Prevention of pre-eclampsia by early antiplatelet therapy. A randomized controlled trial of low-dose aspirin in women at risk from pre-eclampsia. Low-dose aspirin therapy to prevent preeclampsia. Usefulness of aspirin therapy in high-risk pregnant women with abnormal uterine artery Doppler ultrasound at 14-16 weeks pregnancy: randomized controlled clinical trial. A small randomised trial of low-dose aspirin in women at high risk of pre-eclampsia. ECPPA: randomised trial of low dose aspirin for the prevention of maternal and fetal complications in high risk pregnant women. ECPPA (Estudo Colaborativo para Prevenção da Pré-eclampsia com Aspirina) Collaborative Group. Prevention of preeclampsia with low-dose aspirin in healthy, nulliparous pregnant women. The National Institute of Child Health and Human Development Network of Maternal-Fetal Medicine Units. Aspirin (100 mg) used for prevention of pre-eclampsia in nulliparous women: the Essai Régional Aspirine Mère-Enfant study (Part 1). A prospective randomized placebo-controlled trial of low-dose aspirin for prevention of intra-uterine growth retardation.
102 patients at high risk of pre-eclampsia and/or fetal growth retardation were randomly allocated to treatment with 300 mg dipyridamole and 150 mg aspirin daily from 3 months' gestation onwards (group A) or to the control group (group B, no treatment). Group A was twice as likely as group B to have a normal pregnancy. Pre-eclampsia occurred in 6 patients in group B and none in group A. Major complications (fetal death or severe growth retardation) occurred in 9 patients in group B and none in group A. Platelet count and plasma volume were significantly higher in group A than in group B throughout pregnancy. The treatment did not produce serious adverse effects. Antiplatelet therapy given early in pregnancy to high-risk patients may thus protect against pre-eclampsia and fetal growth retardation. To determine whether low-dose aspirin reduces the incidence of pre-eclampsia, reduces perinatal mortality and improves birth weights in pregnant women considered at high risk of developing pre-eclampsia.
                Two-hundred fifty subjects were recruited from the antenatal clinics at Harare Central Hospital with either a previous history of pregnancy-induced hypertension or pre-existing chronic hypertension and were randomized to receive either 75 mg of aspirin (ASA) or placebo (PLA).
                Two-hundred thirty subjects (ASA, n = 113; PLA, n = 117) completed the trial. The odds of developing pre-eclampsia for those on aspirin was 0.72 times those on placebo (95% CI, 0.34-1.52). The mean birth weight was 2774 g for those on aspirin and 2694 g for those on placebo (P = 0.80). No difference was noted in the perinatal deaths (OR = 0.38; 95% CI, 0.10-1.20).
                Prophylactic use of aspirin was not associated with a significant effect on the major pregnancy outcomes assessed in this study. Our aim was to test the hypothesis that acetylsalicylate (aspirin) treatment reduces the incidence or severity of pregnancy-associated hypertension.
                Patients were nulliparous, healthy, and with a singleton gestation at between 20 and 22 weeks' gestation. A sample size of 600 patients was calculated on the basis of p < or = 0.05 and 90% power of observation. A 2-week placebo-controlled "run-in" was used to select compliant patients. Randomization occurred at 24 weeks, with 60 mg of aspirin or placebo treatment from randomization to delivery.
                Follow-up was maintained on 99% of the patients. The randomized patients had a 94% pill compliance index. At randomization, serum thromboxane medians were similar in both groups. Thromboxane B2 levels in the aspirin group decreased significantly from baseline at 29 to 31 weeks, 34 to 36 weeks, and at delivery as compared with an overall increase in the placebo group. Preeclampsia developed in five of 302 women (1.7%) who received aspirin versus 17 of 302 (5.6%) who received the placebo (p = 0.009). Preeclampsia was severe in one aspirin and in six placebo recipients (p = 0.06).
                Daily ingestion of 60 mg of aspirin beginning at 24 weeks' gestation significantly reduced the occurrence of preeclampsia. To assess the effectiveness of low-dose aspirin in the prevention of preeclampsia and intrauterine growth restriction (IUGR) in high-risk pregnant women with abnormal findings at uterine artery Doppler velocimetry performed at 14-16 weeks.
                Randomized controlled clinical trial.
                Department of Obstetrics and Gynecology, Faculty of Medicine, Cairo University, Egypt.
                The trial enrolled 139 women at risk of preeclampsia or IUGR, with abnormal uterine artery Doppler findings that included the presence of unilateral or bilateral diastolic notch, high resistance index (RI), or high pulsatility index (PI) at 14-16 weeks of gestation. The women were randomly allocated into two groups, one receiving aspirin since admission to hospital (n=74) and the other serving as control (n=65). All women were followed up until delivery to assess maternal and perinatal outcomes. T-test was used for comparison of quantitative variables, and categorical variables were compared by chi2 test. OUTCOME CRITERIA: Development of mild or severe preeclampsia, time of onset of preeclampsia, preterm delivery, and the development of IUGR.
                Preeclampsia developed in 35% of women receiving aspirin and 62% of women in the control group (P=0.003), with severe preeclampsia developing in 8% and 23% of women (P=0.215), respectively. Preeclampsia before 37 weeks of gestation was recorded in only 4% of women receiving aspirin as opposed to 83% of controls (P<0.001). In the group of women receiving aspirin, 19% of newborns suffered from IUGR as opposed to 32%of newborns in the control group (P=0.106). There was no significant difference between the two groups in the rate of preterm delivery (P=0.080), mode of delivery (P=0.971), Apgar score <5 after one minute (P=0.273) and after 5 minutes (P=0.941), maternal or neonatal bleeding (P=0.948), and neonatal birth weight (P=0.399).
                Low-dose aspirin administered as early as 14-16 weeks of gestation to pregnant women at high risk of preeclampsia with abnormal uterine Doppler findings may reduce or modify the course of severe preeclampsia. Its effects on the prevention of IUGR need further evaluation. To determine if aspirin (ASA) therapy reduces the incidence of pre-eclampsia in women at high risk of this condition.
                Randomised clinical trial. We recruited pregnant women with gestational age at randomisation <14 weeks, who satisfied the following criteria: chronic hypertension, history of severe pre-eclampsia or eclampsia or intrauterine growth retardation (IUGR) or intrauterine foetal death. Nineteen women in the no-treatment group and 16 in the ASA group were successfully followed up.
                The mean birthweight was higher in the ASA group than in the no-treatment group (2790 g (S.D. 340 g) versus 2616 g (S.D. 779 g)), but the difference was not statistically significant. We found no statistically significant differences between the groups in the proportion of infants with birthweight below 2500 g (13.3% versus 29.4%) and the number of cases with pregnancy-induced hypertension (PIH)/pre-eclampsia (31.3% versus 36.8%).
                These limited data give some support to the potential favourable effect of early treatment with ASA in pregnant women at risk of PIH and IUGR. To determine the effectiveness of low dose aspirin in women at high risk of adverse outcomes associated with pre-eclampsia.
                A collaborative randomised trial comparing the effects of low dose aspirin (60 mg) with placebo on pre-eclampsia and other materno-fetal complications associated with hypertension.
                Twelve teaching maternity hospitals and 182 obstetricians' offices in Brazil.
                One thousand and nine women considered to be at high risk for the development of pre-eclampsia, or its complications, entered the study between 12 and 32 weeks of gestation. They were randomly allocated to receive aspirin (498 women) or placebo (511 women) until delivery, and follow up was obtained for 96%.
                There were no significant differences between the treatment groups in the incidence of proteinuric pre-eclampsia (6.7% aspirin-allocated compared with 6.0% placebo-allocated women), of preterm delivery (22.3% compared with 26.1%), of intrauterine growth retardation (8.5% compared with 10.1%), or of stillbirth and neonatal death (7.3% compared with 6.0%), nor were there significant differences in the incidence of proteinuric pre-eclampsia in any subgroup of women studied, including those who had systolic blood pressures of 120 mmHg or above at entry (8.5% compared with 7.3%) or those who were chronically hypertensive (10.0% compared with 7.1%). Aspirin was not associated with a significant excess of maternal or fetal bleeding.
                The results of this study do not support the routine prophylactic administration of low dose aspirin in pregnancy to any category of high risk women (even those who have chronic hypertension or who are considered to be especially liable to early onset pre-eclampsia). Although low-dose aspirin has been reported to reduce the incidence of preeclampsia among women at high risk for this complication, its efficacy and safety in healthy, nulliparous pregnant women are not known.
                We studied 3135 normotensive nulliparous women who were 13 to 26 weeks pregnant to determine whether treatment with aspirin reduced the incidence of preeclampsia. Of this group, 1570 women received 60 mg of aspirin per day and 1565 received placebo for the remainder of their pregnancies. We also evaluated the effect of aspirin on maternal and neonatal morbidity.
                Of the original group of 3135 women, 2985 (95 percent) were followed throughout pregnancy and the immediate puerperium. The incidence of preeclampsia was lower in the aspirin group (69 of 1485 women [4.6 percent]) than in the placebo group (94 of 1500 women [6.3 percent]) (relative risk, 0.7; 95 percent confidence interval, 0.6 to 1.0; P = 0.05), whereas the incidence of gestational hypertension was 6.7 and 5.9 percent, respectively. There were no significant differences in the infants' birth weight or in the incidence of fetal growth retardation, postpartum hemorrhage, or neonatal bleeding problems between the two groups. Subgroup analysis showed that preeclampsia occurred primarily in women whose initial systolic blood pressure was 120 to 134 mm Hg (incidence among such women, 5.6 percent in the aspirin group vs. 11.9 percent in the placebo group; P = 0.01). The incidence of abruptio placentae was greater among the women who received aspirin (11 women, vs. 2 in the placebo group; P = 0.01).
                Low-dose aspirin decreases the incidence of preeclampsia among nulliparous women, primarily through its effect in those who have elevated systolic blood pressure initially. This treatment does not decrease perinatal morbidity but increases the risk of abruptio placentae. To reduce the incidence of pre-eclampsia in nulliparous women, in accordance with the suggestion of a recent meta-analysis that low dose aspirin might decrease this incidence by more than half if used early enough in and at a sufficient dose during pregnancy (more than 75 mg).
                Multicentre randomised double-blinded placebo-controlled trial.
                Twenty eight centres in Northern of France and one in Belgium.
                Three thousand and two hundred ninety-four nulliparous women recruited between 14 and 20 weeks.
                Randomisation to either 100 mg aspirin or placebo daily from inclusion through 34 weeks.
                Preeclampsia was defined as hypertension (> or =140 and or 90 mmHg) associated with proteinuria (> or =0.5 g/L).
                The aspirin (n = 1644) and placebo (n = 1650) groups did not differ significantly in the mothers' incidence of pre-eclampsia (28 of 1632 [1.7%] vs 26 of 1637 [1.6%]; relative risk, RR, 1.08, 95% CI 0.64-1.83), hypertension, HELLP syndrome or placental abruption, or in the children's incidence of perinatal deaths or birthweight below the 10th centile. The incidence of babies with birthweight below the third centile was significantly higher in the aspirin group, with no explanation. The incidence of maternal side effects was higher in the aspirin group, principally because of a significantly higher rate of haemorrhage.
                Aspirin at a dose of 100 mg does not reduce the incidence of pre-eclampsia in nulliparous women. Aspirin (100 mg) is associated with an increase in bleeding complications. To evaluate the effects of low-dose aspirin on placental circulation and on the prevention of intrauterine growth retardation (IUGR).
                We conducted a prospective randomized, double blind, controlled clinical trial in 84 pregnant women (mainly nulliparous women) at high risk of IUGR. From the 28th-30th week of gestation onward, low dose aspirin (75 mg daily, study group, n = 40) or placebo (control group, n = 44) was given consecutively for 6 to 8 weeks. Pulse-wave umbilical artery Doppler velocimetry was measured before and after drug use.
                The mean value of systolic/diastolic ratio of umbilical artery flow velocity waveforms in the study group was significantly lower than that in the control group after drug use, but there was no difference between the two groups before drug use. The incidences of IRGR and preeclampsia in the study group (7.5% and 10.0% respectively) were significantly lower than those in the control group (27.3% of both). No adverse effects of low dose aspirin on both mother and fetus were observed.
                Low dose aspirin administration (75 mg daily) beginning at the early stage of third trimester may improve the fetoplacental circulation, and thus prevent IUGR and/or preeclampsia effectively.
Antiplatelet agents, largely low-dose aspirin, have moderate benefits when used for prevention of pre-eclampsia and its consequences. Further information is required to assess which women are most likely to benefit, when treatment is best started, and at what dose.
[Note: The 16 citations in the awaiting classification section of the review may alter the conclusions of the review once assessed.]