Prenatal diet, PM2.5 and programming of the infant autonomic response

描述(由申请人提供)：可塑性是关键生命时期环境暴露的结果，影响协调潜在发育过程的生理系统。自主神经系统(ANS)是一种可能的关键调节系统，容易受到围产期环境编程的影响，从而增加儿科和成人疾病的风险。检查候选环境因素的流行病学研究很少，这些因素从子宫开始编程ANS，并探索可能的潜在机制。虽然环境的影响是多种多样的，但在胎儿程序化和自主神经紊乱方面受到关注的因素包括颗粒物空气污染和母亲的饮食(例如，氧化剂/抗氧化剂平衡)。虽然这些因素通常被单独考虑，但不断发展的理论强调了研究它们的综合影响的重要性。与颗粒物污染相关的不良后果的生物学机制包括ANS失衡和氧化应激的诱导被认为具有核心作用。怀孕期间空气污染对母亲的影响可能会破坏胎儿-胎盘氧化剂/抗氧化剂的平衡，并对发育中的ANS产生影响。饮食因素可能对空气污染物的影响起到调节作用。这个调查小组利用哈佛大学代际压力机制编程(PRISM)研究，这是一项产前城市队列研究，增加了营养指标，以研究和检查产前短期(7天平均值)和长期暴露于环境颗粒物污染[PM2.5，黑碳(BC)作为交通相关颗粒物的标志]与6个月大婴儿自主神经功能之间的关系。ANS表型通过神经内分泌学方法进行指标化，分析基础活动条件下和实验室应激源后的唾液淀粉酶水平。电生理学方法也被用来分析ANS的反应性[以呼吸性窦性心律失常(RSA)为指标]对同一实验室应激源的反应。其次，将研究长期和短期的产前环境颗粒物污染、孕妇产前尿液和脐带血中氧化应激生物标记物(F2-Isoprostanes)和婴儿自主神经功能之间的关联，以探索产前污染和婴儿自主神经平衡之间的关联是否通过增强的氧化应激来调节。最后，将检查环境颗粒物污染对6个月大婴儿ANS功能的影响，看看可能保护婴儿免受氧化应激影响的母亲产前饮食因素[例如，-3脂肪酸和抗氧化剂微量营养素(例如，维生素C、维生素E和类黄酮类)]是否会被母亲产前饮食因素改变，这些因素包括食物频率问卷(FFQ)、怀孕期间两次获得的饮食记录和选定的产前确定的母亲血清/血浆生物标记物。

DESCRIPTION (provided by applicant): Plasticity is a consequence of environmental exposures during critical life periods affecting physiological systems orchestrating underlying developmental processes. The autonomic nervous system (ANS) is a putative key regulatory system vulnerable to perinatal environmental programming toward trajectories of enhanced pediatric and adult disease risk. Epidemiological studies that examine candidate environmental factors that program the ANS starting in utero and explore putative underlying mechanisms are scarce. While environmental influences are diverse, factors gaining attention with respect to fetal programming and autonomic disruption include particulate air pollution and maternal diet (e.g., oxidant/antioxidant balance). While these factors have generally been considered independently, evolving theory underscores the importance of studying their integrated effects. Biological mechanisms responsible for adverse outcomes associated with particulate pollution include ANS imbalance and the induction of oxidative stress is thought to have a central role. Air pollution effects on the mother during pregnancy may disrupt fetal-placental oxidant/antioxidant balance with implications for the developing ANS. Dietary factors may play a modulating role on effects of air pollutants. This investigative team leveraged the Harvard Programming of Intergenerational Stress Mechanisms (PRISM) study, a prenatal urban cohort, to add nutritional measures to study and examine associations among prenatal short-term (7-day mean) and chronic exposure to ambient particulate pollution [PM2.5, black carbon (BC) as a marker of traffic-related particles] and autonomic function in 6-month old infants. ANS phenotyping is indexed through a neuroendocrinologial approach analyzing salivary ¿-amylase levels during basal ambulatory conditions and following an in-laboratory stressor. An electrophysiological approach is also employed to analyze ANS reactivity [indexed by respiratory sinus arrhythmia (RSA)] in response to the same in-laboratory stressor. Secondly, associations among long- and short- term prenatal ambient particulate pollution, biomarkers of oxidative stress (F2-isoprostanes) will be examined in maternal prenatal urine and cord blood, and infant autonomic functioning to explore whether associations between prenatal pollution and infant autonomic balance are mediated through enhanced oxidative stress. Finally, ambient particulate pollution will be examined on ANS functioning in 6-month olds to see if the effects are modified by maternal prenatal dietary factors that may protect the infant from oxidative stress [e.g., ?-3 fatt acids and antioxidant micronutrients (e.g., vitamins C and E and flavonoids)] ascertained using a triad approach incorporating a food frequency questionnaire (FFQ), dietary records obtained twice during pregnancy, and select maternal serum/plasma biomarkers ascertained prenatally.