Antiplatelet agents for preventing pre-eclampsia and its complications

Abstract

Aspirin in the prevention of pre-eclampsia in high-risk women* Sir, We thank Dr Thornton for his interest in our article 'Aspirin in the prevention of pre-eclampsia in high-risk women' published in the January 2013 issue of BJOG. 1 He raises four points we would like to respond to: the strength of effect; sample size; exclusion of participants from the main analysis; and trial registration.Dr Thornton concludes the commentary by writing that the effect of aspirin we reported in the meta-analysis for women who also have abnormal uterine artery Doppler waveforms at 14 weeks of gestation differs little from its effect in other high-risk groups. We have difficulty in agreeing with this; in our opinion the risk ratio in our meta-analysis (RR 0.55; 95% CI 0.37-0.83) differs from those reported by the Cochrane review. 2,3 The differences are even better encapsulated by comparing the numbers needed to treat (NNTs). In our meta-analysis, the substantial reduction in risk together with the high initial risk (36%) resulted in an NNT of six for preventing preeclampsia, whereas the Cochrane review reported an NNT for pre-eclampsia of 19 for women at high risk (20% risk) and 119 for women at moderate risk (6%), and concluded that 'further information is required to assess which women are most likely to benefit, when treatment is best started, and at what dose'. The PARIS meta-analysis reported a 10% reduction and an NNT of 56 for women at high risk (18% risk) and 167 for women at moderate risk (6%).In other respects our study represents both the strengths and weaknesses of clinician-initiated trials. With limited funding, from non-commercial sources only, the participating clinicians in ten centres were able to screen 947 women whose history indicated an increased risk of pre-eclampsia, to find those whose uterine artery flow indicates a particularly high risk. As we discuss in the article, in hindsight the criterion chosen was too strict, and only 152 women could be randomised. Although Dr Thornton is correct in stating that 31 of these women discontinued the treatment for various reasons and were excluded from the main analysis, he seems to overlook our description of the intention-to-treat analysis of all randomised women (except those who had a miscarriage), which gave a similar result. We do agree about the shortcomings of the information included in the ISRCTN registration (www.controlled-trials.com/ISRCTN140 30412/), submitted by one member of the study team. For example, variables that were eventually listed in the outcomes section include predictor variables such as biochemical measurements during pregnancy. It should also be noted that the planned number of participants stated on the ISRCTN website, of 1000 women, refers to the women to be screened by Doppler ultrasound, and not those to be eventually randomised, as Dr Thornton stated in his commentary.In our conclusion we echoed the words of the Cochrane review that 'further information is required to assess which women are most likely to benefit', and proposed that...

Hypertensive Disorders of Pregnancy

“… In women considered to be at increased risk for pre-eclampsia on the basis of clinical factors mentioned above, both low dose aspirin and calcium (in the 43 setting of low calcium intake) are recommended for the prevention of preeclampsia (62)(63)(64).…”

Good clinical practice advice: First trimester screening and prevention of pre‐eclampsia in singleton pregnancy

“…[32][33][34] A meta-analysis including more than 26 000 women randomly assigned to low-dose (80-150 mg) aspirin or placebo/no treatment during pregnancy demonstrated that aspirin use was not associated with an increase in intraventricular hemorrhage or other neonatal bleeding. 35 On the basis of currently available evidence, it would be reasonable to continue with low-dose aspirin well into the third trimester of pregnancy.…”

Promoting Early Child Development With Interventions in Health and Nutrition: A Systematic Review

“…23 Reduce complications and neurologic damage from birth asphyxia and associated hypoxia 23 by preventing obstructed labor, being large for gestational age, or postmature births and providing emergency cesarean deliveries and effective resuscitation when required. Special care for preterm and SGA infants Enhance lung adaptation and neuroprotection for vulnerable fetuses before imminent preterm birth with antenatal corticosteroids 27 and magnesium sulfate. 28 Provide appropriate thermal care and support prevention of neonatal infection, especially in preterm neonates who are vulnerable.…”

“…43 Antiplatelet agents can prevent preeclampsia in at-risk women, improve infant growth and birth outcomes, and prevent motor deficits in infancy. 27 Infection and inflammation during pregnancy negatively influence fetal growth and development. Malaria prophylaxis; 44 -46 antibiotic treatment of asymptomatic bacteriuria, 47 a confirmed infection, 48 or preterm membrane rupture 49 ; and smoking cessation interventions 50 can all 5…”