Does low-dose aspirin initiated before 11 weeks' gestation reduce the rate of preeclampsia?

Abstract

OBJECTIVE: DATA: Pre-conception or early administration of low-dose aspirin might improve endometrial growth, placental vascularization and organogenesis. Most studies have evaluated the potential benefit of pre-conception or early administration of low-dose aspirin in women with a history of recurrent pregnancy loss, women who have undergone in vitro fertilization or women with thrombophilia or antiphospholipid syndrome. These women are at an increased risk of placenta-associated complications of pregnancy, including preeclampsia, preterm delivery and fetal growth restriction.

STUDY: We performed a systematic review and meta-analysis to evaluate the effect of low-dose aspirin initiated at <11 weeks' gestation on the risk of preeclampsia, gestational hypertension, or any hypertensive disorder of pregnancy. Secondary outcomes included preterm delivery at <37 weeks' gestation and fetal growth restriction.

STUDY APPRAISAL AND SYNTHESIS METHODS: We searched in MEDLINE via PubMed, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), ClinicalTrials.Gov and the World Health Organization International Clinical Trials Registry Platform (WHO-ICTRP) from 1985 to November 2018. Entry criteria were randomized controlled trials evaluating the effect of aspirin administered at <11 weeks' gestation in preventing preeclampsia and/or hypertensive disorders in pregnancy or improving pregnancy outcomes in women with recurrent miscarriage as compared to placebo or no-treatment and outcome data available or provided by authors for >85% of the study population. Relative risks (RR) with 95% confidence intervals (CI) were calculated for each study and pooled for global analysis as the effect measure. We assessed statistical heterogeneity in each meta-analysis using the Chi2 statistics, I2 and Tau2. Heterogeneity was considered substantial if an I2 was greater than 50% and either the Tau2 was greater than zero, or there was a low P-value (<0.10) in the Chi2 test for heterogeneity. Random-effects meta-analysis, weighted by the size of the studies, was performed to produce an overall summary on aspirin effect for each outcome. Sensitivity analysis by sequential omission of each individual study and by fixed-effects model was performed. Publication bias was not assessed due to the small number of included studies. Statistical analysis was performed using Stata release 14.0 (StataCorp, College Station, TX).

RESULTS: The entry criteria were fulfilled by eight randomized controlled trials on a combined total of 1,426 participants. Low-dose aspirin initiated at <11 weeks' gestation was associated with a non-significant reduction in the risk of preeclampsia (RR 0.52; 95% CI: 0.23-1.17, P=0.115), gestational hypertension (RR 0.49; 95% CI: 0.20-1.21; P=0.121) and any hypertensive disorder of pregnancy (RR 0.59; 95% CI 0.33-1.04, P=0.067). Early low-dose aspirin reduced the risk of preterm delivery (RR 0.52; 95% CI: 0.27-0.97, p=0.040) but had no impact on the risk of fetal growth restriction (RR 1.10; 95% CI 0.58-2.07, P=0.775). Except for preterm delivery and any hypertensive disorder of pregnancy, sensitivity analysis demonstrated similar observations; therefore confirming the robustness of the analysis.

CONCLUSION: The administration of low-dose aspirin at <11 weeks' gestation in high risk women does not decrease the risk of preeclampsia, gestational hypertension, any hypertensive disorder of pregnancy and fetal growth restriction. However, it might reduce the risk of preterm delivery. Larger randomized controlled trials will be required to substantiate the findings.