Abstract：
The ubiquitous presence of phthalate compounds in cosmetics, personal care products and plastics commonly used in toys, food packaging or household products, results in human exposure with adverse effects on reproductive health and fetal development. Following the PRISMA methodology, this systematic review analyzes the effect of prenatal phthalate exposure on major pregnancy complications, such as gestational diabetes, pregnancy-induced hypertension, fetal growth restriction and preterm birth, and its role in fetal neurodevelopment. This review includes >100 articles published in the last 10 years, showing an association between maternal exposure to phthalates and the risk of developing pregnancy complications. Phthalates are negatively associated with motor skills and memory, and also increase the risk of delayed language acquisition, autism spectrum disorder traits, and behavioral deficits, such as attention deficit hyperactivity disorder in children prenatally exposed to phthalates. Di (2-ethylhexyl) phthalate and its metabolites (mono(2-ethylhexyl) phthalate, mono(3-carboxypropyl) phthalate, mono(2-ethyl-5-hydroxyhexyl) phthalate, mono(2-ethyl-5-oxohexyl) phthalate) are the main compounds associated with the above-mentioned pregnancy complications and fetal neurodevelopmental disorders. In addition, this review discusses the molecular mechanisms responsible for various pregnancy complications and neurodevelopmental disorders, and the critical window of exposure, in order to clarify these aspects. Globally, the most common molecular mechanisms involved in the effects of phthalates are endocrine disruption, oxidative stress induction, intrauterine inflammation, and DNA methylation disorders. In general, the critical window of exposure varies depending on the pathophysiology of the complication being studied, although the first trimester is considered an important period because some of the most vulnerable processes (embryogenesis and placentation) begin early in pregnancy. Future research should aim to understand the specific mechanism of the disruptive effect of each component and to establish the toxic dose of phthalates, as well as to elucidate the most critical period of pregnancy for exposure and the long-term consequences for human health.
摘要：
邻苯二甲酸酯化合物在化妆品中的普遍存在，玩具中常用的个人护理产品和塑料，食品包装或家用产品，结果人类暴露对生殖健康和胎儿发育有不利影响。按照PRISMA方法，本系统综述分析了产前邻苯二甲酸盐暴露对主要妊娠并发症的影响，比如妊娠期糖尿病，妊娠高血压,胎儿生长受限和早产，及其在胎儿神经发育中的作用。这篇综述包括过去10年发表的超过100篇文章，显示孕妇接触邻苯二甲酸盐与发生妊娠并发症的风险之间存在关联。邻苯二甲酸盐与运动技能和记忆力呈负相关，还会增加语言习得延迟的风险，自闭症谱系障碍特征，和行为缺陷，如产前接触邻苯二甲酸盐的儿童的注意力缺陷多动障碍。邻苯二甲酸二（2-乙基己基）酯及其代谢物（邻苯二甲酸单（2-乙基己基）酯，单(3-羧基丙基)邻苯二甲酸酯,单(2-乙基-5-羟基己基)邻苯二甲酸酯,单（2-乙基-5-氧代己基）邻苯二甲酸酯）是与上述妊娠并发症和胎儿神经发育障碍有关的主要化合物。此外,这篇综述讨论了各种妊娠并发症和神经发育障碍的分子机制，和暴露的关键窗口，为了澄清这些方面。全球范围内,邻苯二甲酸酯作用中最常见的分子机制是内分泌干扰，氧化应激诱导，宫内炎症,和DNA甲基化紊乱。总的来说,暴露的关键窗口取决于所研究的并发症的病理生理学，虽然孕早期被认为是一个重要的时期，因为一些最脆弱的过程（胚胎发生和胎盘形成）在怀孕早期开始。未来的研究应旨在了解每种成分的破坏性作用的具体机制，并建立邻苯二甲酸酯的毒性剂量，以及阐明怀孕对暴露的最关键时期以及对人类健康的长期影响。
