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      Aspirin versus Placebo in Pregnancies at High Risk for Preterm Preeclampsia

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          Most cited references 23

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          Hypertension in pregnancy. Report of the American College of Obstetricians and Gynecologists’ Task Force on Hypertension in Pregnancy.

           ,   (2013)
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            The global impact of pre-eclampsia and eclampsia.

             Lelia Duley (2009)
            Over half a million women die each year from pregnancy related causes, 99% in low and middle income countries. In many low income countries, complications of pregnancy and childbirth are the leading cause of death amongst women of reproductive years. The Millennium Development Goals have placed maternal health at the core of the struggle against poverty and inequality, as a matter of human rights. Ten percent of women have high blood pressure during pregnancy, and preeclampsia complicates 2% to 8% of pregnancies. Preeclampsia can lead to problems in the liver, kidneys, brain and the clotting system. Risks for the baby include poor growth and prematurity. Although outcome is often good, preeclampsia can be devastating and life threatening. Overall, 10% to 15% of direct maternal deaths are associated with preeclampsia and eclampsia. Where maternal mortality is high, most of deaths are attributable to eclampsia, rather than preeclampsia. Perinatal mortality is high following preeclampsia, and even higher following eclampsia. In low and middle income countries many public hospitals have limited access to neonatal intensive care, and so the mortality and morbidity is likely to be considerably higher than in settings where such facilities are available. The only interventions shown to prevent preeclampsia are antiplatelet agents, primarily low dose aspirin, and calcium supplementation. Treatment is largely symptomatic. Antihypertensive drugs are mandatory for very high blood pressure. Plasma volume expansion, corticosteroids and antioxidant agents have been suggested for severe preeclampsia, but trials to date have not shown benefit. Optimal timing for delivery of women with severe preeclampsia before 32 to 34 weeks' gestation remains a dilemma. Magnesium sulfate can prevent and control eclamptic seizures. For preeclampsia, it more than halves the risk of eclampsia (number needed to treat 100, 95% confidence interval 50 to 100) and probably reduces the risk of maternal death. A quarter of women have side effects, primarily flushing. With clinical monitoring serious adverse effects are rare. Magnesium sulfate is the anticonvulsant of choice for treating eclampsia; more effective than diazepam, phenytoin, or lytic cocktail. Although it is a low cost effective treatment, magnesium sulfate is not available in all low and middle income countries; scaling up its use for eclampsia and severe preeclampsia will contribute to achieving the Millennium Development Goals.
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              Prevention of preeclampsia and intrauterine growth restriction with aspirin started in early pregnancy: a meta-analysis.

              To estimate the effect of low-dose aspirin started in early pregnancy on the incidence of preeclampsia and intrauterine growth restriction (IUGR). A systematic review and meta-analysis were performed through electronic database searches (PubMed, Cochrane, Embase). Randomized controlled trials of pregnant women at risk of preeclampsia who were assigned to receive aspirin or placebo (or no treatment) were reviewed. Secondary outcomes included IUGR, severe preeclampsia and preterm birth. The effect of aspirin was analyzed as a function of gestational age at initiation of the intervention (16 weeks of gestation or less, 16 weeks of gestation or more). Thirty-four randomized controlled trials met the inclusion criteria, including 27 studies (11,348 women) with follow-up for the outcome of preeclampsia. Low-dose aspirin started at 16 weeks or earlier was associated with a significant reduction in preeclampsia (relative risk [RR] 0.47, 95% confidence interval [CI] 0.34-0.65, prevalence in 9.3% treated compared with 21.3% control) and IUGR (RR 0.44, 95% CI 0.30-0.65, 7% treated compared with 16.3% control), whereas aspirin started after 16 weeks was not (preeclampsia: RR 0.81, 95% CI 0.63-1.03, prevalence in 7.3% treated compared with 8.1% control; IUGR: RR 0.98, 95% CI 0.87-1.10, 10.3% treated compared with 10.5% control). Low-dose aspirin started at 16 weeks or earlier also was associated with a reduction in severe preeclampsia (RR 0.09, 95% CI 0.02-0.37, 0.7% treated compared with 15.0% control), gestational hypertension (RR 0.62, 95% CI 0.45-0.84, 16.7% treated compared with 29.7% control), and preterm birth (RR 0.22, 95% CI 0.10-0.49, 3.5% treated compared with 16.9% control). Of note, all studies for which aspirin had been started at 16 weeks or earlier included women identified to be at moderate or high risk for preeclampsia. Low-dose aspirin initiated in early pregnancy is an efficient method of reducing the incidence of preeclampsia and IUGR.
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                Author and article information

                Journal
                New England Journal of Medicine
                N Engl J Med
                New England Journal of Medicine (NEJM/MMS)
                0028-4793
                1533-4406
                August 17 2017
                August 17 2017
                : 377
                : 7
                : 613-622
                10.1056/NEJMoa1704559
                © 2017
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