孕期碘营养与PAEs暴露影响婴儿生长发育的交互作用及机制研究

Salt iodization has been widely used to control and eliminate iodine deficiency disorders (IDD) successfully, while mild-to-moderate iodine deficiency and iodine excess in the world including China has been a new public health problem. Growing evidence suggests that phthalates acid esters (PAEs), one group of environmental endocrine disruptors, can interfere with normal thyroid function. However, the deleterious effects on maternal and infant health of PAEs exposure under different iodine status have yet been reported. In this project, we attempt to recruit 1000 pregnant women whose initial visit is before 14 weeks in Wuhan. We will complete a food-frequency questionnaire and a lifestyle questionnaire at first, second and third trimester, collect pregnancy outcomes and growth data of 1, 6, 12 months infant, and evaluate mental development index (MDI) and psychomotor development index (PDI) of 1 year infant by Bayley Scales of Infant Development (BSID-Ⅱ). At the same time, maternal and infant urine, blood, umbilical cord blood and placenta tissues samples will be collected to measure urinary iodine concentration(UIC), creatinine(Cr), PAEs levels and serum thyroglobulin(Tg), thyroid hormones and the expressions of sodium iodine symporter (NIS), deiodinase type 2 (D2) and deiodinase type 3 (D3) in placenta tissues. We aim to find the most sensitive biomarker to evaluate pregnant iodine status through different index, such as iodine dietary intakes, UIC/Cr and Tg concentration, to explore the interaction of iodine nutrition and PAEs exposure during pregnancy on infant growth and development and the related mechanisms. The achievements of this project will provide scientific evidence for rational iodine supplementation and prevention PAEs exposure during pregnancy to promote maternal and child health.

食盐加碘防治碘缺乏病已取得巨大成就，但包括我国在内的孕期轻、中度碘缺乏和碘过量已成为新的公共卫生问题，干扰甲状腺功能的环境污染物邻苯二甲酸酯（PAEs）广泛存在，孕期不同碘营养状况下PAEs暴露影响母婴健康研究未见报道。本项目拟采用前瞻性队列研究，在武汉市纳入1000名孕妇进行孕早、中、晚期膳食（FFQ）和生活方式调查，追踪妊娠结局及1、6、12个月婴儿生长发育情况，评估（贝利婴儿发展量表Ⅱ）1周岁婴儿智力和行为发展；收集尿液、血液、脐血和胎盘等母婴生物样本，以母体和胎儿甲状腺功能为靶点，检测尿碘、肌酐、尿PAEs和血清Tg及甲状腺激素，胎盘钠碘转运体（NIS）、Ⅱ型脱碘酶（D2）和Ⅲ型脱碘酶（D3）表达。以期探讨评估孕期碘营养的有效灵敏指标，不同孕期碘营养不良和PAEs影响婴儿生长发育的交互作用和机制，为孕期合理补碘和降低PAEs暴露政策制定提供科学依据，提高母婴健康水平。

碘是人体必需微量营养素，对生命早期胎儿和婴儿的生长发育十分重要，但许多国家和地区孕妇碘营养状况不容乐观；环境污染物邻苯二甲酸酯（PAEs）及多环芳烃（PAHs）具有内分泌干扰作用，对母婴健康产生威胁。尚未有相关研究报道孕期不同碘营养状况下PAEs和PAHs对母婴健康的作用及影响。本课题基于前瞻性队列研究设计，监测孕妇碘营养状况及PAEs和PAHs暴露水平，追踪妊娠结局及不同年龄段婴幼儿生长发育情况，并检测胎盘钠碘转运体（NIS）、脱碘酶等分子的表达，探讨孕期碘营养与多种环境污染物对胎儿、婴儿生长发育的交互作用和机制。. 研究结果显示武汉市孕妇碘缺乏现象十分普遍，缺乏比例高达46%，同时又有2.4%孕妇存在碘过量问题，因此有必要加强孕期碘营养监测。研究发现碘营养过量导致胎儿晚期EFW z-score降低，影响1月龄婴儿体重；孕期非适宜碘营养状况影响18月龄幼儿发育行为评分；孕中期尿液PAEs和PAHs与中期FL z-score、出生身长z-score、1月龄婴儿ZLEN、24月龄幼儿的ZLEN以及18月龄幼儿发育行为评分呈显著负相关；进一步分析尿碘与PAEs和PAHs对孕中期B超预估体重（EFW）以及后代24月龄体重Z评分（ZWEI）有交互作用（p <0.05），提示碘营养状态在评价环境污染物发育毒性中的重要作用。此外，胎盘NIS及脱碘酶表达与孕期尿碘、尿PAEs/PAHs水平未呈现显著关联，发现了影响孕期PAEs和PAHs暴露水平的膳食及其他生活方式因素。以上研究结果可为孕期合理补碘和降低污染物暴露措施制定提供科学依据。.