First Trimester Phthalate Exposure And Thyroid Function In Pregnancy Women And Offspring

Backgrounds and Objectives Biological sample monitoring data from around the world have shown that human exposure to phthalates was widespread.Phthalates exposure during pregnancy can interfere with normal thyroid function,and cause irreversible damage on the development of their offsprings.However,the prospective studies on the association of phthalates exposure and thyroid function during pregnancy are limited,and the findings are not consistent.The aim of present study was to investigate urinary phthalate concentrations and thyroid hormones levels in pregnant women during pregnancy in Ma’anshan city,Anhui province,China,and to investigate the associations between first trimester phthalate exposure and thyroid functions in pregnant women and their newborns.Methods This study was based on the Ma’anshan Birth Cohort(MABC)to set up a survey point in the Maternal and Child Health Hospital(MCH)in Ma’anshan City from May 2013 to September 2014.Pregnant women meeting the inclusion criteria were enrolled into the cohort.A standard questionnaire was completed by the women at the first antenatal visit.Seven phthalate metabolites were measured in one-spot urine at enrollment,as were thyroid hormone levels in maternal and cord sera.Specifically,the seven phthalate metabolites were monomethyl phthalate(MMP),monoethyl phthalate(MEP),monobutyl phthalate(MBP),and monobenzyl phthalate(MBz P),Mono(2-ethylhexyl)phthalate(MEHP),mono(2-ethyl-5-oxohexyl)phthalate(MEOHP),and mono(2-ethyl-5-hydroxylhexyl)phthalate(MEHHP),respectively.The thyroid hormone measured included thyroid stimulating hormone(TSH),total thyroxin(TT4),free thyroxin(FT4),and free triiodothyronine(TT3).Of the 3 474 women recruited in MABC,we selected 2 521 women from the pregnant women with single live birth neonate(n = 3 273)after excluding 752 women because of a history of thyroid disease(n = 67),the unavailability of maternal urine(n = 159),serum(n = 86),and cord serum(n = 440).We evaluated the correlations between urinary phthalate metabolites and THs in maternal and cord sera using Spearman rank order correlation.After controlling for confounding factors,multiple linear regression analysis was used to examine the relationship between phthalate metabolites and THs in maternal and cord serum.Results The highest level of serum thyroid hormones in pregnant women was TT3(152.98 ng / d L),the highest level of cord serum was TSH(8.40 μIU / m L).FT4 were the lowest in serum of pregnant women and umbilical cord blood samples,the concentrations were 1.30 ng / d L and 1.23 ng / d L,respectively.Spearman correlation analysis showed that there was a consistent positive correlation among phthalate monoesters by pairwise comparison.Mulivariable linear regression showed that 1 unit increase in natural log(ln)-transformed MEHP and MEHHP was respectively associated with 0.148 μg/d L(95%CI:-0.237~-0.059;P<0.007)and 0.200 μg/d L(95%CI:-0.313~-0.087;P<0.007)decreases in maternal serum TT4.Both MEHP and MEHHP were negatively associated with maternal serum FT4,the regression coefficients were-0.012 ng/d L(95%CI:-0.018~-0.006;P<0.007),and-0.012ng/d L(95%CI:-0.020~-0.005;P<0.007),respectively.An unit increase in ln-transformed urinary MEHP and MEHHP was associated with a 0.092 μIU/m L(95%CI: 0.050~0.133;P<0.007)and 0.153 μIU/m L(95%CI: 0.100~0.215;P<0.007)increase in maternal serum TSH.An inverse association was observed between MBz P and maternal serum TT4 and FT4.MBP was inversely associated with maternal serum TT4.In addition,the multiple linear regression model showed that there was a negative correlation between MEOHP and TSH in cord blood,the correlation coefficient was-0.032(95%CI: -0.062~0.003;P<0.05).MBP was negatively associated with FT4,the correlation coefficient was-0.005(95%CI:-0.009~0.000;P<0.05).Conclusion Several phthalates exposures during the first trimester were associated with altered circulatory thyroid hormone levels of pregnant women and the newborns.Considering the importance of thyroid hormones,additional epidemiological and animal studies are warranted to determine the direction of association between phthalate exposure and THs during pregnancy,and to elucidate the sensitive period of phthalate exposure in pregnancy and specific biological mechanisms.