Abstract：
Prenatal exposure to phthalates (PAEs) is ubiquitous among Chinese neonates. PAEs entering the body will be transformed to various hydrolyzed and oxidated PAE metabolites (mPAEs). PAEs and mPAEs exposure may lead to adverse birth outcomes through disruption of multiple hormone signaling pathways, induction of oxidative stress, and alterations in intracellular signaling processes. In this study, the concentrations of 11 mPAEs in 318 umbilical cord serum samples from neonates in Jinan were quantified with HPLC-ESI-MS. Multiple linear regression, Bayesian kernel machine regression, and quantile g-computation models were utilized to investigate the effects of both individual mPAE and mPAE mixture on birth outcomes. Stratified analysis was performed to explore whether these effects were gender-specific. mPAE mixture was negatively associated with birth length (BL) z-score, birth weight (BW) z-score, head circumference (HC) z-score, and ponderal index (PI). Mono(2-ethylhexyl) phthalate (MEHP) manifested negative associations with BL(z-score), BW(z-score), HC(z-score), and PI, whereas mono(2-carboxymethylhexyl) phthalate (MCMHP) was negatively associated with BW(z-score) and PI within the mPAE mixture. Stratified analysis revealed that the negative associations between mPAE mixture and four birth outcomes were attenuated in female infants, while the positive impact of mono(2-ethyl-5carboxypentyl) phthalate (MECPP) on BL(z-score) and BW(z-score) could be detected only in females. In summary, our findings suggest that prenatal exposure to phthalates may be associated with intrauterine growth restriction, and these effects vary according to the gender of the infant.
摘要：
中国新生儿中邻苯二甲酸酯（PAEs）的产前暴露普遍存在。进入体内的PAEs将转化为各种水解和氧化的PAE代谢物(mPAEs)。PAEs和mPAEs暴露可能通过破坏多种激素信号通路导致不良出生结局。氧化应激的诱导，和细胞内信号传导过程的改变。在这项研究中,采用HPLC-ESI-MS对济南地区318例新生儿脐带血清中11种mPAEs的浓度进行了定量。多元线性回归，贝叶斯核机回归，和分位数g计算模型用于研究个体mPAE和mPAE混合物对出生结局的影响。进行分层分析以探索这些影响是否具有性别特异性。mPAE混合物与出生身长（BL）z评分呈负相关，出生体重（BW）z评分，头围(HC)z值,和体重指数(PI)。邻苯二甲酸单（2-乙基己基）酯（MEHP）与BL（z评分）呈负相关，BW(z-score),HC(z-score),和PI，而邻苯二甲酸单（2-羧甲基己基）酯（MCMHP）与mPAE混合物中的BW（z评分）和PI呈负相关。分层分析显示，mPAE混合物与四种出生结局之间的负相关在女婴中减弱，而邻苯二甲酸单（2-乙基-5-羧基戊基）酯（MECPP）对BL（z评分）和BW（z评分）的积极影响只能在女性中检测到。总之,我们的研究结果表明，产前接触邻苯二甲酸盐可能与宫内生长受限有关，这些影响因婴儿的性别而异。
