Treating hypertension in women of child-bearing age and during pregnancy.

Hypertension is found among 1 to 6% of young women. Treatment aims to decrease cardiovascular risk, the magnitude of which is less dependent on the absolute level of blood pressure (BP) than on associated cardiovascular risk factors, hypertension-related target organ damage and/or concomitant disease. Lifestyle modifications are recommended for all hypertensive individuals. The threshold of BP at which antihypertensive therapy should be initiated is based on absolute cardiovascular risk. Most young women are at low risk and not in need of antihypertensive therapy. All antihypertensive agents appear to be equally efficacious; choice depends on personal preference, social circumstances and an agent's effect on cardiovascular risk factors, target organ damage and/or concomitant disease. Although most agents are appropriate for, and tolerated well by, young women, another consideration remains that of pregnancy, 50% of which are unplanned. A clinician must be aware of a woman's method of contraception and the potential of an antihypertensive agent to cause birth defects following inadvertent exposure in early pregnancy. Conversely, if an oral contraceptive is effective and well tolerated, but the woman's BP becomes mildly elevated, continuing the contraceptive and initiating antihypertensive treatment may not be contraindicated, especially if the ability to plan pregnancy is important (e.g. in type 1 diabetes mellitus). No commonly used antihypertensive is known to be teratogenic, although ACE inhibitors and angiotensin receptor antagonists should be discontinued, and any antihypertensive drugs should be continued in pregnancy only if anticipated benefits outweigh potential reproductive risk(s). The hypertensive disorders of pregnancy complicate 5 to 10% of pregnancies and are a leading cause of maternal and perinatal mortality and morbidity. Treatment aims to improve pregnancy outcome. There is consensus that severe maternal hypertension (systolic BP > or = 170mm Hg and/or diastolic BP > or = 110mm Hg) should be treated immediately to avoid maternal stroke, death and, possibly, eclampsia. Parenteral hydralazine may be associated with a higher risk of maternal hypotension, and intravenous labetalol with neonatal bradycardia. There is no consensus as to whether mild-to-moderate hypertension in pregnancy should be treated: the risks of transient severe hypertension, antenatal hospitalisation, proteinuria at delivery and neonatal respiratory distress syndrome may be decreased by therapy, but intrauterine fetal growth may also be impaired, particularly by atenolol. Methyldopa and other beta-blockers have been used most extensively. Reporting bias and the uncertainty of outcomes as defined warrant cautious interpretation of these findings and preclude treatment recommendations.     

妊娠和哺乳期降压药物选择

目的:了解评估妊娠和哺乳期降压药物使用的风险/效益,为妊娠和哺乳期高血压妇女的降压治疗提供帮助。方法:检索近10余年国内外相关研究文献,筛选部分文献进行总结和分析。结果:通过分析显示:中枢性降压药、受体拮抗剂、钙拮抗剂类中一些药物在妊娠和哺乳期使用的风险/效益较低;利尿剂在妊娠伴发全身水肿且无先兆子痫时使用风险/效益较低;ACEI和ARB类可导致胎儿畸形、肾功能衰竭和死胎等,妊娠期药物使用的风险/效益高,但在哺乳期一些药物如依那普利、卡托普利无明确的禁忌。结论:拉贝洛尔、硝苯地平、甲基多巴等在妊娠和哺乳期使用的安全性和有效性较为肯定,并且受到越来越多的指南推荐。     

How to manage hypertension in pregnancy effectively

The hypertensive disorders of pregnancy (HDP) are a leading cause of maternal mortality and morbidity in both well and under-resourced settings. Maternal, fetal, and neonatal complications of the HDP are concentrated among, but not limited to, women with pre-eclampsia. Pre-eclampsia is a systemic disorder of endothelial cell dysfunction and as such, blood pressure (BP) treatment is but one aspect of its management. The most appropriate BP threshold and goal of antihypertensive treatment are controversial. Variation between international guidelines has more to do with differences in opinion rather than differences in published data. For women with severe hypertension [defined as a sustained systolic BP (sBP) of ≥160 mmHg and/or a diastolic BP (dBP) of ≥110 mmHg], there is consensus that antihypertensive therapy should be given to lower the maternal risk of central nervous system complications. The bulk of the evidence relates to parenteral hydralazine and labetalol, or to oral calcium channel blockers such as nifedipine capsules. There is, however, no consensus regarding management of non-severe hypertension (defined as a sBP of 140-159 mmHg or a dBP of 90-109 mmHg), because the relevant randomized trials have been underpowered to define the maternal and perinatal benefits and risks. Although antihypertensive therapy may decrease the occurrence of BP values of 160-170/100-110 mmHg, therapy may also impair fetal growth. The potential benefits and risks do not seem to be associated with any particular drug or drug class. Oral labetalol and methyldopa are used most commonly, but many different β-adrenoceptor blockers and calcium channel blockers have been studied in clinical trials.     

Pharmacological treatment of hypertension in pregnancy

The hypertensive disorders of pregnancy complicate 5-10% of pregnancies. Of these disorders 70% are pregnancy related (preeclampsia-eclampsia and gestation hypertension) and 30 % are a pre-existing hypertensive condition (chronic hypertension). These disorders are associated with maternal and fetal complications and have a substantial economic impact. This review examined the pharmacological treatment of the hypertensive disorders of pregnancy. There is a general consensus that anti-hypertensive should be given with severe hypertension and this should be in the hospital. The value of antihypertensive drugs in pregnant women with mild hypertension continues to be an area of debate that the evidence is too scanty to securely evaluate the clinical benefits of treating mild hypertension during pregnancy. The choice of the antihypertensive agents depends on individual clinician preference, the specified maternal and foetal benefits and the reproductive complications (teratogenisity, fetotoxicity and neonatal toxicity) of each particular agent. There are unequivocal evidences that Magnesium sulphate is superior to other agents in reducing recurrent eclamptic seizures. There is a strong recent evidence recommended that magnesium sulphate should be considered for women with pre-eclampsia for whom there is concern about the risk of eclampsia.     

Treatment of hypertensive complications in pregnancy

Hypertension is the most common medical disorder during pregnancy. Approximately 70 percent of women diagnosed with hypertension during pregnancy will have gestational hypertension-preeclampsia. The term gestational hypertension-preeclampsia is used to describe a wide spectrum of patients who may have only mild elevation in blood pressure to those with severe hypertension with various organ dysfunctions (acute gestational hypertension, preeclampsia, eclampsia, and the syndrome of hemolysis, elevated liver enzymes, and low platelets (HELLP syndrome). The exact incidence of gestational hypertension-preeclampsia in the United States is unknown. Estimates range from 6% to 8% of all pregnancies. The treatment of hypertensive disorders in pregnancy requires careful assessment of the maternal and fetal conditions. Therapeutic decisions must take into account fetal age, maternal symptoms, tests of fetal well-being, as well as maternal status, in order to ensure the best overall outcome. Treatment of mild gestational hypertension with antihypertensive medications has not been shown to improve outcome, however, in cases of severe disease treatment has been shown to be beneficial. The purpose of this review is to discuss the different treatment modalities used in the hypertensive disorders of pregnancy. Management strategies will not be discussed.     

妊娠期高血压患者的治疗体会

目的探讨妊娠期高血压疾病患者的临床特点及治疗方法。方法回顾分析我科自2011年1月至2012年12月共收治48例妊娠期高血压患者的临床资料进行回顾分析。结果 48例妊娠高血压患者分别经过采取解痉、镇静、降压,积极治疗产后出血等措施,有效控制病情,无严重并发症发生,安全分娩,无孕产妇死亡。结论早期发现引发妊高征的诱因并进行积极有效预防、合理治疗,应根据不同病情、孕周做出不同处理。     

妊娠期高血压疾病药物降压治疗的临床安全性及有效性分析

目的 分析妊娠期高血压疾病的临床表现以及治疗方法,探讨降压药物在妊高症中应用的安全性及有效性.方法 我院收治的134例妊高症患者作为观察组,酌情给予肼苯哒嗪、利血平、硝苯地平、卡托普利等药物进行降压治疗,选择同期我院分娩的正常产妇134例作为对照组.分析对比两组的凝血功能、产后出血、胎盘早剥、以及有无发生妊高症心脏病等并发症.结果 观察组患者出现凝血功能异常、胎盘早剥、妊高症心脏病以及产后出血的患者分别为9.7％、12.69％、8.21％、8.96％,均多于对照组的1.49％、2.24％、0、1.49％(P＜ 0.01).结论 妊高症常导致患者出现各种不良并发症,影响母婴健康,降压治疗能够有效地减少并发症的发生,改善患者的生活质量.     

Management of Hypertension in Pregnancy

Hypertension is an important cause of both maternal and fetal morbidity and mortality in pregnant women. There are still no definitive guidelines as to when and how patients should be treated, but it is important that appropriate treatment is initiated early in patients at highest risk and they are closely monitored. Hypertension in pregnancy can be a difficult condition to diagnose and treat because of the numerous and differing classification systems that have been used in the past. One classification system, which accounts for the multisystem involvement which can occur in pre-eclampsia and eclampsia, divides hypertension in pregnancy into 3 main groups: pre-eclampsia, gestational hypertension and chronic hypertension. Little benefit to the fetus has been shown from treating gestational and chronic hypertension, but studies in this area have been small and would not have had the power to show a difference in outcome between treated and untreated groups. However, the reduction in morbidity and mortality in the treatment of preeclampsia is significant. Therefore, all pregnancies complicated by hypertension require monitoring to detect the possible onset of superimposed pre-eclampsia/eclampsia. Institutions should have a management strategy for those mothers with severe hypertension including a multidisciplinary approach, where the patient is to be monitored and which antihypertensive agents are to be used. It should not be forgotten that the definitive treatment for severe hypertension is delivery of the fetus despite risks to fetal morbidity and mortality. This will reduce blood pressure, but hypertension per se may still persist post partum requiring short term therapy.     

Platelet activation in the hypertensive disorders of pregnancy

The hypertensive disorders of pregnancy, including gestational hypertension, pre-eclampsia and eclampsia, continue to be an important cause of maternal morbidity and mortality. Abnormal placentation is considered to be the main instigating factor, which then leads to widespread maternal endothelial activation and dysfunction. This endothelial perturbation leads to the release of many substances into the circulation, many of which result in platelet activation. For example, there is an imbalance between the levels of prostacyclin (a vasodilator and platelet inhibitor) and thromboxane (a platelet activator and vasoconstrictor), which then results in the maintenance of high blood pressure and complications. It is also likely that platelets play an important part in the pathogenesis of hypertension in pregnancy. The use of antiplatelet drugs has been shown to be effective in reducing the incidence of gestational hypertension in women at high risk and in preventing the complications associated with it. In addition, some antihypertensive agents are effective in reversing platelet activation in essential hypertension and, therefore, their use in pregnancy-induced hypertension may be beneficial in more ways than simply blood pressure reduction.     

Platelet activation in the hypertensive disorders of pregnancy

The hypertensive disorders of pregnancy, including gestational hypertension, pre-eclampsia and eclampsia, continue to be an important cause of maternal morbidity and mortality. Abnormal placentation is considered to be the main instigating factor, which then leads to widespread maternal endothelial activation and dysfunction. This endothelial perturbation leads to the release of many substances into the circulation, many of which result in platelet activation. For example, there is an imbalance between the levels of prostacyclin (a vasodilator and platelet inhibitor) and thromboxane (a platelet activator and vasoconstrictor), which then results in the maintenance of high blood pressure and complications. It is also likely that platelets play an important part in the pathogenesis of hypertension in pregnancy. The use of antiplatelet drugs has been shown to be effective in reducing the incidence of gestational hypertension in women at high risk and in preventing the complications associated with it. In addition, some antihypertensive agents are effective in reversing platelet activation in essential hypertension and, therefore, their use in pregnancy-induced hypertension may be beneficial in more ways than simply blood pressure reduction.     

Recent progress in the therapeutic management of pre-eclampsia

Pre-eclampsia is a pregnancy-specific syndrome of unknown aetiology, observed in 3 – 5% of all pregnancies, associated with pathological vascular lesions in multiple organs, activation of the coagulation system, and maternal multisystemic and fetal complications. Clinically, pre-eclampsia is characterised by the onset of hypertension, proteinuria and oedema, usually beginning in the third trimester. Conventionally, antihypertensive agents are the main pharmacological treatment. Recently, some studies have shown that the treatment of pre-eclampsia with antithrombin concentrate corrects the hypercoagulability and improves the fetal status and the perinatal outcome. No clear evidence supports the use of heparin. A conservative treatment of moderate- to- severe pre-eclampsia, based on the administration of antithrombin concentrate, may allow a significant prolongation of pregnancy and a better neonatal outcome, as well as fewer maternal complications.     

Recent progress in the therapeutic management of pre-eclampsia

Pre-eclampsia is a pregnancy-specific syndrome of unknown aetiology, observed in 3 - 5% of all pregnancies, associated with pathological vascular lesions in multiple organs, activation of the coagulation system, and maternal multisystemic and fetal complications. Clinically, pre-eclampsia is characterised by the onset of hypertension, proteinuria and oedema, usually beginning in the third trimester. Conventionally, antihypertensive agents are the main pharmacological treatment. Recently, some studies have shown that the treatment of pre-eclampsia with antithrombin concentrate corrects the hypercoagulability and improves the fetal status and the perinatal outcome. No clear evidence supports the use of heparin. A conservative treatment of moderate- to- severe pre-eclampsia, based on the administration of antithrombin concentrate, may allow a significant prolongation of pregnancy and a better neonatal outcome, as well as fewer maternal complications.     

Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in women of childbearing age: risks versus benefits

Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are effective and widely used antihypertensive drugs. Exposure to these agents is known to be harmful to the fetus in the second and third trimesters of pregnancy. Concerns have also been raised about the risk of congenital malformations if ACEIs or ARBs are taken during the first trimester of pregnancy. The evidence to date, however, is conflicting and observed malformations may be due to confounders such as undiagnosed diabetes or maternal obesity, other antihypertensive medications or the hypertension itself. Nonetheless, in women who become pregnant while taking an ACEI or ARB, the drug should be stopped as soon as possible. In women with chronic kidney disease and proteinuria, it may be appropriate to continue taking an ACEI or ARB until the pregnancy is confirmed because of the significant benefit to their kidney function and the lower fertility rate in these patients.     

Therapeutic management of type 1 diabetes before and during pregnancy

INTRODUCTION: Pregnancy increases the risks of adverse outcomes for mother and infant in women with type 1 diabetes. Obtaining and maintaining adequate glycemic control during pregnancy is crucial for optimizing outcomes. AREAS COVERED: The importance of prepregnancy planning and treatment during pregnancy is reviewed. The use of insulin analogues and antihypertensive drugs in diabetic pregnancy are in focus. The reader is presented with evidence discussing the importance of prepregnancy counseling and treatment during pregnancy in women with type 1 diabetes. EXPERT OPINION: Tight glycemic control before and during pregnancy is crucial and the prevalence of severe hypoglycemia during pregnancy needs to be reduced. Rapid-acting insulin analogues are regarded as safe to use in pregnancy and studies on long-acting insulin analogues are in the pipeline. Supplementation with folic acid may reduce the risk of malformations. Screening for diabetic retinopathy, diabetic nephropathy and thyroid dysfunction is important, and indications for antihypertensive treatment and treatment of thyroid dysfunction need to be in focus before and during pregnancy.     

Hypertension in pregnancy. Pathophysiology and management

Hypertension in pregnancy has implications for both maternal and fetal welfare. Extrapolation from concepts of mechanisms operating in hypertension in general to pregnancy-related hypertension is not justified. In the latter, the major features are a hyper-adrenergic state, plasma volume reduction and an increased systemic resistance. A reduction in uteroplacental perfusion may result from or may activate the mechanisms that elevate blood pressure. Humoral factors (e.g. hormonal attenuation of vascular reactivity) and prostacyclin deficiency may be central to the disordered physiology. Treatment of hypertension in pregnancy should aim at avoiding the vascular damage due to blood pressure elevation but not cause a reduction in uteroplacental perfusion. Unlike earlier antihypertensive regimens using centrally acting sympatholytics, adrenergic neuron blockers or diuretics, regimens using beta-blockers or combinations of beta-blockers with alpha-blockers or vasodilating agents such as hydralazine permit effective blood pressure control, even in severe hypertension, and pregnancy can often proceed until term or until fetal maturity is secured. Adverse effects on the fetus (growth retardation, cardiorespiratory depression, hypoglycaemia, hyperbilirubinaemia) formerly attributed to beta-blockers are more likely related to poorly controlled hypertension. Specific benefits of maternal beta-adrenoceptor blockade are suggested by evidence for prevention of proteinuric deterioration and a decrease in the incidence and severity of respiratory distress in premature infants. Hypertension in pregnancy still presents a formidable therapeutic challenge and requires comprehensive management with close monitoring of fetal welfare. The presence or development of proteinuria in a hypertensive pregnant woman implies a major increase in risk to the fetus and warrants immediate admission to hospital for specialist management.     

Economics of antihypertensive therapy in the elderly

Because of the high incidence of morbidity and mortality associated with hypertension in the elderly, the treatment of hypertension in this patient group must involve consideration of clinical, humanistic and economic outcomes. The most frequently used method of pharmacoeconomic analysis for antihypertensive therapy involves cost-effectiveness analysis, although several other methods are available. Current evidence reveals a trend toward cost effectiveness of antihypertensive treatment in elderly patients. However, these formal analyses are limited by the need for extrapolation of data regarding efficacy and level of risk from epidemiological and randomised trials, information which is often lacking. To incorporate economic factors into clinical decision making, other measures of economic impact should be explored. The economic impact of antihypertensive therapy is affected by the level of risk for the patient and the efficacy of the treatment. Data indicate that the risk of morbidity and mortality related to hypertension increases with age and that current antihypertensive drugs reduce this risk. When choosing an antihypertensive agent, the following parameters should be considered: acquisition cost, likelihood of adverse effects and other determinants of treatment adherence, and individual predictors of response. The economic outcomes will be maximised if prudent drug selection is supplemented by appropriate diagnostic and classification procedures and reduction of cardiovascular risk factors other than hypertension. The accumulation of data addressing the risks and benefits of therapy for the very old and the comparative efficacy of newer antihypertensive therapies will further clarify the decision-making process.     

妊娠期高血压疾病351例临床分析

目的:探讨妊娠期高血压疾病的治疗、预防效果.方法:对351例妊娠期高血压患者临床资料进行回顾性分析.结果:351例妊娠期高血压疾病患者350例痊愈、孕产妇死亡1例、死胎3例、死产2例.结论:早期发现、合理治疗,可有效预防妊娠期高血压疾病,明显降低孕产妇及围生儿死亡,减少并发症,保证孕产妇和胎儿健康.     

Atenolol in the treatment of pregnancy-induced hypertension.

1 The pharmacological properties of atenolol suggest its possible usefulness in pregnancy-induced hypertension. The pharmacokinetics of atenolol in the pregnant woman, concentrations in cord blood, and its effects on maternal blood pressure and the foetus, are evaluated. 2 We studied 13 pregnant women with hypertension, most of them uncontrolled on methyldopa. Whole blood concentrations and urinary excretion of the drug were measured over 24 h following a 100 mg dose. Effects on maternal blood pressure, pulse rate and foetal heart rate and cardiotocograph were compared for the 4 days before treatment and the first 4 days of treatment. The birth weights and Apgar scores of the babies were recorded. 2 The pharmacokinetics of atenolol (plasma half-life of about 8 h) in pregnant women do not differ from the findings in the non-pregnant. The levels of atenolol in the cord blood were confirmed as approximately equal to those in the maternal blood. 4 In the ten women in whom blood pressure was assessed a small significant fall in blood pressure was observed. 5 A 5% mean fall in foetal heart rate resulted but in one case was a rate below 120 beats/min recorded. There was no evidence of depression of the stress response of the foetal heart. Apgar scores 5 min post partum were satisfactory. 6 Atenolol appears to be safe for use in hypertensive pregnancies. Its effectiveness as an antihypertensive agent in pregnancy requires further controlled evaluation.     

妊娠期高血压疾病降压治疗的安全性探讨

目的对降压治疗妊娠期高血压疾病的安全性及有效性进行探讨。方法对2010年5月～2011年11月在本院就诊的100例妊娠期高血压患者的病例资料进行回顾性分析。通过随机方式将100例患者分为试验组和对照组,试验组患者40例,对照组患者60例。对照组接受传统常规降压药物进行治疗,试验组则通过静脉滴注和口服肼苯哒嗪及利血平等药物进行降压治疗。并对两组患者产后出血以及凝血功能情况进行及时的观察和记录。结果试验组40例患者经治疗后在产后出血以及凝血功能等方面均好于对照组,证明其治疗的安全性和有效性要好于传统方法。结论治疗妊娠期高血压疾病采用肼苯哒嗪、利血平等药物治疗效果较好,安全性高,值得应用。     

并发糖尿病的孕妇控制血糖对妊娠结局的影响

目的了解妊娠合并糖尿病的治疗与妊娠结局的关系。方法对200例妊娠合并糖尿病的产妇临床资料回顾性分析。将200例妊娠合并糖尿病的产妇根据血糖控制水平分为两组：A组为血糖控制达理想水平者,B组为血糖控制不理想及未控制者。收集并比较两组孕产妇及围产儿并发症情况。结果A组孕期血糖控制达理想水平的产妇妊高症、早产、剖宫产、新生儿低血糖、新生儿窒息、死胎的发生率均显著低于孕期血糖控制不理想及未知疗的发生率（P〈0．05）。结论妊娠合并糖尿病的良好控制血糖可降低产妇和围产儿并发症的发生率。