摘要：Background: Maternal thyroid hormones are essential for fetal brain development in early gestation. Perfluoroalkyl substances (PFASs)—widespread and persistent pollutants—have been suggested to interfere with maternal thyroid hormones in the second or third trimesters, but evidence for an association in the early pregnancy period is sparse. Objectives: Our goal was to evaluate the gestational-week specific associations of maternal thyroid-stimulating hormone (TSH) and free thyroxine (fT4) levels with plasma concentrations of six PFAS chemicals in the first and second pregnancy trimester. Methods: A cross-sectional analysis was conducted using 1,366 maternal blood samples collected between gestational weeks (GWs) 5 and 19 (median, 8 gestational weeks) in the Danish National Birth Cohort (DNBC) during 1996–2002. We estimated the percentage changes of serum TSH and fT4 levels according to concentrations (in nanograms per milliliter) of six PFAS chemicals modeled as per interquartile range (IQR) increase or by exposure quartiles. Moreover, we contrasted the estimated week-specific TSH or fT4 levels by PFAS quartile and estimated ORs for binary high or low TSH and fT4 status based on the week-specific distribution according to IQR increase of PFAS. Results: TSH levels followed a U-curve trend in early pregnancy with a nadir at GW10, whereas fT4 levels were less fluctuated in the samples. There were no apparent associations between any of the PFASs and changes of average TSH or fT4 levels in total samples. In gestational-week–specific analyses, we found that the estimated TSH values were higher among the highest perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonate (PFHxS), and perfluoroheptane sulfonate (PFHpS) quartiles compared with the lower quartiles from GW5 to GW10, but the difference became null or even reversed after GW10. For binary outcomes, perfluorodecanoic acid (PFDA) was associated with high fT4 status before GW10 [ OR = 1.46 (95% CI: 1.04, 2.05)]. Conclusions: We observed some gestational-week–specific associations between high exposure to several PFAS and TSH level in early gestations. Further research of the biology and the potential clinical impact regarding thyroid hormones disruptions in early pregnancy is needed.
