广州孕妇孕期邻苯二甲酸酯暴露水平及其与妊娠结局的关系

Phthalate exposure during pregnancy and its relationship with birth outcomes in Guangzhou

[背景]邻苯二甲酸酯(PAEs)是普遍存在的化学增塑剂,是已知的内分泌干扰素,具有生殖毒性。[目的]了解广州地区PAEs暴露对妊娠结局的影响。[方法]以2017年10月-2019年6月期间进入广州市花都区早产儿出生队列的孕妇作为研究对象,共纳入848对母子。利用问卷调查孕妇基本信息、生活行为方式及妊娠结局等信息。并在分娩后采集母亲静脉血和脐带血,采用高效液相色谱串联质谱法测定母血和脐血5种PAEs代谢物含量,包括邻苯二甲酸(2-乙基己基)(MEHP)、邻苯二甲酸单苄基酯(MBz P)、邻苯二甲酸单丁酯(Mn BP)、邻苯二甲酸单甲酯(MMP)、邻苯二甲酸单乙酯(MEP),并分析其对足月儿出生体重Z评分以及自发早产、小于胎龄儿的影响。[结果] 5种PAEs代谢物在母血和脐血中都有检出。除MBz P检出率较低外,其他4种检出率都达98.94%及以上。母血中MEHP、Mn BP、MMP、MEP质量浓度的几何均数(95%CI)为11.48(11.04~11.95)、27.50(26.07~29.01)、1.98(1.89~2.07)、0.30(0.29~0.32)μg·L-1,脐血中为6.78(6.45~7.12)、36.22(34.61~37.91)、2.54(2.41~2.67)、0.34(0.33~0.36)μg·L-1。脐血中4种代谢物的浓度都与母血呈正相关(P <0.001):相关系数最大为MMP(r=0.585),最小为MEHP(r=0.286)。在控制孕妇年龄、孕期被动吸烟时间、妊娠并发症等相关因素后,母血中只有MEHP浓度与747例足月儿出生体重Z评分呈负相关(b=-0.129,95%CI:-0.219~-0.038);脐血中MEP是自发早产的保护因素(OR=0.655,95%CI:0.436~0.985),但又是小于胎龄儿的危险因素(OR=1.574,95%CI:1.063~2.331)。[结论]广州市孕妇普遍暴露于PAEs,新生儿宫内暴露较严重。宫内暴露影响妊娠结局,在增加胎龄的同时减少了出生体重。

[Background] Phthalates(PAEs) are ubiquitous chemical plasticizers and are known endocrine disruptors that are toxic to reproduction.[Objective] This study aims to investigate the effect of exposure to PAEs on birth outcomes among pregnant women in Guangzhou.[Methods] The participants were 848 pregnant women from a premature birth cohort in Huadu District, Guangzhou City from October 2017 to June 2019. Questionnaires were distributed to collect the demographic information, lifestyle, and birth outcomes of pregnant women, and maternal blood and cord blood samples were also collected after delivery. The concentrations of five PAEs metabolites in maternal blood and cord blood were determined by high-performance liquid chromatography-tandem mass spectrometry, including mono(2-ethylhexyl) phthalate(MEHP), monobenzyl phthalate(MBzP), monobutyl phthalate(MnBP), monomethyl phthalate(MMP), and monoethyl phthalate(MEP). The correlations of PAEs metabolites with the birth weight Z-score of term infants, spontaneous premature, and small for gestational age(SGA) were evaluated.[Results] The selected five PAEs were all positive in maternal blood and cord blood samples.The positive rates were all above 98.94% except for MBz P. The concentrations(geometric mean and 95% CI) of MEHP, Mn BP, MMP, and MEP in maternal blood were 11.48(11.04-11.95), 27.50(26.07-29.01), 1.98(1.89-2.07), and 0.30(0.29-0.32) μg·L-1, respectively;while the concentrations in cord blood were 6.78(6.45-7.12), 36.22(34.61-37.91), 2.54(2.41-2.67), and 0.34(0.33-0.36) μg·L-1, respectively. The concentrations of the four PAEs metabolites in cord blood were all correlated to the concentrations in maternal blood(P < 0.001): The largest correlation coefficient was for MMP(r=0.585), and the smallest was for MEHP(r=0.286). After controlling for pregnant age, passive smoking time during pregnancy, pregnancy complications, and other related factors, the birth weight Z-score of the 747 term infants was negatively associated with MEHP concentration in maternal blood(b=-0.129, 95% CI:-0.219--0.038). In cord blood, a greater MEP concentration was associated with a lower risk for spontaneous preterm(OR=0.655, 95% CI: 0.436-0.985), but with a higher risk for SGA(OR=1.574, 95% CI: 1.063-2.331).[Conclusion] The pregnant women in Guangzhou are widely exposed to PAEs and intrauterine exposure level is high. Intrauterine exposure to PAEs affect pregnancy outcomes by increasing gestational age while reducing birth weight.