Abstract：
BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are synthetic chemicals linked to adverse pregnancy outcomes. Although their underlying biological mechanisms are not fully understood, evidence suggests PFAS may disrupt endocrine functions and contribute to oxidative stress (OS) and inflammation.
OBJECTIVE: We examined associations between early pregnancy PFAS exposure and OS biomarkers, exploring potential effect modifications by fetal sex and maternal race.
METHODS: We used data from 469 LIFECODES participants with measured plasma PFAS (median 10 weeks gestation) and repeated measures (median 10, 18, 26, and 35 weeks gestation) of urinary OS biomarkers [8-iso-prostaglandin-F2α (8-isoprostane) and 8-hydroxydeoxyguanosine (8-OHdG)]. Protein damage biomarkers (chlorotyrosine, dityrosine, and nitrotyrosine) were additionally measured in plasma from a subset (N = 167) during the third visit. Associations between each PFAS and OS biomarkers were examined using linear mixed-effects models and multivariable linear regressions, adjusting for potential confounders, including maternal age, race, education level, pre-pregnancy BMI, insurance status, and parity. Effect modifications were evaluated by including an interaction term between each PFAS and fetal sex or maternal race in the models.
RESULTS: We observed significant positive associations between PFOS and 8-isoprostane, with a 9.68% increase in 8-isoprostane levels (95% CI: 0.10%, 20.18%) per interquartile range increase in PFOS. In contrast, PFUA was negatively associated [9.32% (95% CI: -17.68%, -0.11%)], while there were suggestive positive associations for MPAH and PFOA with 8-isoprostane. The associations of several PFAS with 8-OHdG varied by fetal sex, showing generally positive trends in women who delivered females, but negative or null in those who delivered males. No significant effect modification by maternal race was observed.
CONCLUSIONS: This study provides evidence linking PFAS exposure to OS during pregnancy, with potential sex-specific effects of certain PFAS on 8-OHdG. Further research should explore additional OS/inflammatory biomarkers and assess the modifying effects of dietary and behavioral patterns across diverse populations.
OBJECTIVE: We examined associations between early pregnancy PFAS exposure and OS biomarkers, exploring potential effect modifications by fetal sex and maternal race.
METHODS: We used data from 469 LIFECODES participants with measured plasma PFAS (median 10 weeks gestation) and repeated measures (median 10, 18, 26, and 35 weeks gestation) of urinary OS biomarkers [8-iso-prostaglandin-F2α (8-isoprostane) and 8-hydroxydeoxyguanosine (8-OHdG)]. Protein damage biomarkers (chlorotyrosine, dityrosine, and nitrotyrosine) were additionally measured in plasma from a subset (N = 167) during the third visit. Associations between each PFAS and OS biomarkers were examined using linear mixed-effects models and multivariable linear regressions, adjusting for potential confounders, including maternal age, race, education level, pre-pregnancy BMI, insurance status, and parity. Effect modifications were evaluated by including an interaction term between each PFAS and fetal sex or maternal race in the models.
RESULTS: We observed significant positive associations between PFOS and 8-isoprostane, with a 9.68% increase in 8-isoprostane levels (95% CI: 0.10%, 20.18%) per interquartile range increase in PFOS. In contrast, PFUA was negatively associated [9.32% (95% CI: -17.68%, -0.11%)], while there were suggestive positive associations for MPAH and PFOA with 8-isoprostane. The associations of several PFAS with 8-OHdG varied by fetal sex, showing generally positive trends in women who delivered females, but negative or null in those who delivered males. No significant effect modification by maternal race was observed.
CONCLUSIONS: This study provides evidence linking PFAS exposure to OS during pregnancy, with potential sex-specific effects of certain PFAS on 8-OHdG. Further research should explore additional OS/inflammatory biomarkers and assess the modifying effects of dietary and behavioral patterns across diverse populations.
摘要：
背景：全氟烷基和多氟烷基物质（PFAS）是与不良妊娠结局相关的合成化学物质。尽管它们的潜在生物学机制尚未完全了解，有证据表明，PFAS可能会破坏内分泌功能，并导致氧化应激（OS）和炎症。
目的：我们检查了妊娠早期PFAS暴露与OS生物标志物之间的关系，探索胎儿性别和母体种族的潜在效应修饰。
方法：我们使用了469名LIFECODES参与者的数据，这些参与者测量了血浆PFAS（中位妊娠10周）和重复测量（中位妊娠10、18、26和35周）尿OS生物标志物[8-异前列腺素-F2α（8-异前列腺素）和8-羟基脱氧鸟苷（8-OHdG）]。蛋白质损伤生物标志物（氯酪氨酸，二酪氨酸,和硝基酪氨酸）在第三次访视期间在一个子集（N=167）的血浆中进行了额外测量。使用线性混合效应模型和多变量线性回归检查每个PFAS和OS生物标志物之间的关联，调整潜在的混杂因素，包括产妇年龄,种族,教育水平,孕前BMI,保险状况,和平价。通过在模型中包括每个PFAS与胎儿性别或母体种族之间的相互作用项来评估效果修饰。
结果：我们观察到全氟辛烷磺酸和8-异前列腺素之间存在显著正相关，8-异前列腺素水平增加9.68%(95%CI：0.10%，20.18%)全氟辛烷磺酸每四分位数间距增加。相比之下,PFUA呈负相关[9.32%(95%CI:-17.68%,-0.11%)]，而MPAH和PFOA与8-异前列腺素存在暗示性正相关。几种PFAS与8-OHdG的关联因胎儿性别而异，在分娩女性的女性中显示出普遍的积极趋势，但在交付男性的人中否定或无效。未观察到母体种族的显着影响修饰。
结论：这项研究提供了在怀孕期间PFAS暴露于OS的证据，某些PFAS对8-OHdG具有潜在的性别特异性影响。进一步的研究应该探索其他OS/炎症生物标志物，并评估不同人群饮食和行为模式的改变效果。
目的：我们检查了妊娠早期PFAS暴露与OS生物标志物之间的关系，探索胎儿性别和母体种族的潜在效应修饰。
方法：我们使用了469名LIFECODES参与者的数据，这些参与者测量了血浆PFAS（中位妊娠10周）和重复测量（中位妊娠10、18、26和35周）尿OS生物标志物[8-异前列腺素-F2α（8-异前列腺素）和8-羟基脱氧鸟苷（8-OHdG）]。蛋白质损伤生物标志物（氯酪氨酸，二酪氨酸,和硝基酪氨酸）在第三次访视期间在一个子集（N=167）的血浆中进行了额外测量。使用线性混合效应模型和多变量线性回归检查每个PFAS和OS生物标志物之间的关联，调整潜在的混杂因素，包括产妇年龄,种族,教育水平,孕前BMI,保险状况,和平价。通过在模型中包括每个PFAS与胎儿性别或母体种族之间的相互作用项来评估效果修饰。
结果：我们观察到全氟辛烷磺酸和8-异前列腺素之间存在显著正相关，8-异前列腺素水平增加9.68%(95%CI：0.10%，20.18%)全氟辛烷磺酸每四分位数间距增加。相比之下,PFUA呈负相关[9.32%(95%CI:-17.68%,-0.11%)]，而MPAH和PFOA与8-异前列腺素存在暗示性正相关。几种PFAS与8-OHdG的关联因胎儿性别而异，在分娩女性的女性中显示出普遍的积极趋势，但在交付男性的人中否定或无效。未观察到母体种族的显着影响修饰。
结论：这项研究提供了在怀孕期间PFAS暴露于OS的证据，某些PFAS对8-OHdG具有潜在的性别特异性影响。进一步的研究应该探索其他OS/炎症生物标志物，并评估不同人群饮食和行为模式的改变效果。
