Highlights
In this nationwide Swedish cohort of 1,785,088 primiparous women followed for up to 50 years, adverse pregnancy outcomes were associated with a higher maternal risk of nontraumatic subarachnoid hemorrhage.
The strongest associations were seen after placental abruption and hypertensive disorders of pregnancy, with elevated risks also observed after gestational diabetes, preterm birth, and small-for-gestational-age delivery.
Risk was greatest in the early years after delivery and weakened over time, but the signal persisted across analyses, including sibling comparisons that partly addressed shared familial and genetic confounding.
The findings support the concept that pregnancy complications may reveal an underlying vascular vulnerability extending beyond traditional ischemic cardiovascular outcomes.
Background
Adverse pregnancy outcomes (APOs) are increasingly viewed not simply as isolated obstetric events, but as early markers of future maternal cardiometabolic and vascular disease. The strongest evidence to date has linked hypertensive disorders of pregnancy, preterm birth, fetal growth restriction, placental abruption, stillbirth, and gestational diabetes to later hypertension, ischemic heart disease, stroke, heart failure, and chronic kidney disease. However, much less is known about their relationship with nontraumatic subarachnoid hemorrhage (SAH), a comparatively rare but often catastrophic form of stroke.
SAH is most commonly caused by rupture of an intracranial aneurysm and carries high case fatality and substantial long-term disability among survivors. Its epidemiology differs from that of ischemic stroke, with notable sex differences and a complex pathobiology involving arterial wall fragility, hemodynamic stress, smoking, hypertension, and possibly hormonal and reproductive factors. Whether APOs identify women at elevated risk of this specific cerebrovascular event has remained uncertain, in part because SAH is uncommon and long follow-up is required to accumulate enough events for reliable inference.
The current study by Zhang and colleagues addresses this gap using one of the largest and longest population-based reproductive cohorts yet assembled. By leveraging Swedish national registers, the investigators examined whether major APOs in the first pregnancy predict later maternal SAH over as long as five decades. They also explored two related arterial outcomes, aortic aneurysm rupture or dissection and spontaneous coronary artery dissection, thereby placing the findings within a broader framework of systemic vascular fragility.
Study Design
Design and data source
This was a nationwide population-based cohort study using the Swedish Medical Birth Register and linked national health and demographic registers. The cohort included 1,785,088 primiparous women whose first delivery occurred between 1973 and 2014. Follow-up extended from the first birth until December 31, 2023.
Population
The mean maternal age at first birth was 28.2 years. Only primiparous women were included at cohort entry, allowing the first pregnancy to serve as the primary exposure window. Women were subsequently followed longitudinally for incident vascular outcomes.
Exposure definition
The APOs assessed included hypertensive disorders of pregnancy, gestational diabetes, placental abruption, preterm birth, abnormal fetal growth, and stillbirth. Abnormal fetal growth included both small-for-gestational-age and large-for-gestational-age categories, with attention to severity in at least some analyses.
Across the cohort, 759,722 women, or 42.6%, experienced at least one APO. Abnormal fetal growth was the most common APO category.
Outcomes
The primary outcome was nontraumatic SAH. Secondary outcomes were aortic aneurysm rupture or dissection and spontaneous coronary artery dissection. The choice of secondary outcomes is noteworthy because these conditions, like aneurysmal SAH, may reflect arterial wall weakness, connective tissue susceptibility, or extreme vascular stress responses.
Statistical approach
The authors used Cox proportional hazards regression to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). Models were adjusted for calendar year, parity, maternal sociodemographic characteristics, and psychiatric disorders. Sibling analyses were also performed to account for shared familial and genetic factors, strengthening causal interpretation by reducing confounding related to family background.
Key Findings
Overall association between APOs and SAH
During follow-up, 5,751 women experienced SAH, corresponding to 0.32% of the cohort. Although the absolute event rate was low, the very large cohort size allowed the investigators to detect clinically meaningful relative risk differences across APO categories.
Women with APOs had a higher risk of SAH than women without such complications. The largest effect estimates reported in the abstract were for placental abruption and hypertensive disorders of pregnancy. Placental abruption was associated with a 62% higher hazard of SAH (HR, 1.62; 95% CI, 1.29-2.04), while hypertensive disorders of pregnancy were associated with a 58% higher hazard (HR, 1.58; 95% CI, 1.41-1.77).
These estimates are notable for two reasons. First, the confidence intervals do not approach the null in either case, supporting statistical robustness. Second, both exposures are biologically plausible markers of maternal endothelial dysfunction, vascular injury, and abnormal hemodynamic stress, all of which may be relevant to aneurysm formation, growth, or rupture.
Other APOs associated with elevated SAH risk
Additional APOs were also associated with increased SAH risk:
Gestational diabetes: HR, 1.40 (95% CI, 1.04-1.90)
Preterm birth: HR, 1.35 (95% CI, 1.24-1.47)
Small for gestational age: HR, 1.34 (95% CI, 1.26-1.43)
These associations were more modest than those seen for placental abruption and hypertensive disorders of pregnancy, but they are still clinically meaningful, especially because preterm birth and fetal growth restriction are common and may identify a substantial population at long-term vascular risk. The gestational diabetes estimate has a wider confidence interval, suggesting fewer exposed cases or greater uncertainty, but the point estimate still supports a potentially important signal.
Timing of risk
An important finding is that the excess SAH risk was greatest in the first years after delivery and attenuated over time. This temporal pattern suggests that pregnancy may uncover an existing vascular susceptibility that is most evident early postpartum and in the ensuing years, although the abstract does not indicate that risk completely normalized.
From a clinical standpoint, this matters because it argues against viewing APOs as distant historical details with only late-life significance. Instead, some women may enter a higher-risk vascular trajectory soon after a complicated pregnancy. That concept aligns with growing recognition of the “fourth trimester” and early interpregnancy years as critical windows for preventive care.
Accumulation, severity, and phenotype
The authors conclude that risk varied according to the timing, severity, and accumulation of pregnancy complications, implying that APO burden may matter, not just the presence or absence of a single event. Although the abstract does not provide all stratified estimates, this pattern is consistent with a dose-response framework in which more severe placental or hypertensive pathology reflects greater maternal vascular vulnerability.
Clinicians should pay particular attention when multiple APOs coexist, such as hypertensive disorders with preterm birth or fetal growth restriction, since these combinations often point to more profound placental and endothelial dysfunction.
Sibling analyses
The reported associations were consistent in sibling analyses. This is an important strength because reproductive outcomes and vascular disease both cluster within families through shared genetics, early-life environment, and health behaviors. While sibling comparisons cannot eliminate all confounding, consistency in these analyses suggests the findings are not fully explained by familial background.
Secondary vascular outcomes
The study also examined aortic aneurysm rupture or dissection and spontaneous coronary artery dissection. Increased risks of aortic aneurysm rupture or dissection were observed after hypertensive disorders of pregnancy, preterm birth, and severely large for gestational age, with HRs ranging from 1.43 to 1.66. This extension beyond the cerebral circulation is clinically provocative, as it suggests that APOs may identify women with broader arterial wall susceptibility.
Associations with spontaneous coronary artery dissection differed in direction. The abstract does not provide full estimates, but the wording indicates a less uniform pattern than that seen for SAH or aortic events. That heterogeneity is plausible, as spontaneous coronary artery dissection has a distinct pathobiology involving coronary arterial wall dissection, fibromuscular dysplasia, hormonal influences, and peripartum triggers, rather than the classic aneurysm biology that underlies many SAH cases.
Clinical Interpretation
This study reinforces a now well-established principle in women’s health: pregnancy acts as a physiologic stress test. APOs may reveal latent abnormalities in vascular function, endothelial integrity, inflammation, metabolic regulation, or connective tissue biology long before conventional cardiovascular disease becomes clinically apparent.
For neurologists, the paper broadens the conversation beyond ischemic stroke prevention. A history of placental abruption, hypertensive disorders of pregnancy, preterm birth, fetal growth restriction, or gestational diabetes may help identify women with elevated susceptibility to later hemorrhagic cerebrovascular events, particularly SAH. Although the absolute risk remains low, SAH is severe enough that even moderate relative risk increases deserve attention in long-term risk assessment.
For obstetricians, internists, and primary care clinicians, the implications are practical. Detailed pregnancy history should be incorporated into routine cardiovascular and cerebrovascular risk assessment. A woman with prior preeclampsia or placental abruption should not simply be reassured once blood pressure normalizes postpartum; she may warrant longitudinal monitoring of blood pressure, smoking exposure, metabolic health, and perhaps earlier attention to symptoms suggestive of vascular disease.
At the same time, these data do not support indiscriminate screening for intracranial aneurysm in all women with prior APOs. The event remains uncommon, and the study does not establish screening thresholds, cost-effectiveness, or the predictive value of APO history alone. Rather, APOs should be viewed as risk-enhancing clinical markers that may refine preventive counseling and holistic vascular surveillance.
Mechanistic Considerations
Several mechanisms could explain the observed associations. Hypertensive disorders of pregnancy are characterized by endothelial dysfunction, systemic inflammation, altered angiogenic signaling, and sustained increases in later-life hypertension risk. Each of these may contribute to chronic arterial remodeling and aneurysm vulnerability.
Placental abruption and fetal growth restriction often reflect placental vascular malperfusion and maternal vascular underperfusion. These conditions may be manifestations of a maternal vasculopathy that is not confined to the uterus. Preterm birth, especially when medically indicated because of maternal or placental disease, may similarly serve as an integrated marker of maternal vascular dysfunction.
Gestational diabetes may operate through metabolic and inflammatory pathways, increasing long-term risk of diabetes, endothelial injury, and vascular stiffness. The finding that aortic events were also elevated after some APOs lends support to the idea of systemic arterial vulnerability rather than a purely brain-specific process.
Another possibility is that some women harbor connective tissue abnormalities, fibromuscular dysplasia, or genetically mediated vessel wall fragility that increase the likelihood of both obstetric placental complications and later arterial rupture or dissection. The sibling analyses argue that shared familial factors do not fully explain the associations, but they do not exclude individual-level genetic predisposition.
Strengths and Limitations
Strengths
The study’s major strengths are its very large sample size, nationwide coverage, long-term follow-up, and use of high-quality linked registry data. These features are particularly important when studying SAH, a relatively rare outcome. The inclusion of sibling analyses meaningfully strengthens internal validity. The broad range of APO exposures also allows the study to move beyond a sole focus on preeclampsia and consider pregnancy complications as a multidimensional vascular phenotype.
Limitations
As an observational registry-based study, residual confounding remains possible. The abstract does not specify adjustment for some important vascular risk factors such as smoking, chronic hypertension, body mass index, or lipid disorders, all of which could influence both APOs and SAH risk. Diagnostic coding accuracy for specific SAH subtypes, including aneurysmal versus nonaneurysmal SAH, may vary over time. Exposure definitions and obstetric practice also changed over the 1973-2014 enrollment period, potentially affecting classification and comparability.
Generalizability should also be considered. Sweden’s population structure, healthcare access, and reproductive care systems may differ from those in more diverse or resource-limited settings. In addition, the cohort was restricted to women with a registered first birth; results may not fully apply to nulliparous women or those with pregnancies not captured in the register.
Finally, the study demonstrates association, not direct causation. It cannot determine whether APOs themselves biologically contribute to SAH risk or whether they mainly serve as markers of preexisting vascular vulnerability.
Practice and Policy Implications
The findings support more systematic incorporation of pregnancy history into lifelong preventive care. Several professional societies already recognize APOs as risk-enhancing factors for future cardiovascular disease. This study suggests that the implications may extend to severe hemorrhagic cerebrovascular disease as well.
In practice, women with prior hypertensive disorders of pregnancy, placental abruption, preterm birth, fetal growth restriction, or gestational diabetes may benefit from:
Structured postpartum transition to primary care
Early and repeated blood pressure assessment
Aggressive smoking avoidance or cessation support
Metabolic screening after gestational diabetes and other APOs
Education about long-term cardiovascular and cerebrovascular risk
Attention to family history and features suggestive of inherited vascular disorders
Whether future risk models for SAH or aneurysmal disease should incorporate APO history remains an open but important research question.
Conclusion
This 50-year population-based Swedish cohort provides compelling evidence that major adverse pregnancy outcomes are associated with increased maternal risk of nontraumatic subarachnoid hemorrhage. The strongest signals were observed for placental abruption and hypertensive disorders of pregnancy, with additional risk seen after gestational diabetes, preterm birth, and small-for-gestational-age delivery. The excess risk was most pronounced soon after pregnancy and remained consistent in sibling analyses, supporting the view that APOs may reveal an underlying vascular vulnerability rather than merely transient obstetric pathology.
For clinicians, the message is straightforward: a complicated pregnancy may offer an early warning about a woman’s future cerebrovascular health. The challenge now is to translate that warning into better postpartum surveillance, more integrated preventive care, and refined research on who among these women is most likely to benefit from targeted vascular evaluation.
Funding and ClinicalTrials.gov
The abstract does not report funding information or a ClinicalTrials.gov registration number. Readers should consult the final published article in Stroke for full funding, disclosures, and protocol details.
References
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