Long-term neurological consequences of hypertensive disorders of pregnancy: Implications for postpartum monitoring and intervention

Abstract

BACKGROUND

Eclampsia and pre-eclampsia are hypertensive disorders of pregnancy (HDPs) that may pose significant long-term risk to maternal patients during the post-partum period. Acute neurological complications of these conditions include recurrent seizures, cerebral edema, intracerebral hemorrhage, stroke, and altered mental status. The long-term neurological sequelae of each condition, and how they differ, remain understudied.

AIM

To systematically review and compare long-term neurological outcomes including cognitive impairment, and cerebrovascular events in individuals who experience eclampsia and pre-eclampsia.

METHODS

A systematic review was conducted via PubMed including studies published from 2005 to 2025. Eligible studies included human participants with a history of HDP, and results of neurological outcomes assessed at least three months postpartum. Outcomes of interest included cognitive impairment, structural brain changes, and stroke/stroke risk factors.

RESULTS

A total of 49 studies met inclusion criteria for final synthesis. The findings of our literature review suggest individuals with a history of HDP have an elevated long-term risk of stroke, with greatest hazard ratios present in hemorrhagic stroke. Eclampsia was linked to higher stroke risk compared to preeclampsia. In terms of structural outcomes found on imaging, all HDPs were strongly associated with white matter lesions, atrophy, blood-brain barrier (BBB) leakage, and carotid atherosclerosis, supporting a pathway of persistent cerebrovascular and neurovascular injury. Cognitive impairment in patient-reported data showed deficits; however, objective testing showed non-significant differences.

CONCLUSION

These findings suggest that stroke and structural brain abnormalities are well-supported sequelae of long-term HDP complications, particularly in eclampsia, while cognitive outcomes remain heterogeneous. Thus, differentiated postpartum care and neurologic evaluation may be warranted in at-risk mothers. Further studies are needed to confirm these findings, investigate possible external contributing factors, and inform evidence-based risk assessment and surveillance guidelines.

Core Tip: This review of literature examines the neurological consequences for women who have previously experienced gestational hypertension, eclampsia, or preeclampsia. A total of 49 studies were included. After 90 days or greater postpartum, these factors were consistently linked to higher rates of stroke, white matter hyperintensities, structural brain atrophy, and remodeling across studies. The results of this review suggest that pregnancy-related hypertensive disorders may not be isolated obstetrical diseases, but rather long-term risk factors for the development of neurological conditions. Early intervention and surveillance in multidisciplinary treatment, including neurology, vascular medicine, and neurosurgery, may help mitigate negative consequences of disease progression.

INTRODUCTION

Stroke is a leading cause of long-term disability and mortality worldwide; the World Health Organization estimates stroke as the third largest cause of death globally in 2021[1]. Up to 56% of the population with a history of stroke are female[2]. Stroke risks factors are commonly influenced by metabolic factors, including hypertension, diabetes, and dyslipidemia, but for women who have experienced childbearing, stroke risk may also be influenced by hypertensive disorders of pregnancy (HDP), including gestational hypertension, eclampsia, and pre-eclampsia[3].

Pre-eclampsia is a condition characterized by defective remodeling of uterine spiral artery during pregnancy, reducing blood flow volume, and triggering release of widespread pro-inflammatory cytokines that affect multiple organ systems. Eclampsia is further defined as pre-eclampsia with the development of seizures. The exact cause of the development of pre-eclampsia is theorized to be multifactorial, including theories of genetic dysregulation of vascular physiology, as well as imbalance of lipid molecules such as ratios of prostacyclin deficiency and thromboxane excess[4,5]. Pre-eclampsia is a common HDP, with recent literature estimating that approximately 4 million women worldwide are diagnosed with this condition yearly, while eclampsia has been estimated to affect 420000 women/year[6,7].

Current medical guidelines for clinical practice focus on short-term maternal neurological risks; however, long-term cerebrovascular consequences are increasingly recognized and represent a gap in current practices. As medical care in obstetrics and gynecology has improved, maternal deaths from HDP have fallen, with an approximate 30% reduction in global maternal morbidity attributed to hypertensive disorders from 1990 to 2019[8]. Much of this is due to the use of magnesium sulfate for seizure prophylaxis, which was reported to halve the risk of eclampsia and significantly reduce maternal mortality compared with diazepam or placebo in prospective studies[9,10]. This has created a larger population of women with prior pre-eclampsia and eclampsia living into the decades of life when cerebrovascular disease becomes more prevalent, underscoring the need for longitudinal risk management with our current aging population[11-13]. While gestational hypertension presents far less severe morbidity and mortality in pregnancy, recent studies have also implicated this pathology’s effect on long-term cerebrovascular health, indicating a need for review of literature to compare risk values[14]. As we will explore through a review of current literature, stroke has been highly associated with a history of pre-eclampsia and eclampsia, among many of the risk factors associated with stroke development[15].

Despite guideline calls for long-term cardiovascular and neurologic follow-up in women with HDP, routine surveillance remains inconsistent, and most women with prior pre-eclampsia are not systematically monitored for stroke risk[16]. By contrast, in other high-risk neurovascular conditions such as carotid artery stenosis or moyamoya disease, early surgical/endovascular intervention reduces morbidity[17,18]. This gap in care reflects limited awareness and inconsistencies in the existing literature for longitudinal neurological outcomes in HDP, elucidating the need for comprehensive review. This understanding of disease pathology and associations is particularly important for neurosurgical and neurointerventional specialties. Early identification of risk markers indicating surgical intervention, such as microemboli, unstable plaque, aneurysm wall enhancement, or hemodynamic compromise, already provide guides for early intervention in aforementioned conditions and may be applicable in post-partum populations. If pre-eclampsia predisposes women to comparable vascular or structural changes, earlier referral and intervention may be justified; however, the current literature literature is not comprehensive for all risk factors.

The objective of this review is to compile and analyze current literature on the longitudinal sequelae of neurological function in women with prior pre-eclampsia or eclampsia. Neurological outcomes will include stroke, neurovascular changes, structural white matter changes, and cognitive functions that may predict future cerebrovascular events. By organizing and analyzing existing evidence, we hope to highlight opportunities for early surveillance and neurointerventional strategies to optimize outcomes in this high-risk population.

MATERIALS AND METHODS

A systematic literature search was conducted in PubMed for studies published from January 1, 2005 to December 31, 2025, with outcomes having been gathered within this timeframe. The PubMed search utilized Medical Subject Headings terms combined with Boolean logic to identify studies evaluating HDP, which included preeclampsia, eclampsia, and gestational hypertension, and associated neurological outcomes. Desired outcomes included cerebrovascular disease (stroke and related vascular events), seizure disorders/epilepsy, structural brain changes on neuroimaging, and cognitive impairment or decline.

The literature search was restricted to original research articles involving human adult populations. Review articles, conference abstracts, and case reports were excluded. The full Medical Subject Headings string used is reported in Supplementary material. All citations were screened using PRISMA guidelines relevant to our aims (Figure 1). Titles and abstracts were first reviewed for relevance to maternal neurological outcomes; studies reporting exclusively infant/neonatal outcomes were excluded (n = 8). Only articles available in English or with an English translation were considered; however, none needed to be excluded for this reason in our analysis.

Figure 1.

PRISMA flow diagram of PubMed search and study selection. Of the 92 records identified, 49 studies met inclusion criteria after full-text review. Several publications contributed to more than one outcome domain (stroke, structural, cognitive, or mechanistic), yielding 45 unique PubMed records across all analytic tables.

Eligibility criteria required definition of preeclampsia, eclampsia, and/or gestational hypertension; maternal neurological outcomes reported ≥ 3 months postpartum; and specific neurological outcomes present in the maternal population. The ≥ 3-month cutoff was chosen to exclude acute postpartum complications and align with prior literature by the obstetrics and gynecological professional societies, which define a 6-week to 8-week average maternal recovery postpartum period[16].

Full texts of eligible studies were reviewed, and data were extracted into Microsoft Excel tabulations. Extracted variables included study design, setting, sample size, HDP subtypes, follow-up duration timeline, and maternal age at outcome assessment. Outcomes were categorized into four groups: (1) Stroke and cerebrovascular events; (2) Structural and magnetic resonance imaging (MRI)-based neuroimaging outcomes; (3) Cognitive outcomes (objective and subjective outcomes); or (4) Mechanistic or biomarker findings.

Study categorization details

Stroke outcomes: Including ischemic, hemorrhagic, or all-cause stroke incidence. Structural and MRI outcomes: Including white matter hyperintensities, brain atrophy, BBB changes, or neurovascular structural changes. Cognitive outcomes: Including neuropsychological testing, dementia diagnoses, or subjective cognitive assessments (patient self-reported). Mechanistic/biomarker outcomes: Including imaging markers of vascular remodeling, circulating biomarkers, or genetic/epigenetic signals that do not fit in prior categories.

Statistics including hazard ratios (HR), odds ratios, relative risks, and 95% confidence intervals (CIs) were included when available in the studies. If there were any further result outcomes reported, they were placed in the notes of our outcome tables for full clarity of data. After compiling results, the data were gathered into evidence tables summarizing study results across the four categories of outcomes. Several studies contributed to more than one category and were included in each relevant table for completeness.

RESULTS

Overall outcomes

Of the 92 PubMed records screened, 49 studies met inclusion criteria. Eight were excluded for lack of maternal outcomes overall, five for lack of HDP classification, sixteen for absence of maternal neurological outcomes, and fourteen for reporting outcomes within the three-month postpartum period. Two of the included studies utilized the same cohort (Framingham Offspring) but were retained because they evaluated distinct neurological endpoints.

Across these 49 included studies - representing 45 unique publications - twenty-three reported stroke outcomes, ten examined structural and/or MRI-based neurovascular changes, nine assessed cognitive or neuropsychological outcomes, and six investigated biomarkers or mechanistic risk factors related to neurological sequelae, as summarized in Table 1.

Table 1.

Final values for categorical outcomes reported in included studies

Outcome category	No. of studies	Typical maternal age at outcome	Typical follow-up duration
Stroke	[23]	45-55 years	15-20 years (range: 1-50)
Structural/MRI	[10]	50-65 years	15-25 years (range: 5-40)
Cognitive	[9]	55-70 years	20-30 years (range: 10-40)
Mechanistic/biomarker	[6]	35-45 years	7-10 years (range: 1-15)

Follow-up durations were averaged across all studies.

Stroke outcomes

The 23 included studies highlighting stroke and stroke risk factors were fairly consistent in reporting an association of HDP and elevated long-term stroke risk[19-41]. Of these, 12 showed clear effect estimates, national cohort size, or imaging-confirmed stroke outcomes, and thus were chosen for presentation in Table 2. Adjusted hazard and odds ratios typically ranged between 1.3 and 2.0, however, the stroke subtype as well as the HDP subtype caused fluctuations in results, creating hazard ratios and odds ratios between 1.2 all the way to greater than 5.0. Crump et al[20] is an example of a study dividing outcomes by HDP subtypes. The reported results found an increased risk of ischemic stroke after preeclampsia (adjusted HR: 1.36, 95%CI: 1.31-1.41), gestational hypertension (adjusted HR: 1.82, 95%CI: 1.67-1.98), and gestational diabetes (adjusted HR: 1.86, 95%CI: 1.69-2.04). In terms of stroke subtypes, Hung et al[21] reported the risk of ischemic stroke peaked at 1-year to 3-year postpartum (adjusted HR: 2.14), while hemorrhagic stroke risk was more concentrated to the 10-year to 15-year postpartum period (adjusted HR: 4.64).

Table 2.

Summary of representative studies reporting long-term stroke and vascular outcomes in women with a history of hypertensive disorders of pregnancy

Ref.	Design/setting	Exposure/comparison	Sample (exposed/ref)	Follow-up (years)	Stroke outcome(s)	Effect (95%CI)	Notes
Verburgt et al[19], 2025	Case-control, young women with ischemic stroke vs population controls	Any APO; HDP (PE/PIH) vs none	358 stroke/714 ref	Up to prior pregnancies	Ischemic stroke	PE OR: 4.0 (2.4-6.8); HDP OR: 2.0 (1.4-2.7); SGA OR: 2.8 (2.0-3.9); Preterm OR: 2.7 (1.9-4.0)	HDP strongest with large-artery disease; suggests atherosclerotic mechanism in some cryptogenic strokes
Crump et al[20], 2025	Nationwide cohort, Sweden	APOs (PTB, SGA, PE, other HTN, GDM) vs none	35824 stroke/2201393 total	Up to 46	All stroke	PE aHR: 1.36 (1.31-1.41); other HTN 1.82 (1.67-1.98); GDM 1.86 (1.69-2.04); PTB 1.40 (1.36-1.45); SGA 1.26 (1.22-1.29)	Risks persisted 30-46 years; partly explained by shared familial factors
Hung et al[21], 2022	Nationwide cohort, Taiwan	HDP subtypes vs non-HDP	13617 HDP/54468 ref	≤ 17	Any, ischemic, hemorrhagic	Any aHR: 1.71 (1.46-2.00); Isch aHR: 1.60 (1.35-1.89); Hem aHR: 2.98 (2.13-4.18)	Isch peak 1-3 years (aHR: 2.14); Hem peak 10-15 years (aHR: 4.64); highest with CH superimposed PE (aHR: 3.86)
Auger et al[36], 2020	Provincial cohort, Canada	Very/moderate PTB vs term; mediation by maternal vascular disorders (including PE)	1199364	Approximately 10-20	Ischemic stroke hospitalization	Incidence higher with PTB. For 95%CI PE explained 8.3% (very PTB) and 11.0% (moderate PTB) of PTB-stroke association	Specific stroke HRs by PTB reported; PE key mediator of PTB → stroke/CVD
Garovic et al[23], 2020	Historical cohort, Olmsted County (United States)	Prior HDP vs matched referents	571 HDP/1142 ref	Median 36	Any stroke	HR: 2.27 (1.37-3.76)	HDP also increase CAD, CKD, arrhythmia; robust to adjustments
Arnott et al[24], 2020	National registry, Australia	HDP (early-onset < 34 weeks) × smoking vs no HDP	528106 (first births)	10 (risk estimate)	Composite CVD (including ischemic stroke)	EO-HDP, non-smokers HR: 4.90 (3.00-7.80); EO-HDP + smoking HR: 23.5 (13.5-40.5)	Stroke included in composite; strong interaction with smoking
Gastrich et al[25], 2020	Matched cohort, United States	History of PE vs matched controls	6360 PE/325347 ref	Up to several years	Hospitalized stroke	HR: 1.81 (0.75-4.37) (NS)	MI and CV death increase; stroke directionally increase but underpowered
Kuo et al[26], 2018	Nationwide cohort, Taiwan	PE/eclampsia vs age-matched controls	1295 cases/5180 ref	Approximately 10	Cerebrovascular disease (stroke)	Eclampsia HR: 10.71 (3.45-33.24); PE HR: 3.47 (1.46-8.23)	Hemorrhagic stroke: Eclampsia HR: 19.74; PE NS
Lobitz et al[27], 2024	National admin cohort, Australia	Caesarean vs vaginal; adjusted including HDP/DM	14179299	≤ 365 days PP	Stroke readmission	HR: 1.40 (1.26-1.56)	Increase 180-365 days (HR: 1.94)
Lin et al[29], 2016	Nationwide cohort, Taiwan	PIH vs non-PIH	28346 PIH/113384 ref	Approximately 10	Intracranial hemorrhage	aHR: 2.81 (1.58-4.99)	Hemorrhagic risk increasing strongly
Nelander et al[30], 2016	Cohort, Sweden (≥ 65 years)	Any HDP vs none	3232	To late life	Any stroke	HR: 1.36 (borderline)	Attenuated at oldest ages
Akhter et al[35], 2014	Vascular imaging cohort, Norway	Severe PE vs normotensive	42 PE/44 ref	9 years (range 1-13)	Vascular surrogate (carotid IMT/plaques)	Intima 013 ± 0.02 mm vs 0.08 ± 0.01 mm (+63%); I/M ratio 0.27 ± 0.07 vs 0.15 ± 0.03 (+80%); IMT 063 ± 0.12 mm vs 0.61 ± 0.12 mm (+3%); media -7%	Increased carotid intimal thickening and arterial remodeling consistent with early subclinical atherosclerosis after severe PE

Of 23 included studies, 12 with detailed effect estimates, or national cohort data are shown here. CI: Confidence interval; APO: Adverse pregnancy outcome; HDP: Hypertensive disorder of pregnancy; PE: Preeclampsia; PIH: Pregnancy-induced hypertension; Ref: Reference/control group; OR: Odds ratio; SGA: Small for gestational age; HTN: Hypertension; GDM: Gestational diabetes mellitus; PTB: Preterm birth; aHR: Adjusted hazard ratio; CH: Chronic hypertension; HR: Hazard ratio; Isch: Ischemic stroke; Hem: Hemorrhagic stroke; PTB → stroke/CVD: Pathway from preterm birth to stroke or cardiovascular disease; CAD: Coronary artery disease; CKD: Chronic kidney disease; EO-HDP: Early-onset hypertensive disorder of pregnancy; NS: Not significant; MI: Myocardial infarction; CV: Cardiovascular; DM: Diabetes mellitus; I/M: Intima/media ratio; IMT: Intima-media thickness.

Eclampsia and pre-eclampsia were associated with the greatest hazards, with eclampsia tending to be greatly elevated risks. Kuo et al[26] reported markedly elevated risks of hemorrhagic stroke, with HRs of 19.74 (95%CI: 4.71-82.68) following eclampsia and 3.47 (95%CI: 1.46-8.23) following preeclampsia. Similarly, Arnott et al[24] showed that non-smokers had a five times increased risk of composite cardiovascular disease including stroke (HR: 4.90, 95%CI: 3.00-7.80) when compared to the general population. Importantly, this risk rose dramatically in smokers (HR: 23.5, 95%CI: 13.5-40.5), suggesting confounding variables in these outcomes.

Age was also found to play a role in a few of the reported studies. Verburgt et al[19] reported that among women aged 24-31 years, a history of pre-eclampsia increased the odds of later stroke by four times (odds ratio: 4.0, 95%CI: 2.4-6.8). At this young age range, Lobitz et al[27] also reported increased readmission for stroke within one year postpartum (HR: 1.40, 95%CI: 1.26-1.56), with risk highest between 6 months and 12 months (HR: 1.94).

In older cohorts, associations appeared to weaken. Nelander et al[30] observed only borderline associations between HDP and stroke for women 65 years or older (HR: 1.36, 95%CI: 0.98-1.89), suggesting a weaker association as age advances; however, there were few studies that looked at only elderly populations. Overall, the stroke data support an early surge in ischemic events, later-emerging hemorrhagic risks, and particularly strong associations with severe HDP phenotypes such as eclampsia and superimposed preeclampsia. Additionally, several mechanistic and vascular studies evaluating atherosclerotic progression, carotid remodeling, or cardiovascular disease prediction following HDP were included as stroke-risk proxies, given their shared vascular pathophysiology and inclusion of stroke endpoints within composite outcomes[31-41].

Structural and imaging outcomes

A total of 10 studies investigated brain and vascular structure, consistently identifying neurovascular changes through brain imaging techniques years to decades after postpartum, as summarized in Table 3[34,35,41-48]. The most reported outcome amongst studies was increased white matter hyperintensity (WMH) on MRI, which is consistent with small-vessel disease. Aukes et al[47] reported that women with early-onset preeclampsia carried the highest WMH present on scans (P < 0.01), while Postma et al[45] observed WMH in 36% of women with a history of either preeclampsia or eclampsia, when compared with 21% of controls. Aukes et al[48] was the only paper to discuss seizure recurrence, correlating the recurrences to significantly higher WMH volume in women with prior eclampsia (0.041 mL vs 0.004 mL, P = 0.016).

Table 3.

Structural and neuroimaging findings after hypertensive disorders of pregnancy per PubMed analysis, including white matter hyperintensities, brain atrophy, and vascular changes

Ref.	Country/design	Exposure (HDP subtype)	Sample (exposed/ref)	Time since index pregnancy	Imaging modality/measure	Main finding(s)	Notes/adjustments
Hussainali et al[41], 2025	ORACLE substudy, Netherlands	Gestational HTN or PE	63 GH, 30 PE/445 ref (n = 538 total)	Median 14.6 years	MRI markers of CSVD (WMH volume, lacunes, microbleeds)	WMH volume increase after HDP [β = 0.32 (0.08-0.56)]; driven by GH [β = 0.39 (0.10-0.67)]; no differences in lacunes or microbleeds. Trend increase with later chronic HTN	Adjusted for age, BMI, education, ICV
Alers et al[42], 2023	Netherlands; cohort MRI + cognition	Prior PE	96/96 ref	Approximately 15 years	MRI-gray and white matter volumes, WML load, and cognitive testing	Cortical and subcortical gray and white matter volumes decrease after PE; WML burden increase; slower processing speed and impaired executive function vs controls (all P < 0.05)	Adjusted for age, BMI, and education
Canjels et al[43], 2022	Netherlands; case-control MRI	Prior PE	22/13 ref	6.6 years PE vs 9.0 years ref	Contrast-enhanced MRI: BBB leakage (Ki, vl)	BBB leakage higher in PE across whole cerebrum-global WM Ki increase (P = 0.001) and GM Ki increase (P = 0.02); aOR for high Ki approximately 48 (3.5-651) WM, 3.5 (1.1-30.8) GM	Adjusted for age, HTN at MRI, Fazekas
Akhter et al[34], 2019	Sweden; vascular imaging	Prior PE	23/35 ref	Approximately 7 years	Carotid ultrasound: Intima thickness increase, I/M ratio increase, IMT decrease	At 7 years, intima 012 mm vs 0.09 mm, I/M increase (P < 0.001); IMT paradoxically lower. Correlated with MAP and biomarkers	Adjusted for BMI, BP, MAP
Siepmann et al[44], 2017	Germany; cohort imaging	Prior PE	34/40 ref	5-15 years	3T MRI: WM lesions, microstructure (DTI), cortical volumes	Temporal-lobe WM lesion volume increase after PE (P = 0.04); cortical GM volume decrease and DTI showed lower FA in parietal-occipital regions (P < 0.05)	Associations persisted after adjustment for MAP, HDL, and age
Postma et al[52], 2016	Netherlands; cross-sectional	Prior PE	41 eclampsia, 49 PE/47 ref	Approximately 6 years	MRI: WML presence, infarcts, periventricular/subcortical	WML more frequent in PE (40% vs 21%, P = 0.03). Infarcts only in PE. WML not tied to objective cognition	Adjusted for age and risk factors; subcortical WML P = 0.06; infarcts 4 vs 0
Mielke et al[46], 2016	United States; community cohort	History of HDP	286 HDP/297 ref	Approximately 35 years median follow-up	MRI: Total brain volume, WM lesion volume; cognition	Smaller brain volume in HDP (P = 0.023). WMH volume slightly increase (8.9 mL vs 8.1 mL, NS). Processing speed slower in HDP	Adjusted for demographics and vascular risk
Akhter et al[35], 2014	Sweden; case-control	Prior severe PE	42/44 ref	Approximately 9 years (range 1-13)	Carotid wall imaging (intima, I/M, IMT)	Intima 013 mm vs 0.08 mm (+63%); I/M ratio 0.27 vs 0.15 (+80%); IMT no difference	Structural differences persisted after adjustment for BMI, age, BP
Aukes et al[47], 2012	Netherlands; cross-sectional	Prior PE (early vs late onset)	73/75	Approximately 5 years	MRI: WM lesion volume, periventricular WML, infarcts	WML burden increase after PE (β = 0.77; P = 0.04); early-onset PE highest (P < 0.01); periventricular WML 5 vs 0	Current HTN independently increase WML risk
Aukes et al[48], 2009	Netherlands; case-control	Former eclampsia	39/29	Median 7 years (IQR 3-14)	MRI: WML load (volume and severity)	WML volume greater in eclampsia (0.041 mL vs 0.004 mL, P = 0.016). More WML in women with seizures (P = 0.01)	WML load is correlated with seizure recurrence

HDP: Hypertensive disorder of pregnancy; Ref: Reference/control group; HTN: Hypertension; PE: Preeclampsia; GH: Gestational hypertension; MRI: Magnetic resonance imaging; CSVD: Cerebral small-vessel disease; WMH: White-matter hyperintensity; BMI: Body mass index; ICV: Intracranial volume; WML: White-matter lesion; BBB: Blood-brain barrier; K_i: Leakage rate constant; v_l: Leakage volume fraction; WM: White matter; aOR: Adjusted odds ratio; GM: Gray matter; aOR: Adjusted odds ratio; I/M: Intima/media ratio; IMT: Intima-media thickness; BP: Blood pressure; MAP: Mean arterial pressure; DTI: Diffusion tensor imaging; FA: Fractional anisotropy; HDL: High-density lipoprotein; NS: Not significant; β: Regression coefficient; IQR: Interquartile range.

In addition to WMH, structural atrophy and BBB disruption were observed. Mielke et al[46] reported smaller brain volumes in women with HDP (286 mL vs 297 mL, P = 0.023), while Canjels et al[43] found higher BBB leakage across both white and gray matter.

Vascular imaging studies consistently reported carotid atherosclerotic changes. Akhter et al[34] and Akhter et al[35] demonstrated increased intima thickness at 7 years postpartum (0.12 mm vs 0.09 mm, P < 0.001) and vascular changes up to 13 years after pregnancy, independent of common carotid arterial health confounding factors. The imaging data highlighting the persistent WMH, cortical and subcortical atrophy, BBB disruption, and vascular remodeling, supports possibleremodeling, support possible mechanisms of HDP's effect on elevated long-term stroke risk.

Cognitive outcomes

A total of 9 studies assessed cognition after HDP as summarized in Table 4[23,32,42,45,46,48-52]. Between studies, objective testing showed unclear results for matters of executive function and processing speed. Those that showed some evidence of decreased cognitive function were focused on slower processing speeds[45,46,50,51]. Moderate-to-large deficits in executive function, memory, and attention in women with prior eclampsia more than three decades after pregnancy were reported by Fields et al[51].

Table 4.

Cognitive outcomes following hypertensive disorders of pregnancy per PubMed analysis, including objective neuropsychological testing and subjective patient-reported measures

Ref.	Country/design	Exposure (HDP subtype)	Sample (exposed/ref)	Time since index pregnancy	Cognitive measure(s)	Main finding(s)	Notes/adjustments
Alers et al[42], 2023	Netherlands; population cohort	Prior PE	1036/527 ref	≤ 19 years	BRIEF-A executive and working memory composite	Executive function and working memory decrease (aRR: 9.20 and 7.94 at one year; sustained significance at up to 19 years postpartum)	Adjusted for age, BMI, and education
Wang et al[49], 2022	United States; Framingham Offspring study (longitudinal)	Prior PE	142/1107 ref (n = 1249)	Median 12 years	Dementia diagnosis (all-cause, Alzheimer’s, vascular)	PE → increase risk of all-cause dementia (HR: 1.56) and Alzheimer’s dementia (HR: 1.65)	Longitudinal adjudicated outcomes; adjusted for cardiovascular risk
Garovic et al[23], 2020	United States; retrospective cohort (Olmsted County)	GH, PE, superimposed HDP	571 HDP/1142 ref (mothers total number = 7544)	Median approximately 36 years	Dementia diagnosis	Dementia signal present but ns after multiple testing	Adjusted for education, smoking, obesity; CVD endpoints significant
Dayan et al[50], 2018	United States; retrospective cohort (CARDIA)	Prior HDP	193/375 ref (n = 568 total)	25 years at testing	Neuropsychological testing (digit symbol substitution test, Stroop Test Trial 3, Rey Auditory Verbal Learning Test)	Processing speed and executive function decrease (unadjusted P = 0.01-0.05; differences attenuated and ns after adjustment)	Adjusted for age, BMI, hypertension, education, and depression at approximately 18 years postpartum
Fields et al[51], 2017	United States; case-control (Mayo Clinic)	Prior eclampsia	40/40 ref	Approximately 35 years	Neuropsych battery (executive function, memory, attention; trail making B, logical memory I/II, verbal learning, auditory attention)	Executive and memory decrease (d = 0.5-2.0); cognitive impairment 20% vs 8%; CAC increase in impaired hPE group (P = 0.043)	Adjusted for age, education, hypertension, BMI, and medication use; ApoE-4 and mood symptoms were not explanatory
Mielke et al[46], 2016	United States; community cohort + MRI	History of HDP	208/1071 ref	Mid-late life	Processing speed (digit symbol, TMT-A, Stroop) decrease in HDP (all P ≤ 0.035); memory, language, executive ns	Processing speed decrease on digit symbol (P = 0.005), TMT-A (P = 0.035), and Stroop (P = 0.002); memory/Language/executive ns. Processing speed correlated with lower brain injury volume (b = -0.36, P = 0.004)	Adjusted for hypertension duration, nulliparity, and eGFR; results robust in sensitivity models
Postma et al[52], 2016	Netherlands; case-control MRI + neuropsych battery	Prior PE	46 eclamptic + 51 PE/47 ref	Approximately 6 years	Motor speed (TMT-5, P < 0.01); other domains ns	CFQ increase (44 ± 16 vs 36 ± 11, P < 0.001) and HADS increase (11 ± 6 vs 8 ± 5, P < 0.001) in HDP vs controls; no objective cognitive impairment on neuropsych testing	Subjective dysfunction persisted despite normal objective scores; WML not predictive of cognition
Nelander et al[30], 2016	Sweden; population cohort (≥ 65 years)	HDP ± proteinuria	419 HDP/2646 ref	Decades later	Registry diagnosis of dementia	Dementia: 7.6% vs 7.4% (HR: 1.19, 95%CI: 0.79-1.73); CVD: 22.9% vs 19.0% (HR: 1.29, 95%CI: 1.02-1.61); stroke: 13.4% vs 10.7% (HR: 1.36, 95%CI: 1.00-1.81)	Subgroup analysis by proteinuria; registry follow-up
Postma et al[45], 2014	Netherlands; cross-sectional questionnaires ± MRI subset	Eclampsia and PE	46 eclamptic + 51 PE/48 ref	Approximately 6-7 years	CFQ, HADS, neuropsych battery	CFQ and HADS increase in PE/eclampsia vs controls (P < 0.01); visuomotor speed slower (Trail Making B P < 0.001); other domains ns	Persistent subjective cognitive and mood symptoms post-HDP; not time-dependent

HDP: Hypertensive disorders of pregnancy; PE: Preeclampsia; Ref: Reference/control group; BRIEF-A: Behavior Rating Inventory of Executive Function - Adult Version; aRR: Adjusted risk ratio; BMI: Body mass index; HR: Hazard ratio; GH: Gestational hypertension; CVD: Cardiovascular disease; CAC: Coronary artery calcification; hPE: Hypertensive preeclampsia; TMT: Trail Making Test; eGFR: Estimated glomerular filtration rate; CFQ: Cognitive Failures Questionnaire; HADS: Hospital Anxiety and Depression Scale; ApoE-4: Apolipoprotein E ε4 allele; WML: White matter lesion; CI: Confidence interval.

Subjective self-reports of cognitive impairment were consistently elevated. Both papers (2014 and 2016) found significantly higher Cognitive Failures Questionnaire and Hospital Anxiety and Depression Scale scores in HDP groups (all P < 0.01), with women frequently reporting memory difficulties, slowed thinking, and persistent “brain fog”[45,52].

Studies were in agreement regarding increased dementia risk. Nelander et al[30] observed higher dementia prevalence in women with a history of HDPs. Wang et al[49], using the Framingham Offspring cohort, reported a 56% increased risk of all-cause dementia (HR: 1.56, 95%CI: 1.08-2.26) and a 65% increased risk of Alzheimer’s disease (HR: 1.65, 95%CI: 1.01-2.69) in women with a history of preeclampsia. Overall, objective testing often showed small decrements in processing and executive function, while subjective reports repeatedly showed a patient-experienced decrease in cognitive functions. Dementia risk was elevated in population-based cohorts among women with a history of pre-eclampsia.

Mechanistic and biomarker findings

Finally, 6 studies explored biomarkers and mechanisms linking HDP to later neurological disease, shown in Table 5[32,34,37,51,53,54]. Hromadnikova et al[37] demonstrated that women with prior preeclampsia had changes in circulating microRNAs that are theorized to be associated with endothelial injury and vascular remodeling. Akhter et al[34] combined vascular imaging with biomarker analysis and reported increased carotid intima thickness in parallel with elevated laboratory values, such as lipids.

Table 5.

Biomarker and mechanistic studies in women with a history of hypertensive disorders of pregnancy, including vascular imaging, molecular markers, and cardiovascular risk profiles

Ref.	Design and setting	HDP subtype	Sample (exposed/ref)	Time since index pregnancy	Biomarker/mechanistic focus main findings	Notes/adjustments
Venkatesh et al[32], 2025	Secondary analysis, HAPO follow-up study	Prior HDP	476 HDP/3250 ref	10-14 years	ASCVD risk increase in HDP (median 7.0% vs 5.8%, P < 0.001) vs normotensive/no GDM; risk additive when both present. HDL decrease, BMI increase, BP increase, HbA1c increase in exposure groups	Adjusted for BMI, BP, lipid profile
Hromadnikova et al[37], 2019	Case-control, prospective follow-up	Prior PE	101 PE/89 ref	3-11 years	Circulating microRNAs (e.g., miR-17-5p, miR-20b-5p, miR-29a-3p, miR-126-3p, miR-133a-3p, etc.) linked to CVD risk	Standardized serum profiling; corrected for age and BMI
Akhter et al[34], 2019	Case-control, vascular imaging + serum assays	Prior PE	23 PE/35 ref	Approximately 7 years	Intima increase (0.12 mm vs 0.09 mm, P < 0.0001); I/M ratio increase (P < 0.001); Endostatin increase and Apo B increase correlated with vascular remodeling (rs approximately 0.35-0.38, P < 0.01)	Independent of carotid IMT confounders; adjusted for BMI, MAP, and time since follow-up
Orabona et al[53], 2019	Echo/cardiac imaging study	EO-PE, LO-PE	30 EO-PE, 30 LO-PE/30	Approximately 2 years (6 months-4 years)	LV mass increase, concentric remodeling (60% of EO-PE; 53% of LO-PE), diastolic dysfunction in EO-PE > LO-PE	Adjusted for age and hemodynamic parameters
Siepmann et al[44], 2017	MRI + risk factor analysis	Prior PE	34 PE/40 ref	5-15 years	WM lesion volume increase (23.2 ± 24.9 μL vs 10.9 ± 15.0 μL, P < 0.05); lower FA on DTI; correlated with BP and HDL levels	Structural-functional link between microstructure and vascular status
Fields et al[51], 2017	Cognitive cohort with imaging + CVD risk factors	Prior PE	40 PE/39 ref	Approximately 35 years	Coronary artery calcification (endothelial remodeling) increase (67.5 AU vs 0.0 AU, P = 0.043) linked to cognitive impairment; ApoE ε4 ns	Adjusted for HTN, BMI, medications

HDP: Hypertensive disorders of pregnancy; Ref: Reference/control group; HAPO: Hyperglycemia and Adverse Pregnancy Outcome; ASCVD: Atherosclerotic cardiovascular disease; GDM: Gestational diabetes mellitus; HDL: High-density lipoprotein; BMI: Body mass index; BP: Blood pressure; HbA1c: Hemoglobin A1c; PE: Preeclampsia; CVD: Cardiovascular disease; I/M: Intima/media ratio; IMT: Intima-media thickness; Apo B: Apolipoprotein B; MAP: Mean arterial pressure; EO-PE: Early-onset preeclampsia; LO-PE: Late-onset preeclampsia; LV: Left ventricular; WM: White matter; DTI: Diffusion tensor imaging; FA: Fractional anisotropy; HTN: Hypertension; ApoE-4: Apolipoprotein E ε4 allele; ns: Not significant.

Other studies highlighted cardiovascular remodeling as a stroke or neurocognitive disease risk factor. In the short term, Orabona et al[53] observed greater cardiovascular structural changes, including left ventricular mass and concentric remodeling (within two years after preeclampsia). Fields et al[51] found that women with a history of eclampsia had greater coronary artery calcification decades postpartum and further correlated these biomarker changes with cognitive impairment. Venkatesh et al[32] demonstrated higher 10- and 30-year atherosclerotic cardiovascular disease risk scores at a timeframe of 10-14 years after pregnancy.

Biomarker studies were highly focused on cardiovascular biomarkers, indicating a larger concern for endothelial dysfunction, vascular remodeling, and cardiac structural changes long after pregnancy. Along with the intracerebral structural changes, biomarker results suggest a mechanistic background for increased stroke and neurocognitive disease risks.

DISCUSSION

Recent advances in stroke prevention and early recognition of neurocognitive decline have emphasized the value of early prediction prior to progression. Carotid arteries tend to be one of the largest offenders of “silent” microemboli and vulnerable plaque formation that can progress to clinically significant arterial blockage and thus disease response[17,18,54-58]. The extensive literature presented here reported that women with a history of HDPs, particularly preeclampsia and eclampsia, are at a higher long-term risk of stroke. Large population-based studies from Sweden, Taiwan, and Canada, demonstrated large adjusted HRs typically ranging between 1.3 and 2.0 for ischemic stroke, with substantially higher risks for hemorrhagic events the further a patient is from the postpartum period (HRs > 3.0 in eclampsia, suggesting a more severe disease repercussion)[22-30]. Risks were shown to persist for decades after pregnancy, with some studies reporting excess incidence up to 40 years later, highlighting the importance of this topic in our current aging population[30,36,38]. Importantly, the strongest signals emerged in younger women (< 40 years), where stroke risk manifested far earlier than expected[19,27], reinforcing the need for early surveillance and potential early surgical interventions for prevention of serious disease manifestation.

Structural and neuroimaging studies provide a start to considerations in the mechanisms behind increased risk values. Multiple MRI-based investigations confirmed increased WMH, smaller total brain volumes, and evidence of persistent BBB leakage years to decades after complicated pregnancies[37-41,44,45,48]. Carotid artery vascular imaging studies demonstrated increased vessel thickness, cardiovascular remodeling, and dysfunction, all of which are known to be precursors to future cerebrovascular disease[33,34,53]. These findings strengthen the biological causative factors suggesting an acceleration of vascular changes and neurodegeneration that may contribute to stroke risk.

Cognitive outcomes remain more heterogeneous in the data analyzed. Objective neuropsychological testing has yielded mixed results, with some studies reporting deficits in processing speed, executive function, and working memory in several cohorts[49-51], whereas others reported largely null results[52]. The strongest associations to HDP were subjective and patient-reported. Complaints from subjects included forgetfulness, distractibility, and reduced concentration[50,52]. Importantly, dementia diagnoses in older cohorts were also more common, with HRs for all-cause dementia ranging from 1.3-1.6 in longitudinal cohorts[31,48]. This outcome cohort suggests a more subclinical perspective on disease progressions; however, corresponding structural brain changes alongside subjective values raise red flags for disease prediction and progression.

Emerging biomarker and mechanistic studies further support these associations[59-64]. Altered biological factors contributing to endothelial dysfunction and vascular remodeling, elevated serum markers, and higher coronary artery calcification scores in older age all contribute to risk values[33,34,37,51,53,64]. Large-scale risk modeling demonstrated that prior HDP increases estimated 10- and 30-year atherosclerotic cardiovascular disease risk scores, continuing to reinforce the clinical importance of long-term monitoring[54].

Limitations of this literature review include heterogeneity in study design, outcomes assessed, and follow-up duration that ranges widely from 3 months to greater than 40 years. Data sourcing also had high variability between study designs with prospective cohorts, population databases, International Classification of Diseases billing codes, and patient self-report surveys. While there are concerns of sampling bias and reduced comparability, the diversity of methods also provides a wide scope of evidence across populations. Additionally, few included studies systematically examined the demographic and socioeconomic impact on long-term neurological outcomes following HDP. Access to healthcare may vary significantly based on socioeconomic status, region, and race, which likely influences the incidence and severity of these long-term complications.

The correlation between persistent vascular and structural brain changes and history of HDP highlights not only a medical management challenge but also a clear intersection with neurosurgical care, where early recognition and intervention on progressive neurovascular disease may alter long-term outcomes.

Neurosurgery can play a critical role in the long-term care of women with a history of eclampsia or pre-eclampsia to improve outcomes. Structural brain changes such as white matter hyperintensities, cortical atrophy, and vascular remodeling are not only radiological markers but potential precursors of neurosurgical disease states including intracranial atherosclerosis, aneurysm formation, and hemorrhagic stroke[33-35,37-42,52,59-61]. Hemorrhagic stroke is a pathology that can have neurosurgical surveillance in high-risk groups that decreases time to intervention and thus can protect brain tissue from extensive, permanent damage[25,26]. Endovascular neurosurgeons are uniquely positioned to intervene utilizing practices of diagnostic angiography, carotid/intracranial stenting, and embolization. Additionally, as cognitive decline and dementia emerge in this population, functional neurosurgical techniques such as deep brain stimulation or cortical modulation may represent an area of future investigation as the field evolves. Neurosurgery should be considered not only in acute intervention but also as a provider in surveillance pathways and prevention through intervention for this patient population.

Future research considerations

Socioeconomic status may also contribute to the long-term sequelae of pre-eclampsia and eclampsia. Factors related to healthcare disparities, such as limited access to postpartum follow-up, hypertension medication management, and broader social determinants of health likely contribute to increased risk of neurological disease[61]. However, most existing studies have not emphasized these contributing variables, as large database analyses often lack detailed socioeconomic data. Future prospective studies should incorporate socioeconomic factors to solidify the influence on longitudinal neurological and vascular health in this population.

Recent literature suggests that the maternal gut-vaginal microbiome may influence endothelial and immune regulation in HDP[62,63]. Disruption of the microbiome during pregnancy could alter inflammatory pathways and vascular physiology, providing a possible mechanism between HDPs and long-term sequelae presented in this review. This area of research remains understudied; however, the expansion of knowledge on this topic may contribute to affordable and obtainable disease management opportunities.

Eclamptic seizures are known to reduce uteroplacental perfusion during pregnancy, contributing to fetal hypoxia, which in turn may cause fetal neurological disruptions such as developmental delay, preterm birth, or fetal demise[64]. While risk to the fetus is well-documented, the hypoxia from eclamptic seizures can damage maternal cerebral blood vessels, with the potential for long-term neurological sequelae including stroke and persistent structural brain abnormalities. When treated promptly with appropriate acute management, the risk of both maternal and fetal complications can be substantially reduced. However, it is important to note that if treatment is delayed or missed altogether, there may be resultant permanent structural cerebrovascular injury and adverse neurodevelopmental outcomes for both mother and child[9,10,36]. Early administration of magnesium sulfate during eclamptic seizures remains the standard of care for acute management and is a critical component of prevention for neurological complications for both at-risk parties. Given the long-term maternal neurological risks identified in our systematic review, coupled with the well-documented fetal risks, the importance of immediate recognition and appropriate treatment of eclampsia at the time of pregnancy is vital. More precise studies comparing early vs late magnesium sulfate administration during eclamptic seizures may further our understanding of cerebrovascular physiology and pathology in both the mother and fetus.

CONCLUSION

This review suggests reframing of pre-eclampsia and eclampsia as not only an acute obstetric complication handled by obstetrics and gynecology, but also a long-term neurological and vascular risk condition that warrants neurosurgical evaluation. The identified risk factors in this review, including structural brain changes and biomarker trajectories, suggest continued vascular injury that extends after the postpartum period. Early identification of at-risk women, incorporation of neurovascular screening (such as MRI and carotid ultrasound), and close interdisciplinary follow-up may decrease adverse neurological outcomes. While interventional data remain sparse, this literature is strong enough amongst various studies to justify prospective trials to identify if early neurosurgical and vascular interventions could influence morbidity and mortality for this expansive population.