title: Assessing the relationship between perfluoroalkyl substances, thyroid hormones and binding proteins in pregnant women; a longitudinal mixed effects approach.
abstract: The mechanisms involved in thyroid homeostasis are complex, and perfluoroalkyl substances (PFASs) have been indicated to interfere at several levels in this endocrine system. Disruption of the maternal thyroid homeostasis during early pregnancy is of particular concern, where subclinical changes in maternal thyroid hormones (THs) may affect embryonic and foetal development. The present study investigated associations between THs, thyroid binding proteins (TH-BPs) and PFAS concentrations in pregnant women from Northern Norway. Women participating in The Northern Norway Mother-and-Child contaminant Cohort Study (MISA) donated a blood sample at three visits related to their pregnancy and postpartum period (during the second trimester, 3 days and 6 weeks after delivery) in the period 2007-2009. Participants were assigned to quartiles according to PFAS concentrations during the second trimester and mixed effects linear models were used to investigate potential associations between PFASs and repeated measurements of THs, TH-BPs, thyroxin binding capacity and thyroid peroxidase antibodies (anti-TPOs). Women within the highest perfluorooctane sulfonate (PFOS) quartile had 24% higher mean concentrations of thyroid stimulating hormone (TSH) compared to the first quartile at all sampling points. Women within the highest quartiles of perfluorodecanoate (PFDA) had 4% lower mean concentrations of triiodothyronine (T3) and women within the highest quartile of perfluoroundecanoate (PFUnDA) had 3% lower mean concentrations of free triiodothyronine (FT3). Further, the difference in concentrations and the changes between three time points were the same for the PFAS quartiles. Thyroxin binding capacity was associated with all the THs and TH-BPs, and was selected as a holistic adjustment for individual changes in TH homeostasis during pregnancy. Finally, adjusting for maternal iodine status did not influence the model predictions. Findings in the present study suggest modifications of TH homeostasis by PFASs in a background exposed maternal population. The variation in levels of THs between PFAS quartiles was within normal reference ranges and may not be of clinical significance in the pregnant woman. However, subtle individual changes in maternal THs may have significant consequences for foetal health.
authors: Department of Laboratory Medicine, Diagnostic Clinic, University Hospital of Northern Norway, Sykehusveien 38, NO-9038 Tromsø, Norway; Department of Environmental Chemistry, NILU - Norwegian Institute of Air Research, Fram Centre, Hjalmar Johansens gate 14, NO-296 Tromsø, Norway; Department of Community Medicine, Faculty of Health Sciences, University of Tromsø-The Arctic University of Norway, Hansine Hansens veg 18, NO-019 Tromsø, Norway. Electronic address: vivian.berg@uit.no.
authors: Vivian
authors: V
authors: Berg
authors: Department of Laboratory Medicine, Diagnostic Clinic, University Hospital of Northern Norway, Sykehusveien 38, NO-9038 Tromsø, Norway; Department of Environmental Chemistry, NILU - Norwegian Institute of Air Research, Fram Centre, Hjalmar Johansens gate 14, NO-296 Tromsø, Norway; Department of Community Medicine, Faculty of Health Sciences, University of Tromsø-The Arctic University of Norway, Hansine Hansens veg 18, NO-019 Tromsø, Norway.
authors: Therese Haugdahl
authors: TH
authors: Nøst
authors: Department of Community Medicine, Faculty of Health Sciences, University of Tromsø-The Arctic University of Norway, Hansine Hansens veg 18, NO-019 Tromsø, Norway.
authors: Solrunn
authors: S
authors: Hansen
authors: Department of Laboratory Medicine, Diagnostic Clinic, University Hospital of Northern Norway, Sykehusveien 38, NO-9038 Tromsø, Norway.
authors: Astrid
authors: A
authors: Elverland
authors: Department of Community Medicine, Faculty of Health Sciences, University of Tromsø-The Arctic University of Norway, Hansine Hansens veg 18, NO-019 Tromsø, Norway.
authors: Anna-Sofía
authors: AS
authors: Veyhe
authors: Endocrine Research Group, Institute of Clinical Medicine, University of Tromsø-The Arctic University of Norway, Hansine Hansens veg 18, NO-9019 Tromsø, Norway.
authors: Rolf
authors: R
authors: Jorde
authors: Department of Community Medicine, Faculty of Health Sciences, University of Tromsø-The Arctic University of Norway, Hansine Hansens veg 18, NO-019 Tromsø, Norway.
authors: Jon Øyvind
authors: JØ
authors: Odland
authors: Department of Environmental Chemistry, NILU - Norwegian Institute of Air Research, Fram Centre, Hjalmar Johansens gate 14, NO-296 Tromsø, Norway; Department of Community Medicine, Faculty of Health Sciences, University of Tromsø-The Arctic University of Norway, Hansine Hansens veg 18, NO-019 Tromsø, Norway.
authors: Torkjel Manning
authors: TM
authors: Sandanger
mesh_terms: D000328:Adult; D002352:Carrier Proteins / Q000097:blood*; D015331:Cohort Studies; D004785:Environmental Pollutants / Q000097:blood; D005227:Fatty Acids / Q000097:blood; D005260:Female; D005466:Fluorocarbons / Q000097:blood*; D006801:Humans; D016014:Linear Models; D009664:Norway; D011247:Pregnancy; D011262:Pregnancy Trimester, Second / Q000097:blood; D013963:Thyroid Hormones / Q000097:blood*; D013972:Thyrotropin / Q000097:blood
chemical_list: D002352:Carrier Proteins; D004785:Environmental Pollutants; D005227:Fatty Acids; D005466:Fluorocarbons; D013963:Thyroid Hormones; C586085:perfluoroundecanoic acid; D013972:Thyrotropin
keywords: Endocrine disruption; Perfluoroalkyl substances; Pregnant women; Thyroid hormones; Thyroxin binding capacity