Brain Volumes After Hypertensive Pregnancy and Postpartum Blood Pressure Management: A POP-HT Randomized Clinical Trial Imaging Substudy.

Importance: Hypertensive pregnancy increases risk of cognitive decline, stroke, and dementia, especially after preeclampsia. Women with prior hypertensive pregnancy show lower brain volumes, but it was unknown whether early postpartum blood pressure optimization could alter these outcomes. Objective: To evaluate whether an intervention designed to achieve better postpartum blood pressure control after a hypertensive pregnancy is associated with differences in brain volumes around 9 months post partum compared with usual care. Design, Setting, and Participants: This randomized clinical trial, the Physician Optimized Postpartum blood pressure self-management trial (POP-HT), was a prospective, open-label, blinded end-point study conducted at a single tertiary center in the UK. Participants were older than 18 years and had preeclampsia or gestational hypertension requiring antihypertensive treatment at hospital discharge. Enrollment began February 21, 2020; the last follow-up was on November 2, 2021; and the mean follow-up time was approximately 9 months. Secondary outcome analyses (primary results published 2022) were conducted May 2025. Interventions: Telemonitored self-management with research physician-guided titration or usual postnatal care. Main Outcomes and Measures: This substudy analyzed the secondary outcomes T1-weighted magnetic resonance imaging (MRI) brain volumes (gray matter, white matter, cerebrospinal fluid, subcortical structures) acquired approximately 9 months post partum. Analyses used linear regression models adjusted for total intracranial volume. Results: Of 252 eligible participants, 32 declined, and 220 were randomized (mean [SD] age, 33.4 [5.1] years). The T1 brain MRI of 157 participants was available for analysis; 96 participants (63%) had preeclampsia, and 56 (37%) had gestational hypertension. The intervention group (n = 81) had larger total white matter volumes (adjusted mean difference, 11.50 cm3; 95% CI, 2.04 to 20.96; P = .02) compared with the usual care group (n = 71). In usual care, participants with preeclampsia had smaller putamen (adjusted mean difference, -0.83 cm3; 95% CI, -1.20 to -0.46; P < .001), accumbens (adjusted mean difference, -0.15 cm3; 95% CI, -0.24 to -0.05; P = .003), and pallidum (adjusted mean difference, -0.13 cm3; 95% CI, -0.26 to -0.01; P = .04) volumes compared with those with gestational hypertension. These differences were not observed in the intervention group. Conclusions and Relevance: This study found that short-term postpartum optimization of blood pressure control after hypertensive pregnancy was associated with larger brain volumes during the first year post partum. Because brain volume is a surrogate of brain health linked to tissue preservation and cognitive outcomes, these findings suggest potential neurovascular benefits that were most pronounced among women with preeclampsia. Trial Registration: ClinicalTrials.gov Identifier: NCT04273854.