Open this publication in new window or tab >>2025 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]
Cerebral complications of preeclampsia are among the leading causes of maternal mortality. Women with previous preeclampsia and eclampsia have increased long-term risks of cognitive impairment, stroke, and vascular dementia. They report a lower quality of life, concentration issues, and tiredness after childbirth. The pathophysiology of cerebral complications remains unclear, however, is suggested to involve blood-brain barrier (BBB) impairment, loss of cerebral autoregulation, microinfarctions, and edema.
This translational thesis aimed to explore pathophysiological mechanisms of BBB impairment in preeclampsia and to investigate whether preeclampsia and eclampsia increase the risk of neurological disorders and sick leave in the years following childbirth. This was explored through two preclinical laboratory studies and two register-based cohort studies.
The BBB was explored using an in vitro model. Results were correlated to plasma concentrations of cerebral biomarkers. Correlations were estimated with non-parametric tests. Plasma from women with preeclampsia affected the in vitro model of the human BBB by increasing permeability to FITC-Dextran and decreasing transendothelial electrical resistance (TEER) at the cellular level. All cerebral biomarkers were increased in plasma from women with preeclampsia, compared with normotensive pregnancy. Increased plasma concentrations of NfL were correlated to a decrease in TEER over the BBB. Plasma concentrations of tau, NSE and S100B were not associated with TEER.
Associations between gestational hypertension, preeclampsia and eclampsia, and a composite of neurological disorders (migraine, headache, epilepsy, sleep disorders and neurasthenia) were estimated with multivariate Cox regression models. All exposure groups were associated with an increased risk of a composite of neurological disorders, compared with normotensive pregnant women. Gestational hypertension and preeclampsia were associated with increased migraine risk. The strongest association was found between eclampsia and epilepsy.
Associations between preeclampsia and sick leave rates in the second year postpartum were assessed with augmented inverse probability weighting. Women with preeclampsia took more sick leave compared with women without preeclampsia.
In conclusion, plasma from women with preeclampsia impairs BBB function in vitro, and BBB leakage is indicated by correlation between decreased TEER and increased plasma NfL. Women with preeclampsia, particularly eclampsia, face a higher risk of developing neurological disorders postpartum, which may reflect the increased sick leave observed in this group.
Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2025. p. 90
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 2130
Keywords
Preeclampsia, Eclampsia, Blood-Brain Barrier, Cerebral Biomarkers, Neurological Disorders, Sick Leave
National Category
Gynaecology, Obstetrics and Reproductive Medicine
Identifiers
urn:nbn:se:uu:diva-552137 (URN)978-91-513-2411-1 (ISBN)
Public defence
2025-04-25, Humanistiska Teatern, Engelska Parken, Thunbergsvägen 3C, Uppsala, 09:15 (Swedish)
Opponent
Supervisors
2025-04-022025-03-082025-04-02Bibliographically approved