Headaches during pregnancy and the risk of subsequent stroke

Abstract

Background: Primary headache disorder is a known risk factor for stroke in women and usually improves during the first trimester of pregnancy. However, despite this, some women develop headaches during pregnancy (G-HA), and the effect of this headache on subsequent stroke is unknown. In this study, we evaluated the association between G-HA and stroke after delivery in women.

Methods: Based on the Korean National Health Insurance Service database, we included women hospitalized for delivery between 2012 and 2013. G-HA was defined as a headache diagnosed during pregnancy. Primary outcome was any stroke that occurred during the observational periods from delivery to December 31, 2020. All diseases were identified based on data registered in the database using the International Classification of Disease-10^th Revision-Clinical Modification codes.

Results: Of 906,187 pregnant women, G-HA was found in 56,813 (6.3%). During the observational periods, the G-HA ( +) group had a significantly higher risk of any stroke [adjusted hazard ratio (aHR) = 1.59, 95% confidence interval (CI): 1.30-1.95], ischemic stroke (aHR = 1.50, 95% CI: 1.12-2.01), hemorrhagic stroke (aHR = 1.63, 95% CI: 1.23-2.15), and intracerebral hemorrhage (aHR = 1.63, 95% CI: 1.19-2.23) than the G-HA (-) group. When analyzed considering the interaction with history of headache disorder, G-HA showed a significant association with hemorrhagic stroke, but lost its effect on ischemic stroke.

Conclusions: We demonstrated that G-HA was associated with subsequent stroke occurrence after delivery. However, the relationship between G-HA and ischemic stroke is mitigated by a history of pre-pregnancy headache disorder.

Keywords: Female stroke; Headache; Pregnancy; Prognosis; Risk factor; Stroke.

Fig. 1

Cumulative incidence of four clinical outcomes in participants with and without gestational headaches. ICH = intracerebral hemorrhage, SAH = subarachnoid hemorrhage. Compared to women without gestational headache, women with gestational headache had a significantly higher risk of any stroke (A), ischemic stroke (B), and ICH (C). However, gestational headache showed no statistical correlation with SAH

Fig. 2

Adjusted hazard ratio of gestational headache in each of the four clinical outcomes: multivariable cox regression analysis^*. ^*Each outcome was adjusted for age, hypertension, diabetes, functional disability, history of headache, gestational hypertension, and gestational diabetes. Compared with the G-HA (-) group as the reference, the G-HA ( +) group had a significant risk increase for any stroke (59%), ischemic stroke (50%), hemorrhagic stroke (63%), and intracerebral hemorrhage (63%). However, there was no statistical difference between the G-HA ( +) group and the G-HA (-) group in the occurrence of subarachnoid hemorrhage

Fig. 3

Cumulative incidence of four clinical outcomes between groups according to the history of headache disorders and gestational headaches. G-HA = gestational headache, Hx-HA = history of headache disorder. In a comparison between the four groups according to the presence or absence of G-HA and Hx-HA, the [G-HA ( +) & Hx-HA( +)] group showed the highest cumulative incidence rate in all types of stroke outcomes. The [G-HA ( +) & Hx-HA (-)] or the [G-HA (-) & Hx-HA ( +)] groups also showed higher cumulative incidence rates than the [G-HA (-) & Hx-HA (-)] group. However, in ischemic stroke, the [G-HA( +) & Hx-HA(-)] group showed no statistical difference from the [G-HA(-) & Hx-HA(-)] group