Background Hypertensive disorders of pregnancy (HDP) affect nearly 10% of pregnancies in the U.S. and are known to increase risk of severe maternal morbidity and later life cardiovascular disease and stroke. Mental health disorders are common among pregnant individuals and have been linked to high blood pressure and adverse pregnancy outcomes. However, there is limited research investigating the association between history of mental health conditions and HDP.

Objectives We aimed to assess the association of pre-pregnancy mental health disorders with HDP.

Methods We used the NIH All of Us Research Program, which began enrollment in May 2018 and linked participants’ electronic health records (EHRs). First pregnancies with conception dates between October 2015 and September 2021 were identified from EHRs. Risk of HDP was examined among pregnancies of at least 20 weeks of gestation. We assessed the association between a pre-pregnancy mental health diagnosis and the risk of HDP using log-binomial regression models, estimating risk ratios (RR) and 95% confidence intervals, adjusted for racial and ethnic group and maternal age. We examined early pregnancy loss as a secondary outcome among all identified pregnancies. Results were stratified by the timing of pregnancy start relative to enrollment in the All of Us cohort.

Results Among 11,756 pregnancies that occurred prior to study enrollment, we observed a 20% increased risk of HDP associated with pre-pregnancy anxiety and depression (RR 1.20, 95% CI 1.05,1.36) and a 50% increased risk of early pregnancy loss associated with pre-pregnancy anxiety and depression (RR 1.49, 95% CI 1.36,1.64). Among 2,358 pregnancies occurring after enrollment, findings for HDP were generally similar, but associations with early pregnancy loss were attenuated, with imprecise estimates.

Conclusions Prior mental health disorder diagnoses were associated with a modest increase in risk of HDP and early pregnancy loss.

Study question Do pre-pregnancy mental health disorders increase the risk of pregnancy loss or hypertensive disorders of pregnancy (HDP)?

What’s already known Few studies have evaluated pre-pregnancy mental health disorders and pregnancy loss. Findings from prior studies of the association between mental health disorders and HDP are inconsistent, with mental health status often ascertained in early pregnancy thus masking the temporal relationship with HDP.

What this study adds In this study, which leverages the All of Us Research Program cohort, we report an increased risk of HDP associated with pre-pregnancy mental health disorders. Additionally, we found an increased risk of early pregnancy loss associated with pre-pregnancy mental health disorders, suggesting our results may underestimate the risk associated with HDP having conditioned on later gestations.

The authors have declared no competing interest.

CN was supported by National Institute on Minority Health and Health Disparities (NIMHD) Award Number K01-MD013911 (PI: Ncube)

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The All of Us Research Program is reviewed by an internal human subjects review board and all participants provide informed consent. Secondary analyses of de-identified data from the All of Us Research Program is not considered human subjects research.

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Collette N. Ncube ncubebu.edu, Minhyuk Choi mchoi9bu.edu, Ruby Barnard-Mayers rbarmaybu.edu, Scott C Zimmerman szimmbu.edu, Shelli Vodovozov shellivbu.edu, Maria Glymour mglymourbu.edu, Samantha E Parker separkerbu.edu

This study utilized data from the Controlled Tier Dataset [v7] of the All of Us Research Program, accessible to authorized users on the Researcher Workbench. Statistical code used in our analyses are available from [GitHub repository link].