A study published in JAMA Network Open has raised questions about the clinical utility of the U.S. Preventive Services Task Force (USPSTF) guidelines for assessing preeclampsia risk and recommending aspirin prophylaxis (AP) as a preventative treatment. The researchers found that while high-risk factors are valuable in identifying individuals at greater risk of preeclampsia, moderate risk factors lack predictive power, resulting in ineffective and overly broad preventive care strategies.
“Identifying 9 out of 10 women as at risk is not helping and overburdens care teams and pregnant patients, too,” said lead author Thomas McElrath, MD, PhD, vice president of clinical development at Mirvie, the study’s sponsor, and a practicing maternal-fetal medicine physician at Mass General Brigham.
The research analyzed data from 5,684 pregnancies enrolled in the multi-center Miracle of Life study between July 2020 and March 2023. Researchers stratified participants using USPSTF definitions into low, moderate, and high risk based on clinical and demographic factors. Among these, 88.8% were identified as increased risk: 70.3% fell into the moderate-risk group and 18.5% into the high-risk group.
The findings revealed that “moderate-risk factors, in the absence of high-risk factors, had no or low value for estimating the risk of developing preeclampsia, leading to nonspecific recommendation of AP in the moderate risk category,” the researchers wrote. In contrast, high-risk factors like chronic hypertension and prior preeclampsia consistently showed strong associations with preeclampsia incidence.
The study noted that clinicians for women in the moderate-risk category may be uncertain when making aspirin recommendations. The data showed that 82% of high-risk patients were advised to take low-dose AP, but only 37% of those with one or more moderate risk factors received the same AP recommendation.
The current guidelines categorize women as at increased risk if they have at least one high-risk condition or two or more moderate risk factors, such as nulliparity, advanced maternal age, race, or elevated body mass index. However, the study found that among women with two or more moderate risk factors but no high-risk condition, only nulliparity had a modest correlation with preeclampsia, while other characteristics like obesity, advanced maternal age, and race showed minimal or no association.
The over-inclusiveness of the moderate risk group results in nearly nine out of 10 pregnancies being classified as increased risk, which the researchers said undermines the purpose of risk stratification in targeting care. “If the intended utility of the guidelines is to facilitate the focus of clinical attention and limited clinical resources on those at greatest risk of preeclampsia, identifying the majority of the population as at risk does not meet this end,” the researchers wrote.
Previous research laid the foundation for this study by highlighting the need to move beyond demographic and clinical characteristics for predicting obstetric complications. The researchers referenced their own earlier findings showing that maternal race was not a significant predictor of preeclampsia when biological markers were used. “The individualization of risk based on maternal physiology represents a vital remedy to race-based disparity in preeclampsia risk assessment,” the researchers wrote.
While the study’s strength was its nationally representative sample, prospective design, and diverse patient demographics, the researchers acknowledged that it relied on the medical records of patients to determine who had received AP recommendation without verifying actual use.
The results suggest a need to reconsider how preeclampsia risk is assessed and managed. Rather than continue to rely on moderately predictive demographic indicators, the researchers propose a more biologically grounded, individualized approach. “The success of these screening approaches suggests that a test to assess the risk of preeclampsia, based on its biological predictors, would improve upon the present guidelines based on maternal clinical or demographic characteristics,” the researchers wrote.
Future research will focus on validating such biologically based risk stratification tools, including the identification of molecular biomarkers like cell-free RNA, which the Miracle of Life study is already pursuing to analyze more than 200 million data points across 11,000 pregnancies.
