Maternal and Paternal Preconception Environmental Exposures and Children's Health

母亲和父亲的孕前观念 环境暴露与儿童健康

• 批准号: 10321564
• 负责人: Joseph M Braun
• 金额: $ 59.48万
• 依托单位: HARVARD SCHOOL OF PUBLIC HEALTH
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-01-01 至 2024-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10321564
• 关键词: 10 year old; Accounting; Affect; Age; Animals; Anthropometry; Biological; Biometry; Body Composition; Boston; Chemicals; Child; Child Health; Child Welfare; Childhood; Clinic; Cognition; Cohort Studies; Conceptions; Couples; Data; Diet; Disease; Embryo; Endocrine Disruptors; Environment; Environmental Epidemiology; Environmental Exposure; Epidemiology; Epigenetic Process; Exposure to; Family; Fathers; Fertility; Financial cost; Food; Future Generations; General Hospitals; General Population; Germ Cells; Glucose; Health; Heritability; Homeostasis; Human; Impairment; Individual; Insulin; Joints; Life; Lipids; Literature; Massachusetts; Measures; Medical History; Modification; Mothers; Neurodevelopmental Disorder; Obesity; Outcome; Personal Satisfaction; Persons; Pharmaceutical Preparations; Phenotype; Plastics; Play; Pregnancy; Problem behavior; Prospective cohort; Public Health; Reproductive Health; Research; Research Personnel; Risk; Risk Factors; Roentgen Rays; Role; Sampling; Satiation; Serum; Smoking; Stress; Triad Acrylic Resin; Twin Multiple Birth; Urine; Visit; Woman; blood pressure elevation; cardiometabolic risk; cardiometabolism; caregiving; cognitive ability; cohort; consumer product; cost effective; disorder risk; early childhood; environmental chemical exposure; epidemiologic data; epidemiology study; executive function; experimental study; follow-up; hormonal signals; improved; innovation; male; modifiable risk; mother nutrition; multidisciplinary; neurobehavior; neurobehavioral; neurodevelopment; novel; obesity in children; obesity risk; offspring; personal care products; phthalates; prenatal; prospective; sedentary activity; sperm cell

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.

抽象的 儿童肥胖、心脏代谢异常和神经发育障碍普遍存在，影响 儿童及其家庭的健康和福祉，并产生巨大的经济成本。 表明生命早期的环境暴露会增加这些疾病的风险。 有理由强调研究妊娠期和幼儿期的环境暴露， 关于孕产妇孕前暴露对儿童健康甚至儿童健康影响的流行病学数据有限 关于父亲孕前暴露的影响的研究较少。 令人信服的数据表明，母亲和父亲受压力和饮食影响的先入之见 尽管支持配子中编码的可遗传表观遗传修饰的后代表型。 科学前提是孕前环境暴露有可能影响儿童的健康， 几乎完全缺乏对内分泌干扰化学物质的特别关注。 因为它们破坏荷尔蒙信号并改变配子和胚胎的表观遗传编程，这在 可能会对儿童健康产生不利影响的一类值得高度关注的化学品是多功能邻苯二甲酸盐。 许多消费品中使用的化学品，普通人群普遍接触这些化学品。 我们的多学科研究小组提出了一项新的研究，研究对象是以下夫妇所生的孩子： 参与了我们正在进行的前瞻性孕前队列研究，我们之前分析了多次尿液。 受孕前母亲和父亲以及受孕期间女性的邻苯二甲酸酯代谢物样本 在此提案中，我们将对 381 名符合条件的儿童（7-10 岁）进行现场探访。 收集儿童神经行为、人体测量和心脏代谢功能的详细测量结果。 已收集或将收集广泛的母亲、父亲和儿童层面的协变量数据，包括饮食、SES、 我们的具体目标是确定病史、护理环境和体力/久坐活动。 母亲和父亲在孕前单独和/或共同接触邻苯二甲酸盐的程度 与以下因素相关：1) 行为问题增多、执行功能较差、认知能力下降，2) 肥胖增加和饱腹感降低，3）葡萄糖和胰岛素稳态受损，血液增加 我们提出的创新研究代表了一个独特的机会。 确定母亲和父亲孕前接触邻苯二甲酸盐是否会影响儿童的健康，同时还 其他创新包括控制产前和儿童时期的邻苯二甲酸盐接触。 母亲和父亲孕前尿液样本以评估邻苯二甲酸盐暴露，最先进的评估 儿童健康结果，以及使用新的统计方法来研究邻苯二甲酸酯混合物和窗口 我们提出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。 邻苯二甲酸盐暴露对儿童健康的影响，从而确定流行儿童疾病的可改变的危险因素。

项目成果

Paternal and maternal preconception and maternal pregnancy urinary phthalate metabolite and BPA concentrations in relation to child behavior.

父亲和母亲的孕前和母亲怀孕尿邻苯二甲酸酯代谢物和 BPA 浓度与儿童行为的关系。

• DOI: 10.1016/j.envint.2023.108337
• 发表时间: 2024
• 期刊: Environment international
• 影响因子: 11.8
• 作者: Leader,Jordana;Mínguez-Alarcón,Lidia;Williams,PaigeL;Ford,JenniferB;Dadd,Ramace;Chagnon,Olivia;Bellinger,DavidC;Oken,Emily;Calafat,AntoniaM;Hauser,Russ;Braun,JosephM
• 通讯作者: Braun,JosephM

The Effect of Deuteration and Homologation of the Lactam Ring of Nirmatrelvir on Its Biochemical Properties and Oxidative Metabolism.

• DOI: 10.1021/acsbiomedchemau.3c00039
• 发表时间: 2023-12-20
• 期刊: ACS BIO & MED CHEM AU
• 作者: Arutyunova, Elena;Belovodskiy, Alexandr;Chen, Pu;Khan, Muhammad Bashir;Joyce, Michael;Saffran, Holly;Lu, Jimmy;Turner, Zoe;Bai, Bing;Lamer, Tess;Young, Howard S;Vederas, John C;Tyrrell, D Lorne;Lemieux, M Joanne;Nieman, James A
• 通讯作者: Nieman, James A