Background Preeclampsia (PE) is a severe pregnancy complication characterized by hypertension and proteinuria. PE poses a significant threat to women's health, including an increased risk of cardiovascular and renal diseases. Most previous studies have been hypothesis-based, potentially overlooking significant comorbidities. This study conducts a comprehensive, non-hypothesis-based analysis of PE comorbidities using large-scale electronic health records (EHR) data. Method From the University of Michigan (UM) Healthcare System, we collected 4,348 PE patients for the case cohort and 27,377 patients with pregnancies not complicated by PE or related conditions for the control cohort. We first conducted a non-hypothesis-based exploration to identify any comorbidities associated with PE using logistic regression with adjustments to demographics, lifestyles, and medical history. We validated the results by performing logistic regression on the post-PE risks of the identified comorbidities from UKBiobank data. The validation data contain 443 PE cases and 14,954 non-PE controls from UKBiobank. We then conducted survival analysis on comorbidities that exhibited significance in more than 5 consecutive years post-PE. We further examined the racial disparities of identified comorbidities between Caucasian and African American patients. Findings Uncomplicated hypertension, complicated diabetes, congestive heart failure, renal failure, obesity, and hypothyroidism exhibited significantly increased risks in 5 consecutive years after PE in the UM discovery data. Caucasians were more sensitive to PE's impact on hypertension and hypothyroidism compared to African Americans. Validation using UKBiobank data confirmed increased risks in uncomplicated hypertension, complicated diabetes, congestive heart failure, renal failure, and obesity. Interpretation This study addresses the lack of a comprehensive examination of PE's long-term effects utilizing large-scale EHR and modern statistical methods. Our findings underscored the need for long-term monitoring and interventions for women with a history of PE, emphasizing the importance of personalized postpartum care. Notably, the racial disparities observed in the impact of PE on hypertension and hypothyroidism highlight the necessity of tailored aftercare based on ethnicity.

The authors have declared no competing interest.

LXG was supported by grants R01 LM012373 and LM012907 awarded by NLM, R01 HD084633 awarded by NICHD. XY was supported by grant T32GM141746 awarded by NIH/NIGMS

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Ethics committee/IRB of the University of Michigan gave ethical approval for this work

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