Intergenerational Effects of Stress among Low-Income Pregnant Mothers & their Infants

项目摘要：越来越多的研究表明，压力 怀孕期间的经历会导致严重的长期健康问题 母亲和她们的婴儿。一种生物学机制已经在 增加女性患应激相关健康并发症的风险 怀孕是一种应激激素皮质醇。此外，某些遗传因素，如 (5-羟色胺转运体)5-HTTLPR基因的短等位基因，已被认为与 增加一个人对环境压力的皮质醇反应。这些因素的影响 作为母体皮质醇的两种应激生物标志物在胎儿发育过程中具有重要意义 很容易穿过胎盘，潜在地导致胎儿对 产后环境应激源。事实上，一些研究已经表明早期生命 应激源(例如，社会经济逆境、严厉的父母教育)，以加速缩短 儿童的端粒(衡量疾病风险和生物衰老的DNA片段)。 然而，很少有研究确定婴儿端粒长度的出生前和出生后的决定因素 在低收入、长期有压力的家庭中。拟议研究的目标是 前瞻性检查产前孕妇和胎儿皮质醇水平和5- 低收入孕妇HTTLPR基因可预测婴儿的变化 产后前六个月的端粒长度以及某些母亲和 婴儿的特征(例如，暴露于慢性应激源、母亲对 他们的孩子)会影响这些结果。总共将招募125名低收入母亲 在怀孕期间提供唾液样本，以评估其产前皮质醇水平和 5-HTTLPR基因。母亲们也会收集婴儿的头发(在一周内 出生)，以评估胎儿皮质醇水平，以及婴儿的唾液，以评估变化 从出生到产后6个月的端粒长度。据推测，高加索 围产期母儿皮质醇水平与短等位基因5-HTTLPR的关系 母亲将与婴儿出生后端粒长度加速缩短有关 到产后六个月，端粒长度将受到某些母体的调节 和婴儿的特征(例如，母亲对慢性应激源的暴露较大，较少 母亲对婴儿需求的敏感程度)。这一假说已经被提出。 来自主要研究人员和研究合作者收集的初步数据。这个 建议工作的结果对公众健康有重大影响，有助推动 了解产前生物学机制如何促进代际发育 低收入孕妇及其婴儿应激结局的传递 这可能会对后代的健康和疾病风险产生终生影响。是这样的 调查结果还将有助于确定潜在的预防和治疗途径。 发展的关键时期，以优化母亲、她们的孩子、 以及以后的世代。

PROJECT SUMMARY: As demonstrated by a growing number of studies, stress experienced during pregnancy can lead to significant long-term health problems for mothers and their infants. One biological mechanism that has been identified in heightening a woman’s risk for developing stress-related health complications during pregnancy is the stress hormone cortisol. Further, certain genetic factors, such as the short allele of the (serotonin transporter) 5-HTTLPR gene, have been implicated in increasing one’s cortisol response to stressors in the environment. The impact of these two biomarkers of stress is highly significant in fetal development, as maternal cortisol readily crosses the placenta, potentially causing the fetus to become overly sensitive to environmental stressors after childbirth. Indeed, some studies have shown early life stressors (e.g., socioeconomic adversity, harsh parenting) to accelerate the shortening of telomeres (DNA segments that measure disease risk and biological aging) in children. Yet, few studies have identified pre- and postnatal determinants of infant telomere length among low-income, chronically stressed families. The objective of the proposed study is to prospectively examine whether prenatal maternal and fetal cortisol levels and the 5- HTTLPR genotype of low-income pregnant mothers are predictive of changes in infant telomere length over the first six months postpartum and whether certain maternal and infant characteristics (e.g., exposure to chronic stressors, maternal sensitivity towards their infants) influence these outcomes. A total of 125 low-income mothers will be recruited during pregnancy to provide saliva samples that assess their prenatal cortisol levels and 5-HTTLPR genotype. Mothers will also collect their infant’s hair (within one week after birth) to assess fetal cortisol levels, as well as their infant’s saliva to assess for changes in telomere length from birth to six months postpartum. It is hypothesized that heightened prenatal maternal and fetal cortisol levels and the short allele 5-HTTLPR genotype in mothers will be associated with accelerated shortening of infant telomere length from birth to six months postpartum, and that telomere length will be moderated by certain maternal and infant characteristics (e.g., greater maternal exposure to chronic stressors, less maternal sensitivity towards their infant’s needs). This hypothesis has been formulated from preliminary data collected by the principal investigator and study collaborators. The results of the proposed work have substantial public health implications in advancing our understanding of how prenatal biological mechanisms contribute to the intergenerational transmission of stress outcomes among low-income pregnant mothers and their infants that can have lifelong consequences for the offspring’s health and disease risk. Such findings will also help to identify potential avenues for prevention and treatment, during critical periods of development, to optimize health outcomes for mothers, their children, and subsequent generations.