Villanger Gro D, Drover Samantha S M, Nethery Rachel C, Thomsen Cathrine, Sakhi Amrit K, Øvergaard Kristin R, Zeiner Pal, Hoppin Jane A, Reichborn-Kjennerud Ted, Aase Heidi, Engel Stephanie M
Norwegian Institute of Public Health, PO Box 222 Skøyen, N-0213 Oslo, Norway.
Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina and Chapel Hill, Chapel Hill, NC, USA.
Environ Int. 2020 Apr;137:105509. doi: 10.1016/j.envint.2020.105509. Epub 2020 Feb 7.
Human populations, including susceptible subpopulations such as pregnant women and their fetuses, are continuously exposed to phthalates. Phthalates may affect the thyroid hormone system, causing concern for pregnancy health, birth outcomes and child development. Few studies have investigated the joint effect of phthalates on thyroid function in pregnant women, although they are present as a mixture with highly inter-correlated compounds. Additionally, no studies have investigated if the key nutrient for thyroid health, iodine, modifies these relationships.
In this study, we examined the cross-sectional relationships between concentrations of 12 urinary phthalate metabolites and 6 plasma thyroid function biomarkers measured mid-pregnancy (~17 week gestation) in pregnant women (N = 1072), that were selected from a population-based prospective birth cohort, The Norwegian Mother, Father and Child Cohort study (MoBa). We investigated if the phthalate metabolite-thyroid function biomarker associations differed by iodine status by using a validated estimate of habitual dietary iodine intake based on a food frequency questionnaire from the 22nd gestation week. We accounted for the phthalate metabolite mixture by factor analyses, ultimately reducing the exposure into two uncorrelated factors. These factors were used as predictors in multivariable adjusted linear regression models with thyroid function biomarkers as the outcomes.
Factor 1, which included high loadings for mono-iso-butyl phthalate (MiBP), mono-n-butyl phthalate (MnBP), and monobenzyl phthalate (MBzP), was associated with increased total triiodothyronine (TT3) and free T3 index (fT3i). These associations appeared to be driven primarily by women with low iodine intake (<150 µg/day, ~70% of our sample). Iodine intake significantly modified (p-interaction < 0.05) the association of factor 1 with thyroid stimulating hormone (TSH), total thyroxine (TT4) and free T4 index (fT4i), such that only among women in the high iodine intake category (≥150 µg/day, i.e. sufficient) was this factor associated with increased TSH and decreased TT4 and FT4i, respectively. In contrast, factor 2, which included high loadings for di-2-ethylhexyl phthalate metabolites (∑DEHP) and di-iso-nonyl phthalate metabolites (∑DiNP), was associated with a decrease in TT3 and fT3i, which appeared fairly uniform across iodine intake categories.
We find that phthalate exposure is associated with thyroid function in mid-pregnancy among Norwegian women, and that iodine intake, which is essential for thyroid health, could influence some of these relationships.
包括孕妇及其胎儿等易感亚人群在内的人类群体持续暴露于邻苯二甲酸盐中。邻苯二甲酸盐可能会影响甲状腺激素系统，引发对妊娠健康、出生结局和儿童发育的担忧。尽管邻苯二甲酸盐是以高度相互关联的化合物混合物形式存在，但很少有研究调查其对孕妇甲状腺功能的联合影响。此外，尚无研究调查甲状腺健康的关键营养素碘是否会改变这些关系。
在本研究中，我们检测了从基于人群的前瞻性出生队列——挪威母亲、父亲和儿童队列研究（MoBa）中选取的1072名孕妇在妊娠中期（约妊娠17周）时12种尿邻苯二甲酸酯代谢物浓度与6种血浆甲状腺功能生物标志物之间的横断面关系。我们使用基于第22孕周食物频率问卷的习惯性膳食碘摄入量的有效估计值，调查邻苯二甲酸酯代谢物与甲状腺功能生物标志物之间的关联是否因碘状态而异。我们通过因子分析来处理邻苯二甲酸酯代谢物混合物，最终将暴露因素简化为两个不相关的因子。在以甲状腺功能生物标志物为结果的多变量调整线性回归模型中，将这些因子用作预测变量。
因子1包含较高负荷的邻苯二甲酸单异丁酯（MiBP）、邻苯二甲酸单正丁酯（MnBP）和邻苯二甲酸单苄酯（MBzP），与总三碘甲状腺原氨酸（TT3）和游离T3指数（fT3i）升高相关。这些关联似乎主要由碘摄入量低（<150μg/天，约占我们样本的70%）的女性驱动。碘摄入量显著改变（p交互作用<0.05）了因子1与促甲状腺激素（TSH）、总甲状腺素（TT4）和游离T4指数（fT4i）之间的关联，以至于仅在高碘摄入量类别（≥150μg/天，即充足）的女性中，该因子分别与TSH升高以及TT4和FT4i降低相关。相比之下，因子2包含较高负荷的邻苯二甲酸二（2-乙基己基）酯代谢物（∑DEHP）和邻苯二甲酸二异壬酯代谢物（∑DiNP），与TT3和fT3i降低相关，这在不同碘摄入量类别中似乎相当一致。
我们发现，挪威女性在妊娠中期邻苯二甲酸盐暴露与甲状腺功能相关，并且对甲状腺健康至关重要的碘摄入量可能会影响其中一些关系。
