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

描述（由研究者提供）：偏头痛是一种常见的特发性慢性发作性疾病，其特征为重度衰弱性头痛和自主神经系统功能障碍，通常伴有神经系统症状，与紧张型头痛的区别在于中度至重度强度、单侧位置、恶心的存在以及对活动和/或刺激的敏感性。据报道，女性偏头痛的终生患病率在14%-25%之间，在育龄期患病率不断增加。先兆子痫是一种以高血压和蛋白尿为特征的妊娠期血管疾病，在所有妊娠中造成高达8%的并发症，是全世界孕产妇发病的主要原因。一些研究已经证明偏头痛患者中妊娠高血压或先兆子痫的风险增加。方法的局限性阻碍了从现有研究中进行因果推断。我们提出了一项前瞻性队列研究，2,000名孕妇未经产的妇女，以进一步研究偏头痛和先兆子痫之间的关系。本研究的总体目的是评估孕妇孕前偏头痛史和妊娠早期偏头痛症状是否与先兆子痫风险相关，以及在何种程度上与先兆子痫风险相关;（2）评估血小板聚集和活化在先兆子痫中作用的机制假说。我们将在妊娠的前三个月收集母体血液样本。在面对面的采访中，女性将被要求提供有关医生诊断的偏头痛和偏头痛症状的信息。偏头痛筛查阳性和/或报告偏头痛既往医学诊断的女性将与委员会认证的神经科医生进行随访，以确认偏头痛状态。将审查分娩和分娩病历，以收集研究妊娠相关信息。将使用流式细胞术方法评估母体血小板聚集和活化指数。统计分析将集中于确定：（1）孕前偏头痛史与随后的先兆子痫风险相关的程度;（2）妊娠早期偏头痛症状和用于治疗偏头痛的药物是否与先兆子痫风险独立相关;（3）妊娠早期是否存在血小板聚集和活化的生物学标志物，与母亲偏头痛状态和随后的先兆子痫风险有关。关于先兆子痫和偏头痛的流行病学和病理生理学的知识增加，特别是当它们与妊娠期间促炎性血小板粘附于白细胞有关时，将有助于理解潜在的机制，并导致确定可能的预防和治疗策略。偏头痛是一种常见的慢性发作性疾病，其特征是严重的使人衰弱的头痛和自主神经系统功能障碍，在妇女中的终生患病率为14- 25%。先兆子痫是一种妊娠期血管疾病，使多达8%的妊娠并发症，是全世界孕产妇发病的主要原因。一些研究已经证明偏头痛妇女患先兆子痫的风险升高。我们建议的研究将评估母亲孕前偏头痛史和妊娠早期偏头痛症状是否与先兆子痫风险相关以及在多大程度上与先兆子痫风险相关;并评估可能的生理学因素。 这种关联的机制涉及血小板聚集和活化在先兆子痫中的作用。关于先兆子痫和偏头痛的流行病学和病理生理学知识的增加，特别是当它们与妊娠期间促炎性血小板粘附于白细胞有关时，将有助于理解潜在机制，并导致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.