Editorial Comment—Parity and Risk of Subarachnoid Hemorrhage: An Emerging Association
An individual’s risk of developing subarachnoid hemorrhage (SAH) is influenced by genetic and environmental factors.1 Emerging data have helped to shape our understanding of such factors, and the present work by Gaist and colleagues2 provides the most definitive efforts to date concerning the potential (inverse) association of parity and risk of SAH.
SAH possesses a number of unique peculiarities compared with other forms of stroke. Although the incidence of other forms of stroke may be decreasing, that of SAH does not appear to be on the wane. Additionally, an epidemiological sex discrepancy is apparent with SAH (the only form of stroke with a clear preponderance of afflicted women). Female sex also appears to have an association with increased risk of intracranial aneurysm formation and growth.3 Further characterization of this clear sex discrepancy may prove to have some utility in influencing our conceptualization of SAH and its potential prevention and therapy.
A gender gap in SAH has led a number of groups to examine potential hormonal influences on SAH.4–6 Although the risk of SAH (as is the risk of all types of circulatory disorders) appears to be significantly increased around delivery (from 2 days before to 1 day after),6 the overall influence of parity on the risk of developing SAH had heretofore not been clearly established due, at least in part, to methodological and sample size limitations.
The present study by Gaist and colleagues helps to clarify the issue of parity and risk of SAH. Using national Swedish registries and a nested case-control design, the authors demonstrate that parity may provide a modest reduction in the risk of developing SAH. Of those individuals sustaining an episode of SAH, 70% did so 5 years or more after birth of their last child. Additionally, there was a general trend for increasing parity to be associated with correspondingly lower odds ratios. Smoking was once again confirmed as a risk factor for development of SAH.
The present study has a number of significant limitations, however, and the authors provide an earnest discussion of these issues. Despite being the most robust study to date concerning parity and risk of SAH, inadequate power is still apparent as evidenced by the fact that parity was no longer significantly associated with risk of SAH in restricted samples despite the point estimates being similar to those of the overall population studied. The registries themselves have some inherent limitations (missing data, potential misclassification, and no means of corroboration), although the authors cogently address this issue. There also appear to be small differences in certain baseline demographics (such as incidence of cesarean deliveries) between cases and controls. Furthermore, with the available data the authors were not able to control for the distribution of known risk factors for SAH between groups (such as hypertension and alcohol consumption). The follow-up also was not long enough to ensure all women had completed their reproductive history, although separate subgroup analysis of women >40 years of age suggested little potential influence. The above notwithstanding, this was a carefully thought out and overall well-conducted study.
The authors have objectively presented their findings concerning the association of parity with risk of SAH, although many questions remain. Speculation concerning the basis for a potential role of parity in conferring protection against the occurrence of SAH is intriguing. Future study may reveal a biological basis for this association, which, in turn, may contribute to our understanding of the pathogenesis of this disease. Alternatively, consideration of behavioral changes associated with pregnancy and the puerperium may be important. For instance, with a greater proportion of time spent by women in a period in which they may be more health conscious and avoid potential harmful exposures, one could postulate a lower risk of developing a condition dependent on, at least in part, certain environmental influences. Future work concerning the potential influence of parity on outcome may also be revealing. Certain known risk factors such as smoking may have some influence on outcome.7
Ultimately, an individual’s risk of developing a given disease is dependent on a combinatorial mechanism, influenced by genetic and environmental factors. Delineation of predictive factors may provide valuable insight into the biology of disease and may also provide impetus for preventative therapeutic measures. Studies such as the present one by Gaist and colleagues represent a significant contribution to the literature concerning potential factors predicting risk of SAH. Although the mechanism by which increased parity may confer protection against future development of SAH in women remains unknown, further study of this emerging association is clearly warranted and explanation of this peculiar gender gap will hopefully culminate in advancement of our understanding of this lingering and devastating disease.
Kissela BM, Sauerbeck L, Woo D, Khoury J, Carrozzella J, Pancioli A, Jauch E, Moomaw CJ, Shukla R, Gebel J, et al. Subarachnoid hemorrhage: a preventable disease with a heritable component. Stroke. 2002; 33: 1321–1326.
Gaist D, Pedersen L, Cnattingius S, Sørensen HT. Parity and risk of subarachnoid hemorrhage in women: a nested case-control study based on national Swedish registries. Stroke. 2004; 35: 28–33.
Juvela S, Poussa K, Porras M. Factors affecting formation and growth of intracranial aneurysms: a long-term follow-up study. Stroke. 2001; 32: 485–491.
Mhurchu CN, Anderson C, Jamrozik K, Hankey G, Dunbabin D. Hormonal factors and risk of aneurysmal subarachnoid hemorrhage: an international population-based, case-control study. Stroke. 2001; 32: 606–612.
Okamoto K, Horisawa R, Kawamura T, Asai A, Ogino M, Takagi T, Ohno Y. Menstrual and reproductive factors for subarachnoid hemorrhage risk in women: a case-control study in Nagoya, Japan. Stroke. 2001; 32: 2841–2844.