Aspirin For Prevention Of Preeclampsia Research Articles

Editorial summary of symposium on hypertensive disorders of pregnancy

Hypertensive disorders of pregnancy, particularly the preeclampsia/eclampsia syndrome, remain the leading causes of worldwide pregnancy-related maternal and neonatal mortality and morbidity. This group of conditions are a 'riddle wrapped in a mystery inside an enigma' to quote Winston Churchill. We are fortunate to have contributions from leading clinical experts who have devoted many years of their professional careers attempting to solve this conundrum. Dr Jack Moodley has provided us with a perspective on clinical management in underresourced countries. Referral to experts, aggressive treatment of hypertension and use of magnesium sulfate improves care. Dr Shennan focuses on the assessment of risk, close antenatal surveillance and timely delivery. Dr Uzan continues to champion the use of aspirin for prevention of preeclampsia, even though the evidence is contradictory. Dr Sibai addresses the lack of evidence for calcium, vitamin C and E in prevention of preeclampsia. Dr Von Dadelszen is developing a new paradigm for the classification of these disorders and emphasizes the importance of evidence-based intervention. Evidence suggests that treatment of severe hypertension, seizure prophylaxis with magnesium sulfate, and management by experienced healthcare professionals will improve maternal, fetal and neonatal outcomes. Well designed studies will lead to evidence-based improvement in caring for mothers and babies worldwide.

Aspirin for prevention of preeclampsia in women with historical risk factors: a systematic review.

To examine the effectiveness of aspirin in preventing perinatal death and preeclampsia in women with predisposing historical risk factors, such as previous history of preeclampsia, chronic hypertension, diabetes, and renal disease. Searches were conductes in Medline, Embase, Cochrane Library, National Research Register, SCISEARCH, AND ISI Conference Proceedings without any language restrictions, using the following medical subject headings and text words: "aspirin," "antiplatelet*," "salicyl*," "acetylsalicyl*," "platelet aggregation inhibitors," "pre-eclamp*," "preeclamp*," and "hypertens*. We included all randomized trials that evaluated the effectiveness of aspirin compared with placebo or no treatment in women with predisposing historical risk factors and reported clinically relevant perinatal or maternal outcomes. Study selection, quality appraisal, and data extractions were performed independently and in duplicate.We identified 14 relevant trials, including a total of 12,416 women. Meta-analysis showed a significant benefit of aspirin therapy in reducing perinatal death (odds ratio [OR] 0.79, 95% confidence interval [CI] 0.64, 0.96) and preeclampsia (OR 0.86, 95% CI 0.76, 0.96). Aspirin was also associated with a reduction in rates of spontaneous preterm birth (OR 0.86, 95% CI 0.79, 0.94), and an increase of 215 g in mean birth weight (weighted mean difference 215, 95% CI 90, 341). There was no increase in the risk of placental abruption with aspirin (OR 0.98, 95% CI 0.79, 1.21). Funnel plot analysis indicated that publication and related biases were unlikely (Egger test, P =.84). Aspirin reduces the risk of perinatal death and preeclampsia in women with historical risk factors. Given the importance of these outcomes and the safety and low cost of aspirin, aspirin therapy should be considered in women with historical risk factors.

Aspirin for Prevention of Preeclampsia in Women With Historical Risk Factors

Aspirin for Prevention of Preeclampsia in Women With Historical Risk Factors

Perinatal outcome in women with recurrent preeclampsia compared with women who develop preeclampsia as nulliparas

OBJECTIVE: To compare the rates and perinatal outcome in women who experienced preeclampsia in a previous pregnancy to those in women who developed preeclampsia as nulliparas. STUDY DESIGN: This is a secondary analysis of data from 2 separate multi-center trials of aspirin for prevention of preeclampsia. Women who had preeclampsia in a previous pregnancy (n = 598) were compared with nulliparous women (n = 2934). Outcome variables were rates of preeclampsia, preterm delivery at <37 and <35 weeks of gestation, small-for-gestational-age infant, abruptio placentae, and perinatal death. Data were compared by using chi-square analysis and Wilcoxon rank sum test. RESULTS: The rates of preeclampsia and of severe preeclampsia were significantly higher in the previous preeclamptic group as compared to the nulliparous group (17.9% vs 5.3%, P <.0001, and 7.5% vs. 2.4%,P <.0001, respectively). Women who had recurrent preeclampsia experienced more preterm deliveries before 37 and 35 weeks of gestation than nulliparous women who developed preeclampsia. In addition, among women who developed severe preeclampsia, those with recurrent preeclampsia had higher rates of preterm delivery both before 37 weeks (67% vs 33%, P =.0004) and before 35 weeks of gestation (36% vs 19%,P =.041), and higher rates of abruptio placentae (6.7% vs 1.5%) and fetal death (6.7% vs 1.4%) than did nulliparous women. CONCLUSION: Compared to nulliparous women, women with preeclampsia in a previous pregnancy had significantly higher rates of preeclampsia and adverse perinatal outcomes associated with preterm delivery as a result of preeclampsia. (Am J Obstet Gynecol 2002;186:422-6.)

Hypertensive disorders in twin versus singleton gestations

Objective: This study was undertaken to compare rates and severity of gestational hypertension and preeclampsia, as well as perinatal outcomes when these complications develop, between women with twin gestations and those with singleton gestations. Study Design: This was a secondary analysis of prospective data from women with twin (n = 684) and singleton (n = 2946) gestations enrolled in two separate multicenter trials of low-dose aspirin for prevention of preeclampsia. End points were rates of gestational hypertension, rates of preeclampsia, and perinatal outcomes among women with hypertensive disorders. Results: Women with twin gestations had higher rates of gestational hypertension (relative risk, 2.04; 95% confidence interval, 1.60-2.59) and preeclampsia (relative risk, 2.62; 95% confidence interval, 2.03-3.38). In addition, women with gestational hypertension during twin gestations had higher rates of preterm delivery at both <37 weeks’ gestation (51.1% vs 5.9%; P < .0001) and <35 weeks’ gestation (18.2% vs 1.6%; P < .0001) and also had higher rates of small-for-gestational-age infants (14.8% vs 7.0%; P = .04). Moreover, when outcomes associated with preeclampsia were compared, women with twin gestations had significantly higher rates of preterm delivery at <37 weeks’ gestation (66.7% vs 19.6%; P < .0001), preterm delivery at <35 weeks’ gestation (34.5% vs 6.3%; P < .0001), and abruptio placentae (4.7% vs 0.7%; P = .07). In contrast, among women with twin pregnancies, those who remained normotensive had more adverse neonatal outcomes than did those in whom hypertensive complications developed. Conclusions: Rates for both gestational hypertension and preeclampsia are significantly higher among women with twin gestations than among those with singleton gestations. Moreover, women with twin pregnancies and hypertensive complications have higher rates of adverse neonatal outcomes than do those with singleton pregnancies. (Am J Obstet Gynecol 2000;182:938-42.)

Randomised controlled trial of ketanserin and aspirin in prevention of pre-eclampsia

Pre-eclampsia is associated with extensive endothelial-cell damage and platelet activation, resulting in lower production of vasodilator prostaglandins and increased release of the vasoconstrictors thromboxane A2 and serotonin. Damage to endothelial-cell serotonin-1 receptors leaves vasoconstriction and platelet aggregation mediated by serotonin-2 receptors unopposed. We investigated the role of ketanserin, a selective serotonin-2-receptor antagonist, in lowering the rate of pre-eclampsia among pregnant women with mild to moderate hypertension. We recruited 138 pregnant women into a double-blind, randomised, placebo-controlled trial. They had diastolic blood pressure persistently more than 80 mm Hg before 20 weeks' gestation. 69 women received ketanserin and 69 received placebo. Both groups also received aspirin. Patients were initially given two tablets daily, increased to four tablets daily in diastolic blood pressure was more than 90 mm Hg. Primary outcomes were the development of pre-eclampsia and severe hypertension, and perinatal mortality. There were significantly fewer cases of pre-eclampsia (two vs 13; relative risk 0.15 [95% CI 0.04-0.66], p = 0.006) and severe hypertension (six vs 17; p = 0.02) in the ketanserin than in the placebo group. There was also a trend towards less perinatal mortality (one vs six deaths) but this was not significant (p = 0.28). Rates of abruptio placentae and pre-eclampsia before 34 weeks' gestation were lower in the ketanserin group, and mean birthweight was significantly higher. We found an association between the addition of ketanserin to aspirin and a decrease in the number of cases of pre-eclampsia and severe hypertension, as well as improved pregnancy outcome among patients with mild to moderate midtrimester hypertension.

The Predictive Value of Umbilical Artery Doppler Studies for Preeclampsia or Fetal Growth Retardation in a Preeclampsia Prevention Trial

To determine the clinical utility of longitudinal Doppler umbilical artery systolic-diastolic ratios (S/D) to predict the occurrence of either preeclampsia or fetal growth retardation (FGR) in a low-risk population. Healthy nulliparas with singleton gestations were enrolled in a double-blind trial of low-dose (60 mg) aspirin for preeclampsia prevention. Treatment was initiated at 24 weeks and continued until delivery. Continuous-wave Doppler studies were scheduled before assignment to treatment and at 27-31, 32-36, and 37-42 weeks. Preeclampsia was defined as a persistent diastolic blood pressure of at least 90 mmHg with proteinuria, and FGR was defined as birth weight below the tenth percentile. Doppler values were considered abnormal if they exceeded the 90th percentile for the gestational age range in the study population. Summary predictive values were computed for the abnormal S/D at each gestational age interval. To assess the potential effect of the administration of low-dose aspirin, logistic regression was used to model the relation between the Doppler indices, aspirin use, and these abnormal pregnancy outcomes. A total of 1665 Doppler examinations were performed on 565 women. Forty-four fetuses developed FGR and 21 women were diagnosed with preeclampsia. The positive predictive values of an abnormal S/D for the subsequent development of FGR were 13-17% across the gestational age ranges studied, and the positive predictive values for preeclampsia were 0-5%. Aspirin treatment did not affect the relation between the Doppler indices and these outcomes in the logistic regression model. Elevated umbilical artery S/D is not a clinically useful predictor of either FGR or preeclampsia in a low-risk population.