Perfluoroalkyl Substances and Maternal Thyroid Hormones in Early Pregnancy; Findings in the Danish National Birth Cohort

Abstract

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. https://doi.org/10.1289/EHP5482

Exposure to Perflouroalkyl acids and foetal and maternal thyroid status: a review

“…Two studies found significantly decreased maternal TSH levels with increasing PFOS, PFNA, PFDA, PFUnA and PFDoA concentrations [38,46], which might indicate a hyperthyroid maternal state. None of the ten studies investigating the association between PFOA concentration and maternal TSH found any significant results [38][39][40][41][42][43][44][45][46][47]. However, it should be noted that all these PFAAs are often highly intercorrelated.…”

“…We found 15 original publications that fulfilled the inclusion criteria [38][39][40][41][42][43][44][45][46][47][48][49][50][51][52] (Table 2). Study populations varied from 118 to 1366 participants [40,51], conducted in Asia (n = 6), Europe (n = 6) and Northern America (n = 3). Study designs were cross sectional and/or cohort studies.…”

“…Non-significant positive relationships were found with PFOA concentrations. PFOS and PFOA concentrations was mainly non-significantly but positively associated to maternal FT4 levels [38,40] and TT4 levels [39] (Table 8). FT4I was inversely associated to PFOA but not significantly to PFOS [39].…”

Ambient Exposure to Agricultural Pesticides during Pregnancy and Risk of Cerebral Palsy: A Population-Based Study in California

“…A previous study that investigated maternal infections or antibiotic use and CP risk in the offspring also reported the strongest associations in the first trimester [66]. Our own studies in the Danish cohort indicated that endocrine-disrupting compounds might interfere with the dynamics of maternal thyroid hormones in early gestation [67], and maternal thyroid function abnormalities were associated with adverse motor function in young children [68]. The early gestational period might be a critical time window for environmental exposures affecting CP risk.…”

Maternal Plasma Perfluoroalkyl Substances and Miscarriage: A Nested Case–Control Study in the Danish National Birth Cohort

“…The persistent PFAS have been shown to be highly correlated using repeated blood samples in the first and the second trimesters collected in the DNBC (Fei et al 2007). However, effect measure modification by gestational week of sampling is also possible and has recently been suggested for the thyroid hormone changes in early pregnancy (Inoue et al 2019). Our stratified analyses suggested a stronger effect estimate for samples collected after gestational week 8, but the stratified analyses were imprecise and need to be reevaluated in future research.…”