Pregnancy and postpartum as vulnerable exposure windows: phthalates and maternal cardiometabolic health

怀孕和产后是脆弱的暴露窗口：邻苯二甲酸盐和孕产妇心脏代谢健康

• 批准号: 10616783
• 负责人: Emily S Barrett
• 金额: $ 58.06万
• 依托单位: HARVARD SCHOOL OF PUBLIC HEALTH
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-05-02 至 2027-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10616783
• 关键词: Biological Markers; Biological Specimen Banks; Birth; Blood Vessels; Body Composition; Body Weight; C-reactive protein; Cardiovascular Diseases; Cardiovascular system; Chemicals; Childbirth; Chronic Disease; Cohort Studies; Collection; Coupled; Data; Diabetes Mellitus; Diastolic blood pressure; Dibutyl Phthalate; Eligibility Determination; Endocrine; Endocrine disruption; Exposure to; Failure; Fetus; First Pregnancy Trimester; Future; Gestational Diabetes; Health; Hormones; Hypertension; Immune; Individual; Inflammatory; Infrastructure; Knowledge; Late pregnancy; Link; Maternal Health; Maternal Physiology; Measures; Mediating; Metabolic; Metabolic syndrome; Metabolism; Modeling; Mothers; Multiple Pregnancy; Non-Insulin-Dependent Diabetes Mellitus; Nuclear Receptors; Obesity; Outcome; Pathway interactions; Physiological; Postpartum Period; Pregnancy; Research; Risk; Sample Size; Statistical Models; Sum; Third Pregnancy Trimester; Time; Weight; Weight Gain; Woman; Women' s Health; arterial stiffness; body system; cardiometabolism; cohort; critical period; data repository; design; early pregnancy; environmental chemical; follow-up; gestational weight gain; immune function; impaired glucose tolerance; improved; insight; interest; maternal obesity; phthalates; pregnancy hypertension; prenatal; recruit; urinary; waist circumference

Pregnancy is a transformative period when multiple body systems radically adjust to protect and nurture the growing fetus. Increasingly, evidence shows that exposure to metabolism disrupting environmental chemicals such as phthalates, can dysregulate the body’s ability to adapt appropriately to the demands of pregnancy. Phthalates disrupt multiple nuclear receptor and hormone-mediated pathways and in cross-sectional research, they have been linked to obesity, diabetes, cardiovascular disease (CVD), and metabolic syndrome. Our research in multiple pregnancy cohorts demonstrates that elevated concentrations of certain phthalate metabolites are associated with adverse cardiometabolic outcomes including excessive gestational weight gain, gestational diabetes mellitus, and impaired glucose tolerance. In the postpartum, maternal physiology must readjust to the non-pregnant state, a physiological “reset” that may be a second critical period of heightened vulnerability to endocrine disruption. Dysregulation during this time is particularly important given the strong evidence that failure to appropriately adapt to the changing demands of pregnancy and postpartum may increase future risk of chronic disease (e.g. CVD, type 2 diabetes). The over-arching hypothesis of this research is that pregnancy and the postpartum are sensitive windows during which phthalates may dysregulate maternal physiology, leading to long-term cardiometabolic health risks. We propose that comprehensive characterization of cardiometabolic health in the first four years after childbirth will provide key insights into the effects of phthalate exposure during critical prenatal and postpartum windows. This proposal capitalizes on the infrastructure, rich data and biospecimen repositories of two ongoing pregnancy cohort studies, UPSIDE MOMS (UM; R01NR017602) & ERGO (R01ES026166), specifically designed to study maternal cardiometabolic health in pregnancy and postpartum. ERGO and UM had identical eligibility criteria, recruiting women in early pregnancy and following them through the postpartum, with extensive prenatal and postpartum bio-specimen collection, coupled with postpartum maternal cardiometabolic assessments. In the proposed combined UM- ERGO cohort (n=500) we capitalize on a larger sample size to measure maternal urinary phthalate concentrations at 6 time points (1st and 3rd trimesters, 1-3 years postpartum) and examine associations with body composition and cardiometabolic biomarkers at 1-4 years postpartum. Study aims include: (1) Determine associations between pregnancy and postpartum phthalate concentrations and maternal body composition at 1- 4 years postpartum; 2) Examine associations between pregnancy and postpartum phthalate concentrations and maternal cardiometabolic profiles at 1-4 years postpartum; and (3) Employ newer modeling approaches to identify sensitive windows in which phthalates may impact maternal obesity and cardiometabolic measures. Our study is a unique opportunity to examine phthalate exposure in pregnancy and the early postpartum in relation to maternal health over 4 years of intensive follow-up.

怀孕是一个转变时期，当多个身体系统从根本上调整，以保护和培养 胎儿发育越来越多的证据表明，暴露于代谢破坏环境化学品， 如邻苯二甲酸盐，会使身体适应怀孕要求的能力失调。 邻苯二甲酸酯破坏多个核受体和受体介导的通路，在横断面研究中， 它们与肥胖、糖尿病、心血管疾病（CVD）和代谢综合征有关。我们 多胎妊娠队列研究表明，某些邻苯二甲酸酯浓度升高 代谢物与不利的心脏代谢结果相关，包括过度的妊娠期体重增加， 妊娠糖尿病和糖耐量受损。在产后，产妇的生理必须 重新调整到非怀孕状态，这可能是第二个关键时期的生理“重置”， 易受内分泌干扰。在这段时间内的调节障碍是特别重要的， 有证据表明，未能适当地适应怀孕和产后不断变化的需求可能会增加 未来患慢性疾病的风险（例如CVD、2型糖尿病）。这项研究的过度假设是， 怀孕和产后是邻苯二甲酸酯可能失调的敏感窗口， 生理学，导致长期的心脏代谢健康风险。我们建议，全面表征 在分娩后的前四年内心脏代谢健康的变化将为邻苯二甲酸酯的影响提供关键的见解 在关键的产前和产后窗口期间暴露。这项提案利用了基础设施，丰富 两项正在进行的妊娠队列研究的数据和生物样本库，UPSIDE MOMS (UM; R 01 NR 017602）和ERGO（R 01 ES 026166），专门用于研究母体心脏代谢健康 在怀孕和产后。ERGO和UM有相同的资格标准，在早期招募女性 怀孕和产后跟踪他们，广泛的产前和产后生物标本 收集，再加上产后母体心脏代谢评估。在拟议的联合国- ERGO队列（n=500），我们利用较大的样本量来测量母体尿邻苯二甲酸酯 6个时间点（妊娠早期和妊娠晚期、产后1-3年）的浓度并检查与身体的关联 在产后1-4年时的组成和心脏代谢生物标志物。研究目的包括：（1）确定 妊娠和产后邻苯二甲酸酯浓度与母体组成之间的关系 产后4年; 2）检查妊娠和产后邻苯二甲酸酯浓度之间的关联， 产后1-4年的母体心脏代谢概况;（3）采用更新的建模方法， 确定邻苯二甲酸酯可能影响母体肥胖和心脏代谢指标的敏感窗口。我们 这项研究是一个独特的机会，检查邻苯二甲酸酯暴露在怀孕和产后早期的关系， 对产妇健康的影响。