Low-Dose Aspirin for the Prevention of Superimposed Preeclampsia in Women With Chronic Hypertension: A Systematic Review and Meta-analysis

ABSTRACT Women with chronic hypertension are at increased risk for the development of preeclampsia during pregnancy. Low-dose aspirin treatment has been studied in the context of preeclampsia prevention, but there have been conflicting results among different populations. Some reasons for this are heterogeneous treatment regimens including timing, dosage, and even target outcomes. Among populations where there are limited data on the effect of low-dose aspirin on preeclampsia are women with chronic hypertension. This study is a systematic review and meta-analysis designed to analyze the use of low-dose aspirin during pregnancy and to assess whether the treatment reduces the risk of superimposed preeclampsia in women with chronic hypertension. It also aimed to secondarily assess related outcomes such as small for gestational age (SGA), preterm birth, and perinatal mortality. Systematic searches and assessment isolated 9 articles for final analysis. Six of these were randomized controlled trials, and 3 were retrospective cohort studies. Four studies focused on populations of only women with chronic hypertension, and the others included women with several different risk factors for preeclampsia. The retrospective studies and one of the randomized controlled trials compared aspirin treatment with no treatment, and the others compared with a placebo group; all studies used a dose of aspirin between 60 and 150 mg daily. No studies were excluded from the analysis based on risk of bias, as none were determined to be “critical” or “high” risk, although risk of bias was determined to be a contributing factor to low-quality data. Final analysis included a pooled sample size of 1078 individuals with chronic hypertension on low-dose aspirin, compared with 1072 women with chronic hypertension in control groups. This analysis did not find a decreased odds of superimposed preeclampsia in either randomized controlled trials (odds ratio [OR], 0.83; 95% confidence interval [CI], 0.55–1.25) or observational studies (OR, 1.21; 95% CI, 0.78–1.87). No significant differences were found with aspirin treatment, possibly due to risk of bias, heterogeneity, and imprecision. These findings held true when analyzed based on the timing of aspirin treatment induction (before or after 20 weeks' gestation), still finding no difference in the rate of superimposed preeclampsia. Low-dose aspirin treatment did reduce the odds of preterm birth according to a pooled analysis of 2 randomized controlled trials (OR, 0.62; 95% CI, 0.45–0.89). However, neither SGA nor perinatal mortality was shown to be significantly different in a pooled analysis of the studies that reported this outcome. Although these findings did not show statistical significance in reduction of preeclampsia in women with chronic hypertension due to aspirin treatment, the data are suggestive of benefit; many individuals in each study were lost to follow-up, and thus, the results of the analysis are different than they might have been with greater retention. The results from the observational studies show that low-dose aspirin treatment may statistically increase the likelihood of superimposed preeclampsia, but there is a high level of uncertainty associated with these results. They add to the conflicting findings previously present on this topic; more research is necessary with larger and less heterogeneous samples to clarify the association. The findings from this study contradict previous results in samples that include individuals with a variety of risk factors for preeclampsia, but they are consistent with previous research including only individuals with chronic hypertension. This study was limited by the quality of evidence due to heterogeneity and bias but should prompt further research regarding low-dose aspirin treatment in populations with chronic hypertension.