assess the association between different management options of preeclampsia and perinatal death at a public hospital in Ethiopia. METHODS: A document review was conducted on 241 preeclamptic patients' medical files who have been admitted and delivered in Woldia General Hospital from 2011 to 2016. The study was conducted from August 8 - September 10, 2017 in the aforementioned public hospital in Woldia town, Ethiopia. Associations were tested using Pearson chi squared test and binary logistic regression with a p-value < 0.05 considered significant. RESULT: In this study, nearly 20 every 100 neonates from preeclamptic women has been died and the figure was higher (76.59% Vs 23.4%) among neonates from severe preeclamptic women than mild preeclamptic women (p = 0.01). More than two thirds of the patients (69.3%) received magnesium sulfate to prevent convulsion. Perinatal death among women with diastolic blood pressures greater than 110 mmHg at admission was nearly 3 times (Adjusted Odds Ratio (AOR) = 2.824; 95% Confidence Interval (CI) (1.154-6.038)) higher compared to women with diastolic blood pressures below 110 mmHg. CONCLUSION: In the 5-year period, the magnitude of perinatal death among inpatient preeclamptic women was remarkably high and of which stillbirths exceeded pre-discharge early neonatal death. Utilization of magnesium sulfate tended to increase across years. Maternal diastolic blood pressure at admission was significantly associated with perinatal death.


Assuntos
Hospitais Gerais/estatística & dados numéricos , Morte Perinatal , Pré-Eclâmpsia/epidemiologia , Adolescente , Adulto , Anticonvulsivantes/uso terapêutico , Pressão Sanguínea , Diazepam/uso terapêutico , Etiópia/epidemiologia , Feminino , Humanos , Hipertensão/complicações , Recém-Nascido , Modelos Logísticos , Sulfato de Magnésio/uso terapêutico , Razão de Chances , Mortalidade Perinatal/tendências , Pré-Eclâmpsia/tratamento farmacológico , Gravidez , Estudos Retrospectivos , Fatores de Risco , Natimorto/epidemiologia , Fatores de Tempo , Adulto Jovem
10.
BMC Pregnancy Childbirth ; 20(1): 208, 2020 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-32272914

RESUMO

BACKGROUND: Preeclampsia is the major cause of maternal morbidity and mortality in developing countries. Magnesium sulfate is considered first-line therapy against eclampsia and magnesium deficiency in pregnancy has been associated with unfavourable perinatal outcomes. However there are doubts if magnesium supplementation during pregnancy can previne preeclampsia especially in population with high nutritional risk. This trial aims to verify the effect of oral magnesium supplmentation on preeclampsia incidence in low income pregnant women. METHODS: This randomized, double-blind, placebo-controlled trial investigated the effect of oral magnesium citrate supplementation for preeclampsia in low-income Brazilian pregnant women, i.e. annual per capita income of US$ 1025 or less. Participants were admitted to the study with gestational age between 12 and 20 weeks. Magnesium serum level was measured pre-randomization and participants with hypermagnesemia were excluded. After randomizationg participants received magnesium citrate capsule (300 mg magnesium citrate) or a daily placebo capsule, until delivery. Intent-to-treat analysis was performed. RESULTS: A total of 416 pregnant women were screened and 318 enrolled according to the inclusion criteria; 159 for each arm. Twenty-eight pregnant women were lost to follow-up. 55/290 (18.9%) of pregnant women developed preeclampsia; 26/143 (18.1%) in magnesium group and 29/147 (19.7%) in the control group; OR 0.90 (CI 95% 0.48-1.69), p = 0.747. No cases of eclampsia were registered. CONCLUSION: Oral magnesium supplementation did not reduce preeclampsia incidence in low-income and low-risk pregnant women. TRIAL REGISTRATION: Registered at ClinicalTrials.gov (Identifier NCT02032186), December 19, 2013.


Assuntos
Deficiência de Magnésio/tratamento farmacológico , Sulfato de Magnésio/uso terapêutico , Pré-Eclâmpsia/tratamento farmacológico , Adulto , Brasil , Suplementos Nutricionais , Método Duplo-Cego , Feminino , Idade Gestacional , Humanos , Pobreza , Gravidez , Adulto Jovem
11.
PLoS One ; 15(3): e0230488, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32176740

RESUMO

Pregnant women with diabetes mellitus (DM) are at high risk for hypertensive disorder of pregnancy (HDP). Women with poor control DM sometimes have heavy-for-dates infants. However, women with HDP sometimes have light-for-dates infants. We aim to clarify the relationship between glycemic control and fetal growth in women with DM and/or subsequent HDP. Of 7893 women gave singleton birth at or after 22 gestational weeks, we enrolled 154 women with type 1 DM (T1DM) or type 2 DM (T2DM) whose infants did not have fetal abnormalities. Among women with T1DM or T2DM, characteristics of the three groups (with HDP, without HDP, and with chronic hypertension [CH]) were compared. No women with T1DM had CH, but 19 (17.4%) of 109 with T2DM did. HDP incidence was similar between women with T1DM (22.2%) and T2DM without CH (16.7%). Among women with T1DM, the incidences of fetal growth restriction (FGR) with and without HDP were similar. However, among women with T2DM without CH, this incidence was significantly higher among those with HDP (33.3%) than among those without HDP (5.3%), was significantly more common with HbA1c levels at first trimester ≥ 7.2% (33.3%) than with those < 7.2% (5.6%), and significantly more numerous without pre-pregnancy therapies for DM (23.3%) than with them (3.3%). Among women with T2DM and HDP, those with FGR had smaller placenta SDs and higher insulin dosages at delivery than those without light-for-dates. In multivariate analysis, the presence of diabetic nephropathy was a predictor of T1DM and HDP (P = 0.0105), whereas HbA1c levels ≥ 7.2% before pregnancy was a predictor of T2DM and HDP (P = 0.0009). Insulin dosage ≥ 50U/day at delivery (P = 0.0297) and the presence of HDP (P = 0.0116) independently predicted T2DM, HDP, and FGR development. Insufficient pre-pregnancy treatment of DM increased the risk of HDP.


Assuntos
Glicemia/metabolismo , Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Retardo do Crescimento Fetal , Insulina/administração & dosagem , Pré-Eclâmpsia , Gravidez em Diabéticas , Adulto , Doença Crônica , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 1/epidemiologia , Diabetes Mellitus Tipo 1/patologia , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/patologia , Feminino , Retardo do Crescimento Fetal/sangue , Retardo do Crescimento Fetal/tratamento farmacológico , Retardo do Crescimento Fetal/epidemiologia , Retardo do Crescimento Fetal/patologia , Humanos , Placenta/metabolismo , Placenta/patologia , Pré-Eclâmpsia/sangue , Pré-Eclâmpsia/tratamento farmacológico , Pré-Eclâmpsia/epidemiologia , Pré-Eclâmpsia/patologia , Gravidez , Gravidez em Diabéticas/sangue , Gravidez em Diabéticas/tratamento farmacológico , Gravidez em Diabéticas/epidemiologia , Gravidez em Diabéticas/patologia , Estudos Retrospectivos , Fatores de Risco
12.
BJOG ; 127(8): 1018-1025, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32133780

RESUMO

OBJECTIVE: To compare maternal haemodynamics in women at low and high risk for preterm pre-eclampsia (PE), and between those at high risk who are randomised to aspirin or placebo. DESIGN: Prospective, longitudinal observational study. SETTING: Maternity units in six UK hospitals. POPULATION: Women participating in the Aspirin for Prevention of Preterm Pre-eclampsia (ASPRE) trial. The population comprised three groups of women: low risk for preterm PE (n = 1362), high risk for preterm PE treated with aspirin (n = 208) and high risk for preterm PE on placebo (n = 220). METHODS: Women had four visits during pregnancy: 11-14, 19-24, 30-34, and 35-37 weeks' gestation. Blood pressure was measured with a device validated for pregnancy, and PE and maternal haemodynamics were assessed with a bioreactance monitor at each visit. A multilevel linear mixed-effects analysis was performed to examine longitudinal changes of maternal haemodynamic variables, controlling for demographic characteristics, past medical history and medication use. MAIN OUTCOME MEASURES: Longitudinal changes of cardiac output (CO), mean arterial pressure (MAP), and peripheral vascular resistance (PVR). RESULTS: The low-risk group demonstrated the expected changes with an increase in CO and reduction in MAP and PVR, with a quadratic change across gestation. In contrast, the high-risk groups had a declining CO, and higher MAP and PVR during pregnancy. The administration of aspirin did not appear to affect maternal haemodynamics. CONCLUSIONS: Women screened as high risk for preterm PE have a pathological cardiac adaptation to pregnancy and the prophylactic use of aspirin (150 mg oral daily from the first trimester) in this group may not alter this haemodynamic profile. TWEETABLE ABSTRACT: In women at high risk of pre-eclampsia, prophylactic use of aspirin may not alter the impaired maternal cardiac adaptation.


Assuntos
Aspirina/uso terapêutico , Débito Cardíaco/efeitos dos fármacos , Inibidores da Agregação de Plaquetas/uso terapêutico , Pré-Eclâmpsia/prevenção & controle , Gravidez de Alto Risco/efeitos dos fármacos , Adulto , Pressão Arterial/efeitos dos fármacos , Pressão Arterial/fisiologia , Débito Cardíaco/fisiologia , Feminino , Idade Gestacional , Humanos , Estudos Longitudinais , Pré-Eclâmpsia/tratamento farmacológico , Gravidez , Gravidez de Alto Risco/fisiologia , Estudos Prospectivos , Fatores de Risco , Resultado do Tratamento , Resistência Vascular/efeitos dos fármacos , Resistência Vascular/fisiologia
13.
BMC Pregnancy Childbirth ; 20(1): 154, 2020 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-32164643

RESUMO

BACKGROUND: Preeclampsia is a relatively frequent condition during pregnancy and childbirth. The administration of magnesium sulphate as a prophylactic and treatment measure is an evidence-based practice for eclampsia; however, it is not consistently used, compromising the health of pregnant women. This study aimed to assess compliance with recommendations of the International Society for the Study of Hypertension in Pregnancy (ISSHP) for the use of MgSO4 in pregnant women with preeclampsia, before and after the implementation of the World Health Organization Safe Childbirth Checklist (SCC). METHODS: This quasi-experimental study was conducted between July 2015 and July 2016 at a third-level maternity hospital in northeastern Brazil, where the SCC was implemented. Compliance (underuse and overuse of MgSO4) was assessed in biweekly samples of 30 deliveries assessed 6 months before and 6 months after SCC implementation, using indicators based on international guidelines. A total of 720 deliveries were assessed over 1 year using an ad hoc application for reviewing medical records. Aggregated adequate use was estimated for the study period, and the time series measurements were compared to a control chart to assess change. RESULTS: The incidence of preeclampsia was 39.9% (287/720). Among these, 64.8% (186/287) had severe signs or symptoms and needed MgSO4. Underuse (no prescription when needed) of MgSO4 was observed in 74.7% (139/186) of women who needed the drug. Considering all women, non-compliance with the prescription protocol (underuse and overuse) was 20.0% (144/720). After introducing the SCC, the use of MgSO4 in women with preeclampsia with severe features increased from 19.1 to 34.2% (p = 0.025). Longitudinal analysis showed a significant (p < 0.05) ascending curve of adequate use of MgSO4 after the SCC was implemented. CONCLUSIONS: Compliance with recommendations for the use of MgSO4 in preeclampsia was low, but improved after implementation of the SCC. Interventions to improve compliance based on diagnosis and treatment reminders may help in the implementation of this good practice.


Assuntos
Lista de Checagem , Prescrições de Medicamentos/estatística & dados numéricos , Eclampsia/tratamento farmacológico , Sulfato de Magnésio/uso terapêutico , Pré-Eclâmpsia/tratamento farmacológico , Adulto , Brasil/epidemiologia , Eclampsia/epidemiologia , Eclampsia/prevenção & controle , Feminino , Humanos , Estudos Longitudinais , Pré-Eclâmpsia/epidemiologia , Pré-Eclâmpsia/prevenção & controle , Gravidez , Organização Mundial da Saúde , Adulto Jovem
14.
Int J Gynaecol Obstet ; 149(3): 333-338, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32119125

RESUMO

OBJECTIVE: To evaluate the effect of low-dose aspirin, which was administered at or before the 16th week of pregnancy due to maternal characteristics and history of a pre-existing medical condition, on prevention of pre-eclampsia, and on the birth of a small-for-gestational-age (SGA) neonate without pre-eclampsia in nulliparas in primary settings. METHODS: We performed a case-control study using population-based data on 47 271 nulliparas with a singleton pregnancy who delivered in Slovenia from 2013 to 2017. The treated group received low-dose aspirin. For the untreated group, propensity score matching was used to perform a 1:1 matching. In the matched sample, we calculated the odds ratios (OR) with a 95% confidence interval (95% CI) with a two-way test for pre-eclampsia, as well as SGA neonates. RESULTS: In the treated group (n=584), the odds for an SGA neonate were significantly increased by 42.7% (OR 1.427, 95% CI 1.001-2.034). However, we found no significant effect on the odds for pre-eclampsia (OR 1.308, 95% CI 0.847-2.022). CONCLUSIONS: In anticipation of more substantial population-based data studies, in the Slovenian population, preventive treatment with low-dose aspirin due to maternal characteristics and history of a pre-existing medical condition is not beneficial for the prevention of pre-eclampsia and can harm fetal growth.


Assuntos
Aspirina/administração & dosagem , Pré-Eclâmpsia/prevenção & controle , Adulto , Estudos de Casos e Controles , Feminino , Fidelidade a Diretrizes , Humanos , Recém-Nascido , Recém-Nascido Pequeno para a Idade Gestacional , Razão de Chances , Pré-Eclâmpsia/tratamento farmacológico , Gravidez , Eslovênia
15.
Pregnancy Hypertens ; 20: 83-91, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32199147

RESUMO

OBJECTIVES: There is avid interest in pravastatin as a therapeutic intervention for pre-eclampsia, however little is known on statin action on endothelial dysfunction. This study aimed to evaluate the ability of pravastatin, simvastatin and rosuvastatin to reduce pre-eclampsia-associated markers of endothelial dysfunction in human endothelial cells. STUDY DESIGN: Primary human umbilical vein endothelial cells (HUVECs) and uterine microvascular cells (UtMVs) were isolated and treated with 0.2, 2, 20 and 200 µM pravastatin, simvastatin and rosuvastatin for 24 h, either with or without pre-treatment with TNF-α to induce endothelial dysfunction. MAIN OUTCOME MEASURES: Cell viability (MTS) assays were performed and cells were visually inspected. Expression of endothelial dysfunction markers, endothelin-1 (ET-1) and vascular cell adhesion molecule-1 (VCAM-1) were assessed by qPCR (n=3). Intracellular VCAM-1 protein was examined by Western Blotting (n=5). ET-1 and soluble fms-like tyrosine kinase-1 (sFLT-1) protein secretion was assessed by ELISA in HUVEC conditioned media (n=3). RESULTS: High doses of simvastatin and rosuvastatin significantly compromised HUVEC survival. 200 µM simvastatin significantly reduced UtMV survival. Abnormal cell structure was observed with these doses and thus were excluded from further analysis. The statins did not mitigate TNF-α induced ET-1 or VCAM-1 expression in either HUVECs or UtMVs, nor VCAM-1 protein expression in HUVECs. 0.2 µM pravastatin and simvastatin significantly reduced ET-1 and sFLT-1 protein secretion. CONCLUSIONS: Pravastatin significantly reduced secretion of both ET-1 and sFLT-1, key mediators of endothelial dysfunction. Importantly, pravastatin had no toxic effects, in contrast to rosuvastatin and simvastatin. This further supports selection of pravastatin for clinical applications to combat pre-eclampsia.


Assuntos
Endotélio Vascular/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Pravastatina/farmacologia , Pré-Eclâmpsia/tratamento farmacológico , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Endotelina-1/genética , Endotelina-1/metabolismo , Endotélio Vascular/metabolismo , Endotélio Vascular/fisiopatologia , Feminino , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Pravastatina/toxicidade , Pré-Eclâmpsia/genética , Pré-Eclâmpsia/metabolismo , Pré-Eclâmpsia/fisiopatologia , Gravidez , Rosuvastatina Cálcica/farmacologia , Sinvastatina/farmacologia , Molécula 1 de Adesão de Célula Vascular/genética , Molécula 1 de Adesão de Célula Vascular/metabolismo , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/metabolismo
16.
Int J Mol Sci ; 21(4)2020 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-32093005

RESUMO

Preeclampsia (PE) is a pregnancy-specific multisystem disorder and is associated with maladaptation of the maternal cardiovascular system and abnormal placentation. One of the important characteristics in the pathophysiology of PE is a dysfunction of the placenta. Placental insufficiency is associated with poor trophoblast uterine invasion and impaired transformation of the uterine spiral arterioles to high capacity and low impedance vessels and/or abnormalities in the development of chorionic villi. Significant progress in identifying potential molecular targets in the pathophysiology of PE is underway. The human placenta is immunologically functional with the trophoblast able to generate specific and diverse innate immune-like responses through their expression of multimeric self-assembling protein complexes, termed inflammasomes. However, the type of response is highly dependent upon the stimuli, the receptor(s) expressed and activated, the downstream signaling pathways involved, and the timing of gestation. Recent findings highlight that inflammasomes can act as a molecular link for several components at the syncytiotrophoblast surface and also in maternal blood thereby directly influencing each other. Thus, the inflammasome molecular platform can promote adverse inflammatory effects when chronically activated. This review highlights current knowledge in placental inflammasome expression and activity in PE-affected pregnancies, and consequently, vascular dysfunction in PE that must be addressed as an interdependent interactive process.


Assuntos
Inflamassomos/metabolismo , Inflamação/imunologia , Placenta/metabolismo , Pré-Eclâmpsia/imunologia , Pré-Eclâmpsia/metabolismo , Trofoblastos/metabolismo , Feminino , Humanos , Hipertensão/imunologia , Hipertensão/metabolismo , Inflamassomos/genética , Inflamação/metabolismo , Isquemia/imunologia , Isquemia/metabolismo , Neovascularização Patológica/imunologia , Neovascularização Patológica/metabolismo , Placenta/patologia , Pré-Eclâmpsia/tratamento farmacológico , Gravidez , Transdução de Sinais/genética , Transdução de Sinais/imunologia
17.
Am J Obstet Gynecol ; 223(2): 250.e1-250.e11, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32067968

RESUMO

BACKGROUND: Obstetric hypertensive emergency is defined as having systolic blood pressure ≥160 mm Hg or diastolic blood pressure ≥110 mm Hg, confirmed 15 minutes apart. The American College of Obstetricians and Gynecologists recommends that acute-onset, severe hypertension be treated with first line-therapy (intravenous labetalol, intravenous hydralazine or oral nifedipine) within 60 minutes to reduce risk of maternal morbidity and death. OBJECTIVE: Our objective was to identify barriers that lead to delayed treatment of obstetric hypertensive emergency. STUDY DESIGN: A retrospective cohort study was performed that compared women who were treated appropriately within 60 minutes vs those with delay in first-line therapy. We identified 604 patients with discharge diagnoses of chronic hypertension, gestational hypertension, or preeclampsia using International Classification of Diseases-10 codes and obstetric antihypertensive usage in a pharmacy database at 1 academic institution from January 2017 through June 2018. Of these, 267 women (44.2%) experienced obstetric hypertensive emergency in the intrapartum period or within 2 days of delivery; the results from 213 women were used for analysis. We evaluated maternal characteristics, presenting symptoms and circumstances, timing of hypertensive emergency, gestational age at presentation, and administered medications. Chi square, Fisher's exact, Wilcoxon rank-sum, and sample t-tests were used to compare the 2 groups. Univariable logistic regression was applied to determine predictors of delayed treatment. Multivariable regression model was also performed; C-statistic and Hosmer and Lemeshow goodness-of-fit test were used to assess the model fit. A result was considered statistically significant at P<.05. RESULTS: Of the 213 women, 110 (51.6%) had delayed treatment vs 103 (48.4%) who were treated within 60 minutes. Patients who had delayed treatment were 3.2 times more likely to have an initial blood pressure in the nonsevere range vs those who had timely treatment (odds ratio, 3.24; 95% confidence interval, 1.85-5.68). Timeliness of treatment was associated with presence or absence of preeclampsia symptoms; patients without preeclampsia symptoms were 2.7 times more likely to have delayed treatment (odds ratio, 2.68; 95% confidence interval, 1.50-4.80). Patients with hypertensive emergencies that occurred overnight between 10 pm and 6 am were 2.7 times more likely to have delayed treatment vs those emergencies that occurred between 6 am and 10 pm (odds ratio, 2.72; 95% confidence interval, 1.27-5.83). Delayed treatment also had an association with race, with white patients being 1.8 times more likely to have delayed treatment (odds ratio, 1.79; 95% confidence interval, 1.04-3.08). Patients who were treated at <60 minutes had a lower gestational age at presentation vs those with delayed treatment (34.6±5 vs 36.6±4 weeks, respectively; P<.001). For every 1-week increase in gestational age at presentation, there was a 9% increase in the likelihood of delayed treatment (odds ratio, 1.11; 95% confidence interval, 1.04-1.19). Another factor that was associated with delay of treatment was having a complaint of labor symptoms, which made patients 2.2 times as likely to experience treatment delay (odds ratio, 2.17; 95% confidence interval, 1.07-4.41). CONCLUSION: Initial blood pressure in the nonsevere range, absence of preeclampsia symptoms, presentation overnight, white race, having complaint of labor symptoms, and increasing gestational age at presentation are barriers that lead to a delay in the treatment of obstetric hypertensive emergency. Quality improvement initiatives that target these barriers should be instituted to improve timely treatment.


Assuntos
Anti-Hipertensivos/uso terapêutico , Emergências , Grupos Étnicos/estatística & dados numéricos , Hipertensão Induzida pela Gravidez/tratamento farmacológico , Tempo para o Tratamento/estatística & dados numéricos , Administração Intravenosa , Administração Oral , Adulto , Afro-Americanos , Plantão Médico/estatística & dados numéricos , Doença Crônica , Grupo com Ancestrais do Continente Europeu , Feminino , Idade Gestacional , Hispano-Americanos , Humanos , Hidralazina/uso terapêutico , Hipertensão/tratamento farmacológico , Hipertensão/fisiopatologia , Hipertensão Induzida pela Gravidez/fisiopatologia , Labetalol/uso terapêutico , Trabalho de Parto , Nifedipino/uso terapêutico , Pré-Eclâmpsia/tratamento farmacológico , Pré-Eclâmpsia/fisiopatologia , Gravidez , Complicações Cardiovasculares na Gravidez/tratamento farmacológico , Complicações Cardiovasculares na Gravidez/fisiopatologia , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença
18.
Nitric Oxide ; 96: 1-12, 2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-31911124

RESUMO

The three known gasotransmitters, nitric oxide, carbon monoxide, and hydrogen sulfide are involved in key processes throughout pregnancy. Gasotransmitters are known to impact on smooth muscle tone, regulation of immune responses, and oxidative state of cells and their component molecules. Failure of the systems that tightly regulate gasotransmitter production and downstream effects are thought to contribute to common maternal diseases such as preeclampsia and preterm birth. Normal pregnancy-related changes in uterine blood flow depend heavily on gasotransmitter signaling. In preeclampsia, endothelial dysfunction is a major contributor to aberrant gasotransmitter signaling, resulting in hypertension after 20 weeks gestation. Maintenance of pregnancy to term also requires gasotransmitter-mediated uterine quiescence. As the appropriate signals for parturition occur, regulation of gasotransmitter signaling must work in concert with those endocrine signals in order for appropriate labor and delivery timing. Like preeclampsia, preterm birth may have origins in abnormal gasotransmitter signaling. We review the evidence for the involvement of gasotransmitters in preeclampsia and preterm birth, as well as mechanistic and molecular signaling targets.


Assuntos
Monóxido de Carbono/metabolismo , Gasotransmissores/metabolismo , Sulfeto de Hidrogênio/metabolismo , Óxido Nítrico/metabolismo , Complicações na Gravidez/tratamento farmacológico , Animais , Monóxido de Carbono/fisiologia , Monóxido de Carbono/uso terapêutico , Feminino , Gasotransmissores/fisiologia , Gasotransmissores/uso terapêutico , Humanos , Sulfeto de Hidrogênio/uso terapêutico , Óxido Nítrico/fisiologia , Parto/efeitos dos fármacos , Parto/fisiologia , Pré-Eclâmpsia/tratamento farmacológico , Pré-Eclâmpsia/fisiopatologia , Gravidez , Complicações na Gravidez/metabolismo , Complicações na Gravidez/fisiopatologia , Nascimento Prematuro/metabolismo , Nascimento Prematuro/fisiopatologia
19.
Artigo em Inglês | MEDLINE | ID: mdl-31927518

RESUMO

Background Postpartum bleeding and pregnancy induced hypertension - including preeclampsia - remain to be a great cause of maternal mortality. The use of aspirin for preventing preeclampsia has been practiced recently by fetomaternal specialists in Indonesia. This study aimed to analyze the impact of education using an aspirin booklet provided by pharmacists on knowledge and adherence in taking aspirin among pregnant women with high risk for preeclampsia. Methods This was one group of pretest-posttest study. We enrolled all pregnant women with high risk for preeclampsia screened at 11+0-13+6 weeks' gestation at Fetomaternal Clinic, Dr. Ramelan Naval Hospital, Surabaya. All subjects prescribed with low-dose aspirin (100 mg) for preeclampsia prevention received oral and written education using the aspirin booklet and had been followed up for 2 months. Knowledge about aspirin for preeclampsia prevention was measured by a validated questionnaire developed for this study. Adherence to aspirin was measured by pill count method. Results A total of 12 pregnant women with high risk for preeclampsia were included during the study period. This study showed a statistically significant difference on knowledge of preeclampsia prevention before and after receiving oral and written education using aspirin booklet (p-value = 0.020), as well as aspirin adherence (p-value = 0.011). Conclusion The use of oral education and written aspirin booklet provided by pharmacists had impact on knowledge of preeclampsia prevention and adherence in taking aspirin among pregnant women with high risk for preeclampsia. We recommend to conduct randomized control study of adequate number of subjects.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Aspirina/uso terapêutico , Conhecimentos, Atitudes e Prática em Saúde , Adesão à Medicação/estatística & dados numéricos , Folhetos , Educação de Pacientes como Assunto/métodos , Pré-Eclâmpsia/prevenção & controle , Adulto , Relação Dose-Resposta a Droga , Feminino , Idade Gestacional , Humanos , Indonésia , Adesão à Medicação/psicologia , Pré-Eclâmpsia/tratamento farmacológico , Gravidez , Fatores de Risco , Inquéritos e Questionários
20.
Arch Pharm Res ; 43(2): 233-241, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31989480

RESUMO

Preeclampsia is an inflammatory disease which can induce oxidative stress in placenta. Oxidative stress in preeclampsia is regulated by the phosphatidylinositol-3-kinase/Akt/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway. Mangiferin, an anti-oxidative molecule, is reported to ameliorate oxidative stress in the kidney and brain through activating the PI3K/Akt/mTOR pathway. We aimed to investigate the effects of mangiferin in a mouse model of preeclampsia, which was induced by phosphatidylserine/dioleoyl-phosphatidycholine (PS/PC) from day 5 to 17 of pregnancy. The female pregnant mice were divided into five groups according to drug treatment. Animals received mangiferin orally at doses of 10, 20, 40 mg/kg/day from day 0.5 to 17. In preeclampsia mouse model, elevated systolic blood pressure and proteinuria were ameliorated by mangiferin treatment. Mangiferin attenuated fms-like tyrosine kinase-1 and placental growth factor expression and oxidative stress in both blood and placenta of preeclampsia mice. The suppressed PI3K/Akt/mTOR pathway in placenta was activated by mangiferin treatment. This study demonstrates that mangiferin ameliorates placental oxidative stress and activates PI3K/Akt/mTOR pathway in a mouse model of preeclampsia.


Assuntos
Modelos Animais de Doenças , Fosfatidilinositol 3-Quinases/metabolismo , Pré-Eclâmpsia/tratamento farmacológico , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Serina-Treonina Quinases TOR/antagonistas & inibidores , Xantonas/farmacologia , Animais , Pressão Sanguínea/efeitos dos fármacos , Relação Dose-Resposta a Droga , Feminino , Camundongos , Camundongos Endogâmicos ICR , Estrutura Molecular , Estresse Oxidativo/efeitos dos fármacos , Placenta/efeitos dos fármacos , Pré-Eclâmpsia/metabolismo , Gravidez , Proteínas Proto-Oncogênicas c-akt/metabolismo , Relação Estrutura-Atividade , Serina-Treonina Quinases TOR/metabolismo
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