Low-dose aspirin prophylaxis is currently the only intervention promoted by the American College of Obstetricians and Gynecologists, the Society for Maternal-Fetal Medicine, and the United States Preventive Services Task Force for the primary prevention of preeclampsia, a potentially devastating condition for both mother and fetus. The recommendation to prescribe low-dose aspirin to women at elevated risk of preeclampsia was first made by the USPSTF in 2014.(Henderson et al., 2014) And yet, more than six years later, there is little known about the impact of these guidelines on physician prescribing practices. The few studies that have been performed have analyzed only prescription rates among women with the well-recognized “high” risk factors. We are not aware of studies assessing prescribing practices for those women eligible for prophylaxis by multiple “moderate” risk factors. Our study provides insights into both provider familiarity with identifying women at increased risk for preeclampsia and knowledge of the recommendation to prescribe low-dose aspirin prophylaxis for such women.
One study that examined aspirin prescribing practices, performed by Banala et al., focused on the impact of the ACOG committee opinion recommending aspirin use among women with chronic hypertension.(Banala et al., 2020) The authors found that aspirin was offered to these women at a rate of 7% prior to the publication of the guideline and a rate of 70% following publication. Importantly, the authors found that outcomes of preeclampsia, small for gestational age neonate, and preterm birth were not affected by this change in prescribing practice.
A second study, by Boelig and colleagues, assessed provider adherence to aspirin recommendations before and after implementation of a preeclampsia risk assessment tool designed to help identify at-risk women.(Boelig et al., 2020) The study analyzed only prescribing rates for women with one or more “high” risk factor, and did not assess rates for women with multiple “moderate” risk factors. They found that prior to implementation of the screening tool 74% of eligible women were recommended aspirin prophylaxis, compared to 95% following this intervention.
Unlike prior analyses, our study considered both “high” and “moderate” risk factors when determining which patients ought to have been prescribed low-dose aspirin prophylaxis. We found that up to 69% of women deemed at-risk for preeclampsia by the ACOG, SMFM, and USPSTF guidelines were not given a recommendation for aspirin prophylaxis. Despite having the same risk for developing preeclampsia as women with a single “high” risk factor, women who qualified for aspirin prophylaxis solely on the basis of having multiple “moderate” risk factors were significantly less likely to be prescribed low-dose aspirin. But even among women with a single “high” risk factor, aspirin was prescribed at best 75% of the time. The improved prescription rate among women with “high” risk factors may be due to greater recognition of the association between those factors, such as history of preeclampsia or chronic hypertension, and the risk of developing preeclampsia. Another potential explanation is that these women are perhaps more likely to be referred to Maternal-Fetal Medicine specialists, who may be more familiar with the guidelines and more comfortable recommending aspirin therapy.
One curious finding that deserves additional explanation is the apparent reduction in risk of preeclampsia or gestational hypertension and of preeclampsia with severe features in women not taking aspirin. The authors feel that this is not so much a finding refuting the benefits of low-dose aspirin, but rather highlighting the observation that only the women at very highest risk of developing preeclampsia – those with two or more “high risk” factors – were the only ones reliably prescribed aspirin in our cohort. Thus, the finding is interesting and worth noting for completeness, however is not thought to be an accurate representation of the effectiveness of low-dose aspirin.
This study is limited by the retrospective nature of its analysis. Because of this, not all preeclampsia risk factors were able to be reliably assessed when classifying patients and determining their eligibility for aspirin prophylaxis. The impact of these missing risk factors can be estimated and accounted for by the observation that there were 16/669 “low risk” women who received an aspirin prescription. All “high-risk” risk factors were assessed in this group ultimately determined to not be candidates for aspirin prophylaxis by the factors examined in this study, so these sixteen women were either prescribed low-dose aspiring for indications beyond the specific recommendations of ACOG and the USPSTF, or they could theoretically have been identified through possessing two or more of the “moderate-risk” risk factors unable to be assessed in this study. Even if all sixteen of these women did truly meet criteria for low dose aspirin, the key finding of this study that women with multiple “moderate-risk” risk factors are often overlooked as candidates for preeclampsia prophylaxis would remain as the proportion of women without any “high-risk” risk factors who received an indicated low dose aspirin prescription would still be only 26/195 (13%) versus 82/122 (67%) among women with at least one “high-risk” risk factor. Thus, we believe the results of this study are still meaningful because expanding the review to include additional risk factors would only increase the number of eligible women, and thus would likely only enhance our current findings.
These findings indicate a need for further education among generalist obstetrician-gynecologists about screening women for risk factors associated with preeclampsia, with a focus on identifying women with multiple “moderate” risk factors. Prospective studies specifically designed to assess aspirin utilization practices are needed in order to completely define the problem and identify the most critical areas for improvement. Future studies that seek to understand factors motivating prescriber practices will also be important in order to inform interventions aimed at increasing uptake of low-dose aspirin for preeclampsia prophylaxis. Finally, it is critical to study the impact of these efforts on the outcome of interest—preeclampsia and its sequelae—to determine the clinical consequences of fully implementing these guidelines and to assess real-world efficacy of preeclampsia risk factor screening and low-dose aspirin prophylaxis.