Insomnia phenotypes and their impact on maternal and infant health

在每年约400万名孕妇中，失眠和与怀孕有关的睡眠障碍是困扰 到怀孕后期超过50%-60%(200万妇女)。怀孕会引发并加剧失眠 通常延续到产后期的症状。事实上，据报道，高达41%的失业率高达2% 产后数年。尽管失眠很普遍，但通常被认为是生育的一种短暂症状。 对心理或身体健康几乎没有影响。由于这种想法，很少有研究 检查失眠对怀孕/产后产妇心理或身体健康、幸福感或 婴儿结局。这是尽管失眠和新出现的表型(即睡眠不足) 持续时间)似乎会增加抑郁症状和免疫失调以及下丘脑-垂体- 肾上腺轴(HPA)活动。其中每一种都可能随后转化为不良的母体疾病，如 如妊娠期高血压或糖尿病，或不良结局，包括早产。此外，鉴于已知的 产妇发病率对婴儿心理和身体健康的长期后果，有必要审查这些 纵向上迫切需要联合起来。因此，R15提案的一个目标是获得初步数据 关于各种失眠表型的频率，并检查它们与复发的相关性 有产后抑郁症病史的围产期妇女的抑郁症状、免疫和HPA轴活动。我们 还将探讨胎儿性别对婴儿HPA活动的作用，以及失眠(表型)如何改变这种作用。这个 该领域提案的第二个目标是让研究生和本科生接触生物医学。 研究。将招募100名怀孕16-20周的孕妇(18-45岁)作为样本， 在28-31周和产后3个月(与婴儿一起)重新评估，以解决以下问题 目标。目的1：评估复发性抑郁症状和生理失调的程度 在四组孕妇和产后妇女中。1)睡眠时间短的失眠(ISQ++&lt；6 2)睡眠时间正常的失眠(ISQ++≥6小时)；3)短睡者及无失眠者 (ISQ-和≥6小时)；以及4)健康睡眠者(ISQ-和正常睡眠时间≥6小时)。目标2：评估 生理失调在多大程度上中介了失眠和抑郁之间的联系 孕期和产后症状学。生理失调将通过免疫来评估 指标(IL-4、IL-6、IL-8、IL-10和肿瘤坏死因子-α)和HPA轴活动(皮质醇、CAR和斜率)。 探索性目标：(1)评估妊娠期失眠、抑郁和生理失调 受胎儿性别的影响。(2)探讨四种母体婴儿HPA轴异常的程度 失眠症组。我们预计，失眠和睡眠时间短的围产期妇女将有更大的 抑郁症状和生理调节障碍明显优于其他三组。此外，我们预计生理上的 失眠和抑郁之间的联系将在失眠和抑郁之间起中介作用。

Of the ~4 million pregnant women each year, insomnia and pregnancy-related sleep disturbances plague upwards of 50-60% (> 2 million women) by the third trimester. Pregnancy can initiate and exacerbate insomnia symptoms that often extend into the postpartum period. In fact, rates as high as 41% have been reported up to 2 years postpartum. Despite this pervasiveness, insomnia is often considered a transient symptom of childbearing with few consequences for mental or physical health. As a result of this thinking, there have been few studies examining the impact of insomnia on pregnancy/postpartum maternal mental or physical health, well-being or infant outcomes. This is in spite of the fact that insomnia and emerging phenotypes (i.e., with short sleep duration) appear to increase depressive symptomatology and dysregulate immune and hypothalamic-pituitary- adrenal axis (HPA) activity. Each of which may subsequently translate into adverse maternal morbidities, such as gestational hypertension or diabetes, or poor outcomes, including preterm birth. Moreover, given the known long-term consequences of maternal morbidity on infant mental and physical health, the need to examine these associations longitudinally is sorely needed. So, one objective of this R15 proposal is to obtain preliminary data regarding the frequency of various insomnia phenotypes, and examine how they are correlated with recurrent depressive symptomology, immune, and HPA axis activity among perinatal women with a history of PPD. We will also explore the role of fetal sex on infant HPA activity and how it is modified by insomnia (phenotypes). The second objective of this AREA proposal is to expose both graduate and undergraduate students to biomedical research. A sample of 100 pregnant women (18-45 years of age) between 16-20 weeks gestation will be recruited, with reassessment at 28-31 weeks and at 3 months postpartum (along with their infant) to address the following aims. AIM 1: To assess the degree of recurrent depressive symptomatology and physiological dysregulation among four groups of pregnant and postpartum women. 1) insomnia with short sleep duration (ISQ+ + < 6 hours via actigraphy); 2) insomnia with normal sleep duration (ISQ+ + ≥ 6 hours); 3) short sleepers & no insomnia (ISQ- and ≥ 6 hours); and 4) healthy sleepers (ISQ- and normal sleep duration ≥ 6 hours). AIM 2: To assess the extent that physiological dysregulation mediates the association between insomnia and depressive symptomatology during pregnancy and postpartum. Physiological dysregulation will be assessed by immune markers (IL-4, IL-6, IL-8, IL-10 and TNF-α) and HPA axis activity (diurnal release of cortisol, CAR, and slope). Exploratory Aims: (1) To assess whether insomnia, depression and physiological dysregulation during pregnancy is modified by fetal sex. (2) Explore the amount of infant HPA axis dysregulation among the four maternal insomnia groups. We anticipate that perinatal women with insomnia and short sleep duration will have greater depressive symptoms and physiological dysregulation than the other three groups. Also, we expect physiological dysregulation will mediate the association between insomnia and depression.