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Gestational Hypertension, Preeclampsia, and Eclampsia and Future Neurological Disorders
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Clinical Obstetrics.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Clinical Obstetrics. Department of Obstetrics and Gynecology, Stellenbosch University, Cape Town, South Africa;Department of Obstetrics and Gynecology, Gothenburg University, Gothenburg, Sweden;Region Västra Götaland, Sahlgrenska University Hospital, Department of obstetrics and gynecology, Gothenburg, Sweden.ORCID iD: 0000-0001-5202-9428
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Clinical Obstetrics.ORCID iD: 0000-0001-9173-2909
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Clinical Obstetrics.ORCID iD: 0000-0003-4427-1075
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2025 (English)In: JAMA Neurology, ISSN 2168-6149, E-ISSN 2168-6157, Vol. 82, no 2, p. 142-151Article in journal (Refereed) Published
Abstract [en]

Importance  Gestational hypertension, preeclampsia, and eclampsia are established risk factors for stroke and dementia later in life. Whether these pregnancy complications are associated with an increased risk of new-onset neurological disorders within months to years after giving birth is not known.

Objective  To explore whether gestational hypertension, preeclampsia, and eclampsia are associated with new-onset migraine, headache, epilepsy, sleep disorder, or mental fatigue within months to years after giving birth.

Design, Setting, and Participants  In this register-based cohort study, exposures were identified in the Swedish Medical Birth Register from 2005 to 2018. Follow-up was conducted using the National Patient Register, containing diagnoses from specialized inpatient and outpatient care. Follow-up started 42 days after delivery and continued until the first event, death, emigration, or the end of the follow-up period (2019). The risk was calculated with Cox regression analysis and expressed as adjusted hazard ratio (aHR) with a 95% CI. Through the Swedish Medical Birth Register, 659 188 primiparous women with singleton pregnancies between 2005 and 2018 were identified. Women with a diagnosis of chronic hypertension (n = 4271) or a prepregnancy neurological disorder (n = 6532) were excluded. The final study population included 648 385 women. Data analyses were conducted in 2023.

Exposures  Gestational hypertension, preeclampsia, and eclampsia.

Main outcome  The primary outcome was a composite neurological outcome of migraine, headache, epilepsy, sleep disorder, or mental fatigue.

Results  The study included 648 385 women with a mean age of 28.5 (SD, 5.0) years at the time of their first pregnancy. Women with gestational hypertension (n = 11 133), preeclampsia (n = 26 797), and eclampsia (n = 625) all had an association with increased risk for a new-onset neurological disorder compared with women with normotensive pregnancies. The aHR for gestational hypertension was 1.27 (95% CI, 1.12-1.45), 1.32 (95% CI, 1.22-1.42) for preeclampsia, and 1.70 (95% CI, 1.16-2.50) for eclampsia. When exploring individual outcomes, women with eclampsia were associated with more than a 5 times increased risk of epilepsy (aHR, 5.31; 95% CI, 2.85-9.89).

Conclusion and Relevance  In this study, gestational hypertension, preeclampsia, and eclampsia were associated with an increased risk of new-onset migraine, headache, epilepsy, sleep disorder, or mental fatigue within months to years after giving birth. Guidelines recommend follow-up after delivery for women with gestational hypertension and preeclampsia for their increased risk of cardiovascular disease. At these visits, caregivers should also pay attention to persisting or new-onset of neurological symptoms, since this group of women appears to be vulnerable to developing or experiencing neurological disorders.

Place, publisher, year, edition, pages
American Medical Association (AMA), 2025. Vol. 82, no 2, p. 142-151
National Category
Gynaecology, Obstetrics and Reproductive Medicine
Identifiers
URN: urn:nbn:se:uu:diva-548772DOI: 10.1001/jamaneurol.2024.4426ISI: 001385413600001PubMedID: 39714850Scopus ID: 2-s2.0-85218487300OAI: oai:DiVA.org:uu-548772DiVA, id: diva2:1932260
Available from: 2025-01-28 Created: 2025-01-28 Last updated: 2025-04-10Bibliographically approved
In thesis
1. Preeclampsia and the brain: The blood-brain barrier and neurological consequences
Open this publication in new window or tab >>Preeclampsia and the brain: The blood-brain barrier and neurological consequences
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
Available from: 2025-04-02 Created: 2025-03-08 Last updated: 2025-04-02Bibliographically approved

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Friis, ThereseBergman, LinaHesselman, SusanneLindström, LindaJunus, KatjaWikström, Anna-Karin

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