Maternal and Paternal Preconception Environmental Exposures and Children's Health

摘要 儿童肥胖、心脏代谢异常和神经发育障碍很普遍，影响 儿童及其家庭的健康和福祉，并有巨大的财政成本。研究 表明早期生活环境暴露会增加这些疾病的风险。在那里有 有理由强调研究孕期和儿童早期的环境暴露，有 关于母亲先入为主的暴露对儿童健康甚至对儿童健康的影响的流行病学数据有限 关于父亲先入为主的暴露的影响的研究较少。对动物的实验研究提供了 令人信服的数据表明，母亲和父亲的先入为主的压力和改变的饮食会影响 通过在配子中编码的可遗传的表观遗传修饰的后代表型。尽管支持 先入为主的环境暴露有可能影响儿童健康的科学前提， 几乎完全缺乏对人类的研究。扰乱内分泌的化学物质尤其值得关注。 因为它们扰乱荷尔蒙信号并改变配子和胚胎的表观遗传编程，这在 轮流可能会对儿童健康造成不利影响。一类高度关注的化学品是邻苯二甲酸酯，多功能 在许多消费品中使用的化学品，其在普通人群中普遍存在。 我们的多学科研究团队提出了一项关于夫妇所生子女的新研究 参与了我们正在进行的前瞻性先入为主队列研究。我们之前分析了多个尿液 母亲和父亲怀孕前和怀孕期间妇女的邻苯二甲酸酯代谢物样本 怀孕了。在这项建议中，我们将亲自探访381名符合资格的儿童(7-10岁)，并 收集儿童神经行为、人体测量和心脏代谢功能的详细测量。我们有 收集或将收集广泛的母亲、父亲和孩子级别的协变量数据，包括饮食、社会经济状况、 病史、照料环境和身体/久坐活动。我们的具体目标是确定 母亲和父亲怀孕前邻苯二甲酸盐单独和/或联合暴露的程度 与：1)行为问题增加，执行功能较差，以及认知能力降低有关，2) 肥胖增加，饱腹感减少，3)血糖和胰岛素稳态受损，血液增加 压力，和改变的血脂。我们提出的创新研究代表着一个独特的机会 确定母亲和父亲怀孕前接触邻苯二甲酸盐是否会影响儿童健康，同时 控制产前和儿童的邻苯二甲酸盐暴露。其他创新包括提供多个 母亲和父亲的未孕尿样评估邻苯二甲酸盐暴露，最新评估 儿童健康结果，并使用新的统计方法来研究邻苯二甲酸盐混合物和 脆弱性。我们提议的研究将提供关于母亲和父亲先入为主的影响的关键数据。 此外，我们还将研究邻苯二甲酸盐暴露对儿童健康的影响，从而确定流行的儿童疾病的可改变的风险因素。

Abstract Childhood obesity, cardiometabolic abnormalities, and neurodevelopmental disorders are prevalent, impact the health and well-being of children and their families, and have substantial financial costs. Research demonstrates that early life environmental exposures increase the risk of these disorders. While there has been justifiable emphasis on studying environmental exposures during gestation and early childhood, there is limited epidemiologic data on the impact of maternal preconception exposures on children’s health and even less research on the effect of paternal preconception exposures. Experimental studies in animals provide compelling data showing that maternal and paternal preconception exposures to stress and altered diet affect offspring phenotypes through heritable epigenetic modifications encoded in gametes. Despite support for the scientific premise that preconception environmental exposures have the potential to affect children’s health, there is an almost complete lack of human studies. Endocrine disrupting chemicals are of particular concern because they disrupt hormonal signaling and alter epigenetic programming of gametes and embryos, which in turn may adversely affect child health. One class of chemicals of high concern is phthalates, multifunctional chemicals used in many consumer products and for which there is ubiquitous general population exposure. Our multidisciplinary team of investigators proposes a new study of children who were born to couples who participated in our ongoing prospective preconception cohort study. We previously analyzed multiple urine samples for phthalate metabolites from mothers and fathers before conception and from women during pregnancy. In this proposal, we will conduct in-person visits on 381 eligible children (7-10 years of age) and collect detailed measures of child neurobehavior, anthropometry, and cardiometabolic function. We have collected or will collect extensive maternal, paternal, and child-level covariate data, including diet, SES, medical history, caregiving environment, and physical/sedentary activity. Our specific aims are to determine the extent to which maternal and paternal preconception phthalate exposures are individually and/or jointly associated with: 1) increased behavior problems, poorer executive function, and reduced cognitive abilities, 2) increased adiposity and reduced satiety, 3) impaired glucose and insulin homeostasis, increased blood pressure, and altered serum lipids. Our innovative proposed study represents a unique opportunity to determine if maternal and paternal pre-conception phthalate exposure affects children’s health, while also controlling for prenatal and childhood phthalate exposure. Other innovations include the availability of multiple maternal and paternal preconception urine samples to assess phthalate exposure, state of the art assessment of child health outcomes, and use of novel statistical approaches to study phthalate mixtures and windows of vulnerability. Our proposed study will provide critical data on the effect of maternal and paternal preconception phthalate exposure on child health, and thus identify modifiable risk factors for prevalent childhood diseases.