The effect of pregnancy and puerperium on haemorrhage risk in women with cerebral cavernous malformations: a case-crossover study.
- 1Department of Neurosurgery, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy.
- 2Neurology Unit, Dipartimento di Neuroscienze, Organi di Senso e Torace, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy.
- 3Department of Neuroscience, "Giovanni Paolo II" Hospital, Lamezia Terme, Catanzaro, Italy.
Abstract
Introduction
Cerebral cavernous malformations (CCMs) are lesions that may be incidental or present with haemorrhage or focal neurological deficits. Some authors have reported apparent lesion enlargement during pregnancy and hypothesised that hormonal fluctuations may promote CCM growth or haemorrhage. Whether pregnancy increases the risk of symptomatic haemorrhage (SH) from CCMs therefore represents an important clinical concern.Patients and methods
We collected prospective data from patients with CCMs. A case-crossover framework was used to compare the risk of SH during pregnancy-related and non-pregnant observation periods. Pregnancy-related observation periods included pregnancy and the 6-week puerperium, while all other follow-up time after CCM diagnosis was considered non-pregnant. Each woman served as her own control, with the risk of SH during pregnancy-related periods compared with that during her non-pregnant follow-up periods.Results
After screening, the final cohort included 42 women diagnosed with a CCM at 46 years of age or younger. Of these, 23 women experienced at least 1 pregnancy (30.4% familial CCM; 21.7% brainstem CCM) at or after CCM diagnosis, accounting for 40 pregnancies. Overall, 2 SHs occurred during 25.6 pregnancy patient-years, corresponding to an annual SH rate of 7.8% (95% CI, 0.9-28.3), compared with 42 SHs during 420.7 non-pregnancy patient-years, corresponding to an annual SH rate of 10.0% (95% CI, 7.2-13.5). No statistically significant difference was found in the haemorrhagic rates between pregnant vs non-pregnant periods (P = .751). When observation periods were stratified according to a history of prior haemorrhage, no SHs occurred during 10.3 pregnancy patient-years among periods with prior haemorrhage, whereas 8 SHs occurred during 12.7 non-pregnancy patient-years, corresponding to an annual SH rate of 63.0% (95% CI, 27.2-124.2). Among periods without prior haemorrhage, 2 SHs occurred during 15.2 pregnancy patient-years, corresponding to an annual SH rate of 13.1% (95% CI, 1.6-47.5), compared with 34 SHs during 408.0 non-pregnancy patient-years, corresponding to an annual SH rate of 8.3% (95% CI, 5.8-11.6). In this subgroup, generalised estimating equation (GEE)-Poisson analysis showed no significant difference in haemorrhage risk between pregnancy and non-pregnancy periods (incidence rate ratio [IRR] 1.64, 95% CI, 0.44-6.13; P = .462). When analysis was restricted to brainstem CCMs, GEE-Poisson analysis showed no significant difference between pregnancy and non-pregnancy periods (IRR 2.09; 95% CI, 0.36-12.14; P = .411). One SH occurred during 8.2 pregnancy patient-years, corresponding to an annual SH rate of 12.2% (95% CI, 0.3-67.9), vs 6 SHs during 91.6 non-pregnancy patient-years, corresponding to 6.6% (95% CI, 2.4-14.3). Among periods with prior haemorrhage, no SHs occurred during 1.5 pregnancy patient-years (0.0%; 95% CI, 0.0-194.7), vs 2 SHs during 4.4 non-pregnancy patient-years (45.2%; 95% CI, 5.5-163.4). Among periods without prior haemorrhage, 1 SH occurred during 6.7 pregnancy patient-years (15.0%; 95% CI, 0.4-83.6), vs 4 SHs during 87.2 non-pregnancy patient-years (4.6%; 95% CI, 1.3-11.7), with no significant difference on GEE-Poisson analysis (IRR 3.50; 95% CI, 0.62-19.78; P = .156).Conclusion
Pregnancy was not associated with a significantly increased rate of SH in this cohort of women with CCMs. However, the limited number of events during pregnancy and the limited pregnant follow-up require cautious interpretation. Counselling should remain individualised according to lesion location, prior haemorrhagic history, neurological status and treatment history.
Related
- Postpartum risk and prognosis of pregnancy-associated intracerebral haemorrhage: a nationwide cohort-crossover study
- Maternal Obesity and Outcomes During Pregnancy and the Puerperium: A Single-Center Retrospective Observational Study
- Lateral transpetrosal approaches for brainstem cavernous malformations: tailoring the operative trajectory according to lesion location. Illustrative cases.
- When a Seizure Reveals More Than a Hemorrhage: When to Suspect Cerebral Cavernous Malformations.
- Efficacy of Medical Treatment Options for Reducing the Risk of Bleeding in Patients With Sporadic and Familial Cerebral Cavernous Malformations: A Systematic Review and Network Meta-Analysis.
BibTeX
@article{palermo2026effect,
title = {{The effect of pregnancy and puerperium on haemorrhage risk in women with cerebral cavernous malformations: a case-crossover study.}},
author = {Matteo Palermo and Vittoria Viglione and Federico Tosto and Francesco Signorelli and Alessio Albanese and Alessandro Olivi and Francesco Doglietto and Marina Romozzi and Carmelo Lucio Sturiale},
journal = {European stroke journal},
year = {2026},
month = oct,
doi = {10.1093/esj/aakag130},
url = {https://europepmc.org/article/MED/42949441},
note = {CC BY},
}
RIS
TY - JOUR
TI - The effect of pregnancy and puerperium on haemorrhage risk in women with cerebral cavernous malformations: a case-crossover study.
AU - Matteo Palermo
AU - Vittoria Viglione
AU - Federico Tosto
AU - Francesco Signorelli
AU - Alessio Albanese
AU - Alessandro Olivi
AU - Francesco Doglietto
AU - Marina Romozzi
AU - Carmelo Lucio Sturiale
PY - 2026
DA - 2026/10/01
JO - European stroke journal
DO - 10.1093/esj/aakag130
UR - https://europepmc.org/article/MED/42949441
AB - Introduction Cerebral cavernous malformations (CCMs) are lesions that may be incidental or present with haemorrhage or focal neurological deficits. Some authors have reported apparent lesion enlargement during pregnancy and hypothesised that hormonal fluctuations may promote CCM growth or haemorrhage. Whether pregnancy increases the risk of symptomatic haemorrhage (SH) from CCMs therefore represents an important clinical concern.Patients and methods We collected prospective data from patients with CCMs. A case-crossover framework was used to compare the risk of SH during pregnancy-related and non-pregnant observation periods. Pregnancy-related observation periods included pregnancy and the 6-week puerperium, while all other follow-up time after CCM diagnosis was considered non-pregnant. Each woman served as her own control, with the risk of SH during pregnancy-related periods compared with that during her non-pregnant follow-up periods.Results After screening, the final cohort included 42 women diagnosed with a CCM at 46 years of age or younger. Of these, 23 women experienced at least 1 pregnancy (30.4% familial CCM; 21.7% brainstem CCM) at or after CCM diagnosis, accounting for 40 pregnancies. Overall, 2 SHs occurred during 25.6 pregnancy patient-years, corresponding to an annual SH rate of 7.8% (95% CI, 0.9-28.3), compared with 42 SHs during 420.7 non-pregnancy patient-years, corresponding to an annual SH rate of 10.0% (95% CI, 7.2-13.5). No statistically significant difference was found in the haemorrhagic rates between pregnant vs non-pregnant periods (P = .751). When observation periods were stratified according to a history of prior haemorrhage, no SHs occurred during 10.3 pregnancy patient-years among periods with prior haemorrhage, whereas 8 SHs occurred during 12.7 non-pregnancy patient-years, corresponding to an annual SH rate of 63.0% (95% CI, 27.2-124.2). Among periods without prior haemorrhage, 2 SHs occurred during 15.2 pregnancy patient-years, corresponding to an annual SH rate of 13.1% (95% CI, 1.6-47.5), compared with 34 SHs during 408.0 non-pregnancy patient-years, corresponding to an annual SH rate of 8.3% (95% CI, 5.8-11.6). In this subgroup, generalised estimating equation (GEE)-Poisson analysis showed no significant difference in haemorrhage risk between pregnancy and non-pregnancy periods (incidence rate ratio [IRR] 1.64, 95% CI, 0.44-6.13; P = .462). When analysis was restricted to brainstem CCMs, GEE-Poisson analysis showed no significant difference between pregnancy and non-pregnancy periods (IRR 2.09; 95% CI, 0.36-12.14; P = .411). One SH occurred during 8.2 pregnancy patient-years, corresponding to an annual SH rate of 12.2% (95% CI, 0.3-67.9), vs 6 SHs during 91.6 non-pregnancy patient-years, corresponding to 6.6% (95% CI, 2.4-14.3). Among periods with prior haemorrhage, no SHs occurred during 1.5 pregnancy patient-years (0.0%; 95% CI, 0.0-194.7), vs 2 SHs during 4.4 non-pregnancy patient-years (45.2%; 95% CI, 5.5-163.4). Among periods without prior haemorrhage, 1 SH occurred during 6.7 pregnancy patient-years (15.0%; 95% CI, 0.4-83.6), vs 4 SHs during 87.2 non-pregnancy patient-years (4.6%; 95% CI, 1.3-11.7), with no significant difference on GEE-Poisson analysis (IRR 3.50; 95% CI, 0.62-19.78; P = .156).Conclusion Pregnancy was not associated with a significantly increased rate of SH in this cohort of women with CCMs. However, the limited number of events during pregnancy and the limited pregnant follow-up require cautious interpretation. Counselling should remain individualised according to lesion location, prior haemorrhagic history, neurological status and treatment history.
SN - 2396-9873
SN - 2396-9881
ER -