妊娠期全氟化合物暴露与孕妇甲状腺相关激素水平的关联研究

Association between perfluoroalkyl and polyfluoroalkyl substances and maternal thyroid-related hormones in pregnant women

[背景]妊娠期全氟化合物(PFAS)暴露可能影响孕妇甲状腺相关激素水平,但以往研究大多关注含8~10碳的PFAS,缺乏对含更长碳链PFAS的研究。[目的]评估血浆多种PFAS暴露和妊娠期甲状腺相关激素浓度的关联。[方法]基于2016年9月-2018年4月开展的嘉善出生队列,以781例孕妇为研究对象,应用高效液相色谱串联质谱法检测其外周血中13种常见PFAS的浓度,按照各化合物浓度的三分位数将其分为“低浓度组”“中浓度组”和“高浓度组”。应用电化学发光免疫法测定总三碘甲状腺原氨酸(T3)、总甲状腺素(T4)、游离三碘甲状腺原氨酸(FT3)、游离甲状腺素(FT4)、促甲状腺激素(TSH)、甲状腺球蛋白抗体(TG-Ab)和甲状腺过氧化物酶抗体(TPOAb)的浓度。采用多元线性回归,评估多种PFAS浓度和甲状腺相关激素浓度之间的关系。[结果]与全氟十二烷酸(PFDoA)低浓度组相比,PFDoA高浓度组T3浓度变化值为-0.10 nmol·L^(-1),其95%CI为–0.20~0 nmol·L^(-1);FT3浓度变化值为–0.15 pmol·L^(-1),其95%CI为–0.28~–0.02 pmol·L^(-1);FT4浓度变化值为–3.02 pmol·L^(-1),其95%CI为–5.66~–0.39 pmol·L^(-1)。与全氟十三烷酸(PFTrDA)低浓度组相比,PFTrDA高浓度组T3浓度变化值为–0.10 nmol·L^(-1),其95%CI为–0.20~0 nmol·L^(-1)。而与全氟己烷磺酸(PFHxS)低浓度组相比,PFHxS中浓度组T4浓度变化值为6.10 nmol·L^(-1),其95%CI为0.44~11.75 nmol·L^(-1)。未发现PFAS与TSH浓度之间有统计学意义的关联。另外,在TG-Ab和/或TPOAb阳性的孕妇中,发现PFAS和甲状腺相关激素浓度之间的负相关关系更明显。[结论]妊娠期PFAS暴露可影响孕妇甲状腺相关激素稳态,其效应在TG-Ab和/或TPOAb阳性孕妇中更强。

[Background]Exposure to perfluoroalkyl and polyfluoroalkyl substances(PFAS)during pregnancy might affect thyroid-related hormone levels in pregnant women.However,most previous studies focused on the effects of PFAS containing 8-10 carbon atoms,and few studies have estimated the associations between PFAS with longer carbon chain and thyroid-related hormone levels.[Objective]To examine the associations between PFAS exposure and thyroid-related hormones in pregnant women.[Methods]The present study was based on the Jiashan Birth Cohort from September 2016 to April 2018.We analyzed 13 PFAS in maternal blood samples(n=781)by high-performance liquid chromatography-tandem mass spectrometry,as well as total triiodothyronine(T3),total thyroxine(T4),free T3(FT3),free T4(FT4),thyroid stimulating hormone(TSH),thyroglobulin antibody(TG-Ab),and thyroid peroxidase antibody(TPOAb)by electrochemiluminescence immunoassay.PFAS were divided into three groups:low concentration,medium concentration and high concentration according to the tertile of their concentrations.We estimated the associations between PFAS concentrations and thyroid-related hormones in pregnant women by multiple linear regression.[Results]In the multiple linear regression models,a change in perfluorododecanoic acid(PFDoA)concentrations from the low concentration group to the high concentration group was associated with a−0.10(95%CI:−0.20,0)nmol·L^(-1) change in T3,−0.15(95%CI:−0.28,−0.02)pmol·L^(-1) change in FT3,and−3.02(95%CI:−5.66,−0.39)pmol·L^(-1) change in FT4,respectively.A change in perfluorotridecanoic acid(PFTrDA)concentrations from the low concentration group to the high concentration group was associated with a−0.10(95%CI:−0.20,0)nmol·L^(-1) change in T3.Compared with the low concentration group,the concentration of T4 in the medium concentration group of perfluorohexane sulfonate(PFHxS)increased by 6.10(95%CI:0.44,11.75)nmol·L^(-1).No statistically significant associations were found between PFAS and TSH concentration.The negative associations of PFAS with thyroid-related hormones were more pronounced in pregnant women with positive TG-Ab and/or TPOAb.[Conclusion]Exposure to PFAS during pregnancy may affect thyroid-related hormone homeostasis in pregnant women,and the effect is stronger in TG-Ab and/or TPOAb-positive pregnant women.