Severe maternal morbidity (SMM), as defined by the CDC, has been repeatedly associated with maternal mortality, fetal risk, and long-term maternal risk. Research efforts to reduce SMM are also one of PCORI’s research priorities. Racial disparities in SMM are well established, with African American (AA) women at consistently higher risk of SMM than White women. However, factors contributing to racial disparities in SMM are largely unknown, and commonly known socioeconomic factors have not been able to explain these racial disparities. Consequently, strategies to reduce them are absent.
Recent studies have shown that pregnant women with genital herpes simplex virus (GHSV) infection are at higher risk of SMM with strong underlying biological plausibility. The CDC has repeatedly reported that the rate of GHSV infection is four times higher in AA women than White women. This combination makes GHSV infection a likely overlooked factor contributing to racial disparities in SMM. More importantly, recent studies, including this team’s pilot study, have shown that treating women with GHSV infection using existing anti-herpes medications could reduce the SMM risk. Given that it would benefit AA women more because of their higher GHSV infection rate, such treatment could consequently lead to a reduction in racial disparities in SMM.
Currently, there is a significant knowledge gap regarding the benefit of treating GHSV infection to reduce SMM risk and its racial disparities. Pregnant women with GHSV infection, including many AA women, are not being treated. The current CDC guidelines for treating GHSV infection at 36 weeks of gestation are focused on reducing vertical transmission to newborns; thus, the treatment timing is too late for the prevention of SMM. Thus, a potentially effective treatment in reducing racial disparities in SMM is not being implemented because of the lack of data and the existing knowledge gap, which urgently need to be addressed.
To address the important question of racial disparities in SMM and examine the comparative effectiveness of a promising treatment/intervention strategy that could lead to a reduction in SMM risk and racial disparities in SMM, the team will conduct a large cohort study with a two-stage design, combining an electronic medical record (EMR)-based overall cohort (Stage I) of 339,000 pregnant women with a sub-cohort interview (Stage II) of 1,200 pregnant women randomly selected from the Stage I cohort to examine the impact of additional confounders not available from the EMR data. Based on the status of GHSV infection and its treatment, four cohorts will be established for comparison: (a) women with GHSV infection who received treatment early in pregnancy (before the third trimester); (b) women with GHSV infection who received treatment later in pregnancy (during the third trimester); (c) women with GHSV infection without treatment during pregnancy (untreated); and (d) women without GHSV infection (unexposed controls). Data on GHSV infection, SMM diagnosis, race/ethnicity, and potential confounders are available for all 339,000 women from electronic medical records (EMRs). In addition, the sub-cohort of 1,200 participants, randomly selected from each of the four cohorts, will be interviewed to collect data on additional confounders not available from the EMR. A sensitivity analysis will incorporate the additional data collected from the sub-cohort to assess the impact of any potentially unmeasured confounders.
Given that racial disparities in SMM present serious challenges to both clinicians and pregnant women, the proposed study will provide much-needed data from real-world clinical settings to address the comparative effectiveness of treating GHSV infection on reducing racial disparities in SMM. The study findings could have an immediate clinical application to reducing racial disparities in SMM by filling the current knowledge gap.
*All proposed projects, including requested budgets and project periods, are approved subject to a programmatic and budget review by PCORI staff and the negotiation of a formal award contract.