A Prospective Cohort Study of Migraines, Platelet Activation, and Preeclampsia

描述(由研究人员提供)：偏头痛是一种常见的慢性发作性疾病，源于特发性，以严重的衰弱头痛和自主神经系统功能障碍为特征，通常伴有神经系统症状，与紧张型头痛的区别在于强度中等到重度，单侧位置，恶心的存在，以及对活动和/或刺激的敏感性。据报告，妇女一生中偏头痛的患病率在14%至25%之间，在育龄期间患病率有所上升。先兆子痫是一种妊娠血管疾病，以高血压和蛋白尿为特征，高达8%的妊娠合并并发症，是全世界孕产妇发病率的主要原因。一些研究已经证明偏头痛患者患妊娠高血压或先兆子痫的风险增加。方法论上的局限性阻碍了现有研究的因果推断。我们建议对2,000名未分娩孕妇进行前瞻性队列研究，以进一步研究偏头痛和先兆子痫之间的关系。这项拟议研究的总体目标是评估孕妇孕前偏头痛病史和早孕期间的偏头痛症状是否以及在多大程度上与先兆子痫的风险有关；以及(2)评估有关血小板聚集和激活在先兆子痫中的作用的机制假说。我们将在怀孕的前三个月收集孕妇的血液样本。在面谈期间，女性将被要求提供有关医生诊断为偏头痛和偏头痛症状的信息。偏头痛筛查呈阳性和/或报告曾被诊断为偏头痛的女性将接受委员会认证的神经科医生的后续访谈，以确认偏头痛的状况。将审查分娩和分娩的医疗记录，以收集有关研究怀孕的信息。母亲的血小板聚集和活化指数将用流式细胞仪方法进行评估。统计分析将集中于确定：(1)孕前偏头痛病史与随后发生子痫前期风险的关联程度；(2)妊娠早期偏头痛症状和用于治疗偏头痛的药物是否与子痫前期风险独立相关；以及(3)妊娠早期血小板聚集和激活的生物标志物是否与母亲偏头痛状况及随后的子痫前期风险相关。增加关于子痫前期和偏头痛的流行病学和病理生理学知识，特别是与孕期促炎症血小板与白细胞黏附有关的知识，将有助于理解潜在的机制，并有助于确定可能的预防和治疗策略。与公共卫生相关的偏头痛是一种常见的慢性发作性疾病，其特征是严重的衰弱头痛和自主神经系统功能障碍，在女性中终生患病率为14%至25%。先兆子痫是一种妊娠血管疾病，高达8%的妊娠合并有并发症，是全世界孕产妇发病率的主要原因。一些研究证明，偏头痛女性患先兆子痫的风险增加。我们建议的研究将评估孕妇孕前偏头痛病史和早孕期间的偏头痛症状是否以及在多大程度上与先兆子痫的风险相关；并评估可能的生理风险。 这种关联的机制与血小板聚集和激活在先兆子痫中的作用有关。增加关于子痫前期和偏头痛的流行病学和病理生理学知识，特别是与孕期促炎症血小板与白细胞黏附有关的知识，将有助于了解潜在的机制，并有助于确定可能的预防和治疗策略。

DESCRIPTION (provided by investigator): Migraine is a common chronic-episodic disorder of idiopathic origin characterized by severe debilitating headaches and autonomic nervous system dysfunction, often accompanied by neurological symptoms, and distinguished from tension-type headaches by the moderate to severe intensity, unilateral location, the presence of nausea, and sensitivity to activity and/or stimuli. The lifetime prevalence of migraine in women has been reported between 14-25 per cent with increasing prevalence during the childbearing years. Preeclampsia, a vascular disorder of pregnancy, characterized by hypertension and proteinuria, complicates up to 8 per cent of all pregnancies, and it is a leading cause of maternal morbidity worldwide. A handful of studies have documented an elevated risk of pregnancy-induced hypertension or preeclampsia among migraineurs. Methodological limitations hinder causal inference from available studies. We propose a prospective cohort study of 2,000 pregnant nulliparous women to further examine the relationship between migraines and preeclampsia. The overall aim of the proposed research is to evaluate whether, and to what extent, maternal pre-gestational history of migraines and migraines symptom during early pregnancy are associated with preeclampsia risk; and (2) to evaluate mechanistic hypotheses concerning the role of platelet aggregation and activation in preeclampsia. We will collect maternal blood samples during the first trimester of pregnancy. During in-person interviews, women will be asked to provide information regarding physician diagnosed migraine and migraine symptoms. Women who screen positive for migraine and/or who report a prior medical diagnosis of migraine will have a follow-up interview with a board certified neurologist to confirm migraine status. Labor and delivery medical records will be reviewed to collect information about the study pregnancy. Indices of maternal platelet aggregation and activation will be assessed using flow cytometric methods. Statistical analyses will focus on determining: (1) the extent to which a history of pre-gestational migraines is associated with subsequent risk of preeclampsia; (2) whether migraine symptoms in early pregnancy and medications used to treat migraines are independently associated with preeclampsia risk; and (3) whether biological markers of platelet aggregation and activation in early pregnancy, are associated with maternal migraine status and subsequent risk of preeclampsia. Increased knowledge concerning the epidemiology and pathophysiology of preeclampsia and migraines, particularly as they relate to pro- inflammatory platelet adhesion to leukocytes during pregnancy will aid in understanding underlying mechanisms and lead to the identification of possible prevention and therapeutic strategies. PUBLIC HEALTH RELEVANCE Migraine, a common chronic-episodic disorder characterized by severe debilitating headaches and autonomic nervous system dysfunction, has a lifetime prevalence of 14- 25 per cent in women. Preeclampsia, a vascular disorder of pregnancy, complicates up to 8 per cent of pregnancies, and is a leading cause of maternal morbidity worldwide. Some studies have documented an elevated risk of preeclampsia among women with migraines. Our proposed research will evaluate whether, and to what extent, maternal pre-gestational history of migraines and migraine symptoms during early pregnancy are associated with preeclampsia risk; and evaluate possible physiological mechanisms of this association concerning the role of platelet aggregation and activation in preeclampsia. Increased knowledge concerning the epidemiology and pathophysiology of preeclampsia and migraines, particularly as they relate to pro-inflammatory platelets adhesion to leukocytes during pregnancy will aid in understanding underlying mechanisms and lead to the identification of possible prevention and therapeutic strategies.